Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

Barbara A Forey, Alison J Thornton and Peter N Lee

Additional file 7 : MetaDoseCOPD

See Additional file 10 (Intro sheet) for list of tables and page numbers

                                                    Table 1 - E - 1 -

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 1) = 5
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 1

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  11   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   1  14
    BEST  38   m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
   CHEN2  13   m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  19
   CHEN2  16   f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  19
  CLEMEN   4   m   20   60     Eu:West  1960  1982    Pr  Prev      COPD:LF   0 Current       Cigs   Nev any   1  19
   DEAN1  24   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any   1  12
   DEAN1  64   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any   1  12
   DOLL1   7   m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1  14
   DOLL2   4   f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1  14
  ENSTRO   7   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  ENSTRO  16   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  FERRI2  26   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  FERRI2  43   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  GODTFR   6   b   20   99    Eu:Scand  1964  2002    Pr   Inc     COPD:ICD   3 Current        Any   Nev any   1  14
  HOZAWA   4   b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs   1  14
  HUHTI1  26   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs   Nev any   1  14
  HUHTI1  34   f   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs   Nev any   1  14
  HUHTI3  12   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   1 Current        Any   Nev any   1  14
  JACOBS  26   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   6 Current       Cigs  Nev cigs   1   9
   KAHN2  99   m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any   1   9
  KRZYZA   7   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs  Nev cigs   1  14
  KRZYZA  10   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs  Nev cigs   1  14
     LEE  22   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
     LEE  43   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
  LINDST  11   b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs  Nev cigs   5  14
  LUNDB1  11   b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs  Nev cigs   5  14
  MUELLE  25   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   1 Current       Cigs   Nev any   1  14
  NILSSO  10   m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
  NILSSO  15   f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
    PETO   4   m   25   92       Eu:UK  1954  1983    Pr   Inc    COPD:mort   0 Current       Cigs  Nev cigs   1  14
  SPEIZE   7   m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  14
  SPEIZE  10   f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  14
    TODD  22   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  TVERDA   5   m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only  Nev cigs   1   9
  VONHER   9   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
  VONHER  16   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
   WEISS   6   m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any   1   9
     WEN   2   m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  10
  YAMAGU   4   b   40   99   Asia:FarE  1986  1988    CS  Prev      COPD:LF   6 Current       Cigs  Nev cigs   1   9
    YUAN   9   m   45   71   Asia:FarE  1986  1996    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs   1  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 2

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 11  m   1          3       -       2       -      2.79 (  0.41-  18.82)
*BEST   38  m   1         26       -       6       -      6.06 (  2.50-  14.71)
 CHEN2  13  m   6          -       -       8       -      1.72 (  0.50-   5.92)
 CHEN2  16  f   6          -       -      33       -      2.61 (  1.33-   5.13)
 Subtotal CHEN2                                           2.37 (  1.31-   4.29)
 CLEMEN 4   m   0         16     812      11     709      1.27 (  0.59-   2.75)
 DEAN1  24  m   3         97       -      47       -      3.22 (  2.09-   4.97)
 DEAN1  64  f   3         25       -     120       -      1.01 (  0.63-   1.62)
 Subtotal DEAN1                                           1.90 (  1.38-   2.61)
*DOLL1  7   m   2         58       -      12       -      8.60 (  4.64-  15.92)
*DOLL2  4   f   1          3       -       1       -     10.50 (  1.09- 100.95)
*ENSTRO 7   m   1         35       -     103       -      2.84 (  1.94-   4.17)
*ENSTRO 16  f   1         50       -     296       -      1.64 (  1.21-   2.22)
 Subtotal ENSTRO                                          2.03 (  1.60-   2.57)
 FERRI2 26  m   1         16       -      11       -      2.55 (  1.08-   6.04)
 FERRI2 43  f   1         13       -      54       -      1.59 (  0.82-   3.09)
 Subtotal FERRI2                                          1.90 (  1.12-   3.21)
*GODTFR 6   b   3        270       -      71       -      4.03 (  3.02-   5.37)
 HOZAWA 4   b   0        305     759     872    5019      2.31 (  1.99-   2.69)
 HUHTI1 26  m   1         47       -       7       -     10.72 (  4.39-  26.22)
 HUHTI1 34  f   1         10       -      56       -      1.84 (  0.87-   3.88)
 Subtotal HUHTI1                                          3.80 (  2.14-   6.74)
 HUHTI3 12  m   1         42       -       3       -      9.77 (  3.22-  29.61)
*JACOBS 26  m   6         39       -      28       -      2.90 (  1.75-   4.85)
*KAHN2  99  m   1         28       -      31       -      4.14 (  2.48-   6.90)
*KRZYZA 7   m   1          8       -       5       -      2.24 (  0.79-   6.39)
*KRZYZA 10  f   1          6       -      32       -      1.40 (  0.65-   3.01)
 Subtotal KRZYZA                                          1.65 (  0.89-   3.06)
*LEE    22  m   1          4       -       1       -      7.75 (  0.87-  68.85)
*LEE    43  f   0          2     342       5    1694      1.98 (  0.39-  10.17)
 Subtotal LEE                                             3.23 (  0.87-  11.98)
 LINDST 11  b   5          -       -     166       -      1.94 (  1.47-   2.57)
 LUNDB1 11  b   4          -       -      39       -      6.44 (  3.37-  11.60)
 MUELLE 25  m   1          4       -       2       -      4.51 (  0.71-  28.48)
*NILSSO 10  m   2         19       -      31       -      3.30 (  1.86-   5.85)
*NILSSO 15  f   2         18       -      57       -      3.80 (  2.20-   6.57)
 Subtotal NILSSO                                          3.55 (  2.39-   5.28)
*PETO   4   m   0         57    1181       0     295     28.76~(  1.78- 464.04)
*SPEIZE 7   m   1          6       -       0       -     13.00 (  0.73- 230.76)
*SPEIZE 10  f   1          5       -       5       -      6.33 (  1.83-  21.88)
 Subtotal SPEIZE                                          7.09 (  2.27-  22.14)
*TODD   22  m   1          6       -       1       -      8.94 (  1.08-  73.89)
*TVERDA 5   m   2          5       -       7       -      1.86 (  0.59-   5.88)
 VONHER 9   m   0         50     121      63     911      5.98 (  3.94-   9.07)
 VONHER 16  f   0         28     172     137    2888      3.43 (  2.22-   5.30)
 Subtotal VONHER                                          4.58 (  3.39-   6.19)
 WEISS  6   m   0          2      13       2      34      2.62 (  0.33-  20.55)
*WEN    2   m   1         27       -      52       -      1.83 (  1.07-   3.12)
 YAMAGU 4   b   6          -       -     144       -      1.96 (  1.53-   2.53)
*YUAN   9   m   2          9       -      19       -      0.80 (  0.36-   1.77)
Partial Totals          1339    3400    2540   11550
*prospective study                                        ~ With 0.5 adjustment for zero

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 2

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 11  m   1              1.03     1.05     0.01       0.29
*BEST   38  m   1              1.80     4.89     3.58       0.00
 CHEN2  13  m   6              0.54     2.52     0.41       0.39
 CHEN2  16  f   6              0.96     8.43     0.00       0.01
 Subtotal CHEN2                0.86    10.95     0.41
 CLEMEN 4   m   0              0.24     6.41     3.21       0.55
 DEAN1  24  m   3              1.17    20.48     1.02       0.00
 DEAN1  64  f   3              0.01    17.23    15.12       0.97
 Subtotal DEAN1                0.64    37.70    16.13
*DOLL1  7   m   2              2.15    10.11    14.68       0.00
*DOLL2  4   f   1              2.35     0.75     1.48       0.04
*ENSTRO 7   m   1              1.04    26.24     0.25       0.00
*ENSTRO 16  f   1              0.49    41.72     8.52       0.00
 Subtotal ENSTRO               0.71    67.96     8.77
 FERRI2 26  m   1              0.94     5.19     0.00       0.03
 FERRI2 43  f   1              0.46     8.73     2.04       0.17
 Subtotal FERRI2               0.64    13.92     2.04
*GODTFR 6   b   3              1.39    46.38     9.27       0.00
 HOZAWA 4   b   0              0.84   168.29     1.97       0.00
 HUHTI1 26  m   1              2.37     4.81     9.77       0.00
 HUHTI1 34  f   1              0.61     6.87     0.78       0.11
 Subtotal HUHTI1               1.34    11.68    10.55
 HUHTI3 12  m   1              2.28     3.12     5.54       0.00
*JACOBS 26  m   6              1.06    14.79     0.21       0.00
*KAHN2  99  m   1              1.42    14.68     3.30       0.00
*KRZYZA 7   m   1              0.81     3.52     0.07       0.13
*KRZYZA 10  f   1              0.34     6.54     2.44       0.39
 Subtotal KRZYZA               0.50    10.06     2.51
*LEE    22  m   1              2.05     0.80     0.97       0.07
*LEE    43  f   0              0.68     1.44     0.10       0.41
 Subtotal LEE                  1.17     2.24     1.07
 LINDST 11  b   5              0.66    49.24     3.97       0.00
 LUNDB1 11  b   4              1.86    10.06     8.43       0.00
 MUELLE 25  m   1              1.51     1.13     0.35       0.11
*NILSSO 10  m   2              1.19    11.70     0.72       0.00
*NILSSO 15  f   2              1.34    12.84     1.94       0.00
 Subtotal NILSSO               1.27    24.54     2.65
*PETO   4   m   0              3.36     0.50     2.89       0.02
*SPEIZE 7   m   1              2.56     0.46     1.21       0.08
*SPEIZE 10  f   1              1.85     2.50     2.02       0.00
 Subtotal SPEIZE               1.96     2.96     3.23
*TODD   22  m   1              2.19     0.86     1.33       0.04
*TVERDA 5   m   2              0.62     2.91     0.31       0.29
 VONHER 9   m   0              1.79    22.11    15.63       0.00
 VONHER 16  f   0              1.23    20.34     1.67       0.00
 Subtotal VONHER               1.52    42.44    17.30
 WEISS  6   m   0              0.96     0.90     0.00       0.36
*WEN    2   m   1              0.60    13.42     1.57       0.03
 YAMAGU 4   b   6              0.67    60.74     4.55       0.00
*YUAN   9   m   2             -0.22     6.06     8.29       0.58

                       N       40
                      NS       30

                      Wt   640.72
                 Het Chi   139.61
                 Het  df       39
                 Het  P       ***
               Fixed  RR     2.58
                     RRl     2.39
                     RRu     2.78
                      P       +++
              Random  RR     2.89
                     RRl     2.41
                     RRu     3.45
                      P       +++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       40
                      NS       30

                      Wt   640.72
                 Het Chi   139.61
                 Het  df       39
                 Het  P       ***
               Fixed  RR     2.58
                     RRl     2.39
                     RRu     2.78
                      P       +++
              Random  RR     2.89
                     RRl     2.41
                     RRu     3.45
                      P       +++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N        5        24        11        40
                      NS        5        24        11        40

                      Wt   334.71    178.64    127.38    640.72
                 Het Chi    27.13     61.00     28.21    139.61
                 Het  df        4        23        10        39
                 Het  P       ***       ***        **       ***
               Fixed  RR     2.44      3.42      2.01      2.58
                     RRl     2.19      2.95      1.69      2.39
                     RRu     2.71      3.96      2.39      2.78
                      P       +++       +++       +++       +++
              Random  RR     2.75      3.45      2.17      2.89
                     RRl     2.01      2.62      1.56      2.41
                     RRu     3.77      4.54      3.04      3.45
                      P       +++       +++       +++       +++
             Between Chi                                  23.27
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       14        22         3         1        40
                      NS       10        16         3         1        30

                      Wt   286.72    259.00     80.22     14.79    640.72
                 Het Chi    21.50     91.13      4.43      0.00    139.61
                 Het  df       13        21         2         0        39
                 Het  P       (*)       ***      N.S.      N.S.       ***
               Fixed  RR     2.36      3.14      1.81      2.90      2.58
                     RRl     2.11      2.78      1.45      1.74      2.39
                     RRu     2.65      3.55      2.25      4.83      2.78
                      P       +++       +++       +++       +++       +++
              Random  RR     2.57      3.41      1.61      2.90      2.89
                     RRl     2.07      2.54      1.06      1.74      2.41
                     RRu     3.20      4.57      2.47      4.83      3.45
                      P       +++       +++         +       +++       +++
             Between Chi                                            22.56
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                               (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N       25        12        37
                      NS       18         9        27

                      Wt   491.45     69.05    560.50
                 Het Chi    82.76     40.70    123.76
                 Het  df       24        11        36
                 Het  P       ***       ***       ***
               Fixed  RR     2.69      2.89      2.71
                     RRl     2.46      2.28      2.50
                     RRu     2.94      3.65      2.94
                      P       +++       +++       +++
              Random  RR     3.02      3.65      3.10
                     RRl     2.47      2.09      2.56
                     RRu     3.69      6.34      3.75
                      P       +++       +++       +++
             Between Chi                         0.31
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N       27         5         4         3                   1        40
                      NS       20         3         4         2                   1        30

                      Wt   273.67     48.31    248.51     21.00               49.24    640.72
                 Het Chi    87.14      6.35      7.68      5.57                0.00    139.61
                 Het  df       26         4         3         2                   0        39
                 Het  P       ***      N.S.       (*)       (*)                N.S.       ***
               Fixed  RR     2.83      4.46      2.14      3.83                1.94      2.58
                     RRl     2.52      3.36      1.89      2.49                1.47      2.39
                     RRu     3.19      5.91      2.42      5.87                2.57      2.78
                      P       +++       +++       +++       +++                 +++       +++
              Random  RR     3.09      4.34      1.91      3.40                1.94      2.89
                     RRl     2.40      2.82      1.46      1.58                1.47      2.41
                     RRu     3.98      6.69      2.50      7.33                2.57      3.45
                      P       +++       +++       +++        ++                 +++       +++
             Between Chi                                                                32.87
             Between  df                                                                    4
             Between  P                                                                   ***
             Btwn(F)  P                                                                     *

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N       15         8         4        13        40
                      NS       11         6         4         9        30

                      Wt    92.17     81.41     33.86    433.27    640.72
                 Het Chi    43.48     12.75     22.46     54.20    139.61
                 Het  df       14         7         3        12        39
                 Het  P       ***       (*)       ***       ***       ***
               Fixed  RR     2.76      2.01      3.07      2.63      2.58
                     RRl     2.25      1.61      2.19      2.39      2.39
                     RRu     3.38      2.49      4.30      2.89      2.78
                      P       +++       +++       +++       +++       +++
              Random  RR     3.29      2.35      2.56      2.93      2.89
                     RRl     2.17      1.47      0.96      2.33      2.41
                     RRu     4.99      3.76      6.83      3.69      3.45
                      P       +++       +++       (+)       +++       +++
             Between Chi                                             6.73
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2        22        16        40
                      NS        1        17        12        30

                      Wt    37.70    229.50    373.52    640.72
                 Het Chi    12.58     66.13     54.82    139.61
                 Het  df        1        21        15        39
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.90      2.84      2.50      2.58
                     RRl     1.38      2.50      2.26      2.39
                     RRu     2.61      3.24      2.77      2.78
                      P       +++       +++       +++       +++
              Random  RR     1.81      2.96      3.03      2.89
                     RRl     0.58      2.26      2.34      2.41
                     RRu     5.64      3.89      3.93      3.45
                      P      N.S.       +++       +++       +++
             Between Chi                                   6.09
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N       10        22         8                  40
                      NS        8        15         7                  30

                      Wt   148.61    219.59    272.52              640.72
                 Het Chi    35.57     67.26     31.45              139.61
                 Het  df        9        21         7                  39
                 Het  P       ***       ***       ***                 ***
               Fixed  RR     2.94      2.66      2.34                2.58
                     RRl     2.50      2.33      2.08                2.39
                     RRu     3.45      3.04      2.63                2.78
                      P       +++       +++       +++                 +++
              Random  RR     3.01      2.97      2.67                2.89
                     RRl     2.05      2.25      1.86                2.41
                     RRu     4.42      3.93      3.82                3.45
                      P       +++       +++       +++                 +++
             Between Chi                                             5.33
             Between  df                                                2
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        6         7        10        17                  40
                      NS        4         7         7        12                  30

                      Wt   197.33     64.40     66.59    312.40              640.72
                 Het Chi    14.30     13.92     17.16     84.02              139.61
                 Het  df        5         6         9        16                  39
                 Het  P         *         *         *       ***                 ***
               Fixed  RR     2.34      1.98      3.03      2.80                2.58
                     RRl     2.03      1.55      2.38      2.50                2.39
                     RRu     2.69      2.52      3.85      3.12                2.78
                      P       +++       +++       +++       +++                 +++
              Random  RR     2.48      2.31      2.93      3.29                2.89
                     RRl     1.59      1.27      2.03      2.46                2.41
                     RRu     3.88      4.20      4.23      4.39                3.45
                      P       +++        ++       +++       +++                 +++
             Between Chi                                                      10.22
             Between  df                                                          3
             Between  P                                                           *
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        4        36        40
                      NS        3        27        30

                      Wt    41.11    599.61    640.72
                 Het Chi    16.21    120.07    139.61
                 Het  df        3        35        39
                 Het  P        **       ***       ***
               Fixed  RR     1.96      2.63      2.58
                     RRl     1.44      2.42      2.39
                     RRu     2.66      2.85      2.78
                      P       +++       +++       +++
              Random  RR     2.29      2.98      2.89
                     RRl     0.93      2.48      2.41
                     RRu     5.63      3.58      3.45
                      P       (+)       +++       +++
             Between Chi                         3.34
             Between  df                            1
             Between  P                           (*)
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       20         9        11        40
                      NS       15         8         7        30

                      Wt   204.36    260.71    175.66    640.72
                 Het Chi    69.49     23.15     38.22    139.61
                 Het  df       19         8        10        39
                 Het  P       ***        **       ***       ***
               Fixed  RR     2.57      2.30      3.07      2.58
                     RRl     2.24      2.04      2.65      2.39
                     RRu     2.95      2.60      3.56      2.78
                      P       +++       +++       +++       +++
              Random  RR     3.00      2.55      3.05      2.89
                     RRl     2.21      1.83      2.18      2.41
                     RRu     4.08      3.54      4.26      3.45
                      P       +++       +++       +++       +++
             Between Chi                                   8.75
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N       24                  13         3        40
                      NS       19                   8         3        30

                      Wt   470.84              144.24     25.65    640.72
                 Het Chi    73.26               41.97      7.62    139.61
                 Het  df       23                  12         2        39
                 Het  P       ***                 ***         *       ***
               Fixed  RR     2.68                2.06      4.62      2.58
                     RRl     2.44                1.75      3.14      2.39
                     RRu     2.93                2.42      6.81      2.78
                      P       +++                 +++       +++       +++
              Random  RR     3.07                2.26      5.41      2.89
                     RRl     2.49                1.59      2.14      2.41
                     RRu     3.78                3.23     13.65      3.45
                      P       +++                 +++       +++       +++
             Between Chi                                            16.77
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                               (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        8         1         9
                      NS        7         1         8

                      Wt   250.65     10.06    260.71
                 Het Chi    12.05      0.00     23.15
                 Het  df        7         0         8
                 Het  P       (*)      N.S.        **
               Fixed  RR     2.21      6.44      2.30
                     RRl     1.95      3.47      2.04
                     RRu     2.50     11.95      2.60
                      P       +++       +++       +++
              Random  RR     2.16      6.44      2.55
                     RRl     1.67      3.47      1.83
                     RRu     2.81     11.95      3.54
                      P       +++       +++       +++
             Between Chi                        11.10
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        5         8         8        19        40
                      NS        4         7         6        13        30

                      Wt     5.74     22.64     49.87    562.47    640.72
                 Het Chi     1.23     17.75     18.97     95.38    139.61
                 Het  df        4         7         7        18        39
                 Het  P      N.S.         *        **       ***       ***
               Fixed  RR     5.83      1.91      2.83      2.57      2.58
                     RRl     2.57      1.27      2.14      2.36      2.39
                     RRu    13.22      2.89      3.73      2.79      2.78
                      P       +++        ++       +++       +++       +++
              Random  RR     5.83      2.50      2.93      2.89      2.89
                     RRl     2.57      1.21      1.78      2.34      2.41
                     RRu    13.22      5.15      4.81      3.57      3.45
                      P       +++         +       +++       +++       +++
             Between Chi                                             6.28
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        5         8         8        19        40
                      NS        4         7         6        13        30

                      Wt     5.74     22.64     49.87    562.47    640.72
                 Het Chi     1.23     17.75     18.97     95.38    139.61
                 Het  df        4         7         7        18        39
                 Het  P      N.S.         *        **       ***       ***
               Fixed  RR     5.83      1.91      2.83      2.57      2.58
                     RRl     2.57      1.27      2.14      2.36      2.39
                     RRu    13.22      2.89      3.73      2.79      2.78
                      P       +++        ++       +++       +++       +++
              Random  RR     5.83      2.50      2.93      2.89      2.89
                     RRl     2.57      1.21      1.78      2.34      2.41
                     RRu    13.22      5.15      4.81      3.57      3.45
                      P       +++         +       +++       +++       +++
             Between Chi                                             6.28
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       19        21        40
                      NS       14        16        30

                      Wt   417.63    223.09    640.72
                 Het Chi    72.72     61.85    139.61
                 Het  df       18        20        39
                 Het  P       ***       ***       ***
               Fixed  RR     2.42      2.91      2.58
                     RRl     2.19      2.55      2.39
                     RRu     2.66      3.32      2.78
                      P       +++       +++       +++
              Random  RR     2.72      3.10      2.89
                     RRl     2.13      2.35      2.41
                     RRu     3.47      4.08      3.45
                      P       +++       +++       +++
             Between Chi                         5.04
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        2        24        14        40
                      NS        2        18        10        30

                      Wt    49.50    438.35    152.87    640.72
                 Het Chi     2.29     73.60     49.98    139.61
                 Het  df        1        23        13        39
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     4.26      2.45      2.54      2.58
                     RRl     3.23      2.23      2.17      2.39
                     RRu     5.63      2.69      2.98      2.78
                      P       +++       +++       +++       +++
              Random  RR     5.30      2.66      3.10      2.89
                     RRl     2.38      2.15      2.13      2.41
                     RRu    11.82      3.29      4.50      3.45
                      P       +++       +++       +++       +++
             Between Chi                                  13.74
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       25        15                            40
                      NS       18        12                            30

                      Wt   290.77    349.95                        640.72
                 Het Chi    92.07     30.71                        139.61
                 Het  df       24        14                            39
                 Het  P       ***        **                           ***
               Fixed  RR     3.08      2.22                          2.58
                     RRl     2.74      2.00                          2.39
                     RRu     3.45      2.47                          2.78
                      P       +++       +++                           +++
              Random  RR     3.34      2.28                          2.89
                     RRl     2.57      1.84                          2.41
                     RRu     4.33      2.83                          3.45
                      P       +++       +++                           +++
             Between Chi                                            16.84
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                 *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       25        15        40
                      NS       18        12        30

                      Wt   290.77    349.95    640.72
                 Het Chi    92.07     30.71    139.61
                 Het  df       24        14        39
                 Het  P       ***        **       ***
               Fixed  RR     3.08      2.22      2.58
                     RRl     2.74      2.00      2.39
                     RRu     3.45      2.47      2.78
                      P       +++       +++       +++
              Random  RR     3.34      2.28      2.89
                     RRl     2.57      1.84      2.41
                     RRu     4.33      2.83      3.45
                      P       +++       +++       +++
             Between Chi                        16.84
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

                        Number of adjustment variables
                                0         1        2+     Total

                       N        7        19        14        40
                      NS        6        14        11        31

                      Wt   219.97    147.27    273.47    640.72
                 Het Chi    25.44     45.17     68.91    139.61
                 Het  df        6        18        13        39
                 Het  P       ***       ***       ***       ***
               Fixed  RR     2.61      2.52      2.58      2.58
                     RRl     2.28      2.15      2.29      2.39
                     RRu     2.97      2.97      2.91      2.78
                      P       +++       +++       +++       +++
              Random  RR     3.02      3.12      2.69      2.89
                     RRl     1.87      2.30      1.99      2.41
                     RRu     4.88      4.25      3.62      3.45
                      P       +++       +++       +++       +++
             Between Chi                                   0.10
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 4

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  11     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   1  14
    BEST  38     m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
   CHEN2  13     m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  19
   CHEN2  16     f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  19
  CLEMEN   4     m   20   60     Eu:West  1960  1982    Pr  Prev      COPD:LF   0 Current       Cigs   Nev any   1  19
   DEAN1  19 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any   1  12
   DEAN1  59 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any   1  12
   DOLL1   7     m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1  14
   DOLL2   4     f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1  14
  ENSTRO   7     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  ENSTRO  16     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  FERRI2  26     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  FERRI2  43     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  GODTFR   6     b   20   99    Eu:Scand  1964  2002    Pr   Inc     COPD:ICD   3 Current        Any   Nev any   1  14
  HOZAWA   4     b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs   1  14
  HUHTI1  21 x   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs   Nev any   1  14
  HUHTI1  31 x   f   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs   Nev any   1  14
  HUHTI3   7 x   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   0 Current        Any   Nev any   1  14
  JACOBS  18 x   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs   5   9
   KAHN2  99     m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any   1   9
  KRZYZA   7     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs  Nev cigs   1  14
  KRZYZA  10     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs  Nev cigs   1  14
     LEE   8 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
     LEE  43     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
  LINDST  11     b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs  Nev cigs   5  14
  LUNDB1  11     b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs  Nev cigs   5  14
  MUELLE  20 x   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   0 Current       Cigs   Nev any   1  14
  NILSSO  10     m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
  NILSSO  15     f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
    PETO   4     m   25   92       Eu:UK  1954  1983    Pr   Inc    COPD:mort   0 Current       Cigs  Nev cigs   1  14
  SPEIZE   7     m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  14
  SPEIZE  10     f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  14
    TODD   8 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
  TVERDA   5     m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only  Nev cigs   1   9
  VONHER   9     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
  VONHER  16     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
   WEISS   6     m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any   1   9
     WEN   2     m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  10
  YAMAGU   4     b   40   99   Asia:FarE  1986  1988    CS  Prev      COPD:LF   6 Current       Cigs  Nev cigs   1   9
    YUAN   6 x   m   45   71   Asia:FarE  1986  1996    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs   1  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 5

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 11  m   1          3       -       2       -      2.79 (  0.41-  18.82)
*BEST   38  m   1         26       -       6       -      6.06 (  2.50-  14.71)
 CHEN2  13  m   6          -       -       8       -      1.72 (  0.50-   5.92)
 CHEN2  16  f   6          -       -      33       -      2.61 (  1.33-   5.13)
 Subtotal CHEN2                                           2.37 (  1.31-   4.29)
 CLEMEN 4   m   0         16     812      11     709      1.27 (  0.59-   2.75)
 DEAN1  19  m   0         97     256      47     510      4.11 (  2.81-   6.01)
 DEAN1  59  f   0         25     486     120    1538      0.66 (  0.42-   1.03)
 Subtotal DEAN1                                           1.89 (  1.42-   2.53)
*DOLL1  7   m   2         58       -      12       -      8.60 (  4.64-  15.92)
*DOLL2  4   f   1          3       -       1       -     10.50 (  1.09- 100.95)
*ENSTRO 7   m   1         35       -     103       -      2.84 (  1.94-   4.17)
*ENSTRO 16  f   1         50       -     296       -      1.64 (  1.21-   2.22)
 Subtotal ENSTRO                                          2.03 (  1.60-   2.57)
 FERRI2 26  m   1         16       -      11       -      2.55 (  1.08-   6.04)
 FERRI2 43  f   1         13       -      54       -      1.59 (  0.82-   3.09)
 Subtotal FERRI2                                          1.90 (  1.12-   3.21)
*GODTFR 6   b   3        270       -      71       -      4.03 (  3.02-   5.37)
 HOZAWA 4   b   0        305     759     872    5019      2.31 (  1.99-   2.69)
 HUHTI1 21  m   0         47      61       7     115     12.66 (  5.40-  29.69)
 HUHTI1 31  f   0         10      67      56     653      1.74 (  0.85-   3.57)
 Subtotal HUHTI1                                          3.97 (  2.29-   6.87)
 HUHTI3 7   m   0         42     273       3     236     12.10 (  3.70-  39.55)
*JACOBS 18  m   2         30       -      28       -      4.57 (  2.59-   8.06)
*KAHN2  99  m   1         28       -      31       -      4.14 (  2.48-   6.90)
*KRZYZA 7   m   1          8       -       5       -      2.24 (  0.79-   6.39)
*KRZYZA 10  f   1          6       -      32       -      1.40 (  0.65-   3.01)
 Subtotal KRZYZA                                          1.65 (  0.89-   3.06)
*LEE    8   m   0          4     192       1     347      7.23 (  0.81-  64.22)
*LEE    43  f   0          2     342       5    1694      1.98 (  0.39-  10.17)
 Subtotal LEE                                             3.15 (  0.85-  11.68)
 LINDST 11  b   5          -       -     166       -      1.94 (  1.47-   2.57)
 LUNDB1 11  b   4          -       -      39       -      6.44 (  3.37-  11.60)
 MUELLE 20  m   0          4      24       2      57      4.75 (  0.81-  27.69)
*NILSSO 10  m   2         19       -      31       -      3.30 (  1.86-   5.85)
*NILSSO 15  f   2         18       -      57       -      3.80 (  2.20-   6.57)
 Subtotal NILSSO                                          3.55 (  2.39-   5.28)
*PETO   4   m   0         57    1181       0     295     28.76~(  1.78- 464.04)
*SPEIZE 7   m   1          6       -       0       -     13.00 (  0.73- 230.76)
*SPEIZE 10  f   1          5       -       5       -      6.33 (  1.83-  21.88)
 Subtotal SPEIZE                                          7.09 (  2.27-  22.14)
*TODD   8   m   0          6     316       1     520      9.87 (  1.19-  81.63)
*TVERDA 5   m   2          5       -       7       -      1.86 (  0.59-   5.88)
 VONHER 9   m   0         50     121      63     911      5.98 (  3.94-   9.07)
 VONHER 16  f   0         28     172     137    2888      3.43 (  2.22-   5.30)
 Subtotal VONHER                                          4.58 (  3.39-   6.19)
 WEISS  6   m   0          2      13       2      34      2.62 (  0.33-  20.55)
*WEN    2   m   1         27       -      52       -      1.83 (  1.07-   3.12)
 YAMAGU 4   b   6          -       -     144       -      1.96 (  1.53-   2.53)
*YUAN   6   m   1          9       -      19       -      0.80 (  0.36-   1.77)
Partial Totals          1330    5075    2540   15526
*prospective study                                        ~ With 0.5 adjustment for zero

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 5

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 11  m   1              1.03     1.05     0.01       0.29
*BEST   38  m   1              1.80     4.89     3.53       0.00
 CHEN2  13  m   6              0.54     2.52     0.42       0.39
 CHEN2  16  f   6              0.96     8.43     0.00       0.01
 Subtotal CHEN2                0.86    10.95     0.42
 CLEMEN 4   m   0              0.24     6.41     3.26       0.55
 DEAN1  19  m   0              1.41    26.70     5.69       0.00
 DEAN1  59  f   0             -0.42    19.59    36.71       0.07
 Subtotal DEAN1                0.64    46.29    42.40
*DOLL1  7   m   2              2.15    10.11    14.54       0.00
*DOLL2  4   f   1              2.35     0.75     1.47       0.04
*ENSTRO 7   m   1              1.04    26.24     0.22       0.00
*ENSTRO 16  f   1              0.49    41.72     8.74       0.00
 Subtotal ENSTRO               0.71    67.96     8.96
 FERRI2 26  m   1              0.94     5.19     0.00       0.03
 FERRI2 43  f   1              0.46     8.73     2.08       0.17
 Subtotal FERRI2               0.64    13.92     2.09
*GODTFR 6   b   3              1.39    46.38     9.04       0.00
 HOZAWA 4   b   0              0.84   168.29     2.18       0.00
 HUHTI1 21  m   0              2.54     5.28    13.29       0.00
 HUHTI1 31  f   0              0.55     7.45     1.18       0.13
 Subtotal HUHTI1               1.38    12.73    14.47
 HUHTI3 7   m   0              2.49     2.74     6.51       0.00
*JACOBS 18  m   2              1.52    11.92     3.84       0.00
*KAHN2  99  m   1              1.42    14.68     3.22       0.00
*KRZYZA 7   m   1              0.81     3.52     0.07       0.13
*KRZYZA 10  f   1              0.34     6.54     2.48       0.39
 Subtotal KRZYZA               0.50    10.06     2.56
*LEE    8   m   0              1.98     0.81     0.85       0.08
*LEE    43  f   0              0.68     1.44     0.10       0.41
 Subtotal LEE                  1.15     2.24     0.95
 LINDST 11  b   5              0.66    49.24     4.13       0.00
 LUNDB1 11  b   4              1.86    10.06     8.33       0.00
 MUELLE 20  m   0              1.56     1.24     0.45       0.08
*NILSSO 10  m   2              1.19    11.70     0.68       0.00
*NILSSO 15  f   2              1.34    12.84     1.88       0.00
 Subtotal NILSSO               1.27    24.54     2.56
*PETO   4   m   0              3.36     0.50     2.88       0.02
*SPEIZE 7   m   1              2.56     0.46     1.21       0.08
*SPEIZE 10  f   1              1.85     2.50     1.99       0.00
 Subtotal SPEIZE               1.96     2.96     3.20
*TODD   8   m   0              2.29     0.86     1.54       0.03
*TVERDA 5   m   2              0.62     2.91     0.32       0.29
 VONHER 9   m   0              1.79    22.11    15.43       0.00
 VONHER 16  f   0              1.23    20.34     1.60       0.00
 Subtotal VONHER               1.52    42.44    17.03
 WEISS  6   m   0              0.96     0.90     0.00       0.36
*WEN    2   m   1              0.60    13.42     1.62       0.03
 YAMAGU 4   b   6              0.67    60.74     4.74       0.00
*YUAN   6   m   1             -0.22     6.06     8.37       0.58

                       N       40
                      NS       30

                      Wt   647.22
                 Het Chi   174.61
                 Het  df       39
                 Het  P       ***
               Fixed  RR     2.59
                     RRl     2.40
                     RRu     2.80
                      P       +++
              Random  RR     2.96
                     RRl     2.43
                     RRu     3.60
                      P       +++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 6

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       40
                      NS       30

                      Wt   647.22
                 Het Chi   174.61
                 Het  df       39
                 Het  P       ***
               Fixed  RR     2.59
                     RRl     2.40
                     RRu     2.80
                      P       +++
              Random  RR     2.96
                     RRl     2.43
                     RRu     3.60
                      P       +++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N        5        24        11        40
                      NS        5        24        11        40

                      Wt   334.71    182.20    130.32    647.22
                 Het Chi    27.13     65.23     43.65    174.61
                 Het  df        4        23        10        39
                 Het  P       ***       ***       ***       ***
               Fixed  RR     2.44      3.69      1.85      2.59
                     RRl     2.19      3.19      1.56      2.40
                     RRu     2.71      4.27      2.20      2.80
                      P       +++       +++       +++       +++
              Random  RR     2.75      3.67      2.10      2.96
                     RRl     2.01      2.77      1.40      2.43
                     RRu     3.77      4.88      3.16      3.60
                      P       +++       +++       +++       +++
             Between Chi                                  38.59
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       14        22         3         1        40
                      NS       10        16         3         1        30

                      Wt   286.83    268.25     80.22     11.92    647.22
                 Het Chi    21.63    123.29      4.43      0.00    174.61
                 Het  df       13        21         2         0        39
                 Het  P       (*)       ***      N.S.      N.S.       ***
               Fixed  RR     2.36      3.10      1.81      4.57      2.59
                     RRl     2.11      2.75      1.45      2.59      2.40
                     RRu     2.65      3.50      2.25      8.06      2.80
                      P       +++       +++       +++       +++       +++
              Random  RR     2.58      3.46      1.61      4.57      2.96
                     RRl     2.07      2.48      1.06      2.59      2.43
                     RRu     3.21      4.82      2.47      8.06      3.60
                      P       +++       +++         +       +++       +++
             Between Chi                                            25.26
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 6

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2        22        16        40
                      NS        1        17        12        30

                      Wt    46.29    226.64    374.29    647.22
                 Het Chi    37.86     68.78     59.98    174.61
                 Het  df        1        21        15        39
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.89      2.91      2.51      2.59
                     RRl     1.42      2.56      2.27      2.40
                     RRu     2.53      3.32      2.78      2.80
                      P       +++       +++       +++       +++
              Random  RR     1.65      3.06      3.09      2.96
                     RRl     0.27      2.31      2.36      2.43
                     RRu     9.93      4.05      4.04      3.60
                      P      N.S.       +++       +++       +++
             Between Chi                                   7.99
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       20         9        11        40
                      NS       15         8         7        30

                      Wt   210.08    260.43    176.71    647.22
                 Het Chi    99.39     24.31     41.90    174.61
                 Het  df       19         8        10        39
                 Het  P       ***        **       ***       ***
               Fixed  RR     2.60      2.30      3.08      2.59
                     RRl     2.27      2.04      2.66      2.40
                     RRu     2.97      2.60      3.57      2.80
                      P       +++       +++       +++       +++
              Random  RR     3.15      2.58      3.08      2.96
                     RRl     2.20      1.84      2.17      2.43
                     RRu     4.52      3.61      4.36      3.60
                      P       +++       +++       +++       +++
             Between Chi                                   9.00
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        2        24        14        40
                      NS        2        18        10        30

                      Wt    49.12    436.64    161.46    647.22
                 Het Chi     3.13     81.95     76.08    174.61
                 Het  df        1        23        13        39
                 Het  P       (*)       ***       ***       ***
               Fixed  RR     4.28      2.48      2.51      2.59
                     RRl     3.24      2.26      2.15      2.40
                     RRu     5.67      2.72      2.92      2.80
                      P       +++       +++       +++       +++
              Random  RR     5.97      2.75      3.12      2.96
                     RRl     2.13      2.19      2.00      2.43
                     RRu    16.79      3.44      4.87      3.60
                      P       +++       +++       +++       +++
             Between Chi                                  13.45
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 6

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       25        15                            40
                      NS       18        12                            30

                      Wt   300.13    347.09                        647.22
                 Het Chi   124.17     35.79                        174.61
                 Het  df       24        14                            39
                 Het  P       ***        **                           ***
               Fixed  RR     3.05      2.25                          2.59
                     RRl     2.72      2.03                          2.40
                     RRu     3.41      2.50                          2.80
                      P       +++       +++                           +++
              Random  RR     3.38      2.38                          2.96
                     RRl     2.52      1.88                          2.43
                     RRu     4.54      3.01                          3.60
                      P       +++       +++                           +++
             Between Chi                                            14.65
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                               (*)

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       25        15        40
                      NS       18        12        30

                      Wt   300.13    347.09    647.22
                 Het Chi   124.17     35.79    174.61
                 Het  df       24        14        39
                 Het  P       ***        **       ***
               Fixed  RR     3.05      2.25      2.59
                     RRl     2.72      2.03      2.40
                     RRu     3.41      2.50      2.80
                      P       +++       +++       +++
              Random  RR     3.38      2.38      2.96
                     RRl     2.52      1.88      2.43
                     RRu     4.54      3.01      3.60
                      P       +++       +++       +++
             Between Chi                        14.65
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 7

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6      FERRI3 LEBOWI
7        KAHN
11     DONTA1 FERRI1   LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 1 - 8

                                IESCOPD - Meta-analysis of amount smoked : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  HOZAWA HOZAWA     1         ENRIGH/HOZAWA/HARIKK
  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  LUNDB1 LUNDBA     1  LINDBE/LUNDB1/LUNDB2/HEDLUN
    PETO   PETO     1    PETO/HIGGI1/HIGGI2/HIGGI5
  HUHTI1 HUHTI1     1                HUHTI1/HUHTI2
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
     WEN    WEN     1                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
  GODTFR GODTFR     1 GODT/VEST/LANG1+2/SUAD/HOLLN
   KAHN2   KAHN     2                   KAHN/KAHN2

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN   3   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs   Nev any   1   9
          RR|SIG|

        4.84   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 2 -

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 1) = 20
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  12   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
    BEST  39   m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  20
   DEAN1  25   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any  13  22
   DEAN1  65   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any  13  22
   DOLL1   8   m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any  15  24
   DOLL2   5   f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  15  24
  ENSTRO   9   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  ENSTRO  18   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  FERRI2  27   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  FERRI2  44   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  HOZAWA   5   b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  15  29
  HUHTI1  27   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs   Nev any  15  24
  HUHTI3  13   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   1 Current        Any   Nev any  15  24
  JACOBS  20   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  20  29
   KAHN2 100   m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any  10  20
     LEE  24   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
     LEE  45   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
  MUELLE  26   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   1 Current       Cigs   Nev any  15  24
    TODD  24   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  VONHER  11   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
  VONHER  18   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
   WEISS   7   m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any  10  20
     WEN   3   m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs  11  20

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 12  m   1          8       -       2       -      5.93 (  1.14-  30.72)
*BEST   39  m   1         70       -       6       -      9.97 (  4.33-  22.94)
 DEAN1  25  m   3         75       -      47       -      2.56 (  1.64-   4.01)
 DEAN1  65  f   3         21       -     120       -      2.23 (  1.26-   3.95)
 Subtotal DEAN1                                           2.43 (  1.71-   3.45)
*DOLL1  8   m   2         61       -      12       -     11.20 (  6.06-  20.68)
*DOLL2  5   f   1          4       -       1       -     28.50 (  3.19- 255.00)
*ENSTRO 9   m   1        326       -     103       -      8.30 (  6.62-  10.40)
*ENSTRO 18  f   1        309       -     296       -      9.32 (  7.85-  11.06)
 Subtotal ENSTRO                                          8.93 (  7.79-  10.24)
 FERRI2 27  m   1         55       -      11       -      4.99 (  2.42-  10.31)
 FERRI2 44  f   1         28       -      54       -      2.89 (  1.72-   4.87)
 Subtotal FERRI2                                          3.48 (  2.28-   5.31)
 HOZAWA 5   b   0        822    1020     872    5019      4.64 (  4.13-   5.21)
 HUHTI1 27  m   1         86       -       7       -     11.82 (  5.14-  27.19)
 HUHTI3 13  m   1         14       -       3       -      5.92 (  1.80-  19.47)
*JACOBS 20  m   2         61       -      28       -      4.00 (  2.43-   6.58)
*KAHN2  100 m   1        162       -      31       -      8.73 (  5.94-  12.82)
*LEE    24  m   1          7       -       1       -      7.54 (  0.93-  60.98)
*LEE    45  f   0          0     212       5    1694      0.72~(  0.04-  13.06)
 Subtotal LEE                                             3.37 (  0.62-  18.37)
 MUELLE 26  m   1         14       -       2       -      6.82 (  1.41-  33.04)
*TODD   24  m   1          8       -       1       -      9.31 (  1.17-  74.18)
 VONHER 11  m   0        217     174      63     911     18.03 ( 13.04-  24.93)
 VONHER 18  f   0         40      65     137    2888     12.97 (  8.44-  19.93)
 Subtotal VONHER                                         16.00 ( 12.36-  20.73)
 WEISS  7   m   0          8      42       2      34      3.24 (  0.64-  16.27)
*WEN    3   m   1         62       -      52       -      2.65 (  1.68-   4.18)
Partial Totals          2458    1513    1856   10546
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 12  m   1              1.78     1.42     0.00       0.03
*BEST   39  m   1              2.30     5.53     1.21       0.00
 DEAN1  25  m   3              0.94    19.22    15.27       0.00
 DEAN1  65  f   3              0.80    11.77    12.47       0.01
 Subtotal DEAN1                0.89    30.99    27.75
*DOLL1  8   m   2              2.42    10.20     3.48       0.00
*DOLL2  5   f   1              3.35     0.80     1.85       0.00
*ENSTRO 9   m   1              2.12    75.31     6.11       0.00
*ENSTRO 18  f   1              2.23   130.74    21.00       0.00
 Subtotal ENSTRO               2.19   206.05    27.11
 FERRI2 27  m   1              1.61     7.31     0.37       0.00
 FERRI2 44  f   1              1.06    14.19     8.41       0.00
 Subtotal FERRI2               1.25    21.50     8.78
 HOZAWA 5   b   0              1.53   282.25    24.90       0.00
 HUHTI1 27  m   1              2.47     5.54     2.26       0.00
 HUHTI3 13  m   1              1.78     2.71     0.01       0.00
*JACOBS 20  m   2              1.39    15.49     3.07       0.00
*KAHN2  100 m   1              2.17    25.96     2.92       0.00
*LEE    24  m   1              2.02     0.88     0.03       0.06
*LEE    45  f   0             -0.32     0.46     2.13       0.83
 Subtotal LEE                  1.22     1.34     2.16
 MUELLE 26  m   1              1.92     1.54     0.01       0.02
*TODD   24  m   1              2.23     0.89     0.14       0.04
 VONHER 11  m   0              2.89    36.60    41.18       0.00
 VONHER 18  f   0              2.56    20.82    11.14       0.00
 Subtotal VONHER               2.77    57.42    52.32
 WEISS  7   m   0              1.17     1.47     0.64       0.15
*WEN    3   m   1              0.97    18.49    13.58       0.00

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       23
                      NS       18

                      Wt   689.59
                 Het Chi   172.19
                 Het  df       22
                 Het  P       ***
               Fixed  RR     6.24
                     RRl     5.79
                     RRu     6.73
                      P       +++
              Random  RR     6.21
                     RRl     4.72
                     RRu     8.17
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       23
                      NS       18

                      Wt   689.59
                 Het Chi   172.19
                 Het  df       22
                 Het  P       ***
               Fixed  RR     6.24
                     RRl     5.79
                     RRu     6.73
                      P       +++
              Random  RR     6.21
                     RRl     4.72
                     RRu     8.17
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1        16         6        23
                      NS        1        16         6        23

                      Wt   282.25    228.56    178.78    689.59
                 Het Chi     0.00     83.62     45.77    172.19
                 Het  df        0        15         5        22
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     4.64      7.41      8.02      6.24
                     RRl     4.13      6.50      6.93      5.79
                     RRu     5.21      8.43      9.29      6.73
                      P       +++       +++       +++       +++
              Random  RR     4.64      6.62      5.57      6.21
                     RRl     4.13      4.58      2.79      4.72
                     RRu     5.21      9.56     11.16      8.17
                      P       +++       +++       +++       +++
             Between Chi                                  42.80
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       10        11         1         1        23
                      NS        8         8         1         1        18

                      Wt   545.73    109.88     18.49     15.49    689.59
                 Het Chi    65.30     78.88      0.00      0.00    172.19
                 Het  df        9        10         0         0        22
                 Het  P       ***       ***      N.S.      N.S.       ***
               Fixed  RR     6.11      8.58      2.65      4.00      6.24
                     RRl     5.61      7.11      1.68      2.43      5.79
                     RRu     6.64     10.34      4.18      6.58      6.73
                      P       +++       +++       +++       +++       +++
              Random  RR     6.32      7.32      2.65      4.00      6.21
                     RRl     4.59      3.90      1.68      2.43      4.72
                     RRu     8.71     13.74      4.18      6.58      8.17
                      P       +++       +++       +++       +++       +++
             Between Chi                                            28.00
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N       13         9        22
                      NS       10         7        17

                      Wt   619.93     51.16    671.09
                 Het Chi   119.94     28.76    158.23
                 Het  df       12         8        21
                 Het  P       ***       ***       ***
               Fixed  RR     6.61      4.22      6.39
                     RRl     6.11      3.21      5.93
                     RRu     7.16      5.55      6.89
                      P       +++       +++       +++
              Random  RR     7.21      5.46      6.55
                     RRl     5.25      2.86      4.96
                     RRu     9.90     10.43      8.65
                      P       +++       +++       +++
             Between Chi                         9.54
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N       19         2         2                                      23
                      NS       15         1         2                                      18

                      Wt   331.43     57.42    300.74                                  689.59
                 Het Chi    75.10      1.44      5.44                                  172.19
                 Het  df       18         1         1                                      22
                 Het  P       ***      N.S.         *                                     ***
               Fixed  RR     7.16     16.00      4.48                                    6.24
                     RRl     6.43     12.36      4.00                                    5.79
                     RRu     7.98     20.73      5.02                                    6.73
                      P       +++       +++       +++                                     +++
              Random  RR     5.86     15.78      3.67                                    6.21
                     RRl     4.37     11.50      2.13                                    4.72
                     RRu     7.86     21.67      6.30                                    8.17
                      P       +++       +++       +++                                     +++
             Between Chi                                                                90.21
             Between  df                                                                    2
             Between  P                                                                   ***
             Btwn(F)  P                                                                   ***

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N       14         1         2         6        23
                      NS       11         1         2         4        18

                      Wt    98.90      0.80     25.68    564.21    689.59
                 Het Chi    37.67      0.00      6.52    116.50    172.19
                 Het  df       13         0         1         5        22
                 Het  P       ***      N.S.         *       ***       ***
               Fixed  RR     4.68     28.50      6.02      6.56      6.24
                     RRl     3.84      3.19      4.09      6.04      5.79
                     RRu     5.70    254.81      8.86      7.13      6.73
                      P       +++        ++       +++       +++       +++
              Random  RR     4.92     28.50      6.59      7.82      6.21
                     RRl     3.30      3.19      2.40      4.98      4.72
                     RRu     7.33    254.81     18.05     12.28      8.17
                      P       +++        ++       +++       +++       +++
             Between Chi                                            11.50
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2        11        10        23
                      NS        1         9         8        18

                      Wt    30.99    284.75    373.85    689.59
                 Het Chi     0.14     38.74     84.67    172.19
                 Het  df        1        10         9        22
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     2.43      7.96      5.61      6.24
                     RRl     1.71      7.08      5.07      5.79
                     RRu     3.45      8.94      6.21      6.73
                      P       +++       +++       +++       +++
              Random  RR     2.43      6.99      6.90      6.21
                     RRl     1.71      5.09      4.12      4.72
                     RRu     3.45      9.59     11.55      8.17
                      P       +++       +++       +++       +++
             Between Chi                                  48.63
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        3        16         4                  23
                      NS        3        11         4                  18

                      Wt    12.54    372.30    304.75              689.59
                 Het Chi     1.08    118.42      5.36              172.19
                 Het  df        2        15         3                  22
                 Het  P      N.S.       ***      N.S.                 ***
               Fixed  RR    11.18      7.76      4.67                6.24
                     RRl     6.43      7.01      4.18                5.79
                     RRu    19.45      8.59      5.23                6.73
                      P       +++       +++       +++                 +++
              Random  RR    11.18      5.99      4.99                6.21
                     RRl     6.43      4.23      3.50                4.72
                     RRu    19.45      8.50      7.10                8.17
                      P       +++       +++       +++                 +++
             Between Chi                                            47.33
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        2         4         7        10                  23
                      NS        2         4         5         7                  18

                      Wt   287.79      7.15     65.18    329.48              689.59
                 Het Chi     4.75      0.51     15.14    101.29              172.19
                 Het  df        1         3         6         9                  22
                 Het  P         *      N.S.         *       ***                 ***
               Fixed  RR     4.72      5.39      5.26      8.27                6.24
                     RRl     4.21      2.59      4.12      7.42                5.79
                     RRu     5.30     11.22      6.70      9.21                6.73
                      P       +++       +++       +++       +++                 +++
              Random  RR     6.74      5.39      4.83      7.12                6.21
                     RRl     2.74      2.59      3.00      4.68                4.72
                     RRu    16.53     11.22      7.78     10.84                8.17
                      P       +++       +++       +++       +++                 +++
             Between Chi                                                      50.50
             Between  df                                                          3
             Between  P                                                         ***
             Btwn(F)  P                                                         (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        2        21        23
                      NS        1        17        18

                      Wt    30.99    658.60    689.59
                 Het Chi     0.14    143.14    172.19
                 Het  df        1        20        22
                 Het  P      N.S.       ***       ***
               Fixed  RR     2.43      6.53      6.24
                     RRl     1.71      6.05      5.79
                     RRu     3.45      7.04      6.73
                      P       +++       +++       +++
              Random  RR     2.43      7.02      6.21
                     RRl     1.71      5.31      4.72
                     RRu     3.45      9.27      8.17
                      P       +++       +++       +++
             Between Chi                        28.91
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           (*)

                          COPD subtype
                             mort        LF     other     Total

                       N       13         4         6        23
                      NS       10         4         4        18

                      Wt   315.74    287.98     85.87    689.59
                 Het Chi    78.23      0.58     39.83    172.19
                 Het  df       12         3         5        22
                 Het  P       ***      N.S.       ***       ***
               Fixed  RR     7.08      4.65     10.54      6.24
                     RRl     6.34      4.14      8.53      5.79
                     RRu     7.91      5.22     13.02      6.73
                      P       +++       +++       +++       +++
              Random  RR     5.66      4.65      8.17      6.21
                     RRl     3.93      4.14      4.17      4.72
                     RRu     8.14      5.22     16.01      8.17
                      P       +++       +++       +++       +++
             Between Chi                                  53.54
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N       12                   8         3        23
                      NS       10                   5         3        18

                      Wt   397.61              265.50     26.48    689.59
                 Het Chi    94.67               61.15      8.40    172.19
                 Het  df       11                   7         2        22
                 Het  P       ***                 ***         *       ***
               Fixed  RR     5.71                7.14      6.31      6.24
                     RRl     5.17                6.33      4.31      5.79
                     RRu     6.29                8.05      9.23      6.73
                      P       +++                 +++       +++       +++
              Random  RR     6.95                5.03      8.07      6.21
                     RRl     4.31                3.23      3.10      4.72
                     RRu    11.19                7.83     21.06      8.17
                      P       +++                 +++       +++       +++
             Between Chi                                             7.97
             Between  df                                                2
             Between  P                                                 *
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        4                   4
                      NS        4                   4

                      Wt   287.98              287.98
                 Het Chi     0.58                0.58
                 Het  df        3                   3
                 Het  P      N.S.                N.S.
               Fixed  RR     4.65                4.65
                     RRl     4.14                4.14
                     RRu     5.22                5.22
                      P       +++                 +++
              Random  RR     4.65                4.65
                     RRl     4.14                4.14
                     RRu     5.22                5.22
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        3         5         2        13        23
                      NS        3         4         2         9        18

                      Wt     3.82      6.36     24.02    655.39    689.59
                 Het Chi     2.45      2.24      7.47    152.31    172.19
                 Het  df        2         4         1        12        22
                 Het  P      N.S.      N.S.        **       ***       ***
               Fixed  RR     6.90      5.61      3.59      6.37      6.24
                     RRl     2.53      2.58      2.41      5.90      5.79
                     RRu    18.82     12.20      5.36      6.88      6.73
                      P       +++       +++       +++       +++       +++
              Random  RR     7.13      5.61      4.90      6.48      6.21
                     RRl     2.32      2.58      1.34      4.72      4.72
                     RRu    21.86     12.20     17.89      8.90      8.17
                      P       +++       +++         +       +++       +++
             Between Chi                                             7.71
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        3         5         2        13        23
                      NS        3         4         2         9        18

                      Wt     3.82      6.36     24.02    655.39    689.59
                 Het Chi     2.45      2.24      7.47    152.31    172.19
                 Het  df        2         4         1        12        22
                 Het  P      N.S.      N.S.        **       ***       ***
               Fixed  RR     6.90      5.61      3.59      6.37      6.24
                     RRl     2.53      2.58      2.41      5.90      5.79
                     RRu    18.82     12.20      5.36      6.88      6.73
                      P       +++       +++       +++       +++       +++
              Random  RR     7.13      5.61      4.90      6.48      6.21
                     RRl     2.32      2.58      1.34      4.72      4.72
                     RRu    21.86     12.20     17.89      8.90      8.17
                      P       +++       +++         +       +++       +++
             Between Chi                                             7.71
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       12        11        23
                      NS        9         9        18

                      Wt   404.84    284.75    689.59
                 Het Chi   104.87     38.74    172.19
                 Het  df       11        10        22
                 Het  P       ***       ***       ***
               Fixed  RR     5.26      7.96      6.24
                     RRl     4.77      7.08      5.79
                     RRu     5.80      8.94      6.73
                      P       +++       +++       +++
              Random  RR     5.59      6.99      6.21
                     RRl     3.56      5.09      4.72
                     RRu     8.79      9.59      8.17
                      P       +++       +++       +++
             Between Chi                        28.57
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           (*)

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        11        11        23
                      NS        1         9         8        18

                      Wt     2.71    429.61    257.27    689.59
                 Het Chi     0.00    101.36     53.45    172.19
                 Het  df        0        10        10        22
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     5.92      5.52      7.67      6.24
                     RRl     1.80      5.02      6.79      5.79
                     RRu    19.47      6.07      8.67      6.73
                      P        ++       +++       +++       +++
              Random  RR     5.92      6.36      6.03      6.21
                     RRl     1.80      4.18      3.97      4.72
                     RRu    19.47      9.66      9.16      8.17
                      P        ++       +++       +++       +++
             Between Chi                                  17.38
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       20         3                            23
                      NS       15         3                            18

                      Wt   373.36    316.23                        689.59
                 Het Chi   100.22      5.63                        172.19
                 Het  df       19         2                            22
                 Het  P       ***       (*)                           ***
               Fixed  RR     8.31      4.46                          6.24
                     RRl     7.50      3.99                          5.79
                     RRu     9.19      4.98                          6.73
                      P       +++       +++                           +++
              Random  RR     6.98      3.85                          6.21
                     RRl     5.18      2.74                          4.72
                     RRu     9.42      5.41                          8.17
                      P       +++       +++                           +++
             Between Chi                                            66.34
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                **
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       20         3        23
                      NS       15         3        18

                      Wt   373.36    316.23    689.59
                 Het Chi   100.22      5.63    172.19
                 Het  df       19         2        22
                 Het  P       ***       (*)       ***
               Fixed  RR     8.31      4.46      6.24
                     RRl     7.50      3.99      5.79
                     RRu     9.19      4.98      6.73
                      P       +++       +++       +++
              Random  RR     6.98      3.85      6.21
                     RRl     5.18      2.74      4.72
                     RRu     9.42      5.41      8.17
                      P       +++       +++       +++
             Between Chi                        66.34
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                            **

                        Number of adjustment variables
                                0         1        2+     Total

                       N        5        14         4        23
                      NS        4        12         3        19

                      Wt   341.60    291.32     56.67    689.59
                 Het Chi    77.04     44.73     18.23    172.19
                 Het  df        4        13         3        22
                 Het  P       ***       ***       ***       ***
               Fixed  RR     5.69      7.72      3.67      6.24
                     RRl     5.12      6.88      2.83      5.79
                     RRu     6.33      8.66      4.76      6.73
                      P       +++       +++       +++       +++
              Random  RR     7.25      6.60      3.94      6.21
                     RRl     3.06      4.90      2.06      4.72
                     RRu    17.19      8.91      7.54      8.17
                      P       +++       +++       +++       +++
             Between Chi                                  32.19
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  12     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
    BEST  39     m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  20
   DEAN1  20 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  13  22
   DEAN1  60 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  13  22
   DOLL1   8     m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any  15  24
   DOLL2   5     f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  15  24
  ENSTRO   9     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  ENSTRO  18     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  FERRI2  27     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  FERRI2  44     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  HOZAWA   5     b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  15  29
  HUHTI1  22 x   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs   Nev any  15  24
  HUHTI3   8 x   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   0 Current        Any   Nev any  15  24
  JACOBS  20     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  20  29
   KAHN2 100     m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any  10  20
     LEE  10 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
     LEE  45     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
  MUELLE  21 x   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   0 Current       Cigs   Nev any  15  24
    TODD  10 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
  VONHER  11     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
  VONHER  18     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
   WEISS   7     m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any  10  20
     WEN   3     m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs  11  20

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 12  m   1          8       -       2       -      5.93 (  1.14-  30.72)
*BEST   39  m   1         70       -       6       -      9.97 (  4.33-  22.94)
 DEAN1  20  m   0         75     429      47     510      1.90 (  1.29-   2.79)
 DEAN1  60  f   0         21     521     120    1538      0.52 (  0.32-   0.83)
 Subtotal DEAN1                                           1.13 (  0.84-   1.52)
*DOLL1  8   m   2         61       -      12       -     11.20 (  6.06-  20.68)
*DOLL2  5   f   1          4       -       1       -     28.50 (  3.19- 255.00)
*ENSTRO 9   m   1        326       -     103       -      8.30 (  6.62-  10.40)
*ENSTRO 18  f   1        309       -     296       -      9.32 (  7.85-  11.06)
 Subtotal ENSTRO                                          8.93 (  7.79-  10.24)
 FERRI2 27  m   1         55       -      11       -      4.99 (  2.42-  10.31)
 FERRI2 44  f   1         28       -      54       -      2.89 (  1.72-   4.87)
 Subtotal FERRI2                                          3.48 (  2.28-   5.31)
 HOZAWA 5   b   0        822    1020     872    5019      4.64 (  4.13-   5.21)
 HUHTI1 22  m   0         86     105       7     115     13.46 (  5.96-  30.38)
 HUHTI3 8   m   0         14     187       3     236      5.89 (  1.67-  20.80)
*JACOBS 20  m   2         61       -      28       -      4.00 (  2.43-   6.58)
*KAHN2  100 m   1        162       -      31       -      8.73 (  5.94-  12.82)
*LEE    10  m   0          7     364       1     347      6.67 (  0.83-  53.96)
*LEE    45  f   0          0     212       5    1694      0.72~(  0.04-  13.06)
 Subtotal LEE                                             3.12 (  0.57-  16.95)
 MUELLE 21  m   0         14      50       2      57      7.98 (  1.73-  36.83)
*TODD   10  m   0          8     487       1     520      8.54 (  1.07-  68.05)
 VONHER 11  m   0        217     174      63     911     18.03 ( 13.04-  24.93)
 VONHER 18  f   0         40      65     137    2888     12.97 (  8.44-  19.93)
 Subtotal VONHER                                         16.00 ( 12.36-  20.73)
 WEISS  7   m   0          8      42       2      34      3.24 (  0.64-  16.27)
*WEN    3   m   1         62       -      52       -      2.65 (  1.68-   4.18)
Partial Totals          2458    3656    1856   13869
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 12  m   1              1.78     1.42     0.00       0.03
*BEST   39  m   1              2.30     5.53     1.55       0.00
 DEAN1  20  m   0              0.64    25.71    32.82       0.00
 DEAN1  60  f   0             -0.66    17.09   100.96       0.01
 Subtotal DEAN1                0.12    42.79   133.77
*DOLL1  8   m   2              2.42    10.20     4.25       0.00
*DOLL2  5   f   1              3.35     0.80     2.00       0.00
*ENSTRO 9   m   1              2.12    75.31     9.02       0.00
*ENSTRO 18  f   1              2.23   130.74    27.90       0.00
 Subtotal ENSTRO               2.19   206.05    36.92
 FERRI2 27  m   1              1.61     7.31     0.19       0.00
 FERRI2 44  f   1              1.06    14.19     7.13       0.00
 Subtotal FERRI2               1.25    21.50     7.32
 HOZAWA 5   b   0              1.53   282.25    15.69       0.00
 HUHTI1 22  m   0              2.60     5.79     3.98       0.00
 HUHTI3 8   m   0              1.77     2.41     0.00       0.01
*JACOBS 20  m   2              1.39    15.49     2.28       0.00
*KAHN2  100 m   1              2.17    25.96     4.08       0.00
*LEE    10  m   0              1.90     0.88     0.01       0.08
*LEE    45  f   0             -0.32     0.46     2.01       0.83
 Subtotal LEE                  1.14     1.34     2.02
 MUELLE 21  m   0              2.08     1.64     0.15       0.01
*TODD   10  m   0              2.15     0.89     0.13       0.04
 VONHER 11  m   0              2.89    36.60    46.07       0.00
 VONHER 18  f   0              2.56    20.82    13.08       0.00
 Subtotal VONHER               2.77    57.42    59.16
 WEISS  7   m   0              1.17     1.47     0.52       0.15
*WEN    3   m   1              0.97    18.49    11.71       0.00

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       23
                      NS       18

                      Wt   701.45
                 Het Chi   285.55
                 Het  df       22
                 Het  P       ***
               Fixed  RR     5.87
                     RRl     5.45
                     RRu     6.32
                      P       +++
              Random  RR     5.63
                     RRl     4.02
                     RRu     7.90
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       23
                      NS       18

                      Wt   701.45
                 Het Chi   285.55
                 Het  df       22
                 Het  P       ***
               Fixed  RR     5.87
                     RRl     5.45
                     RRu     6.32
                      P       +++
              Random  RR     5.63
                     RRl     4.02
                     RRu     7.90
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1        16         6        23
                      NS        1        16         6        23

                      Wt   282.25    235.10    184.10    701.45
                 Het Chi     0.00    109.65    149.51    285.55
                 Het  df        0        15         5        22
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     4.64      6.99      6.75      5.87
                     RRl     4.13      6.15      5.84      5.45
                     RRu     5.21      7.94      7.80      6.32
                      P       +++       +++       +++       +++
              Random  RR     4.64      6.50      4.06      5.63
                     RRl     4.13      4.31      1.29      4.02
                     RRu     5.21      9.79     12.79      7.90
                      P       +++       +++         +       +++
             Between Chi                                  26.39
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       10        11         1         1        23
                      NS        8         8         1         1        18

                      Wt   545.82    121.64     18.49     15.49    701.45
                 Het Chi    65.40    205.30      0.00      0.00    285.55
                 Het  df        9        10         0         0        22
                 Het  P       ***       ***      N.S.      N.S.       ***
               Fixed  RR     6.11      5.83      2.65      4.00      5.87
                     RRl     5.62      4.88      1.68      2.43      5.45
                     RRu     6.64      6.96      4.18      6.58      6.32
                      P       +++       +++       +++       +++       +++
              Random  RR     6.36      5.93      2.65      4.00      5.63
                     RRl     4.61      2.36      1.68      2.43      4.02
                     RRu     8.75     14.92      4.18      6.58      7.90
                      P       +++       +++       +++       +++       +++
             Between Chi                                            14.84
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2        11        10        23
                      NS        1         9         8        18

                      Wt    42.79    284.75    373.90    701.45
                 Het Chi    17.37     38.75     86.16    285.55
                 Het  df        1        10         9        22
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.13      7.95      5.63      5.87
                     RRl     0.84      7.08      5.09      5.45
                     RRu     1.52      8.93      6.23      6.32
                      P      N.S.       +++       +++       +++
              Random  RR     1.00      6.96      7.07      5.63
                     RRl     0.28      5.07      4.20      4.02
                     RRu     3.57      9.55     11.87      7.90
                      P      N.S.       +++       +++       +++
             Between Chi                                 143.27
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     ***

                          COPD subtype
                             mort        LF     other     Total

                       N       13         4         6        23
                      NS       10         4         4        18

                      Wt   327.54    287.78     86.12    701.45
                 Het Chi   197.96      0.81     40.10    285.55
                 Het  df       12         3         5        22
                 Het  P       ***      N.S.       ***       ***
               Fixed  RR     6.16      4.65     10.63      5.87
                     RRl     5.53      4.15      8.61      5.45
                     RRu     6.87      5.22     13.13      6.32
                      P       +++       +++       +++       +++
              Random  RR     4.79      4.65      8.34      5.63
                     RRl     2.79      4.15      4.25      4.02
                     RRu     8.22      5.22     16.36      7.90
                      P       +++       +++       +++       +++
             Between Chi                                  46.68
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        11        11        23
                      NS        1         9         8        18

                      Wt     2.41    429.96    269.08    701.45
                 Het Chi     0.00    102.89    178.80    285.55
                 Het  df        0        10        10        22
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     5.89      5.54      6.45      5.87
                     RRl     1.67      5.04      5.72      5.45
                     RRu    20.80      6.09      7.27      6.32
                      P        ++       +++       +++       +++
              Random  RR     5.89      6.48      4.78      5.63
                     RRl     1.67      4.25      2.43      4.02
                     RRu    20.80      9.87      9.41      7.90
                      P        ++       +++       +++       +++
             Between Chi                                   3.86
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       20         3                            23
                      NS       15         3                            18

                      Wt   385.22    316.23                        701.45
                 Het Chi   236.12      5.63                        285.55
                 Het  df       19         2                            22
                 Het  P       ***       (*)                           ***
               Fixed  RR     7.36      4.46                          5.87
                     RRl     6.66      3.99                          5.45
                     RRu     8.14      4.98                          6.32
                      P       +++       +++                           +++
              Random  RR     6.15      3.85                          5.63
                     RRl     4.01      2.74                          4.02
                     RRu     9.44      5.41                          7.90
                      P       +++       +++                           +++
             Between Chi                                            43.80
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                               (*)

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       20         3        23
                      NS       15         3        18

                      Wt   385.22    316.23    701.45
                 Het Chi   236.12      5.63    285.55
                 Het  df       19         2        22
                 Het  P       ***       (*)       ***
               Fixed  RR     7.36      4.46      5.87
                     RRl     6.66      3.99      5.45
                     RRu     8.14      4.98      6.32
                      P       +++       +++       +++
              Random  RR     6.15      3.85      5.63
                     RRl     4.01      2.74      4.02
                     RRu     9.44      5.41      7.90
                      P       +++       +++       +++
             Between Chi                        43.80
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6       CHEN2 CLEMEN FERRI3 GODTFR KRZYZA LEBOWI LINDST LUNDB1 NILSSO   PETO SPEIZE TVERDA YAMAGU   YUAN
7        KAHN
11     DONTA1 FERRI1   LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 2 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  HOZAWA HOZAWA     1         ENRIGH/HOZAWA/HARIKK
  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI1 HUHTI1     1                HUHTI1/HUHTI2
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
     WEN    WEN     1                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD
   KAHN2   KAHN     2                   KAHN/KAHN2

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN   4   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs   Nev any  10  20
          RR|SIG|

       11.23   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 3 -

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 1) = 45
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  13   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  25   +
    BEST  40   m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21   +
  CLEMEN   5   m   20   60     Eu:West  1960  1982    Pr  Prev      COPD:LF   0 Current       Cigs   Nev any  21   +
   DEAN1  26   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any  23   +
   DEAN1  66   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any  23   +
   DOLL1   9   m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any  25   +
   DOLL2   6   f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  25   +
  ENSTRO  11   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  ENSTRO  20   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  FERRI2  30   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +
  FERRI2  47   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +
  HOZAWA   6   b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  30   +
  HUHTI1  28   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs   Nev any  25   +
  HUHTI3  14   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   1 Current        Any   Nev any  25   +
  JACOBS  21   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  30   +
   KAHN2 102   m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any  40   +
  LEBOWI  11   m   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   1 Current       Cigs  Nev cigs  21   +
  LEBOWI  23   f   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   1 Current       Cigs  Nev cigs  21   +
     LEE  25   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21   +
     LEE  46   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  21   +
  MUELLE  27   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   1 Current       Cigs   Nev any  25   +
    TODD  25   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21   +
  VONHER  12   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  30   +
  VONHER  19   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  30   +
   WEISS   8   m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any  21   +
     WEN   4   m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs  21   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 13  m   1         22       -       2       -     10.15 (  2.00-  51.42)
*BEST   40  m   1         19       -       6       -     10.38 (  4.15-  25.98)
 CLEMEN 5   m   0         37     645      11     709      3.70 (  1.87-   7.31)
 DEAN1  26  m   3         66       -      47       -      7.87 (  4.70-  13.17)
 DEAN1  66  f   3         24       -     120       -     18.53 (  9.39-  36.56)
 Subtotal DEAN1                                          10.76 (  7.13-  16.22)
*DOLL1  9   m   2         76       -      12       -     22.50 ( 12.30-  41.15)
*DOLL2  6   f   1          2       -       1       -     32.00 (  2.90- 352.92)
*ENSTRO 11  m   1        148       -     103       -     13.54 ( 10.33-  17.75)
*ENSTRO 20  f   1         46       -     296       -     15.33 ( 11.06-  21.23)
 Subtotal ENSTRO                                         14.24 ( 11.57-  17.54)
 FERRI2 30  m   1         19       -      11       -     17.09 (  5.90-  49.47)
 FERRI2 47  f   1          5       -      54       -     65.73 (  4.45- 971.21)
 Subtotal FERRI2                                         20.49 (  7.62-  55.10)
 HOZAWA 6   b   0        382     284     872    5019      7.74 (  6.53-   9.17)
 HUHTI1 28  m   1         39       -       7       -     11.35 (  4.57-  28.15)
 HUHTI3 14  m   1         12       -       3       -     15.33 (  4.45-  52.84)
*JACOBS 21  m   2         12       -      28       -      5.29 (  2.73-  10.25)
*KAHN2  102 m   1         26       -      31       -     15.02 (  8.92-  25.29)
 LEBOWI 11  m   1          6       -       4       -      4.37 (  1.14-  16.80)
 LEBOWI 23  f   1         14       -      36       -      3.19 (  1.65-   6.17)
 Subtotal LEBOWI                                          3.39 (  1.88-   6.13)
*LEE    25  m   1          5       -       1       -      7.88 (  0.93-  67.01)
*LEE    46  f   0          1      90       5    1694      3.76 (  0.44-  31.89)
 Subtotal LEE                                             5.44 (  1.20-  24.68)
 MUELLE 27  m   1         10       -       2       -      5.54 (  1.12-  27.29)
*TODD   25  m   1          6       -       1       -     10.25 (  1.24-  84.76)
 VONHER 12  m   0         73      65      63     911     16.24 ( 10.66-  24.73)
 VONHER 19  f   0          2       5     137    2888      8.43 (  1.62-  43.85)
 Subtotal VONHER                                         15.60 ( 10.38-  23.45)
 WEISS  8   m   0         12      32       2      34      6.38 (  1.32-  30.73)
*WEN    4   m   1          6       -      52       -      1.46 (  0.51-   4.19)
Partial Totals          1070    1121    1907   11255
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 13  m   1              2.32     1.46     0.00       0.01
*BEST   40  m   1              2.34     4.57     0.01       0.00
 CLEMEN 5   m   0              1.31     8.27     7.90       0.00
 DEAN1  26  m   3              2.06    14.47     0.71       0.00
 DEAN1  66  f   3              2.92     8.32     3.35       0.00
 Subtotal DEAN1                2.38    22.79     4.06
*DOLL1  9   m   2              3.11    10.54     7.23       0.00
*DOLL2  6   f   1              3.47     0.67     0.93       0.00
*ENSTRO 11  m   1              2.61    52.44     5.39       0.00
*ENSTRO 20  f   1              2.73    36.14     7.15       0.00
 Subtotal ENSTRO               2.66    88.57    12.54
 FERRI2 30  m   1              2.84     3.40     1.04       0.00
 FERRI2 47  f   1              4.19     0.53     1.91       0.00
 Subtotal FERRI2               3.02     3.93     2.95
 HOZAWA 6   b   0              2.05   133.60     7.59       0.00
 HUHTI1 28  m   1              2.43     4.65     0.10       0.00
 HUHTI3 14  m   1              2.73     2.51     0.50       0.00
*JACOBS 21  m   2              1.67     8.78     3.37       0.00
*KAHN2  102 m   1              2.71    14.15     2.55       0.00
 LEBOWI 11  m   1              1.47     2.12     1.39       0.03
 LEBOWI 23  f   1              1.16     8.83    11.18       0.00
 Subtotal LEBOWI               1.22    10.96    12.57
*LEE    25  m   1              2.06     0.84     0.04       0.06
*LEE    46  f   0              1.33     0.84     0.77       0.22
 Subtotal LEE                  1.69     1.68     0.82
 MUELLE 27  m   1              1.71     1.51     0.49       0.04
*TODD   25  m   1              2.33     0.86     0.00       0.03
 VONHER 12  m   0              2.79    21.71     5.48       0.00
 VONHER 19  f   0              2.13     1.41     0.03       0.01
 Subtotal VONHER               2.75    23.13     5.51
 WEISS  8   m   0              1.85     1.55     0.29       0.02
*WEN    4   m   1              0.38     3.46    12.59       0.48

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       26
                      NS       20

                      Wt   347.63
                 Het Chi    82.02
                 Het  df       25
                 Het  P       ***
               Fixed  RR     9.83
                     RRl     8.85
                     RRu    10.92
                      P       +++
              Random  RR     9.50
                     RRl     7.38
                     RRu    12.22
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       26
                      NS       20

                      Wt   347.63
                 Het Chi    82.02
                 Het  df       25
                 Het  P       ***
               Fixed  RR     9.83
                     RRl     8.85
                     RRu    10.92
                      P       +++
              Random  RR     9.50
                     RRl     7.38
                     RRu    12.22
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1        18         7        26
                      NS        1        18         7        26

                      Wt   133.60    157.29     56.74    347.63
                 Het Chi     0.00     46.64     22.71     82.02
                 Het  df        0        17         6        25
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     7.74     11.14     12.18      9.83
                     RRl     6.53      9.52      9.39      8.85
                     RRu     9.17     13.02     15.80     10.92
                      P       +++       +++       +++       +++
              Random  RR     7.74      9.32     10.85      9.50
                     RRl     6.53      6.83      5.20      7.38
                     RRu     9.17     12.72     22.64     12.22
                      P       +++       +++       +++       +++
             Between Chi                                  12.67
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       12        12         1         1        26
                      NS        9         9         1         1        20

                      Wt   260.29     75.09      3.46      8.78    347.63
                 Het Chi    38.97     24.04      0.00      0.00     82.02
                 Het  df       11        11         0         0        25
                 Het  P       ***         *      N.S.      N.S.       ***
               Fixed  RR     9.71     12.00      1.46      5.29      9.83
                     RRl     8.60      9.57      0.51      2.73      8.85
                     RRu    10.97     15.05      4.18     10.25     10.92
                      P       +++       +++      N.S.       +++       +++
              Random  RR     9.90     11.39      1.46      5.29      9.50
                     RRl     7.12      7.67      0.51      2.73      7.38
                     RRu    13.76     16.89      4.18     10.25     12.22
                      P       +++       +++      N.S.       +++       +++
             Between Chi                                            19.00
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N       16         9        25
                      NS       12         7        19

                      Wt   301.60     42.56    344.16
                 Het Chi    56.31     10.25     69.29
                 Het  df       15         8        24
                 Het  P       ***      N.S.       ***
               Fixed  RR     9.69     12.70     10.02
                     RRl     8.65      9.40      9.01
                     RRu    10.84     17.15     11.13
                      P       +++       +++       +++
              Random  RR     9.36     12.74     10.17
                     RRl     6.99      8.71      8.01
                     RRu    12.53     18.65     12.93
                      P       +++       +++       +++
             Between Chi                         2.74
             Between  df                            1
             Between  P                           (*)
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N       20         4         2                                      26
                      NS       16         2         2                                      20

                      Wt   176.48     34.08    137.07                                  347.63
                 Het Chi    34.93     18.06      9.40                                   82.02
                 Het  df       19         3         1                                      25
                 Het  P         *       ***        **                                     ***
               Fixed  RR    12.29      9.55      7.42                                    9.83
                     RRl    10.60      6.83      6.28                                    8.85
                     RRu    14.24     13.36      8.77                                   10.92
                      P       +++       +++       +++                                     +++
              Random  RR    11.37      6.78      3.66                                    9.50
                     RRl     8.88      2.40      0.72                                    7.38
                     RRu    14.56     19.15     18.60                                   12.22
                      P       +++       +++      N.S.                                     +++
             Between Chi                                                                19.62
             Between  df                                                                    2
             Between  P                                                                   ***
             Btwn(F)  P                                                                     *

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N       16         2         2         6        26
                      NS       12         2         2         4        20

                      Wt    70.61      8.94     19.32    248.77    347.63
                 Het Chi    24.33      2.87     10.04     38.13     82.02
                 Het  df       15         1         1         5        25
                 Het  P       (*)       (*)        **       ***       ***
               Fixed  RR     9.67      4.34     11.65     10.03      9.83
                     RRl     7.66      2.25      7.46      8.86      8.85
                     RRu    12.21      8.37     18.20     11.36     10.92
                      P       +++       +++       +++       +++       +++
              Random  RR     9.58      7.90     10.98      9.90      9.50
                     RRl     6.85      1.05      2.66      6.41      7.38
                     RRu    13.41     59.57     45.37     15.30     12.22
                      P       +++         +       +++       +++       +++
             Between Chi                                             6.64
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2        12        12        26
                      NS        1        10         9        20

                      Wt    22.79    141.55    183.29    347.63
                 Het Chi     3.87     42.57     25.23     82.02
                 Het  df        1        11        11        25
                 Het  P         *       ***        **       ***
               Fixed  RR    10.76     11.94      8.36      9.83
                     RRl     7.13     10.13      7.23      8.85
                     RRu    16.22     14.08      9.66     10.92
                      P       +++       +++       +++       +++
              Random  RR    11.72      9.23      9.01      9.50
                     RRl     5.07      6.14      6.18      7.38
                     RRu    27.07     13.89     13.16     12.22
                      P       +++       +++       +++       +++
             Between Chi                                  10.35
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        6        16         4                  26
                      NS        5        11         4                  20

                      Wt    31.94    167.11    148.58              347.63
                 Het Chi    25.28     27.53      1.99               82.02
                 Het  df        5        15         3                  25
                 Het  P       ***         *      N.S.                 ***
               Fixed  RR     6.94     13.13      7.65                9.83
                     RRl     4.91     11.28      6.51                8.85
                     RRu     9.82     15.27      8.98               10.92
                      P       +++       +++       +++                 +++
              Random  RR     6.86     12.08      7.65                9.50
                     RRl     2.84      9.34      6.51                7.38
                     RRu    16.57     15.64      8.98               12.22
                      P       +++       +++       +++                 +++
             Between Chi                                            27.22
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                **

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        3         4         7        12                  26
                      NS        3         4         5         8                  20

                      Wt   146.52      7.03     29.40    164.68              347.63
                 Het Chi     5.07      1.26      9.47     47.08               82.02
                 Het  df        2         3         6        11                  25
                 Het  P       (*)      N.S.      N.S.       ***                 ***
               Fixed  RR     7.52      9.32     10.70     12.31                9.83
                     RRl     6.39      4.45      7.45     10.57                8.85
                     RRu     8.84     19.52     15.36     14.34               10.92
                      P       +++       +++       +++       +++                 +++
              Random  RR     6.80      9.32     10.53     10.05                9.50
                     RRl     4.05      4.45      6.01      6.92                7.38
                     RRu    11.41     19.52     18.43     14.58               12.22
                      P       +++       +++       +++       +++                 +++
             Between Chi                                                      19.13
             Between  df                                                          3
             Between  P                                                         ***
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        2        24        26
                      NS        1        19        20

                      Wt    22.79    324.84    347.63
                 Het Chi     3.87     77.94     82.02
                 Het  df        1        23        25
                 Het  P         *       ***       ***
               Fixed  RR    10.76      9.76      9.83
                     RRl     7.13      8.76      8.85
                     RRu    16.22     10.89     10.92
                      P       +++       +++       +++
              Random  RR    11.72      9.24      9.50
                     RRl     5.07      7.03      7.38
                     RRu    27.07     12.13     12.22
                      P       +++       +++       +++
             Between Chi                         0.20
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       13         7         6        26
                      NS       10         6         4        20

                      Wt   156.07    158.40     33.16    347.63
                 Het Chi    34.98     12.27      2.40     82.02
                 Het  df       12         6         5        25
                 Het  P       ***       (*)      N.S.       ***
               Fixed  RR    12.51      7.08     15.12      9.83
                     RRl    10.70      6.06     10.76      8.85
                     RRu    14.64      8.27     21.25     10.92
                      P       +++       +++       +++       +++
              Random  RR    10.83      5.60     15.12      9.50
                     RRl     7.79      3.63     10.76      7.38
                     RRu    15.07      8.63     21.25     12.22
                      P       +++       +++       +++       +++
             Between Chi                                  32.36
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N       15                   8         3        26
                      NS       12                   5         3        20

                      Wt   206.25              121.40     19.98    347.63
                 Het Chi    42.03                7.41     10.69     82.02
                 Het  df       14                   7         2        25
                 Het  P       ***                N.S.        **       ***
               Fixed  RR     7.99               13.50     12.05      9.83
                     RRl     6.97               11.30      7.77      8.85
                     RRu     9.16               16.13     18.68     10.92
                      P       +++                 +++       +++       +++
              Random  RR     7.00               13.46     13.13      9.50
                     RRl     4.85               11.11      3.88      7.38
                     RRu    10.10               16.31     44.45     12.22
                      P       +++                 +++       +++       +++
             Between Chi                                            21.89
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        7                   7
                      NS        6                   6

                      Wt   158.40              158.40
                 Het Chi    12.27               12.27
                 Het  df        6                   6
                 Het  P       (*)                 (*)
               Fixed  RR     7.08                7.08
                     RRl     6.06                6.06
                     RRu     8.27                8.27
                      P       +++                 +++
              Random  RR     5.60                5.60
                     RRl     3.63                3.63
                     RRu     8.63                8.63
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        3         6         4        13        26
                      NS        3         5         3         9        20

                      Wt     3.73     14.78     18.99    310.13    347.63
                 Het Chi     1.56      5.02      8.09     43.61     82.02
                 Het  df        2         5         3        12        25
                 Het  P      N.S.      N.S.         *       ***       ***
               Fixed  RR     8.04      5.77      3.81     10.71      9.83
                     RRl     2.91      3.46      2.43      9.58      8.85
                     RRu    22.19      9.60      5.97     11.97     10.92
                      P       +++       +++       +++       +++       +++
              Random  RR     8.04      5.78      3.83     12.48      9.50
                     RRl     2.91      3.46      1.75      9.57      7.38
                     RRu    22.19      9.66      8.41     16.29     12.22
                      P       +++       +++       +++       +++       +++
             Between Chi                                            23.72
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                               (*)

                        Number of COPD cases (excluding unknown)

                       N        3         6         4        13        26
                      NS        3         5         3         9        20

                      Wt     3.73     14.78     18.99    310.13    347.63
                 Het Chi     1.56      5.02      8.09     43.61     82.02
                 Het  df        2         5         3        12        25
                 Het  P      N.S.      N.S.         *       ***       ***
               Fixed  RR     8.04      5.77      3.81     10.71      9.83
                     RRl     2.91      3.46      2.43      9.58      8.85
                     RRu    22.19      9.60      5.97     11.97     10.92
                      P       +++       +++       +++       +++       +++
              Random  RR     8.04      5.78      3.83     12.48      9.50
                     RRl     2.91      3.46      1.75      9.57      7.38
                     RRu    22.19      9.66      8.41     16.29     12.22
                      P       +++       +++       +++       +++       +++
             Between Chi                                            23.72
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                               (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       15        11        26
                      NS       11         9        20

                      Wt   214.35    133.28    347.63
                 Het Chi    36.05     30.50     82.02
                 Het  df       14        10        25
                 Het  P        **       ***       ***
               Fixed  RR     8.32     12.84      9.83
                     RRl     7.28     10.84      8.85
                     RRu     9.51     15.22     10.92
                      P       +++       +++       +++
              Random  RR     8.75     10.55      9.50
                     RRl     6.36      7.18      7.38
                     RRu    12.04     15.50     12.22
                      P       +++       +++       +++
             Between Chi                        15.47
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        14        11        26
                      NS        1        11         8        20

                      Wt     2.51    213.89    131.23    347.63
                 Het Chi     0.00     46.51     11.73     82.02
                 Het  df        0        13        10        25
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR    15.33      7.99     13.64      9.83
                     RRl     4.45      6.99     11.50      8.85
                     RRu    52.83      9.14     16.19     10.92
                      P       +++       +++       +++       +++
              Random  RR    15.33      7.35     13.51      9.50
                     RRl     4.45      5.08     10.93      7.38
                     RRu    52.83     10.62     16.70     12.22
                      P       +++       +++       +++       +++
             Between Chi                                  23.77
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       21         5                            26
                      NS       16         4                            20

                      Wt   190.83    156.80                        347.63
                 Het Chi    29.71     16.45                         82.02
                 Het  df       20         4                            25
                 Het  P       (*)        **                           ***
               Fixed  RR    13.15      6.89                          9.83
                     RRl    11.41      5.90                          8.85
                     RRu    15.15      8.06                         10.92
                      P       +++       +++                           +++
              Random  RR    12.54      4.26                          9.50
                     RRl    10.18      2.37                          7.38
                     RRu    15.46      7.65                         12.22
                      P       +++       +++                           +++
             Between Chi                                            35.85
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                               ***
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       21         5        26
                      NS       16         4        20

                      Wt   190.83    156.80    347.63
                 Het Chi    29.71     16.45     82.02
                 Het  df       20         4        25
                 Het  P       (*)        **       ***
               Fixed  RR    13.15      6.89      9.83
                     RRl    11.41      5.90      8.85
                     RRu    15.15      8.06     10.92
                      P       +++       +++       +++
              Random  RR    12.54      4.26      9.50
                     RRl    10.18      2.37      7.38
                     RRu    15.46      7.65     12.22
                      P       +++       +++       +++
             Between Chi                        35.85
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           ***

                        Number of adjustment variables
                                0         1        2+     Total

                       N        6        16         4        26
                      NS        5        13         3        21

                      Wt   167.39    138.13     42.10    347.63
                 Het Chi    16.44     40.62     13.98     82.02
                 Het  df        5        15         3        25
                 Het  P        **       ***        **       ***
               Fixed  RR     8.18     11.81     11.16      9.83
                     RRl     7.03      9.99      8.25      8.85
                     RRu     9.52     13.95     15.09     10.92
                      P       +++       +++       +++       +++
              Random  RR     7.77      9.61     11.43      9.50
                     RRl     4.69      6.69      5.91      7.38
                     RRu    12.88     13.80     22.09     12.22
                      P       +++       +++       +++       +++
             Between Chi                                  10.98
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  13     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  25   +
    BEST  40     m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21   +
  CLEMEN   5     m   20   60     Eu:West  1960  1982    Pr  Prev      COPD:LF   0 Current       Cigs   Nev any  21   +
   DEAN1  21 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  23   +
   DEAN1  61 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  23   +
   DOLL1   9     m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any  25   +
   DOLL2   6     f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  25   +
  ENSTRO  11     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  ENSTRO  20     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  FERRI2  30     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +
  FERRI2  47     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +
  HOZAWA   6     b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  30   +
  HUHTI1  23 x   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs   Nev any  25   +
  HUHTI3   9 x   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   0 Current        Any   Nev any  25   +
  JACOBS  21     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  30   +
   KAHN2 102     m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any  40   +
  LEBOWI   8 x   m   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  21   +
  LEBOWI  20 x   f   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  21   +
     LEE  11 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  21   +
     LEE  46     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  21   +
  MUELLE  22 x   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   0 Current       Cigs   Nev any  25   +
    TODD  11 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  21   +
  VONHER  12     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  30   +
  VONHER  19     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  30   +
   WEISS   8     m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any  21   +
     WEN   4     m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs  21   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 13  m   1         22       -       2       -     10.15 (  2.00-  51.42)
*BEST   40  m   1         19       -       6       -     10.38 (  4.15-  25.98)
 CLEMEN 5   m   0         37     645      11     709      3.70 (  1.87-   7.31)
 DEAN1  21  m   0         66     237      47     510      3.02 (  2.02-   4.53)
 DEAN1  61  f   0         24     151     120    1538      2.04 (  1.27-   3.26)
 Subtotal DEAN1                                           2.55 (  1.88-   3.47)
*DOLL1  9   m   2         76       -      12       -     22.50 ( 12.30-  41.15)
*DOLL2  6   f   1          2       -       1       -     32.00 (  2.90- 352.92)
*ENSTRO 11  m   1        148       -     103       -     13.54 ( 10.33-  17.75)
*ENSTRO 20  f   1         46       -     296       -     15.33 ( 11.06-  21.23)
 Subtotal ENSTRO                                         14.24 ( 11.57-  17.54)
 FERRI2 30  m   1         19       -      11       -     17.09 (  5.90-  49.47)
 FERRI2 47  f   1          5       -      54       -     65.73 (  4.45- 971.21)
 Subtotal FERRI2                                         20.49 (  7.62-  55.10)
 HOZAWA 6   b   0        382     284     872    5019      7.74 (  6.53-   9.17)
 HUHTI1 23  m   0         39      46       7     115     13.93 (  5.81-  33.39)
 HUHTI3 9   m   0         12      64       3     236     14.75 (  4.04-  53.85)
*JACOBS 21  m   2         12       -      28       -      5.29 (  2.73-  10.25)
*KAHN2  102 m   1         26       -      31       -     15.02 (  8.92-  25.29)
 LEBOWI 8   m   0          6      54       4     172      4.78 (  1.30-  17.56)
 LEBOWI 20  f   0         14     104      36     766      2.86 (  1.49-   5.49)
 Subtotal LEBOWI                                          3.17 (  1.77-   5.68)
*LEE    11  m   0          5     266       1     347      6.52 (  0.77-  55.50)
*LEE    46  f   0          1      90       5    1694      3.76 (  0.44-  31.89)
 Subtotal LEE                                             4.95 (  1.09-  22.47)
 MUELLE 22  m   0         10      46       2      57      6.20 (  1.29-  29.69)
*TODD   11  m   0          6     338       1     520      9.23 (  1.12-  76.33)
 VONHER 12  m   0         73      65      63     911     16.24 ( 10.66-  24.73)
 VONHER 19  f   0          2       5     137    2888      8.43 (  1.62-  43.85)
 Subtotal VONHER                                         15.60 ( 10.38-  23.45)
 WEISS  8   m   0         12      32       2      34      6.38 (  1.32-  30.73)
*WEN    4   m   1          6       -      52       -      1.46 (  0.51-   4.19)
Partial Totals          1070    2427    1907   15516
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 13  m   1              2.32     1.46     0.05       0.01
*BEST   40  m   1              2.34     4.57     0.21       0.00
 CLEMEN 5   m   0              1.31     8.27     5.57       0.00
 DEAN1  21  m   0              1.11    23.47    24.51       0.00
 DEAN1  61  f   0              0.71    17.46    35.03       0.00
 Subtotal DEAN1                0.94    40.93    59.54
*DOLL1  9   m   2              3.11    10.54    10.24       0.00
*DOLL2  6   f   1              3.47     0.67     1.19       0.00
*ENSTRO 11  m   1              2.61    52.44    11.97       0.00
*ENSTRO 20  f   1              2.73    36.14    13.09       0.00
 Subtotal ENSTRO               2.66    88.57    25.06
 FERRI2 30  m   1              2.84     3.40     1.72       0.00
 FERRI2 47  f   1              4.19     0.53     2.24       0.00
 Subtotal FERRI2               3.02     3.93     3.96
 HOZAWA 6   b   0              2.05   133.60     0.88       0.00
 HUHTI1 23  m   0              2.63     5.03     1.29       0.00
 HUHTI3 9   m   0              2.69     2.29     0.73       0.00
*JACOBS 21  m   2              1.67     8.78     1.87       0.00
*KAHN2  102 m   1              2.71    14.15     4.78       0.00
 LEBOWI 8   m   0              1.56     2.27     0.72       0.02
 LEBOWI 20  f   0              1.05     9.08    10.50       0.00
 Subtotal LEBOWI               1.15    11.35    11.23
*LEE    11  m   0              1.88     0.84     0.05       0.09
*LEE    46  f   0              1.33     0.84     0.54       0.22
 Subtotal LEE                  1.60     1.68     0.60
 MUELLE 22  m   0              1.82     1.56     0.14       0.02
*TODD   11  m   0              2.22     0.86     0.01       0.04
 VONHER 12  m   0              2.79    21.71     9.45       0.00
 VONHER 19  f   0              2.13     1.41     0.00       0.01
 Subtotal VONHER               2.75    23.13     9.45
 WEISS  8   m   0              1.85     1.55     0.12       0.02
*WEN    4   m   1              0.38     3.46    10.60       0.48

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       26
                      NS       20

                      Wt   366.37
                 Het Chi   147.51
                 Het  df       25
                 Het  P       ***
               Fixed  RR     8.40
                     RRl     7.58
                     RRu     9.30
                      P       +++
              Random  RR     7.85
                     RRl     5.72
                     RRu    10.76
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       26
                      NS       20

                      Wt   366.37
                 Het Chi   147.51
                 Het  df       25
                 Het  P       ***
               Fixed  RR     8.40
                     RRl     7.58
                     RRu     9.30
                      P       +++
              Random  RR     7.85
                     RRl     5.72
                     RRu    10.76
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1        18         7        26
                      NS        1        18         7        26

                      Wt   133.60    166.64     66.13    366.37
                 Het Chi     0.00     81.05     60.63    147.51
                 Het  df        0        17         6        25
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     7.74      9.60      7.06      8.40
                     RRl     6.53      8.25      5.55      7.58
                     RRu     9.17     11.17      8.99      9.30
                      P       +++       +++       +++       +++
              Random  RR     7.74      8.45      7.29      7.85
                     RRl     6.53      5.72      2.62      5.72
                     RRu     9.17     12.49     20.32     10.76
                      P       +++       +++       +++       +++
             Between Chi                                   5.84
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       12        12         1         1        26
                      NS        9         9         1         1        20

                      Wt   260.74     93.39      3.46      8.78    366.37
                 Het Chi    41.19     80.87      0.00      0.00    147.51
                 Het  df       11        11         0         0        25
                 Het  P       ***       ***      N.S.      N.S.       ***
               Fixed  RR     9.68      6.30      1.46      5.29      8.40
                     RRl     8.57      5.14      0.51      2.73      7.58
                     RRu    10.93      7.71      4.18     10.25      9.30
                      P       +++       +++      N.S.       +++       +++
              Random  RR     9.82      7.79      1.46      5.29      7.85
                     RRl     7.01      4.09      0.51      2.73      5.72
                     RRu    13.74     14.86      4.18     10.25     10.76
                      P       +++       +++      N.S.       +++       +++
             Between Chi                                            25.45
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2        12        12        26
                      NS        1        10         9        20

                      Wt    40.93    141.55    183.90    366.37
                 Het Chi     1.56     42.77     27.84    147.51
                 Het  df        1        11        11        25
                 Het  P      N.S.       ***        **       ***
               Fixed  RR     2.55     11.92      8.36      8.40
                     RRl     1.88     10.11      7.23      7.58
                     RRu     3.47     14.05      9.66      9.30
                      P       +++       +++       +++       +++
              Random  RR     2.53      9.15      9.12      7.85
                     RRl     1.72      6.08      6.15      5.72
                     RRu     3.71     13.77     13.52     10.76
                      P       +++       +++       +++       +++
             Between Chi                                  75.35
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     ***

                          COPD subtype
                             mort        LF     other     Total

                       N       13         7         6        26
                      NS       10         6         4        20

                      Wt   174.21    158.63     33.54    366.37
                 Het Chi   113.77     13.61      2.03    147.51
                 Het  df       12         6         5        25
                 Het  P       ***         *      N.S.       ***
               Fixed  RR     8.77      7.03     15.54      8.40
                     RRl     7.56      6.01     11.08      7.58
                     RRu    10.18      8.21     21.80      9.30
                      P       +++       +++       +++       +++
              Random  RR     7.36      5.49     15.54      7.85
                     RRl     4.29      3.48     11.08      5.72
                     RRu    12.61      8.66     21.80     10.76
                      P       +++       +++       +++       +++
             Between Chi                                  18.10
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        14        11        26
                      NS        1        11         8        20

                      Wt     2.29    214.72    149.37    366.37
                 Het Chi     0.00     49.32     96.40    147.51
                 Het  df        0        13        10        25
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR    14.75      8.00      8.92      8.40
                     RRl     4.04      7.00      7.60      7.58
                     RRu    53.85      9.15     10.48      9.30
                      P       +++       +++       +++       +++
              Random  RR    14.75      7.44      8.10      7.85
                     RRl     4.04      5.11      4.36      5.72
                     RRu    53.85     10.84     15.03     10.76
                      P       +++       +++       +++       +++
             Between Chi                                   1.78
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       21         5                            26
                      NS       16         4                            20

                      Wt   209.18    157.19                        366.37
                 Het Chi   118.03     18.06                        147.51
                 Het  df       20         4                            25
                 Het  P       ***        **                           ***
               Fixed  RR     9.79      6.85                          8.40
                     RRl     8.55      5.86                          7.58
                     RRu    11.21      8.01                          9.30
                      P       +++       +++                           +++
              Random  RR     9.58      4.17                          7.85
                     RRl     6.43      2.27                          5.72
                     RRu    14.27      7.66                         10.76
                      P       +++       +++                           +++
             Between Chi                                            11.42
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       21         5        26
                      NS       16         4        20

                      Wt   209.18    157.19    366.37
                 Het Chi   118.03     18.06    147.51
                 Het  df       20         4        25
                 Het  P       ***        **       ***
               Fixed  RR     9.79      6.85      8.40
                     RRl     8.55      5.86      7.58
                     RRu    11.21      8.01      9.30
                      P       +++       +++       +++
              Random  RR     9.58      4.17      7.85
                     RRl     6.43      2.27      5.72
                     RRu    14.27      7.66     10.76
                      P       +++       +++       +++
             Between Chi                        11.42
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6       CHEN2 GODTFR KRZYZA LINDST LUNDB1 NILSSO   PETO SPEIZE TVERDA YAMAGU   YUAN
7        KAHN
11     DONTA1 FERRI1 FERRI3   LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 3 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  HOZAWA HOZAWA     1         ENRIGH/HOZAWA/HARIKK
  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI1 HUHTI1     1                HUHTI1/HUHTI2
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  LEBOWI LEBOWI     1                 LEBOWI/SILVA
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
     WEN    WEN     1                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD
   KAHN2   KAHN     2                   KAHN/KAHN2

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN   6   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs   Nev any  40   +
          RR|SIG|

       21.98   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 4 -

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 2) = 1
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 1

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    BEST  38   m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  ENSTRO   7   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  ENSTRO  16   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  FERRI2  25   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   1   4
  FERRI2  42   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   1   4
  JACOBS  26   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   6 Current       Cigs  Nev cigs   1   9
   KAHN2  99   m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any   1   9
     LEE  22   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
     LEE  43   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
  LINDST  10   b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs  Nev cigs   1   4
  LUNDB1  10   b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs  Nev cigs   1   4
  NILSSO  10   m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
  NILSSO  15   f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
    TODD  22   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  TVERDA   5   m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only  Nev cigs   1   9
  VONHER   9   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
  VONHER  16   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
   WEISS   6   m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any   1   9
  YAMAGU   4   b   40   99   Asia:FarE  1986  1988    CS  Prev      COPD:LF   6 Current       Cigs  Nev cigs   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 2

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*BEST   38  m   1         26       -       6       -      6.06 (  2.50-  14.71)
*ENSTRO 7   m   1         35       -     103       -      2.84 (  1.94-   4.17)
*ENSTRO 16  f   1         50       -     296       -      1.64 (  1.21-   2.22)
 Subtotal ENSTRO                                          2.03 (  1.60-   2.57)
 FERRI2 25  m   1          2       -      11       -      1.73 (  0.30-   9.90)
 FERRI2 42  f   1         10       -      54       -      2.08 (  0.98-   4.41)
 Subtotal FERRI2                                          2.02 (  1.01-   4.03)
*JACOBS 26  m   6         39       -      28       -      2.90 (  1.75-   4.85)
*KAHN2  99  m   1         28       -      31       -      4.14 (  2.48-   6.90)
*LEE    22  m   1          4       -       1       -      7.75 (  0.87-  68.85)
*LEE    43  f   0          2     342       5    1694      1.98 (  0.39-  10.17)
 Subtotal LEE                                             3.23 (  0.87-  11.98)
 LINDST 10  b   5          -       -     166       -      0.97 (  0.53-   1.77)
 LUNDB1 10  b   4          -       -      39       -      4.39 (  1.66-  11.60)
*NILSSO 10  m   2         19       -      31       -      3.30 (  1.86-   5.85)
*NILSSO 15  f   2         18       -      57       -      3.80 (  2.20-   6.57)
 Subtotal NILSSO                                          3.55 (  2.39-   5.28)
*TODD   22  m   1          6       -       1       -      8.94 (  1.08-  73.89)
*TVERDA 5   m   2          5       -       7       -      1.86 (  0.59-   5.88)
 VONHER 9   m   0         50     121      63     911      5.98 (  3.94-   9.07)
 VONHER 16  f   0         28     172     137    2888      3.43 (  2.22-   5.30)
 Subtotal VONHER                                          4.58 (  3.39-   6.19)
 WEISS  6   m   0          2      13       2      34      2.62 (  0.33-  20.55)
 YAMAGU 4   b   6          -       -     144       -      1.96 (  1.53-   2.53)
Partial Totals           324     648    1182    5527
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*BEST   38  m   1              1.80     4.89     3.49       0.00
*ENSTRO 7   m   1              1.04    26.24     0.20       0.00
*ENSTRO 16  f   1              0.49    41.72     8.93       0.00
 Subtotal ENSTRO               0.71    67.96     9.13
 FERRI2 25  m   1              0.55     1.26     0.21       0.54
 FERRI2 42  f   1              0.73     6.79     0.34       0.06
 Subtotal FERRI2               0.70     8.05     0.55
*JACOBS 26  m   6              1.06    14.79     0.17       0.00
*KAHN2  99  m   1              1.42    14.68     3.15       0.00
*LEE    22  m   1              2.05     0.80     0.96       0.07
*LEE    43  f   0              0.68     1.44     0.11       0.41
 Subtotal LEE                  1.17     2.24     1.06
 LINDST 10  b   5             -0.03    10.57    10.31       0.92
 LUNDB1 10  b   4              1.48     4.07     1.11       0.00
*NILSSO 10  m   2              1.19    11.70     0.66       0.00
*NILSSO 15  f   2              1.34    12.84     1.83       0.00
 Subtotal NILSSO               1.27    24.54     2.49
*TODD   22  m   1              2.19     0.86     1.31       0.04
*TVERDA 5   m   2              0.62     2.91     0.33       0.29
 VONHER 9   m   0              1.79    22.11    15.24       0.00
 VONHER 16  f   0              1.23    20.34     1.55       0.00
 Subtotal VONHER               1.52    42.44    16.79
 WEISS  6   m   0              0.96     0.90     0.00       0.36
 YAMAGU 4   b   6              0.67    60.74     4.91       0.00

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 2

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       19
                      NS       14

                      Wt   259.63
                 Het Chi    54.80
                 Het  df       18
                 Het  P       ***
               Fixed  RR     2.60
                     RRl     2.31
                     RRu     2.94
                      P       +++
              Random  RR     2.87
                     RRl     2.24
                     RRu     3.69
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       19
                      NS       14

                      Wt   259.63
                 Het Chi    54.80
                 Het  df       18
                 Het  P       ***
               Fixed  RR     2.60
                     RRl     2.31
                     RRu     2.94
                      P       +++
              Random  RR     2.87
                     RRl     2.24
                     RRu     3.69
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        3        11         5        19
                      NS        3        11         5        19

                      Wt    75.38    101.14     83.12    259.63
                 Het Chi     7.64     12.63     11.36     54.80
                 Het  df        2        10         4        18
                 Het  P         *      N.S.         *       ***
               Fixed  RR     1.85      3.73      2.29      2.60
                     RRl     1.48      3.07      1.85      2.31
                     RRu     2.32      4.53      2.84      2.94
                      P       +++       +++       +++       +++
              Random  RR     1.86      3.73      2.51      2.87
                     RRl     0.98      2.93      1.64      2.24
                     RRu     3.54      4.74      3.85      3.69
                      P       (+)       +++       +++       +++
             Between Chi                                  23.16
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7        10         1         1        19
                      NS        5         7         1         1        14

                      Wt    96.48     87.62     60.74     14.79    259.63
                 Het Chi    15.63     26.91      0.00      0.00     54.80
                 Het  df        6         9         0         0        18
                 Het  P         *        **      N.S.      N.S.       ***
               Fixed  RR     2.39      3.42      1.96      2.90      2.60
                     RRl     1.96      2.77      1.52      1.74      2.31
                     RRu     2.92      4.22      2.52      4.83      2.94
                      P       +++       +++       +++       +++       +++
              Random  RR     2.73      3.21      1.96      2.90      2.87
                     RRl     1.84      2.11      1.52      1.74      2.24
                     RRu     4.05      4.87      2.52      4.83      3.69
                      P       +++       +++       +++       +++       +++
             Between Chi                                            12.25
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                 11         8        19
                      NS                  8         6        14

                      Wt             132.86    126.77    259.63
                 Het Chi              21.02     33.57     54.80
                 Het  df                 10         7        18
                 Het  P                   *       ***       ***
               Fixed  RR               2.68      2.53      2.60
                     RRl               2.26      2.13      2.31
                     RRu               3.17      3.01      2.94
                      P                 +++       +++       +++
              Random  RR               3.04      2.59      2.87
                     RRl               2.28      1.61      2.24
                     RRu               4.05      4.15      3.69
                      P                 +++       +++       +++
             Between Chi                                   0.21
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       11         3         5        19
                      NS        8         3         3        14

                      Wt   132.86     65.71     61.06    259.63
                 Het Chi    21.02      2.53     25.49     54.80
                 Het  df       10         2         4        18
                 Het  P         *      N.S.       ***       ***
               Fixed  RR     2.68      2.07      3.14      2.60
                     RRl     2.26      1.62      2.45      2.31
                     RRu     3.17      2.63      4.04      2.94
                      P       +++       +++       +++       +++
              Random  RR     3.04      2.31      2.51      2.87
                     RRl     2.28      1.45      1.24      2.24
                     RRu     4.05      3.67      5.07      3.69
                      P       +++       +++         +       +++
             Between Chi                                   5.75
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  9        10        19
                      NS                  7         7        14

                      Wt             155.33    104.30    259.63
                 Het Chi              36.85     17.59     54.80
                 Het  df                  8         9        18
                 Het  P                 ***         *       ***
               Fixed  RR               2.69      2.49      2.60
                     RRl               2.29      2.05      2.31
                     RRu               3.14      3.02      2.94
                      P                 +++       +++       +++
              Random  RR               2.79      2.91      2.87
                     RRl               1.90      2.08      2.24
                     RRu               4.09      4.08      3.69
                      P                 +++       +++       +++
             Between Chi                                   0.36
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 3

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       14         5                            19
                      NS        9         5                            14

                      Wt   166.56     93.07                        259.63
                 Het Chi    34.22     10.13                         54.80
                 Het  df       13         4                            18
                 Het  P        **         *                           ***
               Fixed  RR     3.03      1.99                          2.60
                     RRl     2.60      1.63                          2.31
                     RRu     3.52      2.44                          2.94
                      P       +++       +++                           +++
              Random  RR     3.31      2.04                          2.87
                     RRl     2.47      1.34                          2.24
                     RRu     4.43      3.11                          3.69
                      P       +++       +++                           +++
             Between Chi                                            10.45
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                               (*)

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       14         5        19
                      NS        9         5        14

                      Wt   166.56     93.07    259.63
                 Het Chi    34.22     10.13     54.80
                 Het  df       13         4        18
                 Het  P        **         *       ***
               Fixed  RR     3.03      1.99      2.60
                     RRl     2.60      1.63      2.31
                     RRu     3.52      2.44      2.94
                      P       +++       +++       +++
              Random  RR     3.31      2.04      2.87
                     RRl     2.47      1.34      2.24
                     RRu     4.43      3.11      3.69
                      P       +++       +++       +++
             Between Chi                        10.45
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                           (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 4

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    BEST  38     m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  ENSTRO   7     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  ENSTRO  16     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any   1   9
  FERRI2  25     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   1   4
  FERRI2  42     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   1   4
  JACOBS  17 x   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs   1   4
   KAHN2  99     m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any   1   9
     LEE   8 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
     LEE  43     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
  LINDST  10     b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs  Nev cigs   1   4
  LUNDB1  10     b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs  Nev cigs   1   4
  NILSSO  10     m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
  NILSSO  15     f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   1   7
    TODD   8 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1   9
  TVERDA   5     m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only  Nev cigs   1   9
  VONHER   9     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
  VONHER  16     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any   1   9
   WEISS   6     m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only   Nev any   1   9
  YAMAGU   4     b   40   99   Asia:FarE  1986  1988    CS  Prev      COPD:LF   6 Current       Cigs  Nev cigs   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 5

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*BEST   38  m   1         26       -       6       -      6.06 (  2.50-  14.71)
*ENSTRO 7   m   1         35       -     103       -      2.84 (  1.94-   4.17)
*ENSTRO 16  f   1         50       -     296       -      1.64 (  1.21-   2.22)
 Subtotal ENSTRO                                          2.03 (  1.60-   2.57)
 FERRI2 25  m   1          2       -      11       -      1.73 (  0.30-   9.90)
 FERRI2 42  f   1         10       -      54       -      2.08 (  0.98-   4.41)
 Subtotal FERRI2                                          2.02 (  1.01-   4.03)
*JACOBS 17  m   2          9       -      28       -      2.14 (  0.97-   4.71)
*KAHN2  99  m   1         28       -      31       -      4.14 (  2.48-   6.90)
*LEE    8   m   0          4     192       1     347      7.23 (  0.81-  64.22)
*LEE    43  f   0          2     342       5    1694      1.98 (  0.39-  10.17)
 Subtotal LEE                                             3.15 (  0.85-  11.68)
 LINDST 10  b   5          -       -     166       -      0.97 (  0.53-   1.77)
 LUNDB1 10  b   4          -       -      39       -      4.39 (  1.66-  11.60)
*NILSSO 10  m   2         19       -      31       -      3.30 (  1.86-   5.85)
*NILSSO 15  f   2         18       -      57       -      3.80 (  2.20-   6.57)
 Subtotal NILSSO                                          3.55 (  2.39-   5.28)
*TODD   8   m   0          6     316       1     520      9.87 (  1.19-  81.63)
*TVERDA 5   m   2          5       -       7       -      1.86 (  0.59-   5.88)
 VONHER 9   m   0         50     121      63     911      5.98 (  3.94-   9.07)
 VONHER 16  f   0         28     172     137    2888      3.43 (  2.22-   5.30)
 Subtotal VONHER                                          4.58 (  3.39-   6.19)
 WEISS  6   m   0          2      13       2      34      2.62 (  0.33-  20.55)
 YAMAGU 4   b   6          -       -     144       -      1.96 (  1.53-   2.53)
Partial Totals           294    1156    1182    6394
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*BEST   38  m   1              1.80     4.89     3.58       0.00
*ENSTRO 7   m   1              1.04    26.24     0.25       0.00
*ENSTRO 16  f   1              0.49    41.72     8.51       0.00
 Subtotal ENSTRO               0.71    67.96     8.76
 FERRI2 25  m   1              0.55     1.26     0.20       0.54
 FERRI2 42  f   1              0.73     6.79     0.31       0.06
 Subtotal FERRI2               0.70     8.05     0.51
*JACOBS 17  m   2              0.76     6.15     0.21       0.06
*KAHN2  99  m   1              1.42    14.68     3.30       0.00
*LEE    8   m   0              1.98     0.81     0.86       0.08
*LEE    43  f   0              0.68     1.44     0.10       0.41
 Subtotal LEE                  1.15     2.24     0.96
 LINDST 10  b   5             -0.03    10.57    10.08       0.92
 LUNDB1 10  b   4              1.48     4.07     1.15       0.00
*NILSSO 10  m   2              1.19    11.70     0.72       0.00
*NILSSO 15  f   2              1.34    12.84     1.94       0.00
 Subtotal NILSSO               1.27    24.54     2.66
*TODD   8   m   0              2.29     0.86     1.55       0.03
*TVERDA 5   m   2              0.62     2.91     0.31       0.29
 VONHER 9   m   0              1.79    22.11    15.65       0.00
 VONHER 16  f   0              1.23    20.34     1.67       0.00
 Subtotal VONHER               1.52    42.44    17.32
 WEISS  6   m   0              0.96     0.90     0.00       0.36
 YAMAGU 4   b   6              0.67    60.74     4.54       0.00

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 5

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       19
                      NS       14

                      Wt   251.00
                 Het Chi    54.93
                 Het  df       18
                 Het  P       ***
               Fixed  RR     2.58
                     RRl     2.28
                     RRu     2.92
                      P       +++
              Random  RR     2.83
                     RRl     2.19
                     RRu     3.66
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 6

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       19
                      NS       14

                      Wt   251.00
                 Het Chi    54.93
                 Het  df       18
                 Het  P       ***
               Fixed  RR     2.58
                     RRl     2.28
                     RRu     2.92
                      P       +++
              Random  RR     2.83
                     RRl     2.19
                     RRu     3.66
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        3        11         5        19
                      NS        3        11         5        19

                      Wt    75.38     92.51     83.12    251.00
                 Het Chi     7.64     13.68     11.36     54.93
                 Het  df        2        10         4        18
                 Het  P         *      N.S.         *       ***
               Fixed  RR     1.85      3.75      2.29      2.58
                     RRl     1.48      3.05      1.85      2.28
                     RRu     2.32      4.59      2.84      2.92
                      P       +++       +++       +++       +++
              Random  RR     1.86      3.69      2.51      2.83
                     RRl     0.98      2.82      1.64      2.19
                     RRu     3.54      4.83      3.85      3.66
                      P       (+)       +++       +++       +++
             Between Chi                                  22.25
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7        10         1         1        19
                      NS        5         7         1         1        14

                      Wt    96.48     87.62     60.74      6.15    251.00
                 Het Chi    15.63     27.00      0.00      0.00     54.93
                 Het  df        6         9         0         0        18
                 Het  P         *        **      N.S.      N.S.       ***
               Fixed  RR     2.39      3.42      1.96      2.14      2.58
                     RRl     1.96      2.77      1.52      0.97      2.28
                     RRu     2.92      4.22      2.52      4.72      2.92
                      P       +++       +++       +++       (+)       +++
              Random  RR     2.73      3.21      1.96      2.14      2.83
                     RRl     1.84      2.11      1.52      0.97      2.19
                     RRu     4.05      4.88      2.52      4.72      3.66
                      P       +++       +++       +++       (+)       +++
             Between Chi                                            12.30
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 6

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                 11         8        19
                      NS                  8         6        14

                      Wt             124.23    126.77    251.00
                 Het Chi              21.29     33.57     54.93
                 Het  df                 10         7        18
                 Het  P                   *       ***       ***
               Fixed  RR               2.62      2.53      2.58
                     RRl               2.20      2.13      2.28
                     RRu               3.13      3.01      2.92
                      P                 +++       +++       +++
              Random  RR               2.98      2.59      2.83
                     RRl               2.20      1.61      2.19
                     RRu               4.04      4.15      3.66
                      P                 +++       +++       +++
             Between Chi                                   0.08
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       11         3         5        19
                      NS        8         3         3        14

                      Wt   124.23     65.71     61.06    251.00
                 Het Chi    21.29      2.53     25.49     54.93
                 Het  df       10         2         4        18
                 Het  P         *      N.S.       ***       ***
               Fixed  RR     2.62      2.07      3.14      2.58
                     RRl     2.20      1.62      2.45      2.28
                     RRu     3.13      2.63      4.04      2.92
                      P       +++       +++       +++       +++
              Random  RR     2.98      2.31      2.51      2.83
                     RRl     2.20      1.45      1.24      2.19
                     RRu     4.04      3.67      5.07      3.66
                      P       +++       +++         +       +++
             Between Chi                                   5.63
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  9        10        19
                      NS                  7         7        14

                      Wt             146.70    104.31    251.00
                 Het Chi              37.04     17.69     54.93
                 Het  df                  8         9        18
                 Het  P                 ***         *       ***
               Fixed  RR               2.64      2.49      2.58
                     RRl               2.24      2.06      2.28
                     RRu               3.10      3.02      2.92
                      P                 +++       +++       +++
              Random  RR               2.70      2.92      2.83
                     RRl               1.81      2.08      2.19
                     RRu               4.03      4.09      3.66
                      P                 +++       +++       +++
             Between Chi                                   0.20
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 6

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       14         5                            19
                      NS        9         5                            14

                      Wt   166.57     84.44                        251.00
                 Het Chi    34.31      7.76                         54.93
                 Het  df       13         4                            18
                 Het  P        **      N.S.                           ***
               Fixed  RR     3.03      1.87                          2.58
                     RRl     2.60      1.51                          2.28
                     RRu     3.52      2.32                          2.92
                      P       +++       +++                           +++
              Random  RR     3.31      1.87                          2.83
                     RRl     2.48      1.24                          2.19
                     RRu     4.43      2.81                          3.66
                      P       +++        ++                           +++
             Between Chi                                            12.87
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                 *

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       14         5        19
                      NS        9         5        14

                      Wt   166.57     84.44    251.00
                 Het Chi    34.31      7.76     54.93
                 Het  df       13         4        18
                 Het  P        **      N.S.       ***
               Fixed  RR     3.03      1.87      2.58
                     RRl     2.60      1.51      2.28
                     RRu     3.52      2.32      2.92
                      P       +++       +++       +++
              Random  RR     3.31      1.87      2.83
                     RRl     2.48      1.24      2.19
                     RRu     4.43      2.81      3.66
                      P       +++        ++       +++
             Between Chi                        12.87
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 7

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6      ANDER1  CHEN2 CLEMEN  DEAN1  DOLL1  DOLL2 FERRI3 GODTFR HOZAWA HUHTI1 HUHTI3 KRZYZA LEBOWI   LIAW MUELLE   PETO
       SPEIZE    WEN   YUAN
7        KAHN
11     DONTA1 FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 4 - 8

                                IESCOPD - Meta-analysis of amount smoked : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  LUNDB1 LUNDBA     1  LINDBE/LUNDB1/LUNDB2/HEDLUN
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
    TODD   TODD     1                  LAMBER/TODD
   KAHN2   KAHN     2                   KAHN/KAHN2

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN   3   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs   Nev any   1   9
          RR|SIG|

        4.84   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 5 -

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 2) = 10
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ENSTRO   8   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  19
  ENSTRO  17   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  19
  FERRI2  26   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  FERRI2  43   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  JACOBS  19   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  10  19
     LEE  23   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  19
     LEE  44   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  10  19
  LINDST  11   b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs  Nev cigs   5  14
  LUNDB1  11   b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs  Nev cigs   5  14
  NILSSO  11   m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   8  15
  NILSSO  16   f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   8  15
    TODD  23   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  19
  TVERDA   6   m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only  Nev cigs  10  19
  VONHER  10   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  10  19
  VONHER  17   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  10  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*ENSTRO 8   m   1        125       -     103       -      5.46 (  4.19-   7.11)
*ENSTRO 17  f   1        214       -     296       -      5.69 (  4.73-   6.85)
 Subtotal ENSTRO                                          5.61 (  4.82-   6.53)
 FERRI2 26  m   1         16       -      11       -      2.55 (  1.08-   6.04)
 FERRI2 43  f   1         13       -      54       -      1.59 (  0.82-   3.09)
 Subtotal FERRI2                                          1.90 (  1.12-   3.21)
*JACOBS 19  m   2        104       -      28       -      4.29 (  2.66-   6.92)
*LEE    23  m   1         10       -       1       -      5.54 (  0.71-  43.11)
*LEE    44  f   0          2     606       5    1694      1.12 (  0.22-   5.75)
 Subtotal LEE                                             2.08 (  0.58-   7.49)
 LINDST 11  b   5          -       -     166       -      1.94 (  1.47-   2.57)
 LUNDB1 11  b   4          -       -      39       -      6.44 (  3.37-  11.60)
*NILSSO 11  m   2         36       -      31       -      8.46 (  5.15-  13.90)
*NILSSO 16  f   2         31       -      57       -     11.80 (  7.36-  18.90)
 Subtotal NILSSO                                         10.08 (  7.16-  14.18)
*TODD   23  m   1         12       -       1       -      6.56 (  0.86-  50.33)
*TVERDA 6   m   2         29       -       7       -      4.85 (  2.13-  11.08)
 VONHER 10  m   0        155     266      63     911      8.43 (  6.10-  11.64)
 VONHER 17  f   0         50     132     137    2888      7.98 (  5.53-  11.54)
 Subtotal VONHER                                          8.23 (  6.46-  10.49)
Partial Totals           797    1004     999    5493
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*ENSTRO 8   m   1              1.70    54.95     0.15       0.00
*ENSTRO 17  f   1              1.74   112.05     1.00       0.00
 Subtotal ENSTRO               1.73   167.00     1.15
 FERRI2 26  m   1              0.94     5.19     2.60       0.03
 FERRI2 43  f   1              0.46     8.73    12.17       0.17
 Subtotal FERRI2               0.64    13.92    14.77
*JACOBS 19  m   2              1.46    16.81     0.59       0.00
*LEE    23  m   1              1.71     0.91     0.00       0.10
*LEE    44  f   0              0.11     1.43     3.37       0.89
 Subtotal LEE                  0.73     2.34     3.37
 LINDST 11  b   5              0.66    49.24    47.45       0.00
 LUNDB1 11  b   4              1.86    10.06     0.48       0.00
*NILSSO 11  m   2              2.14    15.59     3.76       0.00
*NILSSO 16  f   2              2.47    17.28    11.72       0.00
 Subtotal NILSSO               2.31    32.86    15.48
*TODD   23  m   1              1.88     0.93     0.05       0.07
*TVERDA 6   m   2              1.58     5.65     0.02       0.00
 VONHER 10  m   0              2.13    36.79     8.72       0.00
 VONHER 17  f   0              2.08    28.39     5.33       0.00
 Subtotal VONHER               2.11    65.18    14.05

                       N       15
                      NS       10

                      Wt   363.98
                 Het Chi    97.42
                 Het  df       14
                 Het  P       ***
               Fixed  RR     5.18
                     RRl     4.67
                     RRu     5.74
                      P       +++
              Random  RR     4.93
                     RRl     3.59
                     RRu     6.77
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       15
                      NS       10

                      Wt   363.98
                 Het Chi    97.42
                 Het  df       14
                 Het  P       ***
               Fixed  RR     5.18
                     RRl     4.67
                     RRu     5.74
                      P       +++
              Random  RR     4.93
                     RRl     3.59
                     RRu     6.77
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        2         8         5        15
                      NS        2         8         5        15

                      Wt    59.29    136.81    167.88    363.98
                 Het Chi    12.02     12.51     29.98     97.42
                 Het  df        1         7         4        14
                 Het  P       ***       (*)       ***       ***
               Fixed  RR     2.38      6.06      5.99      5.18
                     RRl     1.84      5.13      5.15      4.67
                     RRu     3.07      7.17      6.97      5.74
                      P       +++       +++       +++       +++
              Random  RR     3.42      5.83      4.98      4.93
                     RRl     1.06      4.45      2.85      3.59
                     RRu    11.06      7.62      8.69      6.77
                      P         +       +++       +++       +++
             Between Chi                                  42.91
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4        10                   1        15
                      NS        2         7                   1        10

                      Wt   180.91    166.26               16.81    363.98
                 Het Chi    15.92     80.83                0.00     97.42
                 Het  df        3         9                   0        14
                 Het  P        **       ***                N.S.       ***
               Fixed  RR     5.16      5.29                4.29      5.18
                     RRl     4.46      4.55                2.66      4.67
                     RRu     5.97      6.16                6.92      5.74
                      P       +++       +++                 +++       +++
              Random  RR     3.88      5.68                4.29      4.93
                     RRl     2.51      3.35                2.66      3.59
                     RRu     6.00      9.63                6.92      6.77
                      P       +++       +++                 +++       +++
             Between Chi                                             0.68
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  9         6        15
                      NS                  6         4        10

                      Wt             225.59    138.39    363.98
                 Het Chi              16.70     70.29     97.42
                 Het  df                  8         5        14
                 Het  P                   *       ***       ***
               Fixed  RR               5.91      4.17      5.18
                     RRl               5.19      3.53      4.67
                     RRu               6.74      4.93      5.74
                      P                 +++       +++       +++
              Random  RR               6.06      3.97      4.93
                     RRl               4.72      2.03      3.59
                     RRu               7.79      7.77      6.77
                      P                 +++       +++       +++
             Between Chi                                  10.43
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        9         1         5        15
                      NS        6         1         3        10

                      Wt   225.59     10.06    128.33    363.98
                 Het Chi    16.70      0.00     68.24     97.42
                 Het  df        8         0         4        14
                 Het  P         *      N.S.       ***       ***
               Fixed  RR     5.91      6.44      4.03      5.18
                     RRl     5.19      3.47      3.39      4.67
                     RRu     6.74     11.95      4.79      5.74
                      P       +++       +++       +++       +++
              Random  RR     6.06      6.44      3.60      4.93
                     RRl     4.72      3.47      1.67      3.59
                     RRu     7.79     11.95      7.78      6.77
                      P       +++       +++        ++       +++
             Between Chi                                  12.48
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  7         8        15
                      NS                  5         5        10

                      Wt             155.20    208.78    363.98
                 Het Chi              70.30     14.84     97.42
                 Het  df                  6         7        14
                 Het  P                 ***         *       ***
               Fixed  RR               4.18      6.07      5.18
                     RRl               3.58      5.30      4.67
                     RRu               4.90      6.95      5.74
                      P                 +++       +++       +++
              Random  RR               4.02      6.42      4.93
                     RRl               2.27      4.88      3.59
                     RRu               7.14      8.43      6.77
                      P                 +++       +++       +++
             Between Chi                                  12.29
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       11         4                            15
                      NS        6         4                            10

                      Wt   282.23     81.75                        363.98
                 Het Chi    40.13     18.37                         97.42
                 Het  df       10         3                            14
                 Het  P       ***       ***                           ***
               Fixed  RR     6.17      2.82                          5.18
                     RRl     5.49      2.27                          4.67
                     RRu     6.94      3.50                          5.74
                      P       +++       +++                           +++
              Random  RR     5.74      3.84                          4.93
                     RRl     4.28      2.05                          3.59
                     RRu     7.70      7.18                          6.77
                      P       +++       +++                           +++
             Between Chi                                            38.93
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                 *

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       11         4        15
                      NS        6         4        10

                      Wt   282.23     81.75    363.98
                 Het Chi    40.13     18.37     97.42
                 Het  df       10         3        14
                 Het  P       ***       ***       ***
               Fixed  RR     6.17      2.82      5.18
                     RRl     5.49      2.27      4.67
                     RRu     6.94      3.50      5.74
                      P       +++       +++       +++
              Random  RR     5.74      3.84      4.93
                     RRl     4.28      2.05      3.59
                     RRu     7.70      7.18      6.77
                      P       +++       +++       +++
             Between Chi                        38.93
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ENSTRO   8     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  19
  ENSTRO  17     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  10  19
  FERRI2  26     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  FERRI2  43     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any   5  14
  JACOBS  19     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  10  19
     LEE   9 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  10  19
     LEE  44     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  10  19
  LINDST  11     b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs  Nev cigs   5  14
  LUNDB1  11     b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs  Nev cigs   5  14
  NILSSO  11     m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   8  15
  NILSSO  16     f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any   8  15
    TODD   9 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  10  19
  TVERDA   6     m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only  Nev cigs  10  19
  VONHER  10     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  10  19
  VONHER  17     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  10  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*ENSTRO 8   m   1        125       -     103       -      5.46 (  4.19-   7.11)
*ENSTRO 17  f   1        214       -     296       -      5.69 (  4.73-   6.85)
 Subtotal ENSTRO                                          5.61 (  4.82-   6.53)
 FERRI2 26  m   1         16       -      11       -      2.55 (  1.08-   6.04)
 FERRI2 43  f   1         13       -      54       -      1.59 (  0.82-   3.09)
 Subtotal FERRI2                                          1.90 (  1.12-   3.21)
*JACOBS 19  m   2        104       -      28       -      4.29 (  2.66-   6.92)
*LEE    9   m   0         10     673       1     347      5.16 (  0.66-  40.11)
*LEE    44  f   0          2     606       5    1694      1.12 (  0.22-   5.75)
 Subtotal LEE                                             2.03 (  0.56-   7.29)
 LINDST 11  b   5          -       -     166       -      1.94 (  1.47-   2.57)
 LUNDB1 11  b   4          -       -      39       -      6.44 (  3.37-  11.60)
*NILSSO 11  m   2         36       -      31       -      8.46 (  5.15-  13.90)
*NILSSO 16  f   2         31       -      57       -     11.80 (  7.36-  18.90)
 Subtotal NILSSO                                         10.08 (  7.16-  14.18)
*TODD   9   m   0         12    1023       1     520      6.10 (  0.80-  46.78)
*TVERDA 6   m   2         29       -       7       -      4.85 (  2.13-  11.08)
 VONHER 10  m   0        155     266      63     911      8.43 (  6.10-  11.64)
 VONHER 17  f   0         50     132     137    2888      7.98 (  5.53-  11.54)
 Subtotal VONHER                                          8.23 (  6.46-  10.49)
Partial Totals           797    2700     999    6360
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*ENSTRO 8   m   1              1.70    54.95     0.16       0.00
*ENSTRO 17  f   1              1.74   112.05     1.00       0.00
 Subtotal ENSTRO               1.73   167.00     1.16
 FERRI2 26  m   1              0.94     5.19     2.60       0.03
 FERRI2 43  f   1              0.46     8.73    12.16       0.17
 Subtotal FERRI2               0.64    13.92    14.76
*JACOBS 19  m   2              1.46    16.81     0.59       0.00
*LEE    9   m   0              1.64     0.91     0.00       0.12
*LEE    44  f   0              0.11     1.43     3.37       0.89
 Subtotal LEE                  0.71     2.35     3.37
 LINDST 11  b   5              0.66    49.24    47.42       0.00
 LUNDB1 11  b   4              1.86    10.06     0.48       0.00
*NILSSO 11  m   2              2.14    15.59     3.76       0.00
*NILSSO 16  f   2              2.47    17.28    11.73       0.00
 Subtotal NILSSO               2.31    32.86    15.49
*TODD   9   m   0              1.81     0.93     0.02       0.08
*TVERDA 6   m   2              1.58     5.65     0.02       0.00
 VONHER 10  m   0              2.13    36.79     8.74       0.00
 VONHER 17  f   0              2.08    28.39     5.34       0.00
 Subtotal VONHER               2.11    65.18    14.07

                       N       15
                      NS       10

                      Wt   363.98
                 Het Chi    97.39
                 Het  df       14
                 Het  P       ***
               Fixed  RR     5.18
                     RRl     4.67
                     RRu     5.74
                      P       +++
              Random  RR     4.91
                     RRl     3.58
                     RRu     6.75
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       15
                      NS       10

                      Wt   363.98
                 Het Chi    97.39
                 Het  df       14
                 Het  P       ***
               Fixed  RR     5.18
                     RRl     4.67
                     RRu     5.74
                      P       +++
              Random  RR     4.91
                     RRl     3.58
                     RRu     6.75
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        2         8         5        15
                      NS        2         8         5        15

                      Wt    59.29    136.81    167.88    363.98
                 Het Chi    12.02     12.52     29.98     97.39
                 Het  df        1         7         4        14
                 Het  P       ***       (*)       ***       ***
               Fixed  RR     2.38      6.06      5.99      5.18
                     RRl     1.84      5.12      5.15      4.67
                     RRu     3.07      7.16      6.97      5.74
                      P       +++       +++       +++       +++
              Random  RR     3.42      5.81      4.98      4.91
                     RRl     1.06      4.44      2.85      3.58
                     RRu    11.06      7.61      8.69      6.75
                      P         +       +++       +++       +++
             Between Chi                                  42.87
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4        10                   1        15
                      NS        2         7                   1        10

                      Wt   180.91    166.26               16.81    363.98
                 Het Chi    15.92     80.80                0.00     97.39
                 Het  df        3         9                   0        14
                 Het  P        **       ***                N.S.       ***
               Fixed  RR     5.16      5.29                4.29      5.18
                     RRl     4.46      4.54                2.66      4.67
                     RRu     5.97      6.16                6.92      5.74
                      P       +++       +++                 +++       +++
              Random  RR     3.88      5.64                4.29      4.91
                     RRl     2.51      3.33                2.66      3.58
                     RRu     6.00      9.57                6.92      6.75
                      P       +++       +++                 +++       +++
             Between Chi                                             0.67
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  9         6        15
                      NS                  6         4        10

                      Wt             225.59    138.39    363.98
                 Het Chi              16.71     70.29     97.39
                 Het  df                  8         5        14
                 Het  P                   *       ***       ***
               Fixed  RR               5.91      4.17      5.18
                     RRl               5.19      3.53      4.67
                     RRu               6.73      4.93      5.74
                      P                 +++       +++       +++
              Random  RR               6.05      3.97      4.91
                     RRl               4.71      2.03      3.58
                     RRu               7.77      7.77      6.75
                      P                 +++       +++       +++
             Between Chi                                  10.40
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        9         1         5        15
                      NS        6         1         3        10

                      Wt   225.59     10.06    128.33    363.98
                 Het Chi    16.71      0.00     68.24     97.39
                 Het  df        8         0         4        14
                 Het  P         *      N.S.       ***       ***
               Fixed  RR     5.91      6.44      4.03      5.18
                     RRl     5.19      3.47      3.39      4.67
                     RRu     6.73     11.95      4.79      5.74
                      P       +++       +++       +++       +++
              Random  RR     6.05      6.44      3.60      4.91
                     RRl     4.71      3.47      1.67      3.58
                     RRu     7.77     11.95      7.78      6.75
                      P       +++       +++        ++       +++
             Between Chi                                  12.44
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  7         8        15
                      NS                  5         5        10

                      Wt             155.20    208.78    363.98
                 Het Chi              70.30     14.85     97.39
                 Het  df                  6         7        14
                 Het  P                 ***         *       ***
               Fixed  RR               4.18      6.06      5.18
                     RRl               3.58      5.29      4.67
                     RRu               4.90      6.94      5.74
                      P                 +++       +++       +++
              Random  RR               4.02      6.40      4.91
                     RRl               2.27      4.87      3.58
                     RRu               7.14      8.41      6.75
                      P                 +++       +++       +++
             Between Chi                                  12.25
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       11         4                            15
                      NS        6         4                            10

                      Wt   282.23     81.75                        363.98
                 Het Chi    40.15     18.37                         97.39
                 Het  df       10         3                            14
                 Het  P       ***       ***                           ***
               Fixed  RR     6.17      2.82                          5.18
                     RRl     5.49      2.27                          4.67
                     RRu     6.94      3.50                          5.74
                      P       +++       +++                           +++
              Random  RR     5.73      3.84                          4.91
                     RRl     4.27      2.05                          3.58
                     RRu     7.68      7.18                          6.75
                      P       +++       +++                           +++
             Between Chi                                            38.88
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                 *

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       11         4        15
                      NS        6         4        10

                      Wt   282.23     81.75    363.98
                 Het Chi    40.15     18.37     97.39
                 Het  df       10         3        14
                 Het  P       ***       ***       ***
               Fixed  RR     6.17      2.82      5.18
                     RRl     5.49      2.27      4.67
                     RRu     6.94      3.50      5.74
                      P       +++       +++       +++
              Random  RR     5.73      3.84      4.91
                     RRl     4.27      2.05      3.58
                     RRu     7.68      7.18      6.75
                      P       +++       +++       +++
             Between Chi                        38.88
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6      ANDER1   BEST  CHEN2 CLEMEN  DEAN1  DOLL1  DOLL2 FERRI3 GODTFR HOZAWA HUHTI1 HUHTI3   KAHN  KAHN2 KRZYZA LEBOWI
         LIAW MUELLE   PETO SPEIZE  WEISS    WEN YAMAGU   YUAN
11     DONTA1 FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 5 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  LUNDB1 LUNDBA     1  LINDBE/LUNDB1/LUNDB2/HEDLUN
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
    TODD   TODD     1                  LAMBER/TODD

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 6 -

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 2) = 20
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  12   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
   DEAN1  25   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any  13  22
   DEAN1  65   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only   Nev any  13  22
   DOLL1   8   m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any  15  24
   DOLL2   5   f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  15  24
  ENSTRO   9   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  ENSTRO  18   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  FERRI2  27   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  FERRI2  44   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  HOZAWA   5   b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  15  29
  HUHTI1  27   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs   Nev any  15  24
  HUHTI3  13   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   1 Current        Any   Nev any  15  24
  JACOBS  20   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  20  29
     LEE  24   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
     LEE  45   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
  MUELLE  26   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   1 Current       Cigs   Nev any  15  24
    TODD  24   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  VONHER  11   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
  VONHER  18   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
     WEN   3   m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs  11  20

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 12  m   1          8       -       2       -      5.93 (  1.14-  30.72)
 DEAN1  25  m   3         75       -      47       -      2.56 (  1.64-   4.01)
 DEAN1  65  f   3         21       -     120       -      2.23 (  1.26-   3.95)
 Subtotal DEAN1                                           2.43 (  1.71-   3.45)
*DOLL1  8   m   2         61       -      12       -     11.20 (  6.06-  20.68)
*DOLL2  5   f   1          4       -       1       -     28.50 (  3.19- 255.00)
*ENSTRO 9   m   1        326       -     103       -      8.30 (  6.62-  10.40)
*ENSTRO 18  f   1        309       -     296       -      9.32 (  7.85-  11.06)
 Subtotal ENSTRO                                          8.93 (  7.79-  10.24)
 FERRI2 27  m   1         55       -      11       -      4.99 (  2.42-  10.31)
 FERRI2 44  f   1         28       -      54       -      2.89 (  1.72-   4.87)
 Subtotal FERRI2                                          3.48 (  2.28-   5.31)
 HOZAWA 5   b   0        822    1020     872    5019      4.64 (  4.13-   5.21)
 HUHTI1 27  m   1         86       -       7       -     11.82 (  5.14-  27.19)
 HUHTI3 13  m   1         14       -       3       -      5.92 (  1.80-  19.47)
*JACOBS 20  m   2         61       -      28       -      4.00 (  2.43-   6.58)
*LEE    24  m   1          7       -       1       -      7.54 (  0.93-  60.98)
*LEE    45  f   0          0     212       5    1694      0.72~(  0.04-  13.06)
 Subtotal LEE                                             3.37 (  0.62-  18.37)
 MUELLE 26  m   1         14       -       2       -      6.82 (  1.41-  33.04)
*TODD   24  m   1          8       -       1       -      9.31 (  1.17-  74.18)
 VONHER 11  m   0        217     174      63     911     18.03 ( 13.04-  24.93)
 VONHER 18  f   0         40      65     137    2888     12.97 (  8.44-  19.93)
 Subtotal VONHER                                         16.00 ( 12.36-  20.73)
*WEN    3   m   1         62       -      52       -      2.65 (  1.68-   4.18)
Partial Totals          2218    1471    1817   10512
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 12  m   1              1.78     1.42     0.00       0.03
 DEAN1  25  m   3              0.94    19.22    14.74       0.00
 DEAN1  65  f   3              0.80    11.77    12.09       0.01
 Subtotal DEAN1                0.89    30.99    26.83
*DOLL1  8   m   2              2.42    10.20     3.67       0.00
*DOLL2  5   f   1              3.35     0.80     1.88       0.00
*ENSTRO 9   m   1              2.12    75.31     6.80       0.00
*ENSTRO 18  f   1              2.23   130.74    22.68       0.00
 Subtotal ENSTRO               2.19   206.05    29.48
 FERRI2 27  m   1              1.61     7.31     0.32       0.00
 FERRI2 44  f   1              1.06    14.19     8.07       0.00
 Subtotal FERRI2               1.25    21.50     8.39
 HOZAWA 5   b   0              1.53   282.25    22.33       0.00
 HUHTI1 27  m   1              2.47     5.54     2.37       0.00
 HUHTI3 13  m   1              1.78     2.71     0.00       0.00
*JACOBS 20  m   2              1.39    15.49     2.86       0.00
*LEE    24  m   1              2.02     0.88     0.04       0.06
*LEE    45  f   0             -0.32     0.46     2.10       0.83
 Subtotal LEE                  1.22     1.34     2.14
 MUELLE 26  m   1              1.92     1.54     0.02       0.02
*TODD   24  m   1              2.23     0.89     0.15       0.04
 VONHER 11  m   0              2.89    36.60    42.41       0.00
 VONHER 18  f   0              2.56    20.82    11.62       0.00
 Subtotal VONHER               2.77    57.42    54.04
*WEN    3   m   1              0.97    18.49    13.08       0.00

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       20
                      NS       15

                      Wt   656.62
                 Het Chi   167.26
                 Het  df       19
                 Het  P       ***
               Fixed  RR     6.15
                     RRl     5.69
                     RRu     6.63
                      P       +++
              Random  RR     6.01
                     RRl     4.45
                     RRu     8.13
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       20
                      NS       15

                      Wt   656.62
                 Het Chi   167.26
                 Het  df       19
                 Het  P       ***
               Fixed  RR     6.15
                     RRl     5.69
                     RRu     6.63
                      P       +++
              Random  RR     6.01
                     RRl     4.45
                     RRu     8.13
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1        13         6        20
                      NS        1        13         6        20

                      Wt   282.25    195.59    178.78    656.62
                 Het Chi     0.00     81.31     45.77    167.26
                 Het  df        0        12         5        19
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     4.64      7.23      8.02      6.15
                     RRl     4.13      6.28      6.93      5.69
                     RRu     5.21      8.32      9.29      6.63
                      P       +++       +++       +++       +++
              Random  RR     4.64      6.42      5.57      6.01
                     RRl     4.13      4.12      2.79      4.45
                     RRu     5.21     10.00     11.16      8.13
                      P       +++       +++       +++       +++
             Between Chi                                  40.18
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7        11         1         1        20
                      NS        5         8         1         1        15

                      Wt   512.76    109.88     18.49     15.49    656.62
                 Het Chi    59.82     78.88      0.00      0.00    167.26
                 Het  df        6        10         0         0        19
                 Het  P       ***       ***      N.S.      N.S.       ***
               Fixed  RR     5.97      8.58      2.65      4.00      6.15
                     RRl     5.48      7.11      1.68      2.43      5.69
                     RRu     6.51     10.34      4.18      6.58      6.63
                      P       +++       +++       +++       +++       +++
              Random  RR     5.84      7.32      2.65      4.00      6.01
                     RRl     3.98      3.90      1.68      2.43      4.45
                     RRu     8.55     13.74      4.18      6.58      8.13
                      P       +++       +++       +++       +++       +++
             Between Chi                                            28.56
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         9         9        20
                      NS        1         7         7        15

                      Wt    30.99    253.26    372.37    656.62
                 Het Chi     0.14     38.19     84.22    167.26
                 Het  df        1         8         8        19
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     2.43      7.84      5.62      6.15
                     RRl     1.71      6.93      5.08      5.69
                     RRu     3.45      8.87      6.22      6.63
                      P       +++       +++       +++       +++
              Random  RR     2.43      6.45      7.23      6.01
                     RRl     1.71      4.34      4.23      4.45
                     RRu     3.45      9.60     12.36      8.13
                      P       +++       +++       +++       +++
             Between Chi                                  44.71
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                          COPD subtype
                             mort        LF     other     Total

                       N       11         3         6        20
                      NS        8         3         4        15

                      Wt   284.25    286.50     85.87    656.62
                 Het Chi    76.26      0.39     39.83    167.26
                 Het  df       10         2         5        19
                 Het  P       ***      N.S.       ***       ***
               Fixed  RR     6.90      4.66     10.54      6.15
                     RRl     6.15      4.15      8.53      5.69
                     RRu     7.75      5.23     13.02      6.63
                      P       +++       +++       +++       +++
              Random  RR     5.08      4.66      8.17      6.01
                     RRl     3.30      4.15      4.17      4.45
                     RRu     7.81      5.23     16.01      8.13
                      P       +++       +++       +++       +++
             Between Chi                                  50.77
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        10         9        20
                      NS        1         8         6        15

                      Wt     2.71    403.64    250.27    656.62
                 Het Chi     0.00     95.56     51.97    167.26
                 Het  df        0         9         8        19
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     5.92      5.36      7.66      6.15
                     RRl     1.80      4.86      6.77      5.69
                     RRu    19.47      5.91      8.67      6.63
                      P        ++       +++       +++       +++
              Random  RR     5.92      6.12      5.88      6.01
                     RRl     1.80      3.84      3.69      4.45
                     RRu    19.47      9.74      9.37      8.13
                      P        ++       +++       +++       +++
             Between Chi                                  19.73
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       17         3                            20
                      NS       12         3                            15

                      Wt   340.39    316.23                        656.62
                 Het Chi    98.66      5.63                        167.26
                 Het  df       16         2                            19
                 Het  P       ***       (*)                           ***
               Fixed  RR     8.28      4.46                          6.15
                     RRl     7.45      3.99                          5.69
                     RRu     9.21      4.98                          6.63
                      P       +++       +++                           +++
              Random  RR     6.83      3.85                          6.01
                     RRl     4.85      2.74                          4.45
                     RRu     9.64      5.41                          8.13
                      P       +++       +++                           +++
             Between Chi                                            62.97
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                **

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       17         3        20
                      NS       12         3        15

                      Wt   340.39    316.23    656.62
                 Het Chi    98.66      5.63    167.26
                 Het  df       16         2        19
                 Het  P       ***       (*)       ***
               Fixed  RR     8.28      4.46      6.15
                     RRl     7.45      3.99      5.69
                     RRu     9.21      4.98      6.63
                      P       +++       +++       +++
              Random  RR     6.83      3.85      6.01
                     RRl     4.85      2.74      4.45
                     RRu     9.64      5.41      8.13
                      P       +++       +++       +++
             Between Chi                        62.97
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                            **

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  12     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
   DEAN1  20 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  13  22
   DEAN1  60 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  13  22
   DOLL1   8     m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only   Nev any  15  24
   DOLL2   5     f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  15  24
  ENSTRO   9     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  ENSTRO  18     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  20  20
  FERRI2  27     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  FERRI2  44     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  15  24
  HOZAWA   5     b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs  Nev cigs  15  29
  HUHTI1  22 x   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs   Nev any  15  24
  HUHTI3   8 x   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   0 Current        Any   Nev any  15  24
  JACOBS  20     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  20  29
     LEE  10 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
     LEE  45     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
  MUELLE  21 x   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   0 Current       Cigs   Nev any  15  24
    TODD  10 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20  20
  VONHER  11     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
  VONHER  18     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs   Nev any  20  29
     WEN   3     m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs  Nev cigs  11  20

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 12  m   1          8       -       2       -      5.93 (  1.14-  30.72)
 DEAN1  20  m   0         75     429      47     510      1.90 (  1.29-   2.79)
 DEAN1  60  f   0         21     521     120    1538      0.52 (  0.32-   0.83)
 Subtotal DEAN1                                           1.13 (  0.84-   1.52)
*DOLL1  8   m   2         61       -      12       -     11.20 (  6.06-  20.68)
*DOLL2  5   f   1          4       -       1       -     28.50 (  3.19- 255.00)
*ENSTRO 9   m   1        326       -     103       -      8.30 (  6.62-  10.40)
*ENSTRO 18  f   1        309       -     296       -      9.32 (  7.85-  11.06)
 Subtotal ENSTRO                                          8.93 (  7.79-  10.24)
 FERRI2 27  m   1         55       -      11       -      4.99 (  2.42-  10.31)
 FERRI2 44  f   1         28       -      54       -      2.89 (  1.72-   4.87)
 Subtotal FERRI2                                          3.48 (  2.28-   5.31)
 HOZAWA 5   b   0        822    1020     872    5019      4.64 (  4.13-   5.21)
 HUHTI1 22  m   0         86     105       7     115     13.46 (  5.96-  30.38)
 HUHTI3 8   m   0         14     187       3     236      5.89 (  1.67-  20.80)
*JACOBS 20  m   2         61       -      28       -      4.00 (  2.43-   6.58)
*LEE    10  m   0          7     364       1     347      6.67 (  0.83-  53.96)
*LEE    45  f   0          0     212       5    1694      0.72~(  0.04-  13.06)
 Subtotal LEE                                             3.12 (  0.57-  16.95)
 MUELLE 21  m   0         14      50       2      57      7.98 (  1.73-  36.83)
*TODD   10  m   0          8     487       1     520      8.54 (  1.07-  68.05)
 VONHER 11  m   0        217     174      63     911     18.03 ( 13.04-  24.93)
 VONHER 18  f   0         40      65     137    2888     12.97 (  8.44-  19.93)
 Subtotal VONHER                                         16.00 ( 12.36-  20.73)
*WEN    3   m   1         62       -      52       -      2.65 (  1.68-   4.18)
Partial Totals          2218    3614    1817   13835
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 12  m   1              1.78     1.42     0.00       0.03
 DEAN1  20  m   0              0.64    25.71    31.75       0.00
 DEAN1  60  f   0             -0.66    17.09    99.43       0.01
 Subtotal DEAN1                0.12    42.79   131.18
*DOLL1  8   m   2              2.42    10.20     4.50       0.00
*DOLL2  5   f   1              3.35     0.80     2.04       0.00
*ENSTRO 9   m   1              2.12    75.31    10.01       0.00
*ENSTRO 18  f   1              2.23   130.74    30.18       0.00
 Subtotal ENSTRO               2.19   206.05    40.19
 FERRI2 27  m   1              1.61     7.31     0.15       0.00
 FERRI2 44  f   1              1.06    14.19     6.76       0.00
 Subtotal FERRI2               1.25    21.50     6.91
 HOZAWA 5   b   0              1.53   282.25    13.33       0.00
 HUHTI1 22  m   0              2.60     5.79     4.16       0.00
 HUHTI3 8   m   0              1.77     2.41     0.00       0.01
*JACOBS 20  m   2              1.39    15.49     2.07       0.00
*LEE    10  m   0              1.90     0.88     0.02       0.08
*LEE    45  f   0             -0.32     0.46     1.98       0.83
 Subtotal LEE                  1.14     1.34     1.99
 MUELLE 21  m   0              2.08     1.64     0.17       0.01
*TODD   10  m   0              2.15     0.89     0.14       0.04
 VONHER 11  m   0              2.89    36.60    47.60       0.00
 VONHER 18  f   0              2.56    20.82    13.70       0.00
 Subtotal VONHER               2.77    57.42    61.30
*WEN    3   m   1              0.97    18.49    11.17       0.00

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       20
                      NS       15

                      Wt   668.48
                 Het Chi   279.17
                 Het  df       19
                 Het  P       ***
               Fixed  RR     5.76
                     RRl     5.34
                     RRu     6.22
                      P       +++
              Random  RR     5.41
                     RRl     3.73
                     RRu     7.84
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       20
                      NS       15

                      Wt   668.48
                 Het Chi   279.17
                 Het  df       19
                 Het  P       ***
               Fixed  RR     5.76
                     RRl     5.34
                     RRu     6.22
                      P       +++
              Random  RR     5.41
                     RRl     3.73
                     RRu     7.84
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1        13         6        20
                      NS        1        13         6        20

                      Wt   282.25    202.13    184.10    668.48
                 Het Chi     0.00    106.58    149.51    279.17
                 Het  df        0        12         5        19
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     4.64      6.76      6.75      5.76
                     RRl     4.13      5.89      5.84      5.34
                     RRu     5.21      7.76      7.80      6.22
                      P       +++       +++       +++       +++
              Random  RR     4.64      6.31      4.06      5.41
                     RRl     4.13      3.86      1.29      3.73
                     RRu     5.21     10.32     12.79      7.84
                      P       +++       +++         +       +++
             Between Chi                                  23.07
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7        11         1         1        20
                      NS        5         8         1         1        15

                      Wt   512.86    121.64     18.49     15.49    668.48
                 Het Chi    59.93    205.30      0.00      0.00    279.17
                 Het  df        6        10         0         0        19
                 Het  P       ***       ***      N.S.      N.S.       ***
               Fixed  RR     5.98      5.83      2.65      4.00      5.76
                     RRl     5.48      4.88      1.68      2.43      5.34
                     RRu     6.52      6.96      4.18      6.58      6.22
                      P       +++       +++       +++       +++       +++
              Random  RR     5.88      5.93      2.65      4.00      5.41
                     RRl     4.02      2.36      1.68      2.43      3.73
                     RRu     8.62     14.92      4.18      6.58      7.84
                      P       +++       +++       +++       +++       +++
             Between Chi                                            13.93
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         9         9        20
                      NS        1         7         7        15

                      Wt    42.79    253.26    372.43    668.48
                 Het Chi    17.37     38.19     85.71    279.17
                 Het  df        1         8         8        19
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.13      7.84      5.64      5.76
                     RRl     0.84      6.93      5.10      5.34
                     RRu     1.52      8.87      6.24      6.22
                      P      N.S.       +++       +++       +++
              Random  RR     1.00      6.41      7.42      5.41
                     RRl     0.28      4.31      4.33      3.73
                     RRu     3.57      9.54     12.74      7.84
                      P      N.S.       +++       +++       +++
             Between Chi                                 137.90
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N       11         3         6        20
                      NS        8         3         4        15

                      Wt   296.05    286.30     86.12    668.48
                 Het Chi   193.06      0.61     40.10    279.17
                 Het  df       10         2         5        19
                 Het  P       ***      N.S.       ***       ***
               Fixed  RR     5.92      4.66     10.63      5.76
                     RRl     5.29      4.15      8.61      5.34
                     RRu     6.64      5.23     13.13      6.22
                      P       +++       +++       +++       +++
              Random  RR     4.16      4.66      8.34      5.41
                     RRl     2.21      4.15      4.25      3.73
                     RRu     7.85      5.23     16.36      7.84
                      P       +++       +++       +++       +++
             Between Chi                                  45.39
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        10         9        20
                      NS        1         8         6        15

                      Wt     2.41    403.99    262.07    668.48
                 Het Chi     0.00     97.16    177.04    279.17
                 Het  df        0         9         8        19
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     5.89      5.38      6.42      5.76
                     RRl     1.67      4.88      5.68      5.34
                     RRu    20.80      5.93      7.24      6.22
                      P        ++       +++       +++       +++
              Random  RR     5.89      6.25      4.51      5.41
                     RRl     1.67      3.92      2.10      3.73
                     RRu    20.80      9.98      9.69      7.84
                      P        ++       +++       +++       +++
             Between Chi                                   4.96
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N       17         3                            20
                      NS       12         3                            15

                      Wt   352.25    316.23                        668.48
                 Het Chi   233.80      5.63                        279.17
                 Het  df       16         2                            19
                 Het  P       ***       (*)                           ***
               Fixed  RR     7.26      4.46                          5.76
                     RRl     6.54      3.99                          5.34
                     RRu     8.06      4.98                          6.22
                      P       +++       +++                           +++
              Random  RR     5.97      3.85                          5.41
                     RRl     3.65      2.74                          3.73
                     RRu     9.75      5.41                          7.84
                      P       +++       +++                           +++
             Between Chi                                            39.74
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N       17         3        20
                      NS       12         3        15

                      Wt   352.25    316.23    668.48
                 Het Chi   233.80      5.63    279.17
                 Het  df       16         2        19
                 Het  P       ***       (*)       ***
               Fixed  RR     7.26      4.46      5.76
                     RRl     6.54      3.99      5.34
                     RRu     8.06      4.98      6.22
                      P       +++       +++       +++
              Random  RR     5.97      3.85      5.41
                     RRl     3.65      2.74      3.73
                     RRu     9.75      5.41      7.84
                      P       +++       +++       +++
             Between Chi                        39.74
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6        BEST  CHEN2 CLEMEN FERRI3 GODTFR   KAHN  KAHN2 KRZYZA LEBOWI LINDST LUNDB1 NILSSO   PETO SPEIZE TVERDA  WEISS
       YAMAGU   YUAN
11     DONTA1 FERRI1   LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 6 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  HOZAWA HOZAWA     1         ENRIGH/HOZAWA/HARIKK
  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI1 HUHTI1     1                HUHTI1/HUHTI2
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
     WEN    WEN     1                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 7 -

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 2) = 30
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ENSTRO  10   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21  39
  ENSTRO  19   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21  39
  FERRI2  28   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  25  34
  FERRI2  45   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  25  34
   KAHN2 101   m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any  21  39

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*ENSTRO 10  m   1        258       -     103       -     11.99 (  9.39-  15.31)
*ENSTRO 19  f   1        106       -     296       -     12.87 ( 10.13-  16.35)
 Subtotal ENSTRO                                         12.43 ( 10.48-  14.75)
 FERRI2 28  m   1         35       -      11       -      4.91 (  2.27-  10.60)
 FERRI2 45  f   1         13       -      54       -      4.00 (  1.91-   8.37)
 Subtotal FERRI2                                          4.41 (  2.59-   7.52)
*KAHN2  101 m   1        106       -      31       -     11.13 (  7.46-  16.61)
Partial Totals           518       0     495       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*ENSTRO 10  m   1              2.48    64.30     0.25       0.00
*ENSTRO 19  f   1              2.55    67.05     1.19       0.00
 Subtotal ENSTRO               2.52   131.34     1.44
 FERRI2 28  m   1              1.59     6.47     4.46       0.00
 FERRI2 45  f   1              1.39     7.04     7.54       0.00
 Subtotal FERRI2               1.48    13.51    12.01
*KAHN2  101 m   1              2.41    23.98     0.00       0.00

                       N        5
                      NS        3

                      Wt   168.83
                 Het Chi    13.45
                 Het  df        4
                 Het  P        **
               Fixed  RR    11.26
                     RRl     9.69
                     RRu    13.10
                      P       +++
              Random  RR     9.53
                     RRl     6.90
                     RRu    13.15
                      P       +++
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        5
                      NS        3

                      Wt   168.83
                 Het Chi    13.45
                 Het  df        4
                 Het  P        **
               Fixed  RR    11.26
                     RRl     9.69
                     RRu    13.10
                      P       +++
              Random  RR     9.53
                     RRl     6.90
                     RRu    13.15
                      P       +++
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N                  3         2         5
                      NS                  3         2         5

                      Wt              94.75     74.09    168.83
                 Het Chi               4.69      8.70     13.45
                 Het  df                  2         1         4
                 Het  P                 (*)        **        **
               Fixed  RR              11.07     11.52     11.26
                     RRl               9.05      9.17      9.69
                     RRu              13.54     14.46     13.10
                      P                 +++       +++       +++
              Random  RR              10.05      7.58      9.53
                     RRl               6.92      2.42      6.90
                     RRu              14.59     23.69     13.15
                      P                 +++       +++       +++
             Between Chi                                   0.07
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        5                                       5
                      NS        3                                       3

                      Wt   168.83                                  168.83
                 Het Chi    13.45                                   13.45
                 Het  df        4                                       4
                 Het  P        **                                      **
               Fixed  RR    11.26                                   11.26
                     RRl     9.69                                    9.69
                     RRu    13.10                                   13.10
                      P       +++                                     +++
              Random  RR     9.53                                    9.53
                     RRl     6.90                                    6.90
                     RRu    13.15                                   13.15
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  3         2         5
                      NS                  2         1         3

                      Wt             155.33     13.51    168.83
                 Het Chi               0.41      0.14     13.45
                 Het  df                  2         1         4
                 Het  P                N.S.      N.S.        **
               Fixed  RR              12.22      4.41     11.26
                     RRl              10.44      2.59      9.69
                     RRu              14.30      7.52     13.10
                      P                 +++       +++       +++
              Random  RR              12.22      4.41      9.53
                     RRl              10.44      2.59      6.90
                     RRu              14.30      7.52     13.15
                      P                 +++       +++       +++
             Between Chi                                  12.90
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N        3                   2         5
                      NS        2                   1         3

                      Wt   155.33               13.51    168.83
                 Het Chi     0.41                0.14     13.45
                 Het  df        2                   1         4
                 Het  P      N.S.                N.S.        **
               Fixed  RR    12.22                4.41     11.26
                     RRl    10.44                2.59      9.69
                     RRu    14.30                7.52     13.10
                      P       +++                 +++       +++
              Random  RR    12.22                4.41      9.53
                     RRl    10.44                2.59      6.90
                     RRu    14.30                7.52     13.15
                      P       +++                 +++       +++
             Between Chi                                  12.90
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                      **

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  3         2         5
                      NS                  2         1         3

                      Wt              37.49    131.34    168.83
                 Het Chi               7.54      0.16     13.45
                 Het  df                  2         1         4
                 Het  P                   *      N.S.        **
               Fixed  RR               7.97     12.43     11.26
                     RRl               5.79     10.48      9.69
                     RRu              10.98     14.75     13.10
                      P                 +++       +++       +++
              Random  RR               6.40     12.43      9.53
                     RRl               3.16     10.48      6.90
                     RRu              12.93     14.75     13.15
                      P                 +++       +++       +++
             Between Chi                                   5.75
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        5                                       5
                      NS        3                                       3

                      Wt   168.83                                  168.83
                 Het Chi    13.45                                   13.45
                 Het  df        4                                       4
                 Het  P        **                                      **
               Fixed  RR    11.26                                   11.26
                     RRl     9.69                                    9.69
                     RRu    13.10                                   13.10
                      P       +++                                     +++
              Random  RR     9.53                                    9.53
                     RRl     6.90                                    6.90
                     RRu    13.15                                   13.15
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        5                   5
                      NS        3                   3

                      Wt   168.83              168.83
                 Het Chi    13.45               13.45
                 Het  df        4                   4
                 Het  P        **                  **
               Fixed  RR    11.26               11.26
                     RRl     9.69                9.69
                     RRu    13.10               13.10
                      P       +++                 +++
              Random  RR     9.53                9.53
                     RRl     6.90                6.90
                     RRu    13.15               13.15
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ENSTRO  10     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21  39
  ENSTRO  19     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  21  39
  FERRI2  28     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  25  34
  FERRI2  45     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  25  34
   KAHN2 101     m   31   84      Am:USA  1954  1966    Pr   Inc    COPD:mort   1 Current       Cigs   Nev any  21  39

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*ENSTRO 10  m   1        258       -     103       -     11.99 (  9.39-  15.31)
*ENSTRO 19  f   1        106       -     296       -     12.87 ( 10.13-  16.35)
 Subtotal ENSTRO                                         12.43 ( 10.48-  14.75)
 FERRI2 28  m   1         35       -      11       -      4.91 (  2.27-  10.60)
 FERRI2 45  f   1         13       -      54       -      4.00 (  1.91-   8.37)
 Subtotal FERRI2                                          4.41 (  2.59-   7.52)
*KAHN2  101 m   1        106       -      31       -     11.13 (  7.46-  16.61)
Partial Totals           518       0     495       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*ENSTRO 10  m   1              2.48    64.30     0.25       0.00
*ENSTRO 19  f   1              2.55    67.05     1.19       0.00
 Subtotal ENSTRO               2.52   131.34     1.44
 FERRI2 28  m   1              1.59     6.47     4.46       0.00
 FERRI2 45  f   1              1.39     7.04     7.54       0.00
 Subtotal FERRI2               1.48    13.51    12.01
*KAHN2  101 m   1              2.41    23.98     0.00       0.00

                       N        5
                      NS        3

                      Wt   168.83
                 Het Chi    13.45
                 Het  df        4
                 Het  P        **
               Fixed  RR    11.26
                     RRl     9.69
                     RRu    13.10
                      P       +++
              Random  RR     9.53
                     RRl     6.90
                     RRu    13.15
                      P       +++
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        5
                      NS        3

                      Wt   168.83
                 Het Chi    13.45
                 Het  df        4
                 Het  P        **
               Fixed  RR    11.26
                     RRl     9.69
                     RRu    13.10
                      P       +++
              Random  RR     9.53
                     RRl     6.90
                     RRu    13.15
                      P       +++
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N                  3         2         5
                      NS                  3         2         5

                      Wt              94.75     74.09    168.83
                 Het Chi               4.69      8.70     13.45
                 Het  df                  2         1         4
                 Het  P                 (*)        **        **
               Fixed  RR              11.07     11.52     11.26
                     RRl               9.05      9.17      9.69
                     RRu              13.54     14.46     13.10
                      P                 +++       +++       +++
              Random  RR              10.05      7.58      9.53
                     RRl               6.92      2.42      6.90
                     RRu              14.59     23.69     13.15
                      P                 +++       +++       +++
             Between Chi                                   0.07
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        5                                       5
                      NS        3                                       3

                      Wt   168.83                                  168.83
                 Het Chi    13.45                                   13.45
                 Het  df        4                                       4
                 Het  P        **                                      **
               Fixed  RR    11.26                                   11.26
                     RRl     9.69                                    9.69
                     RRu    13.10                                   13.10
                      P       +++                                     +++
              Random  RR     9.53                                    9.53
                     RRl     6.90                                    6.90
                     RRu    13.15                                   13.15
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  3         2         5
                      NS                  2         1         3

                      Wt             155.33     13.51    168.83
                 Het Chi               0.41      0.14     13.45
                 Het  df                  2         1         4
                 Het  P                N.S.      N.S.        **
               Fixed  RR              12.22      4.41     11.26
                     RRl              10.44      2.59      9.69
                     RRu              14.30      7.52     13.10
                      P                 +++       +++       +++
              Random  RR              12.22      4.41      9.53
                     RRl              10.44      2.59      6.90
                     RRu              14.30      7.52     13.15
                      P                 +++       +++       +++
             Between Chi                                  12.90
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N        3                   2         5
                      NS        2                   1         3

                      Wt   155.33               13.51    168.83
                 Het Chi     0.41                0.14     13.45
                 Het  df        2                   1         4
                 Het  P      N.S.                N.S.        **
               Fixed  RR    12.22                4.41     11.26
                     RRl    10.44                2.59      9.69
                     RRu    14.30                7.52     13.10
                      P       +++                 +++       +++
              Random  RR    12.22                4.41      9.53
                     RRl    10.44                2.59      6.90
                     RRu    14.30                7.52     13.15
                      P       +++                 +++       +++
             Between Chi                                  12.90
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                      **

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  3         2         5
                      NS                  2         1         3

                      Wt              37.49    131.34    168.83
                 Het Chi               7.54      0.16     13.45
                 Het  df                  2         1         4
                 Het  P                   *      N.S.        **
               Fixed  RR               7.97     12.43     11.26
                     RRl               5.79     10.48      9.69
                     RRu              10.98     14.75     13.10
                      P                 +++       +++       +++
              Random  RR               6.40     12.43      9.53
                     RRl               3.16     10.48      6.90
                     RRu              12.93     14.75     13.15
                      P                 +++       +++       +++
             Between Chi                                   5.75
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        5                                       5
                      NS        3                                       3

                      Wt   168.83                                  168.83
                 Het Chi    13.45                                   13.45
                 Het  df        4                                       4
                 Het  P        **                                      **
               Fixed  RR    11.26                                   11.26
                     RRl     9.69                                    9.69
                     RRu    13.10                                   13.10
                      P       +++                                     +++
              Random  RR     9.53                                    9.53
                     RRl     6.90                                    6.90
                     RRu    13.15                                   13.15
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        5                   5
                      NS        3                   3

                      Wt   168.83              168.83
                 Het Chi    13.45               13.45
                 Het  df        4                   4
                 Het  P        **                  **
               Fixed  RR    11.26               11.26
                     RRl     9.69                9.69
                     RRu    13.10               13.10
                      P       +++                 +++
              Random  RR     9.53                9.53
                     RRl     6.90                6.90
                     RRu    13.15               13.15
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6      ANDER1   BEST  CHEN2 CLEMEN  DEAN1  DOLL1  DOLL2 DONTA1 FERRI3 GODTFR HOZAWA HUHTI1 HUHTI3 JACOBS KRZYZA LEBOWI
          LEE   LIAW LINDST LUNDB1 MUELLE NILSSO   PETO SPEIZE   TODD TVERDA VONHER  WEISS    WEN YAMAGU   YUAN
7        KAHN
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 7 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
   KAHN2   KAHN     2                   KAHN/KAHN2

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN   5   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs   Nev any  21  39
          RR|SIG|

       17.45   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 8 -

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 2) = 40
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ENSTRO  11   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  ENSTRO  20   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  FERRI2  29   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  35  44
  FERRI2  46   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  35  44

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*ENSTRO 11  m   1        148       -     103       -     13.54 ( 10.33-  17.75)
*ENSTRO 20  f   1         46       -     296       -     15.33 ( 11.06-  21.23)
 Subtotal ENSTRO                                         14.24 ( 11.57-  17.54)
 FERRI2 29  m   1         34       -      11       -     14.96 (  6.25-  35.81)
 FERRI2 46  f   1          7       -      54       -      3.98 (  1.56-  10.17)
 Subtotal FERRI2                                          8.09 (  4.27-  15.32)
Partial Totals           235       0     464       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*ENSTRO 11  m   1              2.61    52.44     0.00       0.00
*ENSTRO 20  f   1              2.73    36.14     0.59       0.00
 Subtotal ENSTRO               2.66    88.57     0.59
 FERRI2 29  m   1              2.71     5.04     0.05       0.00
 FERRI2 46  f   1              1.38     4.37     6.51       0.00
 Subtotal FERRI2               2.09     9.41     6.57

                       N        4
                      NS        2

                      Wt    97.99
                 Het Chi     7.16
                 Het  df        3
                 Het  P       (*)
               Fixed  RR    13.49
                     RRl    11.07
                     RRu    16.44
                      P       +++
              Random  RR    12.38
                     RRl     8.52
                     RRu    17.99
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        4
                      NS        2

                      Wt    97.99
                 Het Chi     7.16
                 Het  df        3
                 Het  P       (*)
               Fixed  RR    13.49
                     RRl    11.07
                     RRu    16.44
                      P       +++
              Random  RR    12.38
                     RRl     8.52
                     RRu    17.99
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  2         2         4
                      NS                  2         2         4

                      Wt              57.48     40.51     97.99
                 Het Chi               0.05      7.09      7.16
                 Het  df                  1         1         3
                 Het  P                N.S.        **       (*)
               Fixed  RR              13.66     13.25     13.49
                     RRl              10.55      9.74     11.07
                     RRu              17.69     18.03     16.44
                      P                 +++       +++       +++
              Random  RR              13.66      8.42     12.38
                     RRl              10.55      2.26      8.52
                     RRu              17.69     31.30     17.99
                      P                 +++        ++       +++
             Between Chi                                   0.02
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4                                       4
                      NS        2                                       2

                      Wt    97.99                                   97.99
                 Het Chi     7.16                                    7.16
                 Het  df        3                                       3
                 Het  P       (*)                                     (*)
               Fixed  RR    13.49                                   13.49
                     RRl    11.07                                   11.07
                     RRu    16.44                                   16.44
                      P       +++                                     +++
              Random  RR    12.38                                   12.38
                     RRl     8.52                                    8.52
                     RRu    17.99                                   17.99
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2         2         4
                      NS                  1         1         2

                      Wt              88.57      9.41     97.99
                 Het Chi               0.33      4.11      7.16
                 Het  df                  1         1         3
                 Het  P                N.S.         *       (*)
               Fixed  RR              14.24      8.09     13.49
                     RRl              11.57      4.27     11.07
                     RRu              17.54     15.32     16.44
                      P                 +++       +++       +++
              Random  RR              14.24      7.81     12.38
                     RRl              11.57      2.13      8.52
                     RRu              17.54     28.57     17.99
                      P                 +++        ++       +++
             Between Chi                                   2.72
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2                   2         4
                      NS        1                   1         2

                      Wt    88.57                9.41     97.99
                 Het Chi     0.33                4.11      7.16
                 Het  df        1                   1         3
                 Het  P      N.S.                   *       (*)
               Fixed  RR    14.24                8.09     13.49
                     RRl    11.57                4.27     11.07
                     RRu    17.54               15.32     16.44
                      P       +++                 +++       +++
              Random  RR    14.24                7.81     12.38
                     RRl    11.57                2.13      8.52
                     RRu    17.54               28.57     17.99
                      P       +++                  ++       +++
             Between Chi                                   2.72
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2         2         4
                      NS                  1         1         2

                      Wt               9.41     88.57     97.99
                 Het Chi               4.11      0.33      7.16
                 Het  df                  1         1         3
                 Het  P                   *      N.S.       (*)
               Fixed  RR               8.09     14.24     13.49
                     RRl               4.27     11.57     11.07
                     RRu              15.32     17.54     16.44
                      P                 +++       +++       +++
              Random  RR               7.81     14.24     12.38
                     RRl               2.13     11.57      8.52
                     RRu              28.57     17.54     17.99
                      P                  ++       +++       +++
             Between Chi                                   2.72
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        4                                       4
                      NS        2                                       2

                      Wt    97.99                                   97.99
                 Het Chi     7.16                                    7.16
                 Het  df        3                                       3
                 Het  P       (*)                                     (*)
               Fixed  RR    13.49                                   13.49
                     RRl    11.07                                   11.07
                     RRu    16.44                                   16.44
                      P       +++                                     +++
              Random  RR    12.38                                   12.38
                     RRl     8.52                                    8.52
                     RRu    17.99                                   17.99
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        4                   4
                      NS        2                   2

                      Wt    97.99               97.99
                 Het Chi     7.16                7.16
                 Het  df        3                   3
                 Het  P       (*)                 (*)
               Fixed  RR    13.49               13.49
                     RRl    11.07               11.07
                     RRu    16.44               16.44
                      P       +++                 +++
              Random  RR    12.38               12.38
                     RRl     8.52                8.52
                     RRu    17.99               17.99
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ENSTRO  11     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  ENSTRO  20     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only   Nev any  40  80
  FERRI2  29     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  35  44
  FERRI2  46     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  35  44

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*ENSTRO 11  m   1        148       -     103       -     13.54 ( 10.33-  17.75)
*ENSTRO 20  f   1         46       -     296       -     15.33 ( 11.06-  21.23)
 Subtotal ENSTRO                                         14.24 ( 11.57-  17.54)
 FERRI2 29  m   1         34       -      11       -     14.96 (  6.25-  35.81)
 FERRI2 46  f   1          7       -      54       -      3.98 (  1.56-  10.17)
 Subtotal FERRI2                                          8.09 (  4.27-  15.32)
Partial Totals           235       0     464       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*ENSTRO 11  m   1              2.61    52.44     0.00       0.00
*ENSTRO 20  f   1              2.73    36.14     0.59       0.00
 Subtotal ENSTRO               2.66    88.57     0.59
 FERRI2 29  m   1              2.71     5.04     0.05       0.00
 FERRI2 46  f   1              1.38     4.37     6.51       0.00
 Subtotal FERRI2               2.09     9.41     6.57

                       N        4
                      NS        2

                      Wt    97.99
                 Het Chi     7.16
                 Het  df        3
                 Het  P       (*)
               Fixed  RR    13.49
                     RRl    11.07
                     RRu    16.44
                      P       +++
              Random  RR    12.38
                     RRl     8.52
                     RRu    17.99
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        4
                      NS        2

                      Wt    97.99
                 Het Chi     7.16
                 Het  df        3
                 Het  P       (*)
               Fixed  RR    13.49
                     RRl    11.07
                     RRu    16.44
                      P       +++
              Random  RR    12.38
                     RRl     8.52
                     RRu    17.99
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  2         2         4
                      NS                  2         2         4

                      Wt              57.48     40.51     97.99
                 Het Chi               0.05      7.09      7.16
                 Het  df                  1         1         3
                 Het  P                N.S.        **       (*)
               Fixed  RR              13.66     13.25     13.49
                     RRl              10.55      9.74     11.07
                     RRu              17.69     18.03     16.44
                      P                 +++       +++       +++
              Random  RR              13.66      8.42     12.38
                     RRl              10.55      2.26      8.52
                     RRu              17.69     31.30     17.99
                      P                 +++        ++       +++
             Between Chi                                   0.02
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4                                       4
                      NS        2                                       2

                      Wt    97.99                                   97.99
                 Het Chi     7.16                                    7.16
                 Het  df        3                                       3
                 Het  P       (*)                                     (*)
               Fixed  RR    13.49                                   13.49
                     RRl    11.07                                   11.07
                     RRu    16.44                                   16.44
                      P       +++                                     +++
              Random  RR    12.38                                   12.38
                     RRl     8.52                                    8.52
                     RRu    17.99                                   17.99
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2         2         4
                      NS                  1         1         2

                      Wt              88.57      9.41     97.99
                 Het Chi               0.33      4.11      7.16
                 Het  df                  1         1         3
                 Het  P                N.S.         *       (*)
               Fixed  RR              14.24      8.09     13.49
                     RRl              11.57      4.27     11.07
                     RRu              17.54     15.32     16.44
                      P                 +++       +++       +++
              Random  RR              14.24      7.81     12.38
                     RRl              11.57      2.13      8.52
                     RRu              17.54     28.57     17.99
                      P                 +++        ++       +++
             Between Chi                                   2.72
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2                   2         4
                      NS        1                   1         2

                      Wt    88.57                9.41     97.99
                 Het Chi     0.33                4.11      7.16
                 Het  df        1                   1         3
                 Het  P      N.S.                   *       (*)
               Fixed  RR    14.24                8.09     13.49
                     RRl    11.57                4.27     11.07
                     RRu    17.54               15.32     16.44
                      P       +++                 +++       +++
              Random  RR    14.24                7.81     12.38
                     RRl    11.57                2.13      8.52
                     RRu    17.54               28.57     17.99
                      P       +++                  ++       +++
             Between Chi                                   2.72
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2         2         4
                      NS                  1         1         2

                      Wt               9.41     88.57     97.99
                 Het Chi               4.11      0.33      7.16
                 Het  df                  1         1         3
                 Het  P                   *      N.S.       (*)
               Fixed  RR               8.09     14.24     13.49
                     RRl               4.27     11.57     11.07
                     RRu              15.32     17.54     16.44
                      P                 +++       +++       +++
              Random  RR               7.81     14.24     12.38
                     RRl               2.13     11.57      8.52
                     RRu              28.57     17.54     17.99
                      P                  ++       +++       +++
             Between Chi                                   2.72
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        4                                       4
                      NS        2                                       2

                      Wt    97.99                                   97.99
                 Het Chi     7.16                                    7.16
                 Het  df        3                                       3
                 Het  P       (*)                                     (*)
               Fixed  RR    13.49                                   13.49
                     RRl    11.07                                   11.07
                     RRu    16.44                                   16.44
                      P       +++                                     +++
              Random  RR    12.38                                   12.38
                     RRl     8.52                                    8.52
                     RRu    17.99                                   17.99
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        4                   4
                      NS        2                   2

                      Wt    97.99               97.99
                 Het Chi     7.16                7.16
                 Het  df        3                   3
                 Het  P       (*)                 (*)
               Fixed  RR    13.49               13.49
                     RRl    11.07               11.07
                     RRu    16.44               16.44
                      P       +++                 +++
              Random  RR    12.38               12.38
                     RRl     8.52                8.52
                     RRu    17.99               17.99
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6      ANDER1   BEST  CHEN2 CLEMEN  DEAN1  DOLL1  DOLL2 DONTA1 FERRI3 GODTFR HOZAWA HUHTI1 HUHTI3 JACOBS   KAHN  KAHN2
       KRZYZA LEBOWI    LEE   LIAW LINDST LUNDB1 MUELLE NILSSO   PETO SPEIZE   TODD TVERDA VONHER  WEISS    WEN YAMAGU
         YUAN
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 8 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 40
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 9 -

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) vs never smoking base
6) Key value (scheme 2) = 999
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 1

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  FERRI2  30   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +
  FERRI2  47   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 2

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 FERRI2 30  m   1         19       -      11       -     17.09 (  5.90-  49.47)
 FERRI2 47  f   1          5       -      54       -     65.73 (  4.45- 971.21)
 Subtotal FERRI2                                         20.49 (  7.62-  55.10)
Partial Totals            24       0      65       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 FERRI2 30  m   1              2.84     3.40     0.11       0.00
 FERRI2 47  f   1              4.19     0.53     0.72       0.00
 Subtotal FERRI2               3.02     3.93     0.83

                       N        2
                      NS        1

                      Wt     3.93
                 Het Chi     0.83
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
              Random  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        2
                      NS        1

                      Wt     3.93
                 Het Chi     0.83
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
              Random  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt               3.40      0.53      3.93
                 Het Chi               0.00      0.00      0.83
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR              17.09     65.73     20.49
                     RRl               5.90      4.45      7.62
                     RRu              49.49    971.05     55.10
                      P                 +++        ++       +++
              Random  RR              17.09     65.73     20.49
                     RRl               5.90      4.45      7.62
                     RRu              49.49    971.05     55.10
                      P                 +++        ++       +++
             Between Chi                                   0.83
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2                                       2
                      NS        1                                       1

                      Wt     3.93                                    3.93
                 Het Chi     0.83                                    0.83
                 Het  df        1                                       1
                 Het  P      N.S.                                    N.S.
               Fixed  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
              Random  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                            2         2
                      NS                            1         1

                      Wt                         3.93      3.93
                 Het Chi                         0.83      0.83
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
              Random  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                            2         2
                      NS                            1         1

                      Wt                         3.93      3.93
                 Het Chi                         0.83      0.83
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
              Random  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               3.93                3.93
                 Het Chi               0.83                0.83
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR              20.49               20.49
                     RRl               7.62                7.62
                     RRu              55.10               55.10
                      P                 +++                 +++
              Random  RR              20.49               20.49
                     RRl               7.62                7.62
                     RRu              55.10               55.10
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 3

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2                                       2
                      NS        1                                       1

                      Wt     3.93                                    3.93
                 Het Chi     0.83                                    0.83
                 Het  df        1                                       1
                 Het  P      N.S.                                    N.S.
               Fixed  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
              Random  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2                   2
                      NS        1                   1

                      Wt     3.93                3.93
                 Het Chi     0.83                0.83
                 Het  df        1                   1
                 Het  P      N.S.                N.S.
               Fixed  RR    20.49               20.49
                     RRl     7.62                7.62
                     RRu    55.10               55.10
                      P       +++                 +++
              Random  RR    20.49               20.49
                     RRl     7.62                7.62
                     RRu    55.10               55.10
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 4

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  FERRI2  30     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +
  FERRI2  47     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs   Nev any  45   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 5

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 FERRI2 30  m   1         19       -      11       -     17.09 (  5.90-  49.47)
 FERRI2 47  f   1          5       -      54       -     65.73 (  4.45- 971.21)
 Subtotal FERRI2                                         20.49 (  7.62-  55.10)
Partial Totals            24       0      65       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 FERRI2 30  m   1              2.84     3.40     0.11       0.00
 FERRI2 47  f   1              4.19     0.53     0.72       0.00
 Subtotal FERRI2               3.02     3.93     0.83

                       N        2
                      NS        1

                      Wt     3.93
                 Het Chi     0.83
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
              Random  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        2
                      NS        1

                      Wt     3.93
                 Het Chi     0.83
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
              Random  RR    20.49
                     RRl     7.62
                     RRu    55.10
                      P       +++
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt               3.40      0.53      3.93
                 Het Chi               0.00      0.00      0.83
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR              17.09     65.73     20.49
                     RRl               5.90      4.45      7.62
                     RRu              49.49    971.05     55.10
                      P                 +++        ++       +++
              Random  RR              17.09     65.73     20.49
                     RRl               5.90      4.45      7.62
                     RRu              49.49    971.05     55.10
                      P                 +++        ++       +++
             Between Chi                                   0.83
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2                                       2
                      NS        1                                       1

                      Wt     3.93                                    3.93
                 Het Chi     0.83                                    0.83
                 Het  df        1                                       1
                 Het  P      N.S.                                    N.S.
               Fixed  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
              Random  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                            2         2
                      NS                            1         1

                      Wt                         3.93      3.93
                 Het Chi                         0.83      0.83
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
              Random  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                            2         2
                      NS                            1         1

                      Wt                         3.93      3.93
                 Het Chi                         0.83      0.83
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
              Random  RR                        20.49     20.49
                     RRl                         7.62      7.62
                     RRu                        55.10     55.10
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               3.93                3.93
                 Het Chi               0.83                0.83
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR              20.49               20.49
                     RRl               7.62                7.62
                     RRu              55.10               55.10
                      P                 +++                 +++
              Random  RR              20.49               20.49
                     RRl               7.62                7.62
                     RRu              55.10               55.10
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 6

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2                                       2
                      NS        1                                       1

                      Wt     3.93                                    3.93
                 Het Chi     0.83                                    0.83
                 Het  df        1                                       1
                 Het  P      N.S.                                    N.S.
               Fixed  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
              Random  RR    20.49                                   20.49
                     RRl     7.62                                    7.62
                     RRu    55.10                                   55.10
                      P       +++                                     +++
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2                   2
                      NS        1                   1

                      Wt     3.93                3.93
                 Het Chi     0.83                0.83
                 Het  df        1                   1
                 Het  P      N.S.                N.S.
               Fixed  RR    20.49               20.49
                     RRl     7.62                7.62
                     RRu    55.10               55.10
                      P       +++                 +++
              Random  RR    20.49               20.49
                     RRl     7.62                7.62
                     RRu    55.10               55.10
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 7

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
5       CHEN1 HAWTHO KULLER   LIU1
6      ANDER1   BEST  CHEN2 CLEMEN  DEAN1  DOLL1  DOLL2 DONTA1 ENSTRO FERRI3 GODTFR HOZAWA HUHTI1 HUHTI3 JACOBS   KAHN
        KAHN2 KRZYZA LEBOWI    LEE   LIAW LINDST LUNDB1 MUELLE NILSSO   PETO SPEIZE   TODD TVERDA VONHER  WEISS    WEN
       YAMAGU   YUAN
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 9 - 8

                               IESCOPD - Meta-analysis of amount smoked : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - E - 10 -

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for amount smoked
5) High vs low base
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) SMKSTA  : current, ever
8) PROD    : cigarettes, cigarettes only, any product
9) The highest vs lowest category
10) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 1

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

  ANDER1  15   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs      14  25   +
    BEST  42   m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only       9  21   +
   CHEN1   2   m   35   84   Asia:FarE  1972  1997    Pr   Inc    COPD:mort   5 Current       Cigs      19  20   +
   CHEN2  15   m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      19  20   +
   CHEN2  18   f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      19  20   +
  CLEMEN   6   m   20   60     Eu:West  1960  1982    Pr  Prev      COPD:LF   0 Current       Cigs      19  21   +
   DEAN1  28   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only      12  23   +
   DEAN1  68   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   3 Current MCigs only      12  23   +
   DOLL1  11   m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only      14  25   +
   DOLL2   8   f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only      14  25   +
  ENSTRO  15   m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only       9  40  80
  ENSTRO  24   f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only       9  40  80
  FERRI2  35   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs       4  45   +
  FERRI2  52   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs       4  45   +
  GODTFR   8   b   20   99    Eu:Scand  1964  2002    Pr   Inc     COPD:ICD   3 Current        Any      14  15   +
  HOZAWA   8   b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs      14  30   +
  HUHTI1  30   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs      14  25   +
  HUHTI1  36   f   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   1 Current       Cigs      14  15   +
  HUHTI3  16   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   1 Current        Any      14  25   +
  JACOBS  25   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs       4  30   +
    KAHN   9   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs       9  40   +
  KRZYZA   9   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs      14  15   +
  KRZYZA  12   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs      14  15   +
  LEBOWI  12   m   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   1 Current       Cigs      20  21   +
  LEBOWI  24   f   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   1 Current       Cigs      20  21   +
     LEE  28   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   1 Current  Cigs only       9  21   +
     LEE  49   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only       9  21   +
  LINDST  14   b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs       4  15   +
    LIU1   5   m   35   69   Asia:FarE  1986  1998    CC  Prev    COPD:mort   3 Current       Cigs      19  21   +
  LUNDB1  14   b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs       4  15   +
  MUELLE  29   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   1 Current       Cigs      14  25   +
  NILSSO  14   m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only       7  16   +
  NILSSO  19   f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only       7  16   +
    PETO   6   m   25   92       Eu:UK  1954  1983    Pr   Inc    COPD:mort   0 Current       Cigs      14  15   +
  SPEIZE   9   m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs      14  15   +
  SPEIZE  12   f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs      14  15   +
    TODD  28   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current  Cigs only       9  21   +
  TVERDA   9   m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only       9  20   +
  VONHER  15   m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs       9  30   +
  VONHER  22   f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs       9  30   +
   WEISS  10   m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only       9  21   +
     WEN   6   m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs      10  21   +
  YAMAGU   6   b   40   99   Asia:FarE  1986  1988    CS  Prev      COPD:LF   6 Current       Cigs       9  10   +
    YUAN  11   m   45   71   Asia:FarE  1986  1996    Pr   Inc    COPD:mort   2 Current       Cigs      19  20   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 2

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 15  m   1         22       -       3       -      3.63 (  0.86-  15.26)
*BEST   42  m   1         19       -      26       -      1.71 (  1.01-   2.89)
*CHEN1  2   m   5         37       -      29       -      1.95 (  1.20-   3.17)
 CHEN2  15  m   6          -       -       -       -      2.71 (  0.95-   7.72)
 CHEN2  18  f   6          -       -       -       -      2.09 (  1.14-   3.84)
 Subtotal CHEN2                                           2.23 (  1.32-   3.77)
 CLEMEN 6   m   0         37     645      16     812      2.91 (  1.60-   5.28)
 DEAN1  28  m   3         66       -      97       -      2.44 (  1.54-   3.87)
 DEAN1  68  f   3         24       -      25       -     18.35 (  8.73-  38.55)
 Subtotal DEAN1                                           4.28 (  2.89-   6.32)
*DOLL1  11  m   2         76       -      58       -      2.62 (  1.86-   3.68)
*DOLL2  8   f   1          2       -       3       -      3.05 (  0.51-  18.24)
*ENSTRO 15  m   1        148       -      35       -      4.77 (  3.31-   6.86)
*ENSTRO 24  f   1         46       -      50       -      9.35 (  6.24-  14.01)
 Subtotal ENSTRO                                          6.45 (  4.92-   8.45)
 FERRI2 35  m   1         19       -       2       -      9.88 (  1.58-  61.86)
 FERRI2 52  f   1          5       -      10       -     31.55 (  1.98- 501.57)
 Subtotal FERRI2                                         14.08 (  3.05-  64.93)
*GODTFR 8   b   3        813       -     270       -      1.83 (  1.58-   2.11)
 HOZAWA 8   b   0        382     284     305     759      3.35 (  2.73-   4.10)
 HUHTI1 30  m   1         39       -      47       -      1.09 (  0.59-   1.99)
 HUHTI1 36  f   1          4       -      10       -      8.88 (  1.72-  45.97)
 Subtotal HUHTI1                                          1.40 (  0.79-   2.48)
 HUHTI3 16  m   1         12       -      42       -      1.58 (  0.76-   3.33)
*JACOBS 25  m   2         12       -       9       -      2.47 (  1.09-   5.61)
*KAHN   9   m   2        113       -     105       -      4.54 (  3.48-   5.92)
*KRZYZA 9   m   1         23       -       8       -      1.39 (  0.68-   2.83)
*KRZYZA 12  f   1          6       -       6       -      1.88 (  0.68-   5.21)
 Subtotal KRZYZA                                          1.54 (  0.86-   2.75)
 LEBOWI 12  m   1          6       -      13       -      0.86 (  0.31-   2.39)
 LEBOWI 24  f   1         14       -      22       -      2.00 (  0.98-   4.09)
 Subtotal LEBOWI                                          1.52 (  0.84-   2.72)
*LEE    28  m   1          5       -       4       -      1.02 (  0.28-   3.73)
*LEE    49  f   0          1      90       2     342      1.90 (  0.17-  20.72)
 Subtotal LEE                                             1.17 (  0.38-   3.67)
 LINDST 14  b   5          -       -       -       -      2.67 (  1.42-   5.03)
 LIU1   5   m   3          -       -       -       -      1.74 (  1.50-   2.01)
 LUNDB1 14  b   4          -       -       -       -      1.83 (  0.64-   5.26)
 MUELLE 29  m   1         10       -       4       -      1.20 (  0.32-   4.56)
*NILSSO 14  m   2         35       -      19       -      4.33 (  2.44-   7.69)
*NILSSO 19  f   2         10       -      18       -      4.02 (  1.87-   8.62)
 Subtotal NILSSO                                          4.22 (  2.66-   6.67)
*PETO   6   m   0         35     855      57    1181      0.85 (  0.56-   1.28)
*SPEIZE 9   m   1          7       -       6       -      0.96 (  0.32-   2.85)
*SPEIZE 12  f   1          4       -       5       -      0.51 (  0.14-   1.92)
 Subtotal SPEIZE                                          0.74 (  0.32-   1.71)
*TODD   28  m   1          6       -       6       -      1.15 (  0.37-   3.52)
*TVERDA 9   m   2          9       -       5       -      2.05 (  0.69-   6.11)
 VONHER 15  m   0         73      65      50     121      2.72 (  1.70-   4.35)
 VONHER 22  f   0          2       5      28     172      2.46 (  0.45-  13.29)
 Subtotal VONHER                                          2.70 (  1.72-   4.24)
 WEISS  10  m   0         12      32       2      13      2.44 (  0.48-  12.44)
*WEN    6   m   1          6       -      27       -      0.80 (  0.27-   2.37)
 YAMAGU 6   b   6          -       -       -       -      1.02 (  0.78-   1.32)
*YUAN   11  m   2         20       -       9       -      2.50 (  1.15-   5.44)
Partial Totals          2160    1976    1433    3400
*prospective study

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 2

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 15  m   1              1.29     1.86     0.45       0.08
*BEST   42  m   1              0.54    13.90     0.94       0.05
*CHEN1  2   m   5              0.67    16.28     0.27       0.01
 CHEN2  15  m   6              1.00     3.50     0.14       0.06
 CHEN2  18  f   6              0.74    10.42     0.04       0.02
 Subtotal CHEN2                0.80    13.92     0.18
 CLEMEN 6   m   0              1.07    10.83     0.80       0.00
 DEAN1  28  m   3              0.89    18.10     0.16       0.00
 DEAN1  68  f   3              2.91     6.97    31.10       0.00
 Subtotal DEAN1                1.45    25.06    31.26
*DOLL1  11  m   2              0.96    33.00     0.91       0.00
*DOLL2  8   f   1              1.12     1.20     0.12       0.22
*ENSTRO 15  m   1              1.56    28.93    16.96       0.00
*ENSTRO 24  f   1              2.24    23.49    48.62       0.00
 Subtotal ENSTRO               1.86    52.42    65.57
 FERRI2 35  m   1              2.29     1.14     2.55       0.01
 FERRI2 52  f   1              3.45     0.50     3.54       0.01
 Subtotal FERRI2               2.64     1.64     6.08
*GODTFR 8   b   3              0.60   183.64     6.80       0.00
 HOZAWA 8   b   0              1.21    93.15    15.76       0.00
 HUHTI1 30  m   1              0.09    10.40     5.25       0.78
 HUHTI1 36  f   1              2.18     1.42     2.74       0.01
 Subtotal HUHTI1               0.34    11.82     7.99
 HUHTI3 16  m   1              0.46     7.04     0.81       0.22
*JACOBS 25  m   2              0.90     5.72     0.07       0.03
*KAHN   9   m   2              1.51    54.43    27.92       0.00
*KRZYZA 9   m   1              0.33     7.56     1.65       0.37
*KRZYZA 12  f   1              0.63     3.71     0.10       0.22
 Subtotal KRZYZA               0.43    11.26     1.75
 LEBOWI 12  m   1             -0.15     3.68     3.31       0.77
 LEBOWI 24  f   1              0.69     7.53     0.08       0.06
 Subtotal LEBOWI               0.42    11.21     3.39
*LEE    28  m   1              0.02     2.29     1.38       0.98
*LEE    49  f   0              0.64     0.67     0.02       0.60
 Subtotal LEE                  0.16     2.96     1.40
 LINDST 14  b   5              0.98     9.61     0.33       0.00
 LIU1   5   m   3              0.55   179.39    10.58       0.00
 LUNDB1 14  b   4              0.60     3.46     0.13       0.26
 MUELLE 29  m   1              0.18     2.18     0.82       0.79
*NILSSO 14  m   2              1.47    11.66     5.22       0.00
*NILSSO 19  f   2              1.39     6.58     2.33       0.00
 Subtotal NILSSO               1.44    18.24     7.54
*PETO   6   m   0             -0.16    22.68    20.96       0.43
*SPEIZE 9   m   1             -0.04     3.21     2.25       0.94
*SPEIZE 12  f   1             -0.67     2.24     4.84       0.31
 Subtotal SPEIZE              -0.30     5.45     7.10
*TODD   28  m   1              0.14     3.03     1.31       0.81
*TVERDA 9   m   2              0.72     3.23     0.02       0.20
 VONHER 15  m   0              1.00    17.44     0.72       0.00
 VONHER 22  f   0              0.90     1.35     0.01       0.30
 Subtotal VONHER               0.99    18.79     0.73
 WEISS  10  m   0              0.89     1.45     0.01       0.28
*WEN    6   m   1             -0.22     3.26     3.39       0.69
 YAMAGU 6   b   6              0.02    55.52    33.51       0.88
*YUAN   11  m   2              0.92     6.36     0.09       0.02

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 2

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       44
                      NS       33

                      Wt   884.01
                 Het Chi   259.01
                 Het  df       43
                 Het  P       ***
               Fixed  RR     2.22
                     RRl     2.08
                     RRu     2.37
                      P       +++
              Random  RR     2.32
                     RRl     1.90
                     RRu     2.83
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 3

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       44
                      NS       33

                      Wt   884.01
                 Het Chi   259.01
                 Het  df       43
                 Het  P       ***
               Fixed  RR     2.22
                     RRl     2.08
                     RRu     2.37
                      P       +++
              Random  RR     2.32
                     RRl     1.90
                     RRu     2.83
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        5        27        12        44
                      NS        5        27        12        44

                      Wt   345.38    472.56     66.08    884.01
                 Het Chi    52.12    108.65     54.42    259.01
                 Het  df        4        26        11        43
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.98      2.16      4.79      2.22
                     RRl     1.78      1.98      3.76      2.08
                     RRu     2.20      2.37      6.09      2.37
                      P       +++       +++       +++       +++
              Random  RR     1.97      2.06      3.71      2.32
                     RRl     1.24      1.64      1.99      1.90
                     RRu     3.14      2.58      6.94      2.83
                      P        ++       +++       +++       +++
             Between Chi                                  43.82
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       16        22         5         1        44
                      NS       11        16         5         1        33

                      Wt   251.62    365.86    260.81      5.72    884.01
                 Het Chi    68.88     80.17     15.84      0.00    259.01
                 Het  df       15        21         4         0        43
                 Het  P       ***       ***        **      N.S.       ***
               Fixed  RR     3.61      2.04      1.56      2.47      2.22
                     RRl     3.19      1.84      1.38      1.09      2.08
                     RRu     4.08      2.26      1.76      5.60      2.37
                      P       +++       +++       +++         +       +++
              Random  RR     2.76      2.31      1.51      2.47      2.32
                     RRl     1.97      1.78      1.07      1.09      1.90
                     RRu     3.88      3.01      2.14      5.60      2.83
                      P       +++       +++         +         +       +++
             Between Chi                                            94.13
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                               ***

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 3

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N       27        12        39
                      NS       19         9        28

                      Wt   505.59    117.62    623.20
                 Het Chi   134.89     57.23    197.77
                 Het  df       26        11        38
                 Het  P       ***       ***       ***
               Fixed  RR     2.69      2.11      2.57
                     RRl     2.46      1.76      2.37
                     RRu     2.93      2.53      2.78
                      P       +++       +++       +++
              Random  RR     2.58      2.32      2.49
                     RRl     2.00      1.44      2.00
                     RRu     3.32      3.73      3.10
                      P       +++       +++       +++
             Between Chi                         5.65
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N       27         8         5         3                   1        44
                      NS       20         5         5         2                   1        33

                      Wt   464.38     54.97    337.68     17.38                9.61    884.01
                 Het Chi   176.11     10.06     55.65      0.29                0.00    259.01
                 Het  df       26         7         4         2                   0        43
                 Het  P       ***      N.S.       ***      N.S.                N.S.       ***
               Fixed  RR     2.52      1.89      1.91      2.14                2.67      2.22
                     RRl     2.30      1.45      1.71      1.34                1.42      2.08
                     RRu     2.76      2.46      2.12      3.43                5.03      2.37
                      P       +++       +++       +++        ++                  ++       +++
              Random  RR     2.77      1.73      1.74      2.14                2.67      2.32
                     RRl     2.06      1.22      1.06      1.34                1.42      1.90
                     RRu     3.72      2.46      2.85      3.43                5.03      2.83
                      P       +++        ++         +        ++                  ++       +++
             Between Chi                                                                16.90
             Between  df                                                                    4
             Between  P                                                                    **
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N       17         8         6        13        44
                      NS       12         6         6         9        33

                      Wt   136.59    106.95    244.00    396.49    884.01
                 Het Chi    71.47     16.12      5.69     87.29    259.01
                 Het  df       16         7         5        12        43
                 Het  P       ***         *      N.S.       ***       ***
               Fixed  RR     2.94      1.13      1.89      2.66      2.22
                     RRl     2.49      0.94      1.67      2.41      2.08
                     RRu     3.48      1.37      2.14      2.94      2.37
                      P       +++      N.S.       +++       +++       +++
              Random  RR     2.54      1.27      1.97      3.03      2.32
                     RRl     1.65      0.88      1.67      2.17      1.90
                     RRu     3.92      1.83      2.33      4.24      2.83
                      P       +++      N.S.       +++       +++       +++
             Between Chi                                            78.44
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                                **
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 3

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        3        23        18        44
                      NS        2        18        13        33

                      Wt   204.45    447.92    231.64    884.01
                 Het Chi    38.25    144.01     69.83    259.01
                 Het  df        2        22        17        43
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.94      2.41      2.13      2.22
                     RRl     1.69      2.19      1.87      2.08
                     RRu     2.23      2.64      2.42      2.37
                      P       +++       +++       +++       +++
              Random  RR     4.00      2.23      2.16      2.32
                     RRl     1.40      1.67      1.54      1.90
                     RRu    11.48      2.98      3.03      2.83
                      P        ++       +++       +++       +++
             Between Chi                                   6.93
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N       12        24         8                  44
                      NS        9        17         7                  33

                      Wt   281.18    425.35    177.49              884.01
                 Het Chi    20.63    176.55     57.07              259.01
                 Het  df       11        23         7                  43
                 Het  P         *       ***       ***                 ***
               Fixed  RR     2.05      2.39      2.10                2.22
                     RRl     1.82      2.18      1.82                2.08
                     RRu     2.30      2.63      2.44                2.37
                      P       +++       +++       +++                 +++
              Random  RR     2.28      2.43      2.10                2.32
                     RRl     1.80      1.75      1.20                1.90
                     RRu     2.89      3.39      3.67                2.83
                      P       +++       +++        ++                 +++
             Between Chi                                             4.77
             Between  df                                                2
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        6         8        10        20                  44
                      NS        4         8         7        14                  33

                      Wt   129.72    211.11     44.37    498.81              884.01
                 Het Chi    14.78      3.97      9.86    209.70              259.01
                 Het  df        5         7         9        19                  43
                 Het  P         *      N.S.      N.S.       ***                 ***
               Fixed  RR     2.93      1.80      1.89      2.29                2.22
                     RRl     2.46      1.57      1.41      2.09                2.08
                     RRu     3.48      2.06      2.54      2.50                2.37
                      P       +++       +++       +++       +++                 +++
              Random  RR     2.50      1.80      1.90      2.42                2.32
                     RRl     1.63      1.57      1.37      1.72                1.90
                     RRu     3.85      2.06      2.62      3.40                2.83
                      P       +++       +++       +++       +++                 +++
             Between Chi                                                      20.71
             Between  df                                                          3
             Between  P                                                         ***
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 3

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        4        40        44
                      NS        3        30        33

                      Wt    50.97    833.04    884.01
                 Het Chi    51.63    206.73    259.01
                 Het  df        3        39        43
                 Het  P       ***       ***       ***
               Fixed  RR     1.99      2.23      2.22
                     RRl     1.51      2.09      2.08
                     RRu     2.61      2.39      2.37
                      P       +++       +++       +++
              Random  RR     2.93      2.28      2.32
                     RRl     0.85      1.87      1.90
                     RRu    10.08      2.78      2.83
                      P       (+)       +++       +++
             Between Chi                         0.66
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       22        11        11        44
                      NS       17         9         7        33

                      Wt   446.64    196.10    241.27    884.01
                 Het Chi   174.76     55.91     18.51    259.01
                 Het  df       21        10        10        43
                 Het  P       ***       ***         *       ***
               Fixed  RR     2.46      2.06      1.95      2.22
                     RRl     2.24      1.79      1.72      2.08
                     RRu     2.70      2.37      2.21      2.37
                      P       +++       +++       +++       +++
              Random  RR     2.47      1.75      2.33      2.32
                     RRl     1.79      1.14      1.73      1.90
                     RRu     3.41      2.67      3.15      2.83
                      P       +++        ++       +++       +++
             Between Chi                                   9.83
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N       26                  14         4        44
                      NS       20                   9         4        33

                      Wt   540.56              124.14    219.32    884.01
                 Het Chi   127.22               86.51      5.41    259.01
                 Het  df       25                  13         3        43
                 Het  P       ***                 ***      N.S.       ***
               Fixed  RR     2.11                3.70      1.87      2.22
                     RRl     1.94                3.10      1.64      2.08
                     RRu     2.30                4.41      2.14      2.37
                      P       +++                 +++       +++       +++
              Random  RR     1.97                3.33      2.10      2.32
                     RRl     1.56                1.99      1.57      1.90
                     RRu     2.51                5.57      2.81      2.83
                      P       +++                 +++       +++       +++
             Between Chi                                            39.87
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 3

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N       10         1        11
                      NS        8         1         9

                      Wt   192.64      3.46    196.10
                 Het Chi    55.87      0.00     55.91
                 Het  df        9         0        10
                 Het  P       ***      N.S.       ***
               Fixed  RR     2.06      1.83      2.06
                     RRl     1.79      0.64      1.79
                     RRu     2.38      5.25      2.37
                      P       +++      N.S.       +++
              Random  RR     1.74      1.83      1.75
                     RRl     1.11      0.64      1.14
                     RRu     2.73      5.25      2.67
                      P         +      N.S.        ++
             Between Chi                         0.05
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        5         9        10        20        44
                      NS        4         8         7        14        33

                      Wt    10.28     51.60     79.69    742.44    884.01
                 Het Chi     3.55      4.84     12.86    211.90    259.01
                 Het  df        4         8         9        19        43
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR     1.14      2.05      1.38      2.37      2.22
                     RRl     0.62      1.56      1.11      2.20      2.08
                     RRu     2.11      2.70      1.72      2.54      2.37
                      P      N.S.       +++        ++       +++       +++
              Random  RR     1.14      2.05      1.45      3.24      2.32
                     RRl     0.62      1.56      1.09      2.44      1.90
                     RRu     2.11      2.70      1.91      4.31      2.83
                      P      N.S.       +++        ++       +++       +++
             Between Chi                                            25.87
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        5         9        10        20        44
                      NS        4         8         7        14        33

                      Wt    10.28     51.60     79.69    742.44    884.01
                 Het Chi     3.55      4.84     12.86    211.90    259.01
                 Het  df        4         8         9        19        43
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR     1.14      2.05      1.38      2.37      2.22
                     RRl     0.62      1.56      1.11      2.20      2.08
                     RRu     2.11      2.70      1.72      2.54      2.37
                      P      N.S.       +++        ++       +++       +++
              Random  RR     1.14      2.05      1.45      3.24      2.32
                     RRl     0.62      1.56      1.09      2.44      1.90
                     RRu     2.11      2.70      1.91      4.31      2.83
                      P      N.S.       +++        ++       +++       +++
             Between Chi                                            25.87
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 3

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       22        22        44
                      NS       16        17        33

                      Wt   446.92    437.09    884.01
                 Het Chi   110.34    143.61    259.01
                 Het  df       21        21        43
                 Het  P       ***       ***       ***
               Fixed  RR     2.06      2.39      2.22
                     RRl     1.88      2.18      2.08
                     RRu     2.26      2.63      2.37
                      P       +++       +++       +++
              Random  RR     2.41      2.19      2.32
                     RRl     1.82      1.62      1.90
                     RRu     3.20      2.96      2.83
                      P       +++       +++       +++
             Between Chi                         5.06
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        2        28        14        44
                      NS        2        21        10        33

                      Wt   190.68    538.83    154.50    884.01
                 Het Chi     0.15    138.61     65.19    259.01
                 Het  df        1        27        13        43
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     1.82      2.04      3.78      2.22
                     RRl     1.58      1.88      3.23      2.08
                     RRu     2.10      2.22      4.43      2.37
                      P       +++       +++       +++       +++
              Random  RR     1.82      1.96      3.38      2.32
                     RRl     1.58      1.54      2.26      1.90
                     RRu     2.10      2.49      5.06      2.83
                      P       +++       +++       +++       +++
             Between Chi                                  55.06
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                        Number of adjustment variables
                                0         1        2+     Total

                       N        7        20        17        44
                      NS        6        14        14        34

                      Wt   147.57    128.57    607.88    884.01
                 Het Chi    34.65     95.84    115.63    259.01
                 Het  df        6        19        16        43
                 Het  P       ***       ***       ***       ***
               Fixed  RR     2.60      2.72      2.05      2.22
                     RRl     2.21      2.28      1.89      2.08
                     RRu     3.05      3.23      2.22      2.37
                      P       +++       +++       +++       +++
              Random  RR     2.20      2.01      2.60      2.32
                     RRl     1.27      1.30      2.01      1.90
                     RRu     3.83      3.11      3.37      2.83
                      P        ++        ++       +++       +++
             Between Chi                                  12.89
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 4

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

  ANDER1  15     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1 Current       Cigs      14  25   +
    BEST  42     m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only       9  21   +
   CHEN1   1 x   m   35   84   Asia:FarE  1972  1997    Pr   Inc    COPD:mort   1 Current       Cigs      19  20   +
   CHEN2  15     m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      19  20   +
   CHEN2  18     f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      19  20   +
  CLEMEN   6     m   20   60     Eu:West  1960  1982    Pr  Prev      COPD:LF   0 Current       Cigs      19  21   +
   DEAN1  23 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only      12  23   +
   DEAN1  63 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only      12  23   +
   DOLL1  11     m   20   99       Eu:UK  1951  1994    Pr   Inc    COPD:mort   2 Current  Cigs only      14  25   +
   DOLL2   8     f   20   99       Eu:UK  1951  1980    Pr   Inc    COPD:mort   1 Current  Cigs only      14  25   +
  ENSTRO  15     m   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only       9  40  80
  ENSTRO  24     f   30   99      Am:USA  1960  2003    Pr   Inc    COPD:mort   1 Current  Cigs only       9  40  80
  FERRI2  35     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs       4  45   +
  FERRI2  52     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1 Current       Cigs       4  45   +
  GODTFR   8     b   20   99    Eu:Scand  1964  2002    Pr   Inc     COPD:ICD   3 Current        Any      14  15   +
  HOZAWA   8     b   45   64      Am:USA  1987  2006    CS  Prev      COPD:LF   0 Current       Cigs      14  30   +
  HUHTI1  25 x   m   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs      14  25   +
  HUHTI1  33 x   f   40   64    Eu:Scand  1961  1965    CS  Prev    CB/EM/Ast   0 Current       Cigs      14  15   +
  HUHTI3  11 x   m   25   69    Eu:Scand  1968  1978    CS  Prev      COPD:LF   0 Current        Any      14  25   +
  JACOBS  25     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2 Current       Cigs       4  30   +
    KAHN   9     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2 Current       Cigs       9  40   +
  KRZYZA   9     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs      14  15   +
  KRZYZA  12     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1 Current       Cigs      14  15   +
  LEBOWI   9 x   m   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   0 Current       Cigs      20  21   +
  LEBOWI  21 x   f   15   96      Am:USA  1972  1977    CS  Prev      COPD:LF   0 Current       Cigs      20  21   +
     LEE  14 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only       9  21   +
     LEE  49     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only       9  21   +
  LINDST  14     b   20   69    Eu:Scand     *  2001    CS  Prev        CB/EM   5 Current       Cigs       4  15   +
    LIU1   5     m   35   69   Asia:FarE  1986  1998    CC  Prev    COPD:mort   3 Current       Cigs      19  21   +
  LUNDB1  14     b   46   77    Eu:Scand  1996  2003    CS  Prev      COPD:LF   4 Current       Cigs       4  15   +
  MUELLE  24 x   m   20   69      Am:USA  1967  1971    CS  Prev      COPD:LF   0 Current       Cigs      14  25   +
  NILSSO  14     m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only       7  16   +
  NILSSO  19     f   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current  Cigs only       7  16   +
    PETO   6     m   25   92       Eu:UK  1954  1983    Pr   Inc    COPD:mort   0 Current       Cigs      14  15   +
  SPEIZE   9     m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs      14  15   +
  SPEIZE  12     f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1 Current       Cigs      14  15   +
    TODD  14 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only       9  21   +
  TVERDA   9     m   35   65    Eu:Scand  1972  1993    Pr   Inc    COPD:mort   2 Current  Cigs only       9  20   +
  VONHER  15     m   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs       9  30   +
  VONHER  22     f   30   99    Eu:Scand  1978  2000    CS  Prev        CB/EM   0 Current       Cigs       9  30   +
   WEISS  10     m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only       9  21   +
     WEN   6     m   35   99   Asia:FarE  1982  2004    Pr   Inc    COPD:mort   1 Current       Cigs      10  21   +
  YAMAGU   6     b   40   99   Asia:FarE  1986  1988    CS  Prev      COPD:LF   6 Current       Cigs       9  10   +
    YUAN   8 x   m   45   71   Asia:FarE  1986  1996    Pr   Inc    COPD:mort   1 Current       Cigs      19  20   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 5

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 15  m   1         22       -       3       -      3.63 (  0.86-  15.26)
*BEST   42  m   1         19       -      26       -      1.71 (  1.01-   2.89)
*CHEN1  1   m   1         37       -      29       -      1.67 (  1.03-   2.72)
 CHEN2  15  m   6          -       -       -       -      2.71 (  0.95-   7.72)
 CHEN2  18  f   6          -       -       -       -      2.09 (  1.14-   3.84)
 Subtotal CHEN2                                           2.23 (  1.32-   3.77)
 CLEMEN 6   m   0         37     645      16     812      2.91 (  1.60-   5.28)
 DEAN1  23  m   0         66     237      97     256      0.73 (  0.51-   1.05)
 DEAN1  63  f   0         24     151      25     486      3.09 (  1.71-   5.57)
 Subtotal DEAN1                                           1.08 (  0.80-   1.47)
*DOLL1  11  m   2         76       -      58       -      2.62 (  1.86-   3.68)
*DOLL2  8   f   1          2       -       3       -      3.05 (  0.51-  18.24)
*ENSTRO 15  m   1        148       -      35       -      4.77 (  3.31-   6.86)
*ENSTRO 24  f   1         46       -      50       -      9.35 (  6.24-  14.01)
 Subtotal ENSTRO                                          6.45 (  4.92-   8.45)
 FERRI2 35  m   1         19       -       2       -      9.88 (  1.58-  61.86)
 FERRI2 52  f   1          5       -      10       -     31.55 (  1.98- 501.57)
 Subtotal FERRI2                                         14.08 (  3.05-  64.93)
*GODTFR 8   b   3        813       -     270       -      1.83 (  1.58-   2.11)
 HOZAWA 8   b   0        382     284     305     759      3.35 (  2.73-   4.10)
 HUHTI1 25  m   0         39      46      47      61      1.10 (  0.62-   1.95)
 HUHTI1 33  f   0          4       3      10      67      8.93 (  1.74-  45.95)
 Subtotal HUHTI1                                          1.38 (  0.81-   2.37)
 HUHTI3 11  m   0         12      64      42     273      1.22 (  0.61-   2.45)
*JACOBS 25  m   2         12       -       9       -      2.47 (  1.09-   5.61)
*KAHN   9   m   2        113       -     105       -      4.54 (  3.48-   5.92)
*KRZYZA 9   m   1         23       -       8       -      1.39 (  0.68-   2.83)
*KRZYZA 12  f   1          6       -       6       -      1.88 (  0.68-   5.21)
 Subtotal KRZYZA                                          1.54 (  0.86-   2.75)
 LEBOWI 9   m   0          6      54      13     100      0.85 (  0.31-   2.38)
 LEBOWI 21  f   0         14     104      22     314      1.92 (  0.95-   3.89)
 Subtotal LEBOWI                                          1.48 (  0.83-   2.64)
*LEE    14  m   0          5     266       4     192      0.90 (  0.25-   3.32)
*LEE    49  f   0          1      90       2     342      1.90 (  0.17-  20.72)
 Subtotal LEE                                             1.07 (  0.34-   3.36)
 LINDST 14  b   5          -       -       -       -      2.67 (  1.42-   5.03)
 LIU1   5   m   3          -       -       -       -      1.74 (  1.50-   2.01)
 LUNDB1 14  b   4          -       -       -       -      1.83 (  0.64-   5.26)
 MUELLE 24  m   0         10      46       4      24      1.30 (  0.37-   4.60)
*NILSSO 14  m   2         35       -      19       -      4.33 (  2.44-   7.69)
*NILSSO 19  f   2         10       -      18       -      4.02 (  1.87-   8.62)
 Subtotal NILSSO                                          4.22 (  2.66-   6.67)
*PETO   6   m   0         35     855      57    1181      0.85 (  0.56-   1.28)
*SPEIZE 9   m   1          7       -       6       -      0.96 (  0.32-   2.85)
*SPEIZE 12  f   1          4       -       5       -      0.51 (  0.14-   1.92)
 Subtotal SPEIZE                                          0.74 (  0.32-   1.71)
*TODD   14  m   0          6     338       6     316      0.93 (  0.30-   2.87)
*TVERDA 9   m   2          9       -       5       -      2.05 (  0.69-   6.11)
 VONHER 15  m   0         73      65      50     121      2.72 (  1.70-   4.35)
 VONHER 22  f   0          2       5      28     172      2.46 (  0.45-  13.29)
 Subtotal VONHER                                          2.70 (  1.72-   4.24)
 WEISS  10  m   0         12      32       2      13      2.44 (  0.48-  12.44)
*WEN    6   m   1          6       -      27       -      0.80 (  0.27-   2.37)
 YAMAGU 6   b   6          -       -       -       -      1.02 (  0.78-   1.32)
*YUAN   8   m   1         20       -       9       -      2.28 (  1.04-   4.99)
Partial Totals          2160    3285    1433    5489
*prospective study

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 5

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 15  m   1              1.29     1.86     0.56       0.08
*BEST   42  m   1              0.54    13.90     0.56       0.05
*CHEN1  1   m   1              0.51    16.29     0.83       0.04
 CHEN2  15  m   6              1.00     3.50     0.24       0.06
 CHEN2  18  f   6              0.74    10.42     0.00       0.02
 Subtotal CHEN2                0.80    13.92     0.24
 CLEMEN 6   m   0              1.07    10.83     1.19       0.00
 DEAN1  23  m   0             -0.31    29.77    32.56       0.09
 DEAN1  63  f   0              1.13    11.07     1.69       0.00
 Subtotal DEAN1                0.08    40.84    34.25
*DOLL1  11  m   2              0.96    33.00     1.68       0.00
*DOLL2  8   f   1              1.12     1.20     0.17       0.22
*ENSTRO 15  m   1              1.56    28.93    19.67       0.00
*ENSTRO 24  f   1              2.24    23.49    52.68       0.00
 Subtotal ENSTRO               1.86    52.42    72.35
 FERRI2 35  m   1              2.29     1.14     2.75       0.01
 FERRI2 52  f   1              3.45     0.50     3.69       0.01
 Subtotal FERRI2               2.64     1.64     6.45
*GODTFR 8   b   3              0.60   183.64     3.27       0.00
 HOZAWA 8   b   0              1.21    93.15    20.60       0.00
 HUHTI1 25  m   0              0.10    11.76     4.85       0.74
 HUHTI1 33  f   0              2.19     1.43     3.02       0.01
 Subtotal HUHTI1               0.32    13.19     7.87
 HUHTI3 11  m   0              0.20     7.91     2.31       0.58
*JACOBS 25  m   2              0.90     5.72     0.16       0.03
*KAHN   9   m   2              1.51    54.43    32.70       0.00
*KRZYZA 9   m   1              0.33     7.56     1.26       0.37
*KRZYZA 12  f   1              0.63     3.71     0.04       0.22
 Subtotal KRZYZA               0.43    11.26     1.30
 LEBOWI 9   m   0             -0.16     3.68     2.94       0.76
 LEBOWI 21  f   0              0.65     7.71     0.06       0.07
 Subtotal LEBOWI               0.39    11.39     3.00
*LEE    14  m   0             -0.10     2.27     1.60       0.88
*LEE    49  f   0              0.64     0.67     0.01       0.60
 Subtotal LEE                  0.07     2.94     1.61
 LINDST 14  b   5              0.98     9.61     0.57       0.00
 LIU1   5   m   3              0.55   179.39     6.07       0.00
 LUNDB1 14  b   4              0.60     3.46     0.06       0.26
 MUELLE 24  m   0              0.27     2.42     0.54       0.68
*NILSSO 14  m   2              1.47    11.66     6.18       0.00
*NILSSO 19  f   2              1.39     6.58     2.81       0.00
 Subtotal NILSSO               1.44    18.24     8.99
*PETO   6   m   0             -0.16    22.68    18.47       0.43
*SPEIZE 9   m   1             -0.04     3.21     1.95       0.94
*SPEIZE 12  f   1             -0.67     2.24     4.46       0.31
 Subtotal SPEIZE              -0.30     5.45     6.41
*TODD   14  m   0             -0.07     3.06     1.98       0.91
*TVERDA 9   m   2              0.72     3.23     0.00       0.20
 VONHER 15  m   0              1.00    17.44     1.20       0.00
 VONHER 22  f   0              0.90     1.35     0.04       0.30
 Subtotal VONHER               0.99    18.79     1.23
 WEISS  10  m   0              0.89     1.45     0.03       0.28
*WEN    6   m   1             -0.22     3.26     3.01       0.69
 YAMAGU 6   b   6              0.02    55.52    28.62       0.88
*YUAN   8   m   1              0.82     6.25     0.05       0.04

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 5

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       44
                      NS       33

                      Wt   902.35
                 Het Chi   267.12
                 Het  df       43
                 Het  P       ***
               Fixed  RR     2.09
                     RRl     1.96
                     RRu     2.23
                      P       +++
              Random  RR     2.09
                     RRl     1.72
                     RRu     2.55
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 6

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       44
                      NS       33

                      Wt   902.35
                 Het Chi   267.12
                 Het  df       43
                 Het  P       ***
               Fixed  RR     2.09
                     RRl     1.96
                     RRu     2.23
                      P       +++
              Random  RR     2.09
                     RRl     1.72
                     RRu     2.55
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        5        27        12        44
                      NS        5        27        12        44

                      Wt   345.38    486.60     70.37    902.35
                 Het Chi    52.12    144.05     41.62    267.12
                 Het  df        4        26        11        43
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.98      1.99      3.89      2.09
                     RRl     1.78      1.82      3.08      1.96
                     RRu     2.20      2.17      4.91      2.23
                      P       +++       +++       +++       +++
              Random  RR     1.97      1.87      3.06      2.09
                     RRl     1.24      1.45      1.79      1.72
                     RRu     3.14      2.40      5.23      2.55
                      P        ++       +++       +++       +++
             Between Chi                                  29.33
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N       16        22         5         1        44
                      NS       11        16         5         1        33

                      Wt   252.04    383.88    260.71      5.72    902.35
                 Het Chi    69.23     76.00     14.56      0.00    267.12
                 Het  df       15        21         4         0        43
                 Het  P       ***       ***        **      N.S.       ***
               Fixed  RR     3.60      1.80      1.54      2.47      2.09
                     RRl     3.18      1.62      1.37      1.09      1.96
                     RRu     4.07      1.98      1.74      5.60      2.23
                      P       +++       +++       +++         +       +++
              Random  RR     2.76      1.91      1.45      2.47      2.09
                     RRl     1.96      1.49      1.03      1.09      1.72
                     RRu     3.87      2.44      2.02      5.60      2.55
                      P       +++       +++         +         +       +++
             Between Chi                                           107.33
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                               ***

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 6

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        3        23        18        44
                      NS        2        18        13        33

                      Wt   220.23    447.82    234.30    902.35
                 Het Chi    24.07    147.01     72.08    267.12
                 Het  df        2        22        17        43
                 Het  P       ***       ***       ***       ***
               Fixed  RR     1.59      2.38      2.10      2.09
                     RRl     1.40      2.17      1.85      1.96
                     RRu     1.82      2.62      2.39      2.23
                      P       +++       +++       +++       +++
              Random  RR     1.54      2.17      2.12      2.09
                     RRl     0.78      1.62      1.51      1.72
                     RRu     3.02      2.91      2.98      2.55
                      P      N.S.       +++       +++       +++
             Between Chi                                  23.96
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N       22        11        11        44
                      NS       17         9         7        33

                      Wt   462.32    197.39    242.64    902.35
                 Het Chi   188.10     57.50     18.89    267.12
                 Het  df       21        10        10        43
                 Het  P       ***       ***         *       ***
               Fixed  RR     2.20      2.03      1.94      2.09
                     RRl     2.01      1.77      1.71      1.96
                     RRu     2.41      2.34      2.20      2.23
                      P       +++       +++       +++       +++
              Random  RR     2.07      1.70      2.32      2.09
                     RRl     1.49      1.11      1.72      1.72
                     RRu     2.87      2.61      3.14      2.55
                      P       +++         +       +++       +++
             Between Chi                                   2.64
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        2        28        14        44
                      NS        2        21        10        33

                      Wt   191.55    540.52    170.29    902.35
                 Het Chi     1.25    139.39    109.29    267.12
                 Het  df        1        27        13        43
                 Het  P      N.S.       ***       ***       ***
               Fixed  RR     1.80      2.03      2.74      2.09
                     RRl     1.56      1.86      2.36      1.96
                     RRu     2.07      2.20      3.18      2.23
                      P       +++       +++       +++       +++
              Random  RR     1.73      1.93      2.51      2.09
                     RRl     1.32      1.52      1.54      1.72
                     RRu     2.27      2.46      4.10      2.55
                      P       +++       +++       +++       +++
             Between Chi                                  17.19
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 7

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR BROGGE  CHEN3  CHENG  COCCI DEJONG DEMARC DETORR DICKIN EKBERG  FIDAN FORAST FUKUCH
       GEIJER GULSVI HAMMO2 HARDIE HARIKK HEDMAN HIGGI4     HO HUHTI2 ITABAS JAENDI JOHANN KACHEL KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2    LAI   LAM1   LAM2   LAM3  LANGE LINDBE   LIU2  MADOR MANNI1 MANNI2 MANNI3
       MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE NIEPSU NIHLEN   PEAT PELKON PEREZP  PRICE
       RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI VESTBO
       VIEGI2 VOLLM1 VOLLM2   WALD WATSON WILSO1 WOJTYN   XIAO     XU ZIELI1 ZIELI2 ZIETKO
6      HAWTHO KULLER
10     DONTA1 FERRI1 FERRI3  KAHN2   LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - E - 10 - 8

                               IESCOPD - Meta-analysis of amount smoked : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  HOZAWA HOZAWA     1         ENRIGH/HOZAWA/HARIKK
  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  LUNDB1 LUNDBA     1  LINDBE/LUNDB1/LUNDB2/HEDLUN
    PETO   PETO     1    PETO/HIGGI1/HIGGI2/HIGGI5
  HUHTI1 HUHTI1     1                HUHTI1/HUHTI2
  ENSTRO HAMMO2     2                HAMMO2/ENSTRO
  LEBOWI LEBOWI     1                 LEBOWI/SILVA
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
     WEN    WEN     1                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
  GODTFR GODTFR     1 GODT/VEST/LANG1+2/SUAD/HOLLN
    KAHN   KAHN     1                   KAHN/KAHN2

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

  HAWTHO   5   m   45   76       Eu:UK  1965  1978    Pr   Inc    COPD:mort   1 Current       Cigs      17  23   +
  KULLER   9   m   35   63      Am:USA  1972  1989    Pr   Inc    COPD:mort   0 Current       Cigs      15  46   +
          RR|SIG|

        0.53   n
        1.10   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - F - 1 -

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for age started
5) vs never smoking base
6) Key value = 26
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 1

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  29   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  25   +
   DEAN1  69   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  25   +
     LEE  29   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20   +
     LEE  53   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20   +
    LIAW  13   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  25   +
    TODD  29   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 2

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  29  m   0         15      75      47     510      2.17 (  1.16-   4.07)
 DEAN1  69  f   0         26     274     120    1538      1.22 (  0.78-   1.89)
 Subtotal DEAN1                                           1.47 (  1.03-   2.12)
*LEE    29  m   0          4     293       1     347      4.74 (  0.53-  42.15)
*LEE    53  f   0          3     614       5    1694      1.66 (  0.40-   6.91)
 Subtotal LEE                                             2.27 (  0.69-   7.50)
*LIAW   13  b   2          -       -       -       -      2.20 (  1.20-   4.10)
*TODD   29  m   0          8     375       1     520     11.09 (  1.39-  88.32)
Partial Totals            56    1631     174    4609
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  29  m   0              0.77     9.69     0.48       0.02
 DEAN1  69  f   0              0.20    19.57     2.47       0.39
 Subtotal DEAN1                0.39    29.26     2.96
*LEE    29  m   0              1.56     0.80     0.81       0.16
*LEE    53  f   0              0.50     1.88     0.00       0.49
 Subtotal LEE                  0.82     2.69     0.82
*LIAW   13  b   2              0.79    10.18     0.57       0.01
*TODD   29  m   0              2.41     0.89     3.07       0.02

                       N        6
                      NS        4

                      Wt    43.02
                 Het Chi     7.42
                 Het  df        5
                 Het  P      N.S.
               Fixed  RR     1.74
                     RRl     1.29
                     RRu     2.34
                      P       +++
              Random  RR     1.91
                     RRl     1.25
                     RRu     2.91
                      P        ++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 3

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        6
                      NS        4

                      Wt    43.02
                 Het Chi     7.42
                 Het  df        5
                 Het  P      N.S.
               Fixed  RR     1.74
                     RRl     1.29
                     RRu     2.34
                      P       +++
              Random  RR     1.91
                     RRl     1.25
                     RRu     2.91
                      P        ++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N        1         3         2         6
                      NS        1         3         2         6

                      Wt    10.18     11.38     21.45     43.02
                 Het Chi     0.00      2.48      0.16      7.42
                 Het  df        0         2         1         5
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     2.20      2.61      1.25      1.74
                     RRl     1.19      1.46      0.82      1.29
                     RRu     4.07      4.66      1.91      2.34
                      P         +        ++      N.S.       +++
              Random  RR     2.20      3.07      1.25      1.91
                     RRl     1.19      1.31      0.82      1.25
                     RRu     4.07      7.20      1.91      2.91
                      P         +        ++      N.S.        ++
             Between Chi                                   4.77
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  5         1                   6
                      NS                  3         1                   4

                      Wt              32.84     10.18               43.02
                 Het Chi               6.67      0.00                7.42
                 Het  df                  4         0                   5
                 Het  P                N.S.      N.S.                N.S.
               Fixed  RR               1.61      2.20                1.74
                     RRl               1.15      1.19                1.29
                     RRu               2.27      4.07                2.34
                      P                  ++         +                 +++
              Random  RR               1.92      2.20                1.91
                     RRl               1.09      1.19                1.25
                     RRu               3.38      4.07                2.91
                      P                   +         +                  ++
             Between Chi                                             0.75
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 3

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4                   6
                      NS        1         3                   4

                      Wt    29.26     13.76               43.02
                 Het Chi     2.17      2.79                7.42
                 Het  df        1         3                   5
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     1.47      2.46                1.74
                     RRl     1.03      1.45                1.29
                     RRu     2.12      4.17                2.34
                      P         +       +++                 +++
              Random  RR     1.55      2.46                1.91
                     RRl     0.89      1.45                1.25
                     RRu     2.72      4.17                2.91
                      P      N.S.       +++                  ++
             Between Chi                                   2.45
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        6                             6
                      NS        4                             4

                      Wt    43.02                         43.02
                 Het Chi     7.42                          7.42
                 Het  df        5                             5
                 Het  P      N.S.                          N.S.
               Fixed  RR     1.74                          1.74
                     RRl     1.29                          1.29
                     RRu     2.34                          2.34
                      P       +++                           +++
              Random  RR     1.91                          1.91
                     RRl     1.25                          1.25
                     RRu     2.91                          2.91
                      P        ++                            ++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         5         6
                      NS                  1         3         4

                      Wt              10.18     32.84     43.02
                 Het Chi               0.00      6.67      7.42
                 Het  df                  0         4         5
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               2.20      1.61      1.74
                     RRl               1.19      1.15      1.29
                     RRu               4.07      2.27      2.34
                      P                   +        ++       +++
              Random  RR               2.20      1.92      1.91
                     RRl               1.19      1.09      1.25
                     RRu               4.07      3.38      2.91
                      P                   +         +        ++
             Between Chi                                   0.75
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 3

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        5         1                             6
                      NS        3         1                             4

                      Wt    32.84     10.18                         43.02
                 Het Chi     6.67      0.00                          7.42
                 Het  df        4         0                             5
                 Het  P      N.S.      N.S.                          N.S.
               Fixed  RR     1.61      2.20                          1.74
                     RRl     1.15      1.19                          1.29
                     RRu     2.27      4.07                          2.34
                      P        ++         +                           +++
              Random  RR     1.92      2.20                          1.91
                     RRl     1.09      1.19                          1.25
                     RRu     3.38      4.07                          2.91
                      P         +         +                            ++
             Between Chi                                             0.75
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        5         1         6
                      NS        3         1         4

                      Wt    32.84     10.18     43.02
                 Het Chi     6.67      0.00      7.42
                 Het  df        4         0         5
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     1.61      2.20      1.74
                     RRl     1.15      1.19      1.29
                     RRu     2.27      4.07      2.34
                      P        ++         +       +++
              Random  RR     1.92      2.20      1.91
                     RRl     1.09      1.19      1.25
                     RRu     3.38      4.07      2.91
                      P         +         +        ++
             Between Chi                         0.75
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 4

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  29     m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  25   +
   DEAN1  69     f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  25   +
     LEE  29     m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20   +
     LEE  53     f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20   +
    LIAW  13     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  25   +
    TODD  29     m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  20   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 5

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  29  m   0         15      75      47     510      2.17 (  1.16-   4.07)
 DEAN1  69  f   0         26     274     120    1538      1.22 (  0.78-   1.89)
 Subtotal DEAN1                                           1.47 (  1.03-   2.12)
*LEE    29  m   0          4     293       1     347      4.74 (  0.53-  42.15)
*LEE    53  f   0          3     614       5    1694      1.66 (  0.40-   6.91)
 Subtotal LEE                                             2.27 (  0.69-   7.50)
*LIAW   13  b   2          -       -       -       -      2.20 (  1.20-   4.10)
*TODD   29  m   0          8     375       1     520     11.09 (  1.39-  88.32)
Partial Totals            56    1631     174    4609
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  29  m   0              0.77     9.69     0.48       0.02
 DEAN1  69  f   0              0.20    19.57     2.47       0.39
 Subtotal DEAN1                0.39    29.26     2.96
*LEE    29  m   0              1.56     0.80     0.81       0.16
*LEE    53  f   0              0.50     1.88     0.00       0.49
 Subtotal LEE                  0.82     2.69     0.82
*LIAW   13  b   2              0.79    10.18     0.57       0.01
*TODD   29  m   0              2.41     0.89     3.07       0.02

                       N        6
                      NS        4

                      Wt    43.02
                 Het Chi     7.42
                 Het  df        5
                 Het  P      N.S.
               Fixed  RR     1.74
                     RRl     1.29
                     RRu     2.34
                      P       +++
              Random  RR     1.91
                     RRl     1.25
                     RRu     2.91
                      P        ++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 6

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        6
                      NS        4

                      Wt    43.02
                 Het Chi     7.42
                 Het  df        5
                 Het  P      N.S.
               Fixed  RR     1.74
                     RRl     1.29
                     RRu     2.34
                      P       +++
              Random  RR     1.91
                     RRl     1.25
                     RRu     2.91
                      P        ++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N        1         3         2         6
                      NS        1         3         2         6

                      Wt    10.18     11.38     21.45     43.02
                 Het Chi     0.00      2.48      0.16      7.42
                 Het  df        0         2         1         5
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     2.20      2.61      1.25      1.74
                     RRl     1.19      1.46      0.82      1.29
                     RRu     4.07      4.66      1.91      2.34
                      P         +        ++      N.S.       +++
              Random  RR     2.20      3.07      1.25      1.91
                     RRl     1.19      1.31      0.82      1.25
                     RRu     4.07      7.20      1.91      2.91
                      P         +        ++      N.S.        ++
             Between Chi                                   4.77
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  5         1                   6
                      NS                  3         1                   4

                      Wt              32.84     10.18               43.02
                 Het Chi               6.67      0.00                7.42
                 Het  df                  4         0                   5
                 Het  P                N.S.      N.S.                N.S.
               Fixed  RR               1.61      2.20                1.74
                     RRl               1.15      1.19                1.29
                     RRu               2.27      4.07                2.34
                      P                  ++         +                 +++
              Random  RR               1.92      2.20                1.91
                     RRl               1.09      1.19                1.25
                     RRu               3.38      4.07                2.91
                      P                   +         +                  ++
             Between Chi                                             0.75
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 6

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4                   6
                      NS        1         3                   4

                      Wt    29.26     13.76               43.02
                 Het Chi     2.17      2.79                7.42
                 Het  df        1         3                   5
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     1.47      2.46                1.74
                     RRl     1.03      1.45                1.29
                     RRu     2.12      4.17                2.34
                      P         +       +++                 +++
              Random  RR     1.55      2.46                1.91
                     RRl     0.89      1.45                1.25
                     RRu     2.72      4.17                2.91
                      P      N.S.       +++                  ++
             Between Chi                                   2.45
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        6                             6
                      NS        4                             4

                      Wt    43.02                         43.02
                 Het Chi     7.42                          7.42
                 Het  df        5                             5
                 Het  P      N.S.                          N.S.
               Fixed  RR     1.74                          1.74
                     RRl     1.29                          1.29
                     RRu     2.34                          2.34
                      P       +++                           +++
              Random  RR     1.91                          1.91
                     RRl     1.25                          1.25
                     RRu     2.91                          2.91
                      P        ++                            ++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         5         6
                      NS                  1         3         4

                      Wt              10.18     32.84     43.02
                 Het Chi               0.00      6.67      7.42
                 Het  df                  0         4         5
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               2.20      1.61      1.74
                     RRl               1.19      1.15      1.29
                     RRu               4.07      2.27      2.34
                      P                   +        ++       +++
              Random  RR               2.20      1.92      1.91
                     RRl               1.19      1.09      1.25
                     RRu               4.07      3.38      2.91
                      P                   +         +        ++
             Between Chi                                   0.75
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 6

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        5         1                             6
                      NS        3         1                             4

                      Wt    32.84     10.18                         43.02
                 Het Chi     6.67      0.00                          7.42
                 Het  df        4         0                             5
                 Het  P      N.S.      N.S.                          N.S.
               Fixed  RR     1.61      2.20                          1.74
                     RRl     1.15      1.19                          1.29
                     RRu     2.27      4.07                          2.34
                      P        ++         +                           +++
              Random  RR     1.92      2.20                          1.91
                     RRl     1.09      1.19                          1.25
                     RRu     3.38      4.07                          2.91
                      P         +         +                            ++
             Between Chi                                             0.75
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        5         1         6
                      NS        3         1         4

                      Wt    32.84     10.18     43.02
                 Het Chi     6.67      0.00      7.42
                 Het  df        4         0         5
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     1.61      2.20      1.74
                     RRl     1.15      1.19      1.29
                     RRu     2.27      4.07      2.34
                      P        ++         +       +++
              Random  RR     1.92      2.20      1.91
                     RRl     1.09      1.19      1.25
                     RRu     3.38      4.07      2.91
                      P         +         +        ++
             Between Chi                         0.75
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 7

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR DICKIN  DOLL1
        DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FORAST FUKUCH GODTFR GULSVI HAMMO2 HARDIE HARIKK HEDMAN
       HIGGI4     HO HOZAWA HUHTI1 HUHTI2 HUHTI3 ITABAS JACOBS JAENDI JOHANN KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KRZYZA KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI LINDBE LINDST   LIU2
       LUNDB1  MADOR MANNI1 MANNI2 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE MUELLE
       NIEPSU NIHLEN   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA SPEIZE
       STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD WATSON  WEISS
          WEN WILSO1 WOJTYN   XIAO     XU YAMAGU ZIELI1 ZIELI2 ZIETKO
5      GEIJER HAWTHO   LIU1 NILSSO   YUAN
6       CHEN2  CHEN3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 1 - 8

                                  IESCOPD - Meta-analysis of age started : key value 26
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    LIAW    WEN     2                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - F - 2 -

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for age started
5) vs never smoking base
6) Key value = 18
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 1

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   CHEN3  11   m   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   2 Current       Cigs  Nev cigs  18  22
   CHEN3  14   f   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   2 Current       Cigs  Nev cigs  18  22
   DEAN1  31   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  15  19
   DEAN1  71   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  15  19
     LEE  30   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  16  19
    TODD  30   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  16  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 2

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 CHEN3  11  m   2        119       -      89       -      2.43 (  1.26-   4.69)
 CHEN3  14  f   2        201       -     265       -      2.56 (  1.84-   3.57)
 Subtotal CHEN3                                           2.53 (  1.88-   3.41)
 DEAN1  31  m   0        118     485      47     510      2.64 (  1.84-   3.78)
 DEAN1  71  f   0         21     504     120    1538      0.53 (  0.33-   0.86)
 Subtotal DEAN1                                           1.47 (  1.10-   1.96)
*LEE    30  m   0         13     730       1     347      6.18 (  0.81-  47.05)
*TODD   30  m   0         15    1115       1     520      7.00 (  0.93-  52.82)
Partial Totals           487    2834     523    2915
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 CHEN3  11  m   2              0.89     8.90     0.40       0.01
 CHEN3  14  f   2              0.94    34.98     2.47       0.00
 Subtotal CHEN3                0.93    43.87     2.87
 DEAN1  31  m   0              0.97    29.61     2.60       0.00
 DEAN1  71  f   0             -0.63    17.07    28.93       0.01
 Subtotal DEAN1                0.39    46.68    31.53
*LEE    30  m   0              1.82     0.93     1.23       0.08
*TODD   30  m   0              1.95     0.94     1.52       0.06

                       N        6
                      NS        4

                      Wt    92.42
                 Het Chi    37.14
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.96
                     RRl     1.60
                     RRu     2.41
                      P       +++
              Random  RR     2.11
                     RRl     1.08
                     RRu     4.11
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 3

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        6
                      NS        4

                      Wt    92.42
                 Het Chi    37.14
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.96
                     RRl     1.60
                     RRu     2.41
                      P       +++
              Random  RR     2.11
                     RRl     1.08
                     RRu     4.11
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  4         2         6
                      NS                  4         2         6

                      Wt              40.38     52.05     92.42
                 Het Chi               1.60     28.18     37.14
                 Het  df                  3         1         5
                 Het  P                N.S.       ***       ***
               Fixed  RR               2.70      1.53      1.96
                     RRl               1.99      1.17      1.60
                     RRu               3.68      2.01      2.41
                      P                 +++        ++       +++
              Random  RR               2.70      1.18      2.11
                     RRl               1.99      0.25      1.08
                     RRu               3.68      5.48      4.11
                      P                 +++      N.S.         +
             Between Chi                                   7.36
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2         4                             6
                      NS        1         3                             4

                      Wt    43.87     48.55                         92.42
                 Het Chi     0.02     31.69                         37.14
                 Het  df        1         3                             5
                 Het  P      N.S.       ***                           ***
               Fixed  RR     2.53      1.56                          1.96
                     RRl     1.88      1.18                          1.60
                     RRu     3.41      2.07                          2.41
                      P       +++        ++                           +++
              Random  RR     2.53      2.18                          2.11
                     RRl     1.88      0.64                          1.08
                     RRu     3.41      7.48                          4.11
                      P       +++      N.S.                             +
             Between Chi                                             5.43
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 3

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         2         2         6
                      NS        1         2         1         4

                      Wt    46.68      1.87     43.87     92.42
                 Het Chi    27.65      0.01      0.02     37.14
                 Het  df        1         1         1         5
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     1.47      6.58      2.53      1.96
                     RRl     1.10      1.57      1.88      1.60
                     RRu     1.96     27.55      3.41      2.41
                      P        ++        ++       +++       +++
              Random  RR     1.20      6.58      2.53      2.11
                     RRl     0.25      1.57      1.88      1.08
                     RRu     5.73     27.55      3.41      4.11
                      P      N.S.        ++       +++         +
             Between Chi                                   9.46
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4                   2         6
                      NS        3                   1         4

                      Wt    48.55               43.87     92.42
                 Het Chi    31.69                0.02     37.14
                 Het  df        3                   1         5
                 Het  P       ***                N.S.       ***
               Fixed  RR     1.56                2.53      1.96
                     RRl     1.18                1.88      1.60
                     RRu     2.07                3.41      2.41
                      P        ++                 +++       +++
              Random  RR     2.18                2.53      2.11
                     RRl     0.64                1.88      1.08
                     RRu     7.48                3.41      4.11
                      P      N.S.                 +++         +
             Between Chi                                   5.43
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2         4         6
                      NS                  1         3         4

                      Wt              43.87     48.55     92.42
                 Het Chi               0.02     31.69     37.14
                 Het  df                  1         3         5
                 Het  P                N.S.       ***       ***
               Fixed  RR               2.53      1.56      1.96
                     RRl               1.88      1.18      1.60
                     RRu               3.41      2.07      2.41
                      P                 +++        ++       +++
              Random  RR               2.53      2.18      2.11
                     RRl               1.88      0.64      1.08
                     RRu               3.41      7.48      4.11
                      P                 +++      N.S.         +
             Between Chi                                   5.43
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 3

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        4         2                             6
                      NS        3         1                             4

                      Wt    48.55     43.87                         92.42
                 Het Chi    31.69      0.02                         37.14
                 Het  df        3         1                             5
                 Het  P       ***      N.S.                           ***
               Fixed  RR     1.56      2.53                          1.96
                     RRl     1.18      1.88                          1.60
                     RRu     2.07      3.41                          2.41
                      P        ++       +++                           +++
              Random  RR     2.18      2.53                          2.11
                     RRl     0.64      1.88                          1.08
                     RRu     7.48      3.41                          4.11
                      P      N.S.       +++                             +
             Between Chi                                             5.43
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        4         2         6
                      NS        3         1         4

                      Wt    48.55     43.87     92.42
                 Het Chi    31.69      0.02     37.14
                 Het  df        3         1         5
                 Het  P       ***      N.S.       ***
               Fixed  RR     1.56      2.53      1.96
                     RRl     1.18      1.88      1.60
                     RRu     2.07      3.41      2.41
                      P        ++       +++       +++
              Random  RR     2.18      2.53      2.11
                     RRl     0.64      1.88      1.08
                     RRu     7.48      3.41      4.11
                      P      N.S.       +++         +
             Between Chi                         5.43
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 4

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   CHEN3   5 x   m   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   0 Current       Cigs  Nev cigs  18  22
   CHEN3   8 x   f   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   0 Current       Cigs  Nev cigs  18  22
   DEAN1  31     m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  15  19
   DEAN1  71     f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any  15  19
     LEE  30     m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  16  19
    TODD  30     m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any  16  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 5

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 CHEN3  5   m   0        119       -      89       -      2.51 (  1.34-   4.71)
 CHEN3  8   f   0        201       -     265       -      2.60 (  1.87-   3.62)
 Subtotal CHEN3                                           2.58 (  1.93-   3.46)
 DEAN1  31  m   0        118     485      47     510      2.64 (  1.84-   3.78)
 DEAN1  71  f   0         21     504     120    1538      0.53 (  0.33-   0.86)
 Subtotal DEAN1                                           1.47 (  1.10-   1.96)
*LEE    30  m   0         13     730       1     347      6.18 (  0.81-  47.05)
*TODD   30  m   0         15    1115       1     520      7.00 (  0.93-  52.82)
Partial Totals           487    2834     523    2915
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 CHEN3  5   m   0              0.92     9.72     0.53       0.00
 CHEN3  8   f   0              0.96    35.22     2.55       0.00
 Subtotal CHEN3                0.95    44.94     3.08
 DEAN1  31  m   0              0.97    29.61     2.40       0.00
 DEAN1  71  f   0             -0.63    17.07    29.45       0.01
 Subtotal DEAN1                0.39    46.68    31.85
*LEE    30  m   0              1.82     0.93     1.20       0.08
*TODD   30  m   0              1.95     0.94     1.49       0.06

                       N        6
                      NS        4

                      Wt    93.49
                 Het Chi    37.63
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.99
                     RRl     1.62
                     RRu     2.43
                      P       +++
              Random  RR     2.13
                     RRl     1.09
                     RRu     4.15
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 6

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        6
                      NS        4

                      Wt    93.49
                 Het Chi    37.63
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.99
                     RRl     1.62
                     RRu     2.43
                      P       +++
              Random  RR     2.13
                     RRl     1.09
                     RRu     4.15
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  4         2         6
                      NS                  4         2         6

                      Wt              41.21     52.29     93.49
                 Het Chi               1.56     28.80     37.63
                 Het  df                  3         1         5
                 Het  P                N.S.       ***       ***
               Fixed  RR               2.72      1.55      1.99
                     RRl               2.00      1.18      1.62
                     RRu               3.69      2.03      2.43
                      P                 +++        ++       +++
              Random  RR               2.72      1.19      2.13
                     RRl               2.00      0.25      1.09
                     RRu               3.69      5.61      4.15
                      P                 +++      N.S.         +
             Between Chi                                   7.27
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2         4                             6
                      NS        1         3                             4

                      Wt    44.94     48.55                         93.49
                 Het Chi     0.01     31.69                         37.63
                 Het  df        1         3                             5
                 Het  P      N.S.       ***                           ***
               Fixed  RR     2.58      1.56                          1.99
                     RRl     1.93      1.18                          1.62
                     RRu     3.46      2.07                          2.43
                      P       +++        ++                           +++
              Random  RR     2.58      2.18                          2.13
                     RRl     1.93      0.64                          1.09
                     RRu     3.46      7.48                          4.15
                      P       +++      N.S.                             +
             Between Chi                                             5.92
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 6

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         2         2         6
                      NS        1         2         1         4

                      Wt    46.68      1.87     44.94     93.49
                 Het Chi    27.65      0.01      0.01     37.63
                 Het  df        1         1         1         5
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     1.47      6.58      2.58      1.99
                     RRl     1.10      1.57      1.93      1.62
                     RRu     1.96     27.55      3.46      2.43
                      P        ++        ++       +++       +++
              Random  RR     1.20      6.58      2.58      2.13
                     RRl     0.25      1.57      1.93      1.09
                     RRu     5.73     27.55      3.46      4.15
                      P      N.S.        ++       +++         +
             Between Chi                                   9.96
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4                   2         6
                      NS        3                   1         4

                      Wt    48.55               44.94     93.49
                 Het Chi    31.69                0.01     37.63
                 Het  df        3                   1         5
                 Het  P       ***                N.S.       ***
               Fixed  RR     1.56                2.58      1.99
                     RRl     1.18                1.93      1.62
                     RRu     2.07                3.46      2.43
                      P        ++                 +++       +++
              Random  RR     2.18                2.58      2.13
                     RRl     0.64                1.93      1.09
                     RRu     7.48                3.46      4.15
                      P      N.S.                 +++         +
             Between Chi                                   5.92
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2         4         6
                      NS                  1         3         4

                      Wt              44.94     48.55     93.49
                 Het Chi               0.01     31.69     37.63
                 Het  df                  1         3         5
                 Het  P                N.S.       ***       ***
               Fixed  RR               2.58      1.56      1.99
                     RRl               1.93      1.18      1.62
                     RRu               3.46      2.07      2.43
                      P                 +++        ++       +++
              Random  RR               2.58      2.18      2.13
                     RRl               1.93      0.64      1.09
                     RRu               3.46      7.48      4.15
                      P                 +++      N.S.         +
             Between Chi                                   5.92
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 6

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        4         2                             6
                      NS        3         1                             4

                      Wt    48.55     44.94                         93.49
                 Het Chi    31.69      0.01                         37.63
                 Het  df        3         1                             5
                 Het  P       ***      N.S.                           ***
               Fixed  RR     1.56      2.58                          1.99
                     RRl     1.18      1.93                          1.62
                     RRu     2.07      3.46                          2.43
                      P        ++       +++                           +++
              Random  RR     2.18      2.58                          2.13
                     RRl     0.64      1.93                          1.09
                     RRu     7.48      3.46                          4.15
                      P      N.S.       +++                             +
             Between Chi                                             5.92
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        4         2         6
                      NS        3         1         4

                      Wt    48.55     44.94     93.49
                 Het Chi    31.69      0.01     37.63
                 Het  df        3         1         5
                 Het  P       ***      N.S.       ***
               Fixed  RR     1.56      2.58      1.99
                     RRl     1.18      1.93      1.62
                     RRu     2.07      3.46      2.43
                      P        ++       +++       +++
              Random  RR     2.18      2.58      2.13
                     RRl     0.64      1.93      1.09
                     RRu     7.48      3.46      4.15
                      P      N.S.       +++         +
             Between Chi                         5.92
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 7

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR DICKIN  DOLL1
        DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FORAST FUKUCH GODTFR GULSVI HAMMO2 HARDIE HARIKK HEDMAN
       HIGGI4     HO HOZAWA HUHTI1 HUHTI2 HUHTI3 ITABAS JACOBS JAENDI JOHANN KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KRZYZA KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI LINDBE LINDST   LIU2
       LUNDB1  MADOR MANNI1 MANNI2 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE MUELLE
       NIEPSU NIHLEN   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA SPEIZE
       STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD WATSON  WEISS
          WEN WILSO1 WOJTYN   XIAO     XU YAMAGU ZIELI1 ZIELI2 ZIETKO
5      GEIJER HAWTHO   LIU1 NILSSO   YUAN
6       CHEN2   LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 2 - 8

                                  IESCOPD - Meta-analysis of age started : key value 18
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    TODD   TODD     1                  LAMBER/TODD

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - F - 3 -

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for age started
5) vs never smoking base
6) Key value = 14
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 1

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   CHEN2  20   m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  17
   CHEN2  23   f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  17
   CHEN3  12   m   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   2 Current       Cigs  Nev cigs  13  17
   CHEN3  15   f   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   2 Current       Cigs  Nev cigs  13  17
   DEAN1  32   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any   1  14
   DEAN1  72   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any   1  14
     LEE  31   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1  15
    TODD  31   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1  15

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 2

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 CHEN2  20  m   6          -       -       8       -      3.94 (  1.64-   9.44)
 CHEN2  23  f   6          -       -      33       -      5.42 (  3.15-   9.33)
 Subtotal CHEN2                                           4.96 (  3.13-   7.87)
 CHEN3  12  m   2        299       -      89       -      3.66 (  2.09-   6.40)
 CHEN3  15  f   2        424       -     265       -      3.60 (  2.66-   4.86)
 Subtotal CHEN3                                           3.61 (  2.77-   4.71)
 DEAN1  32  m   0         38     165      47     510      2.50 (  1.57-   3.97)
 DEAN1  72  f   0          4     109     120    1538      0.47 (  0.17-   1.30)
 Subtotal DEAN1                                           1.88 (  1.23-   2.86)
*LEE    31  m   0          9     442       1     347      7.07 (  0.90-  55.50)
*TODD   31  m   0          7     639       1     520      5.70 (  0.70-  46.15)
Partial Totals           781    1355     564    2915
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 CHEN2  20  m   6              1.37     5.02     0.14       0.00
 CHEN2  23  f   6              1.69    13.03     3.05       0.00
 Subtotal CHEN2                1.60    18.05     3.18
 CHEN3  12  m   2              1.30    12.27     0.10       0.00
 CHEN3  15  f   2              1.28    42.30     0.23       0.00
 Subtotal CHEN3                1.28    54.57     0.34
 DEAN1  32  m   0              0.92    17.98     1.52       0.00
 DEAN1  72  f   0             -0.75     3.73    14.34       0.15
 Subtotal DEAN1                0.63    21.71    15.86
*LEE    31  m   0              1.96     0.90     0.51       0.06
*TODD   31  m   0              1.74     0.88     0.25       0.10

                       N        8
                      NS        5

                      Wt    96.11
                 Het Chi    20.13
                 Het  df        7
                 Het  P        **
               Fixed  RR     3.34
                     RRl     2.74
                     RRu     4.08
                      P       +++
              Random  RR     3.12
                     RRl     2.07
                     RRu     4.70
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 3

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        8
                      NS        5

                      Wt    96.11
                 Het Chi    20.13
                 Het  df        7
                 Het  P        **
               Fixed  RR     3.34
                     RRl     2.74
                     RRu     4.08
                      P       +++
              Random  RR     3.12
                     RRl     2.07
                     RRu     4.70
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  5         3         8
                      NS                  5         3         8

                      Wt              37.05     59.06     96.11
                 Het Chi               2.39     17.54     20.13
                 Het  df                  4         2         7
                 Het  P                N.S.       ***        **
               Fixed  RR               3.15      3.47      3.34
                     RRl               2.29      2.69      2.74
                     RRu               4.35      4.47      4.08
                      P                 +++       +++       +++
              Random  RR               3.15      2.38      3.12
                     RRl               2.29      0.92      2.07
                     RRu               4.35      6.21      4.70
                      P                 +++       (+)       +++
             Between Chi                                   0.20
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         4                             8
                      NS        2         3                             5

                      Wt    72.62     23.49                         96.11
                 Het Chi     1.73     11.09                         20.13
                 Het  df        3         3                             7
                 Het  P      N.S.         *                            **
               Fixed  RR     3.91      2.06                          3.34
                     RRl     3.11      1.37                          2.74
                     RRu     4.92      3.08                          4.08
                      P       +++       +++                           +++
              Random  RR     3.91      2.09                          3.12
                     RRl     3.11      0.66                          2.07
                     RRu     4.92      6.61                          4.70
                      P       +++      N.S.                           +++
             Between Chi                                             7.31
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 3

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         2         4         8
                      NS        1         2         2         5

                      Wt    21.71      1.78     72.62     96.11
                 Het Chi     8.62      0.02      1.73     20.13
                 Het  df        1         1         3         7
                 Het  P        **      N.S.      N.S.        **
               Fixed  RR     1.88      6.35      3.91      3.34
                     RRl     1.23      1.46      3.11      2.74
                     RRu     2.86     27.59      4.92      4.08
                      P        ++         +       +++       +++
              Random  RR     1.16      6.35      3.91      3.12
                     RRl     0.23      1.46      3.11      2.07
                     RRu     5.91     27.59      4.92      4.70
                      P      N.S.         +       +++       +++
             Between Chi                                   9.76
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4                   4         8
                      NS        3                   2         5

                      Wt    23.49               72.62     96.11
                 Het Chi    11.09                1.73     20.13
                 Het  df        3                   3         7
                 Het  P         *                N.S.        **
               Fixed  RR     2.06                3.91      3.34
                     RRl     1.37                3.11      2.74
                     RRu     3.08                4.92      4.08
                      P       +++                 +++       +++
              Random  RR     2.09                3.91      3.12
                     RRl     0.66                3.11      2.07
                     RRu     6.61                4.92      4.70
                      P      N.S.                 +++       +++
             Between Chi                                   7.31
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  4         4         8
                      NS                  2         3         5

                      Wt              72.62     23.49     96.11
                 Het Chi               1.73     11.09     20.13
                 Het  df                  3         3         7
                 Het  P                N.S.         *        **
               Fixed  RR               3.91      2.06      3.34
                     RRl               3.11      1.37      2.74
                     RRu               4.92      3.08      4.08
                      P                 +++       +++       +++
              Random  RR               3.91      2.09      3.12
                     RRl               3.11      0.66      2.07
                     RRu               4.92      6.61      4.70
                      P                 +++      N.S.       +++
             Between Chi                                   7.31
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 3

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        4         4                             8
                      NS        3         2                             5

                      Wt    23.49     72.62                         96.11
                 Het Chi    11.09      1.73                         20.13
                 Het  df        3         3                             7
                 Het  P         *      N.S.                            **
               Fixed  RR     2.06      3.91                          3.34
                     RRl     1.37      3.11                          2.74
                     RRu     3.08      4.92                          4.08
                      P       +++       +++                           +++
              Random  RR     2.09      3.91                          3.12
                     RRl     0.66      3.11                          2.07
                     RRu     6.61      4.92                          4.70
                      P      N.S.       +++                           +++
             Between Chi                                             7.31
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        4         4         8
                      NS        3         2         5

                      Wt    23.49     72.62     96.11
                 Het Chi    11.09      1.73     20.13
                 Het  df        3         3         7
                 Het  P         *      N.S.        **
               Fixed  RR     2.06      3.91      3.34
                     RRl     1.37      3.11      2.74
                     RRu     3.08      4.92      4.08
                      P       +++       +++       +++
              Random  RR     2.09      3.91      3.12
                     RRl     0.66      3.11      2.07
                     RRu     6.61      4.92      4.70
                      P      N.S.       +++       +++
             Between Chi                         7.31
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 4

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   CHEN2  20     m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  17
   CHEN2  23     f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs  Nev cigs   1  17
   CHEN3   6 x   m   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   0 Current       Cigs  Nev cigs  13  17
   CHEN3   9 x   f   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   0 Current       Cigs  Nev cigs  13  17
   DEAN1  32     m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any   1  14
   DEAN1  72     f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only   Nev any   1  14
     LEE  31     m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1  15
    TODD  31     m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only   Nev any   1  15

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 5

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 CHEN2  20  m   6          -       -       8       -      3.94 (  1.64-   9.44)
 CHEN2  23  f   6          -       -      33       -      5.42 (  3.15-   9.33)
 Subtotal CHEN2                                           4.96 (  3.13-   7.87)
 CHEN3  6   m   0        299       -      89       -      4.22 (  2.45-   7.27)
 CHEN3  9   f   0        424       -     265       -      4.30 (  3.19-   5.79)
 Subtotal CHEN3                                           4.28 (  3.30-   5.56)
 DEAN1  32  m   0         38     165      47     510      2.50 (  1.57-   3.97)
 DEAN1  72  f   0          4     109     120    1538      0.47 (  0.17-   1.30)
 Subtotal DEAN1                                           1.88 (  1.23-   2.86)
*LEE    31  m   0          9     442       1     347      7.07 (  0.90-  55.50)
*TODD   31  m   0          7     639       1     520      5.70 (  0.70-  46.15)
Partial Totals           781    1355     564    2915
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 CHEN2  20  m   6              1.37     5.02     0.02       0.00
 CHEN2  23  f   6              1.69    13.03     1.93       0.00
 Subtotal CHEN2                1.60    18.05     1.95
 CHEN3  6   m   0              1.44    12.99     0.23       0.00
 CHEN3  9   f   0              1.46    43.24     1.02       0.00
 Subtotal CHEN3                1.45    56.23     1.25
 DEAN1  32  m   0              0.92    17.98     2.73       0.00
 DEAN1  72  f   0             -0.75     3.73    15.82       0.15
 Subtotal DEAN1                0.63    21.71    18.55
*LEE    31  m   0              1.96     0.90     0.38       0.06
*TODD   31  m   0              1.74     0.88     0.17       0.10

                       N        8
                      NS        5

                      Wt    97.77
                 Het Chi    22.30
                 Het  df        7
                 Het  P        **
               Fixed  RR     3.69
                     RRl     3.03
                     RRu     4.50
                      P       +++
              Random  RR     3.30
                     RRl     2.15
                     RRu     5.07
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 6

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        8
                      NS        5

                      Wt    97.77
                 Het Chi    22.30
                 Het  df        7
                 Het  P        **
               Fixed  RR     3.69
                     RRl     3.03
                     RRu     4.50
                      P       +++
              Random  RR     3.30
                     RRl     2.15
                     RRu     5.07
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  5         3         8
                      NS                  5         3         8

                      Wt              37.77     60.00     97.77
                 Het Chi               3.12     18.50     22.30
                 Het  df                  4         2         7
                 Het  P                N.S.       ***        **
               Fixed  RR               3.32      3.94      3.69
                     RRl               2.41      3.06      3.03
                     RRu               4.57      5.08      4.50
                      P                 +++       +++       +++
              Random  RR               3.32      2.54      3.30
                     RRl               2.41      0.95      2.15
                     RRu               4.57      6.76      5.07
                      P                 +++       (+)       +++
             Between Chi                                   0.68
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         4                             8
                      NS        2         3                             5

                      Wt    74.28     23.49                         97.77
                 Het Chi     0.67     11.09                         22.30
                 Het  df        3         3                             7
                 Het  P      N.S.         *                            **
               Fixed  RR     4.44      2.06                          3.69
                     RRl     3.53      1.37                          3.03
                     RRu     5.57      3.08                          4.50
                      P       +++       +++                           +++
              Random  RR     4.44      2.09                          3.30
                     RRl     3.53      0.66                          2.15
                     RRu     5.57      6.61                          5.07
                      P       +++      N.S.                           +++
             Between Chi                                            10.54
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                               (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 6

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         2         4         8
                      NS        1         2         2         5

                      Wt    21.71      1.78     74.28     97.77
                 Het Chi     8.62      0.02      0.67     22.30
                 Het  df        1         1         3         7
                 Het  P        **      N.S.      N.S.        **
               Fixed  RR     1.88      6.35      4.44      3.69
                     RRl     1.23      1.46      3.53      3.03
                     RRu     2.86     27.59      5.57      4.50
                      P        ++         +       +++       +++
              Random  RR     1.16      6.35      4.44      3.30
                     RRl     0.23      1.46      3.53      2.15
                     RRu     5.91     27.59      5.57      5.07
                      P      N.S.         +       +++       +++
             Between Chi                                  12.99
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4                   4         8
                      NS        3                   2         5

                      Wt    23.49               74.28     97.77
                 Het Chi    11.09                0.67     22.30
                 Het  df        3                   3         7
                 Het  P         *                N.S.        **
               Fixed  RR     2.06                4.44      3.69
                     RRl     1.37                3.53      3.03
                     RRu     3.08                5.57      4.50
                      P       +++                 +++       +++
              Random  RR     2.09                4.44      3.30
                     RRl     0.66                3.53      2.15
                     RRu     6.61                5.57      5.07
                      P      N.S.                 +++       +++
             Between Chi                                  10.54
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                     (*)

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  4         4         8
                      NS                  2         3         5

                      Wt              74.28     23.49     97.77
                 Het Chi               0.67     11.09     22.30
                 Het  df                  3         3         7
                 Het  P                N.S.         *        **
               Fixed  RR               4.44      2.06      3.69
                     RRl               3.53      1.37      3.03
                     RRu               5.57      3.08      4.50
                      P                 +++       +++       +++
              Random  RR               4.44      2.09      3.30
                     RRl               3.53      0.66      2.15
                     RRu               5.57      6.61      5.07
                      P                 +++      N.S.       +++
             Between Chi                                  10.54
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                     (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 6

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        4         4                             8
                      NS        3         2                             5

                      Wt    23.49     74.28                         97.77
                 Het Chi    11.09      0.67                         22.30
                 Het  df        3         3                             7
                 Het  P         *      N.S.                            **
               Fixed  RR     2.06      4.44                          3.69
                     RRl     1.37      3.53                          3.03
                     RRu     3.08      5.57                          4.50
                      P       +++       +++                           +++
              Random  RR     2.09      4.44                          3.30
                     RRl     0.66      3.53                          2.15
                     RRu     6.61      5.57                          5.07
                      P      N.S.       +++                           +++
             Between Chi                                            10.54
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                               (*)

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        4         4         8
                      NS        3         2         5

                      Wt    23.49     74.28     97.77
                 Het Chi    11.09      0.67     22.30
                 Het  df        3         3         7
                 Het  P         *      N.S.        **
               Fixed  RR     2.06      4.44      3.69
                     RRl     1.37      3.53      3.03
                     RRu     3.08      5.57      4.50
                      P       +++       +++       +++
              Random  RR     2.09      4.44      3.30
                     RRl     0.66      3.53      2.15
                     RRu     6.61      5.57      5.07
                      P      N.S.       +++       +++
             Between Chi                        10.54
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                           (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 7

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR DICKIN  DOLL1
        DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FORAST FUKUCH GODTFR GULSVI HAMMO2 HARDIE HARIKK HEDMAN
       HIGGI4     HO HOZAWA HUHTI1 HUHTI2 HUHTI3 ITABAS JACOBS JAENDI JOHANN KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KRZYZA KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI LINDBE LINDST   LIU2
       LUNDB1  MADOR MANNI1 MANNI2 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE MUELLE
       NIEPSU NIHLEN   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA SPEIZE
       STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD WATSON  WEISS
          WEN WILSO1 WOJTYN   XIAO     XU YAMAGU ZIELI1 ZIELI2 ZIETKO
5      GEIJER HAWTHO   LIU1 NILSSO   YUAN
6        LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 3 - 8

                                  IESCOPD - Meta-analysis of age started : key value 14
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    TODD   TODD     1                  LAMBER/TODD

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - F - 4 -

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for age started
5) Young vs old base
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) SMKSTA  : current, ever
8) PROD    : cigarettes, cigarettes only, any product
9) The youngest vs oldest category
10) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 1

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-LO|LOW| HI|

   CHEN2  21   m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      18   1  17
   CHEN2  24   f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      18   1  17
   CHEN3  13   m   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   2 Current       Cigs      18  13  17
   CHEN3  16   f   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   2 Current       Cigs      18  13  17
   DEAN1  38   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   2 Current MCigs only      25   1  14
   DEAN1  78   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   2 Current MCigs only      25   1  14
  GEIJER   3   m   40   70     Eu:West  1998  2006    Pr   Inc      COPD:LF   0 Current       Cigs      16   1  15
     LEE  35   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   2 Current  Cigs only      20   1  15
     LEE  56   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   2 Current  Cigs only      20   1  19
    LIAW  17   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs      25   1  20
    LIU1  10   m   35   69   Asia:FarE  1986  1998    CC  Prev    COPD:mort   3 Current       Cigs      25   1  19
  NILSSO  26   m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current        Any      25   1  19
    TODD  35   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   2 Current  Cigs only      20   1  15
    YUAN  12   m   45   71   Asia:FarE  1986  1996    Pr   Inc    COPD:mort   3    Ever       Cigs      25   1  24

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 2

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 CHEN2  21  m   6          -       -       -       -      1.20 (  0.53-   2.69)
 CHEN2  24  f   6          -       -       -       -      1.88 (  1.05-   3.34)
 Subtotal CHEN2                                           1.62 (  1.01-   2.59)
 CHEN3  13  m   2        299       -     119       -      1.51 (  0.90-   2.52)
 CHEN3  16  f   2        424       -     201       -      1.41 (  1.04-   1.90)
 Subtotal CHEN3                                           1.43 (  1.11-   1.86)
 DEAN1  38  m   2         38       -      15       -      1.10 (  0.57-   2.15)
 DEAN1  78  f   2          4       -      26       -      0.95 (  0.30-   2.95)
 Subtotal DEAN1                                           1.06 (  0.60-   1.88)
*GEIJER 3   m   0         22     154      11     245      3.18 (  1.59-   6.38)
*LEE    35  m   2          9       -       4       -      1.56 (  0.48-   5.01)
*LEE    56  f   2          2       -       3       -      0.99 (  0.17-   5.93)
 Subtotal LEE                                             1.36 (  0.51-   3.62)
*LIAW   17  b   2          -       -       -       -      1.69 (  0.75-   3.83)
 LIU1   10  m   3          -       -       -       -      1.38 (  1.27-   1.51)
*NILSSO 26  m   2         37       -       1       -      6.20 (  0.85-  45.19)
*TODD   35  m   2          7       -       8       -      0.60 (  0.22-   1.64)
*YUAN   12  m   3          -       -       -       -      3.70 (  1.41-   9.73)
Partial Totals           842     154     388     245
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 CHEN2  21  m   6              0.18     5.82     0.15       0.66
 CHEN2  24  f   6              0.63    11.48     0.97       0.03
 Subtotal CHEN2                0.48    17.30     1.11
 CHEN3  13  m   2              0.41    14.49     0.07       0.12
 CHEN3  16  f   2              0.34    42.31     0.00       0.03
 Subtotal CHEN3                0.36    56.81     0.07
 DEAN1  38  m   2              0.10     8.72     0.53       0.78
 DEAN1  78  f   2             -0.05     2.94     0.45       0.93
 Subtotal DEAN1                0.06    11.66     0.98
*GEIJER 3   m   0              1.16     7.95     5.30       0.00
*LEE    35  m   2              0.44     2.79     0.03       0.46
*LEE    56  f   2             -0.01     1.22     0.15       0.99
 Subtotal LEE                  0.31     4.01     0.18
*LIAW   17  b   2              0.52     5.78     0.19       0.21
 LIU1   10  m   3              0.32   512.86     0.19       0.00
*NILSSO 26  m   2              1.82     0.97     2.14       0.07
*TODD   35  m   2             -0.51     3.81     2.76       0.32
*YUAN   12  m   3              1.31     4.12     3.85       0.01

                       N       14
                      NS       10

                      Wt   625.26
                 Het Chi    16.78
                 Het  df       13
                 Het  P      N.S.
               Fixed  RR     1.41
                     RRl     1.30
                     RRu     1.52
                      P       +++
              Random  RR     1.49
                     RRl     1.26
                     RRu     1.76
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 3

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       14
                      NS       10

                      Wt   625.26
                 Het Chi    16.78
                 Het  df       13
                 Het  P      N.S.
               Fixed  RR     1.41
                     RRl     1.30
                     RRu     1.52
                      P       +++
              Random  RR     1.49
                     RRl     1.26
                     RRu     1.76
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         9         4        14
                      NS        1         9         4        14

                      Wt     5.78    561.54     57.94    625.26
                 Het Chi     0.00     15.00      1.51     16.78
                 Het  df        0         8         3        13
                 Het  P      N.S.       (*)      N.S.      N.S.
               Fixed  RR     1.69      1.40      1.45      1.41
                     RRl     0.75      1.29      1.12      1.30
                     RRu     3.82      1.52      1.88      1.52
                      P      N.S.       +++        ++       +++
              Random  RR     1.69      1.56      1.45      1.49
                     RRl     0.75      1.16      1.12      1.26
                     RRu     3.82      2.10      1.88      1.76
                      P      N.S.        ++        ++       +++
             Between Chi                                   0.27
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         7         3                  14
                      NS        2         5         3                  10

                      Wt    74.10     28.40    522.76              625.26
                 Het Chi     1.02     11.31      4.19               16.78
                 Het  df        3         6         2                  13
                 Het  P      N.S.       (*)      N.S.                N.S.
               Fixed  RR     1.48      1.47      1.39                1.41
                     RRl     1.17      1.02      1.28                1.30
                     RRu     1.85      2.12      1.52                1.52
                      P       +++         +       +++                 +++
              Random  RR     1.48      1.43      1.74                1.49
                     RRl     1.17      0.82      1.05                1.26
                     RRu     1.85      2.47      2.88                1.76
                      P       +++      N.S.         +                 +++
             Between Chi                                             0.27
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 3

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N        2         9        11
                      NS        2         5         7

                      Wt     8.92     93.58    102.50
                 Het Chi     0.39      5.00     12.33
                 Het  df        1         8        10
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     3.42      1.36      1.47
                     RRl     1.78      1.11      1.21
                     RRu     6.60      1.67      1.79
                      P       +++        ++       +++
              Random  RR     3.42      1.36      1.48
                     RRl     1.78      1.11      1.16
                     RRu     6.60      1.67      1.88
                      P       +++        ++        ++
             Between Chi                         6.94
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                            **

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        6                   3         3         2                  14
                      NS        4                   3         2         1                  10

                      Wt    20.45              522.76     25.25     56.81              625.26
                 Het Chi     4.72                4.19      3.28      0.05               16.78
                 Het  df        5                   2         2         1                  13
                 Het  P      N.S.                N.S.      N.S.      N.S.                N.S.
               Fixed  RR     1.09                1.39      2.00      1.43                1.41
                     RRl     0.71                1.28      1.35      1.11                1.30
                     RRu     1.68                1.52      2.95      1.86                1.52
                      P      N.S.                 +++       +++        ++                 +++
              Random  RR     1.09                1.74      1.98      1.43                1.49
                     RRl     0.71                1.05      1.19      1.11                1.26
                     RRu     1.68                2.88      3.29      1.86                1.76
                      P      N.S.                   +        ++        ++                 +++
             Between Chi                                                                 4.54
             Between  df                                                                    3
             Between  P                                                                  N.S.
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        5                   3         6        14
                      NS        3                   3         4        10

                      Wt    19.48              522.76     83.03    625.26
                 Het Chi     1.63                4.19      7.04     16.78
                 Het  df        4                   2         5        13
                 Het  P      N.S.                N.S.      N.S.      N.S.
               Fixed  RR     1.00                1.39      1.61      1.41
                     RRl     0.64                1.28      1.30      1.30
                     RRu     1.56                1.52      2.00      1.52
                      P      N.S.                 +++       +++       +++
              Random  RR     1.00                1.74      1.70      1.49
                     RRl     0.64                1.05      1.27      1.26
                     RRu     1.56                2.88      2.27      1.76
                      P      N.S.                   +       +++       +++
             Between Chi                                             3.92
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 3

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        3         7         4        14
                      NS        2         6         2        10

                      Wt   524.52     26.64     74.10    625.26
                 Het Chi     0.84     10.97      1.02     16.78
                 Het  df        2         6         3        13
                 Het  P      N.S.       (*)      N.S.      N.S.
               Fixed  RR     1.37      2.02      1.48      1.41
                     RRl     1.26      1.38      1.17      1.30
                     RRu     1.49      2.95      1.85      1.52
                      P       +++       +++       +++       +++
              Random  RR     1.37      1.93      1.48      1.49
                     RRl     1.26      1.12      1.17      1.26
                     RRu     1.49      3.34      1.85      1.76
                      P       +++         +       +++       +++
             Between Chi                                   3.95
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        1        10         3                  14
                      NS        1         6         3                  10

                      Wt     0.97    606.44     17.85              625.26
                 Het Chi     0.00      5.02      1.89               16.78
                 Het  df        0         9         2                  13
                 Het  P      N.S.      N.S.      N.S.                N.S.
               Fixed  RR     6.20      1.38      2.68                1.41
                     RRl     0.85      1.27      1.69                1.30
                     RRu    45.21      1.49      4.27                1.52
                      P       (+)       +++       +++                 +++
              Random  RR     6.20      1.38      2.68                1.49
                     RRl     0.85      1.27      1.69                1.26
                     RRu    45.21      1.49      4.27                1.76
                      P       (+)       +++       +++                 +++
             Between Chi                                             9.87
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                                **

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        4         3         3         4                  14
                      NS        2         3         2         3                  10

                      Wt    74.10    524.93      7.82     18.41              625.26
                 Het Chi     1.02      9.34      1.48      3.28               16.78
                 Het  df        3         2         2         3                  13
                 Het  P      N.S.        **      N.S.      N.S.                N.S.
               Fixed  RR     1.48      1.41      0.91      1.35                1.41
                     RRl     1.17      1.29      0.45      0.85                1.30
                     RRu     1.85      1.53      1.84      2.13                1.52
                      P       +++       +++      N.S.      N.S.                 +++
              Random  RR     1.48      2.29      0.91      1.36                1.49
                     RRl     1.17      1.11      0.45      0.83                1.26
                     RRu     1.85      4.72      1.84      2.22                1.76
                      P       +++         +      N.S.      N.S.                 +++
             Between Chi                                                       1.67
             Between  df                                                          3
             Between  P                                                        N.S.
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 3

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        4        10        14
                      NS        2         8        10

                      Wt    68.46    556.80    625.26
                 Het Chi     0.98     15.72     16.78
                 Het  df        3         9        13
                 Het  P      N.S.       (*)      N.S.
               Fixed  RR     1.36      1.41      1.41
                     RRl     1.08      1.30      1.30
                     RRu     1.73      1.53      1.52
                      P         +       +++       +++
              Random  RR     1.36      1.68      1.49
                     RRl     1.08      1.24      1.26
                     RRu     1.73      2.28      1.76
                      P         +       +++       +++
             Between Chi                         0.08
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        9         1         4        14
                      NS        7         1         2        10

                      Wt   543.21      7.95     74.10    625.26
                 Het Chi    10.12      0.00      1.02     16.78
                 Het  df        8         0         3        13
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     1.38      3.18      1.48      1.41
                     RRl     1.27      1.59      1.17      1.30
                     RRu     1.50      6.38      1.85      1.52
                      P       +++        ++       +++       +++
              Random  RR     1.39      3.18      1.48      1.49
                     RRl     1.06      1.59      1.17      1.26
                     RRu     1.83      6.38      1.85      1.76
                      P         +        ++       +++       +++
             Between Chi                                   5.65
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N        8         1         3         2        14
                      NS        5         1         2         2        10

                      Wt    82.90      7.95     15.78    518.64    625.26
                 Het Chi     6.24      0.00      4.80      0.23     16.78
                 Het  df        7         0         2         1        13
                 Het  P      N.S.      N.S.       (*)      N.S.      N.S.
               Fixed  RR     1.43      3.18      1.47      1.38      1.41
                     RRl     1.16      1.59      0.90      1.27      1.30
                     RRu     1.78      6.38      2.41      1.51      1.52
                      P        ++        ++      N.S.       +++       +++
              Random  RR     1.43      3.18      1.55      1.38      1.49
                     RRl     1.16      1.59      0.69      1.27      1.26
                     RRu     1.78      6.38      3.50      1.51      1.76
                      P        ++        ++      N.S.       +++       +++
             Between Chi                                             5.50
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 3

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N                  1         1
                      NS                  1         1

                      Wt               7.95      7.95
                 Het Chi               0.00      0.00
                 Het  df                  0         0
                 Het  P                N.S.      N.S.
               Fixed  RR               3.18      3.18
                     RRl               1.59      1.59
                     RRu               6.38      6.38
                      P                  ++        ++
              Random  RR               3.18      3.18
                     RRl               1.59      1.59
                     RRu               6.38      6.38
                      P                  ++        ++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        1         5         2         6        14
                      NS        1         4         1         4        10

                      Wt     7.95     17.72     17.30    582.30    625.26
                 Het Chi     0.00      6.84      0.78      3.19     16.78
                 Het  df        0         4         1         5        13
                 Het  P      N.S.      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     3.18      1.54      1.62      1.38      1.41
                     RRl     1.59      0.97      1.01      1.27      1.30
                     RRu     6.38      2.46      2.59      1.50      1.52
                      P        ++       (+)         +       +++       +++
              Random  RR     3.18      1.51      1.62      1.38      1.49
                     RRl     1.59      0.80      1.01      1.27      1.26
                     RRu     6.38      2.83      2.59      1.50      1.76
                      P        ++      N.S.         +       +++       +++
             Between Chi                                             5.98
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        1         5         2         6        14
                      NS        1         4         1         4        10

                      Wt     7.95     17.72     17.30    582.30    625.26
                 Het Chi     0.00      6.84      0.78      3.19     16.78
                 Het  df        0         4         1         5        13
                 Het  P      N.S.      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     3.18      1.54      1.62      1.38      1.41
                     RRl     1.59      0.97      1.01      1.27      1.30
                     RRu     6.38      2.46      2.59      1.50      1.52
                      P        ++       (+)         +       +++       +++
              Random  RR     3.18      1.51      1.62      1.38      1.49
                     RRl     1.59      0.80      1.01      1.27      1.26
                     RRu     6.38      2.83      2.59      1.50      1.76
                      P        ++      N.S.         +       +++       +++
             Between Chi                                             5.98
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 3

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N        7         7        14
                      NS        4         6        10

                      Wt   598.62     26.64    625.26
                 Het Chi     2.20     10.97     16.78
                 Het  df        6         6        13
                 Het  P      N.S.       (*)      N.S.
               Fixed  RR     1.38      2.02      1.41
                     RRl     1.28      1.38      1.30
                     RRu     1.50      2.95      1.52
                      P       +++       +++       +++
              Random  RR     1.38      1.93      1.49
                     RRl     1.28      1.12      1.26
                     RRu     1.50      3.34      1.76
                      P       +++         +       +++
             Between Chi                         3.61
             Between  df                            1
             Between  P                           (*)
             Btwn(F)  P                           (*)

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1         8         5        14
                      NS        1         6         3        10

                      Wt     0.97    604.81     19.48    625.26
                 Het Chi     0.00     10.67      1.63     16.78
                 Het  df        0         7         4        13
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     6.20      1.42      1.00      1.41
                     RRl     0.85      1.31      0.64      1.30
                     RRu    45.21      1.54      1.56      1.52
                      P       (+)       +++      N.S.       +++
              Random  RR     6.20      1.58      1.00      1.49
                     RRl     0.85      1.30      0.64      1.26
                     RRu    45.21      1.91      1.56      1.76
                      P       (+)       +++      N.S.       +++
             Between Chi                                   4.48
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                        Number of adjustment variables
                                0         1        2+     Total

                       N        1                  13        14
                      NS        1                   9        10

                      Wt     7.95              617.31    625.26
                 Het Chi     0.00               11.42     16.78
                 Het  df        0                  12        13
                 Het  P      N.S.                N.S.      N.S.
               Fixed  RR     3.18                1.39      1.41
                     RRl     1.59                1.29      1.30
                     RRu     6.38                1.51      1.52
                      P        ++                 +++       +++
              Random  RR     3.18                1.39      1.49
                     RRl     1.59                1.29      1.26
                     RRu     6.38                1.51      1.76
                      P        ++                 +++       +++
             Between Chi                                   5.36
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                       *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 4

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-LO|LOW| HI|

   CHEN2  21     m   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      18   1  17
   CHEN2  24     f   35   64   Am:Canada  1994  2000    CS  Prev        CB/EM   6 Current       Cigs      18   1  17
   CHEN3   7 x   m   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   0 Current       Cigs      18  13  17
   CHEN3  10 x   f   35   64   Am:Canada  2000  2003    CS  Prev   COPD/CB/EM   0 Current       Cigs      18  13  17
   DEAN1  35 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only      25   1  14
   DEAN1  75 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0 Current MCigs only      25   1  14
  GEIJER   3     m   40   70     Eu:West  1998  2006    Pr   Inc      COPD:LF   0 Current       Cigs      16   1  15
     LEE  33 x   m   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only      20   1  15
     LEE  55 x   f   35   82       Eu:UK  1964  1979    Pr   Inc    COPD:mort   0 Current  Cigs only      20   1  19
    LIAW  17     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs      25   1  20
    LIU1  10     m   35   69   Asia:FarE  1986  1998    CC  Prev    COPD:mort   3 Current       Cigs      25   1  19
  NILSSO  26     m   18   99    Eu:Scand  1963  2001    Pr   Inc    COPD:mort   2 Current        Any      25   1  19
    TODD  33 x   m   35   81       Eu:UK  1965  1978    Pr   Inc    COPD:mort   0 Current  Cigs only      20   1  15
    YUAN  12     m   45   71   Asia:FarE  1986  1996    Pr   Inc    COPD:mort   3    Ever       Cigs      25   1  24

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 5

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 CHEN2  21  m   6          -       -       -       -      1.20 (  0.53-   2.69)
 CHEN2  24  f   6          -       -       -       -      1.88 (  1.05-   3.34)
 Subtotal CHEN2                                           1.62 (  1.01-   2.59)
 CHEN3  7   m   0        299       -     119       -      1.68 (  0.77-   3.66)
 CHEN3  10  f   0        424       -     201       -      1.65 (  1.23-   2.22)
 Subtotal CHEN3                                           1.65 (  1.25-   2.18)
 DEAN1  35  m   0         38     165      15      75      1.15 (  0.60-   2.22)
 DEAN1  75  f   0          4     109      26     274      0.39 (  0.13-   1.13)
 Subtotal DEAN1                                           0.86 (  0.49-   1.50)
*GEIJER 3   m   0         22     154      11     245      3.18 (  1.59-   6.38)
*LEE    33  m   0          9     442       4     293      1.49 (  0.46-   4.80)
*LEE    55  f   0          2     588       3     614      0.70 (  0.12-   4.15)
 Subtotal LEE                                             1.19 (  0.45-   3.16)
*LIAW   17  b   2          -       -       -       -      1.69 (  0.75-   3.83)
 LIU1   10  m   3          -       -       -       -      1.38 (  1.27-   1.51)
*NILSSO 26  m   2         37       -       1       -      6.20 (  0.85-  45.19)
*TODD   33  m   0          7     639       8     375      0.51 (  0.19-   1.40)
*YUAN   12  m   3          -       -       -       -      3.70 (  1.41-   9.73)
Partial Totals           842    2097     388    1876
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 CHEN2  21  m   6              0.18     5.82     0.16       0.66
 CHEN2  24  f   6              0.63    11.48     0.93       0.03
 Subtotal CHEN2                0.48    17.30     1.09
 CHEN3  7   m   0              0.52     6.32     0.19       0.19
 CHEN3  10  f   0              0.50    44.07     1.05       0.00
 Subtotal CHEN3                0.50    50.39     1.24
 DEAN1  35  m   0              0.14     8.90     0.37       0.67
 DEAN1  75  f   0             -0.95     3.32     5.58       0.08
 Subtotal DEAN1               -0.16    12.22     5.95
*GEIJER 3   m   0              1.16     7.95     5.23       0.00
*LEE    33  m   0              0.40     2.81     0.01       0.50
*LEE    55  f   0             -0.36     1.20     0.60       0.69
 Subtotal LEE                  0.17     4.02     0.61
*LIAW   17  b   2              0.52     5.78     0.18       0.21
 LIU1   10  m   3              0.32   512.86     0.30       0.00
*NILSSO 26  m   2              1.82     0.97     2.13       0.07
*TODD   33  m   0             -0.67     3.79     3.89       0.19
*YUAN   12  m   3              1.31     4.12     3.81       0.01

                       N       14
                      NS       10

                      Wt   619.40
                 Het Chi    24.44
                 Het  df       13
                 Het  P         *
               Fixed  RR     1.41
                     RRl     1.31
                     RRu     1.53
                      P       +++
              Random  RR     1.51
                     RRl     1.20
                     RRu     1.89
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 6

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       14
                      NS       10

                      Wt   619.40
                 Het Chi    24.44
                 Het  df       13
                 Het  P         *
               Fixed  RR     1.41
                     RRl     1.31
                     RRu     1.53
                      P       +++
              Random  RR     1.51
                     RRl     1.20
                     RRu     1.89
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         9         4        14
                      NS        1         9         4        14

                      Wt     5.78    553.55     60.07    619.40
                 Het Chi     0.00     16.02      7.76     24.44
                 Het  df        0         8         3        13
                 Het  P      N.S.         *       (*)         *
               Fixed  RR     1.69      1.40      1.53      1.41
                     RRl     0.75      1.29      1.19      1.31
                     RRu     3.82      1.52      1.98      1.53
                      P      N.S.       +++       +++       +++
              Random  RR     1.69      1.58      1.23      1.51
                     RRl     0.75      1.13      0.69      1.20
                     RRu     3.82      2.20      2.20      1.89
                      P      N.S.        ++      N.S.       +++
             Between Chi                                   0.65
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         7         3                  14
                      NS        2         5         3                  10

                      Wt    67.69     28.95    522.76              619.40
                 Het Chi     0.79     17.55      4.19               24.44
                 Het  df        3         6         2                  13
                 Het  P      N.S.        **      N.S.                   *
               Fixed  RR     1.64      1.28      1.39                1.41
                     RRl     1.30      0.89      1.28                1.31
                     RRu     2.09      1.85      1.52                1.53
                      P       +++      N.S.       +++                 +++
              Random  RR     1.64      1.18      1.74                1.51
                     RRl     1.30      0.60      1.05                1.20
                     RRu     2.09      2.34      2.88                1.89
                      P       +++      N.S.         +                 +++
             Between Chi                                             1.91
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 6

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        3         7         4        14
                      NS        2         6         2        10

                      Wt   525.08     26.63     67.69    619.40
                 Het Chi     5.60     13.25      0.79     24.44
                 Het  df        2         6         3        13
                 Het  P       (*)         *      N.S.         *
               Fixed  RR     1.36      1.93      1.64      1.41
                     RRl     1.25      1.32      1.30      1.31
                     RRu     1.49      2.83      2.09      1.53
                      P       +++       +++       +++       +++
              Random  RR     1.04      1.81      1.64      1.51
                     RRl     0.60      0.99      1.30      1.20
                     RRu     1.81      3.32      2.09      1.89
                      P      N.S.       (+)       +++       +++
             Between Chi                                   4.81
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        9         1         4        14
                      NS        7         1         2        10

                      Wt   543.76      7.95     67.69    619.40
                 Het Chi    16.37      0.00      0.79     24.44
                 Het  df        8         0         3        13
                 Het  P         *      N.S.      N.S.         *
               Fixed  RR     1.37      3.18      1.64      1.41
                     RRl     1.26      1.59      1.30      1.31
                     RRu     1.49      6.38      2.09      1.53
                      P       +++        ++       +++       +++
              Random  RR     1.27      3.18      1.64      1.51
                     RRl     0.86      1.59      1.30      1.20
                     RRu     1.87      6.38      2.09      1.89
                      P      N.S.        ++       +++       +++
             Between Chi                                   7.28
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1         8         5        14
                      NS        1         6         3        10

                      Wt     0.97    598.40     20.03    619.40
                 Het Chi     0.00     11.71      4.77     24.44
                 Het  df        0         7         4        13
                 Het  P      N.S.      N.S.      N.S.         *
               Fixed  RR     6.20      1.44      0.83      1.41
                     RRl     0.85      1.33      0.54      1.31
                     RRu    45.21      1.56      1.29      1.53
                      P       (+)       +++      N.S.       +++
              Random  RR     6.20      1.68      0.81      1.51
                     RRl     0.85      1.35      0.49      1.20
                     RRu    45.21      2.08      1.32      1.89
                      P       (+)       +++      N.S.       +++
             Between Chi                                   7.96
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 7

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR DICKIN  DOLL1
        DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FORAST FUKUCH GODTFR GULSVI HAMMO2 HARDIE HARIKK HEDMAN
       HIGGI4     HO HOZAWA HUHTI1 HUHTI2 HUHTI3 ITABAS JACOBS JAENDI JOHANN KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KRZYZA KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI LINDBE LINDST   LIU2
       LUNDB1  MADOR MANNI1 MANNI2 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE MUELLE
       NIEPSU NIHLEN   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA SPEIZE
       STERLI  STROM  TAGER   TANG   THUN TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD WATSON  WEISS
          WEN WILSO1 WOJTYN   XIAO     XU YAMAGU ZIELI1 ZIELI2 ZIETKO
6      HAWTHO

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - F - 4 - 8

                     IESCOPD - Meta-analysis of age started : highest (=youngest) vs lowest (=oldest)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    LIAW    WEN     2                     WEN/LIAW
    TODD   TODD     1                  LAMBER/TODD

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-LO|LOW| HI|

  HAWTHO   7   m   45   76       Eu:UK  1965  1978    Pr   Inc    COPD:mort   3 Current       Cigs      20   1  14
          RR|SIG|

        3.42   n

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 1 -

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 1) = 5
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  16   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  ANDER1  25   f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  DEMARC  12   b   20   44       Multi  1991  2004    CS  Prev      COPD:LF   4 Current       Cigs   Nev any   1  14
  FERRI2  58   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  FERRI2  72   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  JOHANN   4   b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
     KIM   8   m   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs  Nev cigs   1  10
     KIM  13   f   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs  Nev cigs   1  10
  KOJIMA   7   m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1  19
  KOJIMA  12   f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1  19
    LIAW  18   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs   1  19
  MENEZ2   7   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ3   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ4   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ5   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ6   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  PEREZP   2   f   40   99 Am:Sth/Cent  1992  1996    CC  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1  10
    SHIN  11   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   3    Ever       Cigs  Nev cigs   0   9
    XIAO   4   b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs   0  19
      XU  10   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs   0  14
      XU  20   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs   0  14
  ZIELI1   6   b    0   99     Eu:East  1999  2001    CS  Prev      COPD:LF   1    Ever       Cigs  Nev cigs   1   9
  ZIELI2   7   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 16  m   1          3       -       2       -      2.31 (  0.37-  14.37)
 ANDER1 25  f   1          4       -      16       -      0.66 (  0.20-   2.18)
 Subtotal ANDER1                                          0.96 (  0.35-   2.61)
 DEMARC 12  b   4         77       -     156       -      1.08 (  0.81-   1.44)
 FERRI2 58  m   1         20       -      11       -      2.71 (  1.19-   6.16)
 FERRI2 72  f   1         24       -      54       -      1.43 (  0.85-   2.40)
 Subtotal FERRI2                                          1.72 (  1.11-   2.66)
 JOHANN 4   b   0         26     515      22     842      1.93 (  1.08-   3.45)
 KIM    8   m   1         17       -      23       -      1.04 (  0.53-   2.06)
 KIM    13  f   1          1       -      61       -      0.47 (  0.08-   2.69)
 Subtotal KIM                                             0.94 (  0.50-   1.77)
 KOJIMA 7   m   0         20     880      19    1871      2.24 (  1.19-   4.21)
 KOJIMA 12  f   0          2     159      20    3545      2.23 (  0.52-   9.62)
 Subtotal KOJIMA                                          2.24 (  1.25-   4.00)
*LIAW   18  b   2          -       -       -       -      1.60 (  0.80-   3.40)
 MENEZ2 7   b   0         27       -      52       -      1.09 (  0.66-   1.79)
 MENEZ3 4   b   0         48       -      62       -      0.72 (  0.48-   1.08)
 MENEZ4 4   b   0         18       -      34       -      1.05 (  0.58-   1.89)
 MENEZ5 4   b   0         16       -      58       -      0.72 (  0.40-   1.31)
 MENEZ6 4   b   0         34       -      36       -      1.68 (  1.03-   2.74)
 PEREZP 2   f   0         12      39      45     145      0.99 (  0.48-   2.05)
 SHIN   11  b   3          9       -      49       -      1.10 (  0.50-   2.60)
 XIAO   4   b   0         30      25      21      56      3.20 (  1.54-   6.64)
 XU     10  m   13       139       -     450       -      1.07 (  0.85-   1.34)
 XU     20  f   13        21       -     647       -      2.27 (  1.36-   3.77)
 Subtotal XU                                              1.21 (  0.98-   1.49)
 ZIELI1 6   b   1        206       -     316       -      1.26 (  1.03-   1.53)
 ZIELI2 7   b   0       1486    9875    1262    8933      1.07 (  0.98-   1.15)
Partial Totals          2240   11493    3416   15392
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 16  m   1              0.84     1.15     0.59       0.37
 ANDER1 25  f   1             -0.42     2.69     0.77       0.50
 Subtotal ANDER1              -0.04     3.84     1.36
 DEMARC 12  b   4              0.08    46.42     0.09       0.60
 FERRI2 58  m   1              1.00     5.68     4.37       0.02
 FERRI2 72  f   1              0.36    14.26     0.80       0.18
 Subtotal FERRI2               0.54    19.95     5.17
 JOHANN 4   b   0              0.66    11.49     3.33       0.03
 KIM    8   m   1              0.04     8.34     0.05       0.91
 KIM    13  f   1             -0.76     1.24     0.95       0.40
 Subtotal KIM                 -0.06     9.58     1.01
 KOJIMA 7   m   0              0.81     9.59     4.50       0.01
 KOJIMA 12  f   0              0.80     1.80     0.83       0.28
 Subtotal KOJIMA               0.81    11.38     5.34
*LIAW   18  b   2              0.47     7.34     0.90       0.20
 MENEZ2 7   b   0              0.09    15.44     0.02       0.73
 MENEZ3 4   b   0             -0.33    23.37     4.70       0.11
 MENEZ4 4   b   0              0.05    11.01     0.06       0.87
 MENEZ5 4   b   0             -0.33    10.92     2.20       0.28
 MENEZ6 4   b   0              0.52    16.05     2.55       0.04
 PEREZP 2   f   0             -0.01     7.24     0.12       0.98
 SHIN   11  b   3              0.10     5.65     0.00       0.82
 XIAO   4   b   0              1.16     7.20     7.84       0.00
 XU     10  m   13             0.07    74.16     0.20       0.56
 XU     20  f   13             0.82    14.78     7.23       0.00
 Subtotal XU                   0.19    88.94     7.44
 ZIELI1 6   b   1              0.23    98.13     1.21       0.02
 ZIELI2 7   b   0              0.06   595.75     1.94       0.12

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       23
                      NS       18

                      Wt   989.70
                 Het Chi    45.27
                 Het  df       22
                 Het  P        **
               Fixed  RR     1.13
                     RRl     1.06
                     RRu     1.20
                      P       +++
              Random  RR     1.25
                     RRl     1.09
                     RRu     1.44
                      P        ++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       23
                      NS       18

                      Wt   989.70
                 Het Chi    45.27
                 Het  df       22
                 Het  P        **
               Fixed  RR     1.13
                     RRl     1.06
                     RRu     1.20
                      P       +++
              Random  RR     1.25
                     RRl     1.09
                     RRu     1.44
                      P        ++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N       12         5         6        23
                      NS       12         5         6        23

                      Wt   848.77     98.92     42.02    989.70
                 Het Chi    24.39      9.11      7.58     45.27
                 Het  df       11         4         5        22
                 Het  P         *       (*)      N.S.        **
               Fixed  RR     1.10      1.22      1.48      1.13
                     RRl     1.03      1.00      1.10      1.06
                     RRu     1.18      1.49      2.01      1.20
                      P        ++         +         +       +++
              Random  RR     1.18      1.51      1.38      1.25
                     RRl     1.00      0.98      0.91      1.09
                     RRu     1.38      2.34      2.08      1.44
                      P         +       (+)      N.S.        ++
             Between Chi                                   4.20
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         3         9         7        23
                      NS        2         3         6         7        18

                      Wt    23.79    705.37    130.10    130.44    989.70
                 Het Chi     4.01      6.07     18.66      8.39     45.27
                 Het  df        3         2         8         6        22
                 Het  P      N.S.         *         *      N.S.        **
               Fixed  RR     1.56      1.10      1.34      1.02      1.13
                     RRl     1.05      1.02      1.13      0.86      1.06
                     RRu     2.33      1.19      1.59      1.21      1.20
                      P         +         +       +++      N.S.       +++
              Random  RR     1.57      1.21      1.56      1.02      1.25
                     RRl     0.93      0.98      1.12      0.82      1.09
                     RRu     2.64      1.50      2.19      1.26      1.44
                      P       (+)       (+)        ++      N.S.        ++
             Between Chi                                             8.14
             Between  df                                                3
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N       16         2        18
                      NS       13         1        14

                      Wt   835.96      3.84    839.80
                 Het Chi    27.42      1.26     28.76
                 Het  df       15         1        17
                 Het  P         *      N.S.         *
               Fixed  RR     1.11      0.96      1.11
                     RRl     1.04      0.35      1.04
                     RRu     1.19      2.61      1.19
                      P        ++      N.S.        ++
              Random  RR     1.20      1.01      1.19
                     RRl     1.02      0.32      1.02
                     RRu     1.40      3.24      1.39
                      P         +      N.S.         +
             Between Chi                         0.08
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        4                   1         5        12         1        23
                      NS        2                   1         5         9         1        18

                      Wt    23.79                7.34    168.93    782.44      7.20    989.70
                 Het Chi     4.01                0.00      3.59     23.96      0.00     45.27
                 Het  df        3                   0         4        11         0        22
                 Het  P      N.S.                N.S.      N.S.         *      N.S.        **
               Fixed  RR     1.56                1.60      1.23      1.08      3.20      1.13
                     RRl     1.05                0.78      1.05      1.01      1.54      1.06
                     RRu     2.33                3.30      1.42      1.16      6.64      1.20
                      P         +                N.S.        ++         +        ++       +++
              Random  RR     1.57                1.60      1.23      1.15      3.20      1.25
                     RRl     0.93                0.78      1.05      0.96      1.54      1.09
                     RRu     2.64                3.30      1.42      1.39      6.64      1.44
                      P       (+)                N.S.        ++      N.S.        ++        ++
             Between Chi                                                                13.71
             Between  df                                                                    4
             Between  P                                                                    **
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        4                   2        17        23
                      NS        2                   2        14        18

                      Wt    23.79               14.58    951.33    989.70
                 Het Chi     4.01                0.83     37.62     45.27
                 Het  df        3                   1        16        22
                 Het  P      N.S.                N.S.        **        **
               Fixed  RR     1.56                1.26      1.12      1.13
                     RRl     1.05                0.76      1.05      1.06
                     RRu     2.33                2.11      1.19      1.20
                      P         +                N.S.       +++       +++
              Random  RR     1.57                1.26      1.23      1.25
                     RRl     0.93                0.76      1.06      1.09
                     RRu     2.64                2.11      1.42      1.44
                      P       (+)                N.S.        ++        ++
             Between Chi                                             2.80
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         1        20        23
                      NS        2         1        15        18

                      Wt    14.45      7.34    967.92    989.70
                 Het Chi     4.96      0.00     36.33     45.27
                 Het  df        1         0        19        22
                 Het  P         *      N.S.        **        **
               Fixed  RR     1.78      1.60      1.12      1.13
                     RRl     1.06      0.78      1.05      1.06
                     RRu     2.98      3.30      1.19      1.20
                      P         +      N.S.       +++       +++
              Random  RR     1.78      1.60      1.21      1.25
                     RRl     0.56      0.78      1.06      1.09
                     RRu     5.61      3.30      1.39      1.44
                      P      N.S.      N.S.        ++        ++
             Between Chi                                   3.98
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        5         9         9                  23
                      NS        5         5         8                  18

                      Wt   753.16    135.60    100.94              989.70
                 Het Chi    10.66     16.79     10.48               45.27
                 Het  df        4         8         8                  22
                 Het  P         *         *      N.S.                  **
               Fixed  RR     1.10      1.39      1.02                1.13
                     RRl     1.03      1.17      0.84                1.06
                     RRu     1.18      1.64      1.24                1.20
                      P        ++       +++      N.S.                 +++
              Random  RR     1.20      1.66      1.03                1.25
                     RRl     0.99      1.22      0.81                1.09
                     RRu     1.47      2.26      1.29                1.44
                      P       (+)        ++      N.S.                  ++
             Between Chi                                             7.35
             Between  df                                                2
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        1         4         3        15                  23
                      NS        1         2         2        13                  18

                      Wt    46.42     15.22     31.43    896.63              989.70
                 Het Chi     0.00      3.32      1.76     29.54               45.27
                 Het  df        0         3         2        14                  22
                 Het  P      N.S.      N.S.      N.S.        **                  **
               Fixed  RR     1.08      1.81      1.79      1.10                1.13
                     RRl     0.81      1.09      1.26      1.03                1.06
                     RRu     1.44      2.99      2.54      1.18                1.20
                      P      N.S.         +        ++        ++                 +++
              Random  RR     1.08      1.76      1.79      1.17                1.25
                     RRl     0.81      1.00      1.26      1.01                1.09
                     RRu     1.44      3.08      2.54      1.36                1.44
                      P      N.S.         +        ++         +                  ++
             Between Chi                                                      10.64
             Between  df                                                          3
             Between  P                                                           *
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N                 23        23
                      NS                 18        18

                      Wt             989.70    989.70
                 Het Chi              45.27     45.27
                 Het  df                 22        22
                 Het  P                  **        **
               Fixed  RR               1.13      1.13
                     RRl               1.06      1.06
                     RRu               1.20      1.20
                      P                 +++       +++
              Random  RR               1.25      1.25
                     RRl               1.09      1.09
                     RRu               1.44      1.44
                      P                  ++        ++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1        15         7        23
                      NS        1        13         4        18

                      Wt     7.34    862.43    119.93    989.70
                 Het Chi     0.00     21.88     17.88     45.27
                 Het  df        0        14         6        22
                 Het  P      N.S.       (*)        **        **
               Fixed  RR     1.60      1.10      1.35      1.13
                     RRl     0.78      1.03      1.13      1.06
                     RRu     3.30      1.17      1.62      1.20
                      P      N.S.        ++       +++       +++
              Random  RR     1.60      1.14      1.69      1.25
                     RRl     0.78      0.99      1.12      1.09
                     RRu     3.30      1.30      2.55      1.44
                      P      N.S.       (+)         +        ++
             Between Chi                                   5.51
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N       13         4         4         2        23
                      NS       11         3         2         2        18

                      Wt   336.99    614.38     23.79     14.54    989.70
                 Het Chi    22.34      6.20      4.01      1.75     45.27
                 Het  df       12         3         3         1        22
                 Het  P         *      N.S.      N.S.      N.S.        **
               Fixed  RR     1.16      1.08      1.56      2.26      1.13
                     RRl     1.04      1.00      1.05      1.35      1.06
                     RRu     1.29      1.17      2.33      3.77      1.20
                      P        ++       (+)         +        ++       +++
              Random  RR     1.16      1.31      1.57      2.26      1.25
                     RRl     0.98      0.87      0.93      1.15      1.09
                     RRu     1.37      1.99      2.64      4.45      1.44
                      P       (+)      N.S.       (+)         +        ++
             Between Chi                                            10.97
             Between  df                                                3
             Between  P                                                 *
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        9         6        15
                      NS        7         6        13

                      Wt   774.16     88.27    862.43
                 Het Chi     9.18     12.67     21.88
                 Het  df        8         5        14
                 Het  P      N.S.         *       (*)
               Fixed  RR     1.10      1.08      1.10
                     RRl     1.02      0.87      1.03
                     RRu     1.18      1.33      1.17
                      P        ++      N.S.        ++
              Random  RR     1.13      1.10      1.14
                     RRl     1.01      0.79      0.99
                     RRu     1.26      1.55      1.30
                      P         +      N.S.       (+)
             Between Chi                         0.03
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N                  6         8         9        23
                      NS                  5         7         6        18

                      Wt              36.64     94.30    858.77    989.70
                 Het Chi               8.64     17.95     16.68     45.27
                 Het  df                  5         7         8        22
                 Het  P                N.S.         *         *        **
               Fixed  RR               1.39      1.18      1.11      1.13
                     RRl               1.01      0.96      1.04      1.06
                     RRu               1.93      1.44      1.19      1.20
                      P                   +      N.S.        ++       +++
              Random  RR               1.40      1.25      1.21      1.25
                     RRl               0.89      0.89      1.04      1.09
                     RRu               2.19      1.76      1.41      1.44
                      P                N.S.      N.S.         +        ++
             Between Chi                                             2.00
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N                  6         8         9        23
                      NS                  5         7         6        18

                      Wt              36.64     94.30    858.77    989.70
                 Het Chi               8.64     17.95     16.68     45.27
                 Het  df                  5         7         8        22
                 Het  P                N.S.         *         *        **
               Fixed  RR               1.39      1.18      1.11      1.13
                     RRl               1.01      0.96      1.04      1.06
                     RRu               1.93      1.44      1.19      1.20
                      P                   +      N.S.        ++       +++
              Random  RR               1.40      1.25      1.21      1.25
                     RRl               0.89      0.89      1.04      1.09
                     RRu               2.19      1.76      1.41      1.44
                      P                N.S.      N.S.         +        ++
             Between Chi                                             2.00
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       22         1        23
                      NS       17         1        18

                      Wt   982.36      7.34    989.70
                 Het Chi    44.37      0.00     45.27
                 Het  df       21         0        22
                 Het  P        **      N.S.        **
               Fixed  RR     1.12      1.60      1.13
                     RRl     1.06      0.78      1.06
                     RRu     1.20      3.30      1.20
                      P       +++      N.S.       +++
              Random  RR     1.25      1.60      1.25
                     RRl     1.08      0.78      1.09
                     RRu     1.43      3.30      1.44
                      P        ++      N.S.        ++
             Between Chi                         0.90
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 23                  23
                      NS                 18                  18

                      Wt             989.70              989.70
                 Het Chi              45.27               45.27
                 Het  df                 22                  22
                 Het  P                  **                  **
               Fixed  RR               1.13                1.13
                     RRl               1.06                1.06
                     RRu               1.20                1.20
                      P                 +++                 +++
              Random  RR               1.25                1.25
                     RRl               1.09                1.09
                     RRu               1.44                1.44
                      P                  ++                  ++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3        20                            23
                      NS        2        16                            18

                      Wt    66.36    923.34                        989.70
                 Het Chi     4.65     39.97                         45.27
                 Het  df        2        19                            22
                 Het  P       (*)        **                            **
               Fixed  RR     1.24      1.12                          1.13
                     RRl     0.98      1.05                          1.06
                     RRu     1.58      1.19                          1.20
                      P       (+)       +++                           +++
              Random  RR     1.42      1.24                          1.25
                     RRl     0.91      1.06                          1.09
                     RRu     2.22      1.44                          1.44
                      P      N.S.        ++                            ++
             Between Chi                                             0.65
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3        20        23
                      NS        2        16        18

                      Wt    66.36    923.34    989.70
                 Het Chi     4.65     39.97     45.27
                 Het  df        2        19        22
                 Het  P       (*)        **        **
               Fixed  RR     1.24      1.12      1.13
                     RRl     0.98      1.05      1.06
                     RRu     1.58      1.19      1.20
                      P       (+)       +++       +++
              Random  RR     1.42      1.24      1.25
                     RRl     0.91      1.06      1.09
                     RRu     2.22      1.44      1.44
                      P      N.S.        ++        ++
             Between Chi                         0.65
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                        Number of adjustment variables
                                0         1        2+     Total

                       N       11         7         5        23
                      NS       10         4         4        18

                      Wt   709.85    131.50    148.35    989.70
                 Het Chi    27.30      6.59      8.11     45.27
                 Het  df       10         6         4        22
                 Het  P        **      N.S.       (*)        **
               Fixed  RR     1.09      1.28      1.18      1.13
                     RRl     1.01      1.08      1.01      1.06
                     RRu     1.17      1.52      1.39      1.20
                      P         +        ++         +       +++
              Random  RR     1.26      1.29      1.28      1.25
                     RRl     0.99      1.04      0.97      1.09
                     RRu     1.60      1.61      1.68      1.44
                      P       (+)         +       (+)        ++
             Between Chi                                   3.28
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  16     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  ANDER1  25     f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  DEMARC   9 x   b   20   44       Multi  1991  2004    CS  Prev      COPD:LF   0 Current       Cigs   Nev any   1  14
  FERRI2  58     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  FERRI2  72     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  JOHANN   4     b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
     KIM   8     m   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs  Nev cigs   1  10
     KIM  13     f   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs  Nev cigs   1  10
  KOJIMA   7     m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1  19
  KOJIMA  12     f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1  19
    LIAW  18     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs   1  19
  MENEZ2   7     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ3   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ4   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ5   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ6   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  PEREZP   2     f   40   99 Am:Sth/Cent  1992  1996    CC  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1  10
    SHIN   6 x   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   0   9
    XIAO   4     b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs   0  19
      XU   5 x   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs   0  14
      XU  15 x   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs   0  14
  ZIELI1   3 x   b    0   99     Eu:East  1999  2001    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  ZIELI2   7     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 16  m   1          3       -       2       -      2.31 (  0.37-  14.37)
 ANDER1 25  f   1          4       -      16       -      0.66 (  0.20-   2.18)
 Subtotal ANDER1                                          0.96 (  0.35-   2.61)
 DEMARC 9   b   0         77    3000     156    6176      1.02 (  0.77-   1.34)
 FERRI2 58  m   1         20       -      11       -      2.71 (  1.19-   6.16)
 FERRI2 72  f   1         24       -      54       -      1.43 (  0.85-   2.40)
 Subtotal FERRI2                                          1.72 (  1.11-   2.66)
 JOHANN 4   b   0         26     515      22     842      1.93 (  1.08-   3.45)
 KIM    8   m   1         17       -      23       -      1.04 (  0.53-   2.06)
 KIM    13  f   1          1       -      61       -      0.47 (  0.08-   2.69)
 Subtotal KIM                                             0.94 (  0.50-   1.77)
 KOJIMA 7   m   0         20     880      19    1871      2.24 (  1.19-   4.21)
 KOJIMA 12  f   0          2     159      20    3545      2.23 (  0.52-   9.62)
 Subtotal KOJIMA                                          2.24 (  1.25-   4.00)
*LIAW   18  b   2          -       -       -       -      1.60 (  0.80-   3.40)
 MENEZ2 7   b   0         27       -      52       -      1.09 (  0.66-   1.79)
 MENEZ3 4   b   0         48       -      62       -      0.72 (  0.48-   1.08)
 MENEZ4 4   b   0         18       -      34       -      1.05 (  0.58-   1.89)
 MENEZ5 4   b   0         16       -      58       -      0.72 (  0.40-   1.31)
 MENEZ6 4   b   0         34       -      36       -      1.68 (  1.03-   2.74)
 PEREZP 2   f   0         12      39      45     145      0.99 (  0.48-   2.05)
 SHIN   6   b   0          9     108      49     730      1.24 (  0.59-   2.60)
 XIAO   4   b   0         30      25      21      56      3.20 (  1.54-   6.64)
 XU     5   m   0        139    2675     450    5584      0.64 (  0.53-   0.78)
 XU     15  f   0         21     141     647   13773      3.17 (  1.99-   5.05)
 Subtotal XU                                              0.82 (  0.68-   0.98)
 ZIELI1 3   b   0        206    1105     316    1884      1.11 (  0.92-   1.34)
 ZIELI2 7   b   0       1486    9875    1262    8933      1.07 (  0.98-   1.15)
Partial Totals          2240   18522    3416   43539
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 16  m   1              0.84     1.15     0.69       0.37
 ANDER1 25  f   1             -0.42     2.69     0.62       0.50
 Subtotal ANDER1              -0.04     3.84     1.30
 DEMARC 9   b   0              0.02    50.27     0.11       0.91
 FERRI2 58  m   1              1.00     5.68     4.96       0.02
 FERRI2 72  f   1              0.36    14.26     1.24       0.18
 Subtotal FERRI2               0.54    19.95     6.20
 JOHANN 4   b   0              0.66    11.49     4.08       0.03
 KIM    8   m   1              0.04     8.34     0.00       0.91
 KIM    13  f   1             -0.76     1.24     0.83       0.40
 Subtotal KIM                 -0.06     9.58     0.84
 KOJIMA 7   m   0              0.81     9.59     5.29       0.01
 KOJIMA 12  f   0              0.80     1.80     0.98       0.28
 Subtotal KOJIMA               0.81    11.38     6.27
*LIAW   18  b   2              0.47     7.34     1.22       0.20
 MENEZ2 7   b   0              0.09    15.44     0.01       0.73
 MENEZ3 4   b   0             -0.33    23.37     3.58       0.11
 MENEZ4 4   b   0              0.05    11.01     0.00       0.87
 MENEZ5 4   b   0             -0.33    10.92     1.67       0.28
 MENEZ6 4   b   0              0.52    16.05     3.33       0.04
 PEREZP 2   f   0             -0.01     7.24     0.04       0.98
 SHIN   6   b   0              0.22     7.03     0.17       0.57
 XIAO   4   b   0              1.16     7.20     8.72       0.00
 XU     5   m   0             -0.44   100.31    25.26       0.00
 XU     15  f   0              1.15    17.75    21.13       0.00
 Subtotal XU                  -0.20   118.06    46.39
 ZIELI1 3   b   0              0.11   105.77     0.19       0.28
 ZIELI2 7   b   0              0.06   595.75     0.00       0.12

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       23
                      NS       18

                      Wt  1031.69
                 Het Chi    84.11
                 Het  df       22
                 Het  P       ***
               Fixed  RR     1.07
                     RRl     1.00
                     RRu     1.13
                      P         +
              Random  RR     1.25
                     RRl     1.04
                     RRu     1.49
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       23
                      NS       18

                      Wt  1031.69
                 Het Chi    84.11
                 Het  df       22
                 Het  P       ***
               Fixed  RR     1.07
                     RRl     1.00
                     RRu     1.13
                      P         +
              Random  RR     1.25
                     RRl     1.04
                     RRu     1.49
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N       12         5         6        23
                      NS       12         5         6        23

                      Wt   861.64    125.06     44.99   1031.69
                 Het Chi    22.81     25.12     14.00     84.11
                 Het  df       11         4         5        22
                 Het  P         *       ***         *       ***
               Fixed  RR     1.08      0.79      1.74      1.07
                     RRl     1.01      0.66      1.30      1.00
                     RRu     1.16      0.94      2.33      1.13
                      P         +        --       +++         +
              Random  RR     1.14      1.42      1.41      1.25
                     RRl     0.98      0.70      0.80      1.04
                     RRu     1.33      2.90      2.49      1.49
                      P       (+)      N.S.      N.S.         +
             Between Chi                                  22.17
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         3         9         7        23
                      NS        2         3         6         7        18

                      Wt    23.79    713.01    160.60    134.29   1031.69
                 Het Chi     4.01      4.09     62.73      8.17     84.11
                 Het  df        3         2         8         6        22
                 Het  P      N.S.      N.S.       ***      N.S.       ***
               Fixed  RR     1.56      1.08      0.99      1.00      1.07
                     RRl     1.05      1.01      0.85      0.84      1.00
                     RRu     2.33      1.16      1.16      1.18      1.13
                      P         +         +      N.S.      N.S.         +
              Random  RR     1.57      1.13      1.53      1.00      1.25
                     RRl     0.93      0.96      0.86      0.81      1.04
                     RRu     2.64      1.33      2.69      1.23      1.49
                      P       (+)      N.S.      N.S.      N.S.         +
             Between Chi                                             5.11
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         1        20        23
                      NS        2         1        15        18

                      Wt    14.45      7.34   1009.91   1031.69
                 Het Chi     4.96      0.00     74.03     84.11
                 Het  df        1         0        19        22
                 Het  P         *      N.S.       ***       ***
               Fixed  RR     1.78      1.60      1.05      1.07
                     RRl     1.06      0.78      0.99      1.00
                     RRu     2.98      3.30      1.12      1.13
                      P         +      N.S.       (+)         +
              Random  RR     1.78      1.60      1.20      1.25
                     RRl     0.56      0.78      1.00      1.04
                     RRu     5.61      3.30      1.44      1.49
                      P      N.S.      N.S.       (+)         +
             Between Chi                                   5.12
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1        15         7        23
                      NS        1        13         4        18

                      Wt     7.34    875.30    149.05   1031.69
                 Het Chi     0.00     20.15     61.30     84.11
                 Het  df        0        14         6        22
                 Het  P      N.S.      N.S.       ***       ***
               Fixed  RR     1.60      1.08      0.97      1.07
                     RRl     0.78      1.01      0.83      1.00
                     RRu     3.30      1.15      1.14      1.13
                      P      N.S.         +      N.S.         +
              Random  RR     1.60      1.10      1.66      1.25
                     RRl     0.78      0.97      0.83      1.04
                     RRu     3.30      1.25      3.36      1.49
                      P      N.S.      N.S.      N.S.         +
             Between Chi                                   2.66
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 23                  23
                      NS                 18                  18

                      Wt            1031.69             1031.69
                 Het Chi              84.11               84.11
                 Het  df                 22                  22
                 Het  P                 ***                 ***
               Fixed  RR               1.07                1.07
                     RRl               1.00                1.00
                     RRu               1.13                1.13
                      P                   +                   +
              Random  RR               1.25                1.25
                     RRl               1.04                1.04
                     RRu               1.49                1.49
                      P                   +                   +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3        20                            23
                      NS        2        16                            18

                      Wt    70.22    961.48                       1031.69
                 Het Chi     5.58     77.75                         84.11
                 Het  df        2        19                            22
                 Het  P       (*)       ***                           ***
               Fixed  RR     1.18      1.06                          1.07
                     RRl     0.93      0.99                          1.00
                     RRu     1.49      1.13                          1.13
                      P      N.S.       (+)                             +
              Random  RR     1.40      1.23                          1.25
                     RRl     0.86      1.01                          1.04
                     RRu     2.28      1.49                          1.49
                      P      N.S.         +                             +
             Between Chi                                             0.78
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3        20        23
                      NS        2        16        18

                      Wt    70.22    961.48   1031.69
                 Het Chi     5.58     77.75     84.11
                 Het  df        2        19        22
                 Het  P       (*)       ***       ***
               Fixed  RR     1.18      1.06      1.07
                     RRl     0.93      0.99      1.00
                     RRu     1.49      1.13      1.13
                      P      N.S.       (+)         +
              Random  RR     1.40      1.23      1.25
                     RRl     0.86      1.01      1.04
                     RRu     2.28      1.49      1.49
                      P      N.S.         +         +
             Between Chi                         0.78
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      FUKUCH MANNI2 SPEIZE
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 1 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 5
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  DEMARC DEMARC     1         DEMARC/URRUTI/DEMEER
  JOHANN JOHANN     1         HARDIE/JOHANN/BROGGE
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
    LIAW    WEN     2                     WEN/LIAW
  MENEZ3 MENEZ3     1                 AMIGO/MENEZ3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 2 -

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 1) = 20
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  18   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  17  24
  ANDER1  26   f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   9  24
  FERRI2  60   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
  FERRI2  74   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
  KOJIMA   8   m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  39
  KOJIMA  13   f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  39
    LIAW  19   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  20  40
    XIAO   5   b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs  20  40
      XU  11   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs  14  25
      XU  21   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs  14  25
  ZIELI2   9   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  29

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 18  m   1          6       -       2       -      6.61 (  1.22-  35.67)
 ANDER1 26  f   1          5       -      16       -      1.40 (  0.46-   4.21)
 Subtotal ANDER1                                          2.23 (  0.88-   5.64)
 FERRI2 60  m   1         32       -      11       -      4.68 (  2.15-  10.19)
 FERRI2 74  f   1         20       -      54       -      3.35 (  1.84-   6.10)
 Subtotal FERRI2                                          3.79 (  2.36-   6.10)
 KOJIMA 8   m   0         43    1642      19    1871      2.58 (  1.50-   4.44)
 KOJIMA 13  f   0          2      32      20    3545     11.08 (  2.49-  49.38)
 Subtotal KOJIMA                                          3.06 (  1.83-   5.10)
*LIAW   19  b   2          -       -       -       -      2.00 (  1.00-   4.10)
 XIAO   5   b   0         32      12      21      56      7.11 (  3.10-  16.34)
 XU     11  m   13       171       -     450       -      1.24 (  1.00-   1.54)
 XU     21  f   13        13       -     647       -      2.75 (  1.38-   5.48)
 Subtotal XU                                              1.33 (  1.08-   1.64)
 ZIELI2 9   b   0       4412   18809    1262    8933      1.66 (  1.55-   1.78)
Partial Totals          4736   20495    2502   14405
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 18  m   1              1.89     1.35     2.52       0.03
 ANDER1 26  f   1              0.34     3.13     0.11       0.55
 Subtotal ANDER1               0.80     4.48     2.63
 FERRI2 60  m   1              1.54     6.35     6.63       0.00
 FERRI2 74  f   1              1.21    10.70     5.06       0.00
 Subtotal FERRI2               1.33    17.04    11.69
 KOJIMA 8   m   0              0.95    12.98     2.36       0.00
 KOJIMA 13  f   0              2.40     1.72     6.10       0.00
 Subtotal KOJIMA               1.12    14.70     8.46
*LIAW   19  b   2              0.69     7.72     0.23       0.05
 XIAO   5   b   0              1.96     5.55    11.52       0.00
 XU     11  m   13             0.22    82.42     7.72       0.05
 XU     21  f   13             1.01     8.08     1.94       0.00
 Subtotal XU                   0.29    90.50     9.66
 ZIELI2 9   b   0              0.51   844.48     0.17       0.00

                       N       11
                      NS        7

                      Wt   984.48
                 Het Chi    44.36
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.68
                     RRl     1.58
                     RRu     1.79
                      P       +++
              Random  RR     2.53
                     RRl     1.87
                     RRu     3.43
                      P       +++
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       11
                      NS        7

                      Wt   984.48
                 Het Chi    44.36
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.68
                     RRl     1.58
                     RRu     1.79
                      P       +++
              Random  RR     2.53
                     RRl     1.87
                     RRu     3.43
                      P       +++
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N        3         4         4        11
                      NS        3         4         4        11

                      Wt   857.75    103.10     23.63    984.48
                 Het Chi    11.91     17.98      4.94     44.36
                 Het  df        2         3         3        10
                 Het  P        **       ***      N.S.       ***
               Fixed  RR     1.68      1.51      3.04      1.68
                     RRl     1.57      1.24      2.03      1.58
                     RRu     1.80      1.83      4.55      1.79
                      P       +++       +++       +++       +++
              Random  RR     2.64      2.64      3.07      2.53
                     RRl     1.22      1.25      1.75      1.87
                     RRu     5.73      5.58      5.38      3.43
                      P         +         +       +++       +++
             Between Chi                                   9.53
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         1         6                  11
                      NS        2         1         4                   7

                      Wt    21.53    844.48    118.47              984.48
                 Het Chi     3.71      0.00     29.79               44.36
                 Het  df        3         0         5                  10
                 Het  P      N.S.      N.S.       ***                 ***
               Fixed  RR     3.40      1.66      1.64                1.68
                     RRl     2.23      1.55      1.37                1.58
                     RRu     5.18      1.78      1.96                1.79
                      P       +++       +++       +++                 +++
              Random  RR     3.37      1.66      2.86                2.53
                     RRl     2.05      1.55      1.57                1.87
                     RRu     5.54      1.78      5.24                3.43
                      P       +++       +++       +++                 +++
             Between Chi                                            10.86
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N        5         2         7
                      NS        3         1         4

                      Wt   876.23      4.48    880.71
                 Het Chi    20.19      2.27     22.79
                 Het  df        4         1         6
                 Het  P       ***      N.S.       ***
               Fixed  RR     1.70      2.23      1.71
                     RRl     1.60      0.88      1.60
                     RRu     1.82      5.64      1.82
                      P       +++       (+)       +++
              Random  RR     3.05      2.65      2.92
                     RRl     1.78      0.59      1.81
                     RRu     5.24     11.87      4.70
                      P       +++      N.S.       +++
             Between Chi                         0.33
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        4                   1                   5         1        11
                      NS        2                   1                   3         1         7

                      Wt    21.53                7.72              949.68      5.55    984.48
                 Het Chi     3.71                0.00               17.66      0.00     44.36
                 Het  df        3                   0                   4         0        10
                 Het  P      N.S.                N.S.                  **      N.S.       ***
               Fixed  RR     3.40                2.00                1.64      7.11      1.68
                     RRl     2.23                0.99                1.54      3.10      1.58
                     RRu     5.18                4.05                1.75     16.34      1.79
                      P       +++                 (+)                 +++       +++       +++
              Random  RR     3.37                2.00                1.88      7.11      2.53
                     RRl     2.05                0.99                1.38      3.10      1.87
                     RRu     5.54                4.05                2.58     16.34      3.43
                      P       +++                 (+)                 +++       +++       +++
             Between Chi                                                                22.99
             Between  df                                                                    3
             Between  P                                                                   ***
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        4                   1         6        11
                      NS        2                   1         4         7

                      Wt    21.53                7.72    955.24    984.48
                 Het Chi     3.71                0.00     29.53     44.36
                 Het  df        3                   0         5        10
                 Het  P      N.S.                N.S.       ***       ***
               Fixed  RR     3.40                2.00      1.66      1.68
                     RRl     2.23                0.99      1.55      1.58
                     RRu     5.18                4.05      1.76      1.79
                      P       +++                 (+)       +++       +++
              Random  RR     3.37                2.00      2.30      2.53
                     RRl     2.05                0.99      1.60      1.87
                     RRu     5.54                4.05      3.30      3.43
                      P       +++                 (+)       +++       +++
             Between Chi                                            11.12
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        1         1         9        11
                      NS        1         1         5         7

                      Wt     5.55      7.72    971.21    984.48
                 Het Chi     0.00      0.00     32.52     44.36
                 Het  df        0         0         8        10
                 Het  P      N.S.      N.S.       ***       ***
               Fixed  RR     7.11      2.00      1.67      1.68
                     RRl     3.10      0.99      1.57      1.58
                     RRu    16.34      4.05      1.78      1.79
                      P       +++       (+)       +++       +++
              Random  RR     7.11      2.00      2.31      2.53
                     RRl     3.10      0.99      1.70      1.87
                     RRu    16.34      4.05      3.13      3.43
                      P       +++       (+)       +++       +++
             Between Chi                                  11.84
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        2         8         1                  11
                      NS        2         4         1                   7

                      Wt   850.04    126.73      7.72              984.48
                 Het Chi    11.67     32.39      0.00               44.36
                 Het  df        1         7         0                  10
                 Het  P       ***       ***      N.S.                 ***
               Fixed  RR     1.68      1.72      2.00                1.68
                     RRl     1.57      1.44      0.99                1.58
                     RRu     1.79      2.05      4.05                1.79
                      P       +++       +++       (+)                 +++
              Random  RR     3.23      2.84      2.00                2.53
                     RRl     0.78      1.70      0.99                1.87
                     RRu    13.37      4.75      4.05                3.43
                      P      N.S.       +++       (+)                 +++
             Between Chi                                             0.30
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N                  4         2         5                  11
                      NS                  2         1         4                   7

                      Wt              19.18     17.04    948.25              984.48
                 Het Chi               5.84      0.45     20.98               44.36
                 Het  df                  3         1         4                  10
                 Het  P                N.S.      N.S.       ***                 ***
               Fixed  RR               2.84      3.79      1.64                1.68
                     RRl               1.82      2.36      1.54                1.58
                     RRu               4.45      6.10      1.75                1.79
                      P                 +++       +++       +++                 +++
              Random  RR               3.30      3.79      1.97                2.53
                     RRl               1.52      2.36      1.40                1.87
                     RRu               7.14      6.10      2.76                3.43
                      P                  ++       +++       +++                 +++
             Between Chi                                                      17.10
             Between  df                                                          2
             Between  P                                                         ***
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N                 11        11
                      NS                  7         7

                      Wt             984.48    984.48
                 Het Chi              44.36     44.36
                 Het  df                 10        10
                 Het  P                 ***       ***
               Fixed  RR               1.68      1.68
                     RRl               1.58      1.58
                     RRu               1.79      1.79
                      P                 +++       +++
              Random  RR               2.53      2.53
                     RRl               1.87      1.87
                     RRu               3.43      3.43
                      P                 +++       +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1         3         7        11
                      NS        1         2         4         7

                      Wt     7.72    859.18    117.58    984.48
                 Het Chi     0.00      8.62     35.48     44.36
                 Het  df        0         2         6        10
                 Het  P      N.S.         *       ***       ***
               Fixed  RR     2.00      1.68      1.71      1.68
                     RRl     0.99      1.57      1.43      1.58
                     RRu     4.05      1.79      2.05      1.79
                      P       (+)       +++       +++       +++
              Random  RR     2.00      2.54      3.00      2.53
                     RRl     0.99      1.32      1.62      1.87
                     RRu     4.05      4.92      5.55      3.43
                      P       (+)        ++       +++       +++
             Between Chi                                   0.27
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N        2         3         4         2        11
                      NS        1         2         2         2         7

                      Wt    90.50    859.18     21.53     13.27    984.48
                 Het Chi     4.67      8.62      3.71      5.20     44.36
                 Het  df        1         2         3         1        10
                 Het  P         *         *      N.S.         *       ***
               Fixed  RR     1.33      1.68      3.40      3.40      1.68
                     RRl     1.08      1.57      2.23      1.99      1.58
                     RRu     1.64      1.79      5.18      5.82      1.79
                      P        ++       +++       +++       +++       +++
              Random  RR     1.72      2.54      3.37      3.70      2.53
                     RRl     0.80      1.32      2.05      1.07      1.87
                     RRu     3.71      4.92      5.54     12.81      3.43
                      P      N.S.        ++       +++         +       +++
             Between Chi                                            22.17
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        3                   3
                      NS        2                   2

                      Wt   859.18              859.18
                 Het Chi     8.62                8.62
                 Het  df        2                   2
                 Het  P         *                   *
               Fixed  RR     1.68                1.68
                     RRl     1.57                1.57
                     RRu     1.79                1.79
                      P       +++                 +++
              Random  RR     2.54                2.54
                     RRl     1.32                1.32
                     RRu     4.92                4.92
                      P        ++                  ++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N                  4         2         5        11
                      NS                  3         1         3         7

                      Wt              17.76     14.70    952.02    984.48
                 Het Chi               8.06      3.23     21.13     44.36
                 Het  df                  3         1         4        10
                 Het  P                   *       (*)       ***       ***
               Fixed  RR               3.06      3.06      1.65      1.68
                     RRl               1.92      1.83      1.55      1.58
                     RRu               4.87      5.10      1.76      1.79
                      P                 +++       +++       +++       +++
              Random  RR               3.19      4.50      2.05      2.53
                     RRl               1.40      1.12      1.48      1.87
                     RRu               7.26     18.01      2.85      3.43
                      P                  ++         +       +++       +++
             Between Chi                                            11.95
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N                  4         2         5        11
                      NS                  3         1         3         7

                      Wt              17.76     14.70    952.02    984.48
                 Het Chi               8.06      3.23     21.13     44.36
                 Het  df                  3         1         4        10
                 Het  P                   *       (*)       ***       ***
               Fixed  RR               3.06      3.06      1.65      1.68
                     RRl               1.92      1.83      1.55      1.58
                     RRu               4.87      5.10      1.76      1.79
                      P                 +++       +++       +++       +++
              Random  RR               3.19      4.50      2.05      2.53
                     RRl               1.40      1.12      1.48      1.87
                     RRu               7.26     18.01      2.85      3.43
                      P                  ++         +       +++       +++
             Between Chi                                            11.95
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       10         1        11
                      NS        6         1         7

                      Wt   976.76      7.72    984.48
                 Het Chi    44.13      0.00     44.36
                 Het  df        9         0        10
                 Het  P       ***      N.S.       ***
               Fixed  RR     1.68      2.00      1.68
                     RRl     1.58      0.99      1.58
                     RRu     1.79      4.05      1.79
                      P       +++       (+)       +++
              Random  RR     2.62      2.00      2.53
                     RRl     1.89      0.99      1.87
                     RRu     3.62      4.05      3.43
                      P       +++       (+)       +++
             Between Chi                         0.23
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 11                  11
                      NS                  7                   7

                      Wt             984.48              984.48
                 Het Chi              44.36               44.36
                 Het  df                 10                  10
                 Het  P                 ***                 ***
               Fixed  RR               1.68                1.68
                     RRl               1.58                1.58
                     RRu               1.79                1.79
                      P                 +++                 +++
              Random  RR               2.53                2.53
                     RRl               1.87                1.87
                     RRu               3.43                3.43
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2         9                            11
                      NS        1         6                             7

                      Wt    17.04    967.44                        984.48
                 Het Chi     0.45     32.48                         44.36
                 Het  df        1         8                            10
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.79      1.66                          1.68
                     RRl     2.36      1.56                          1.58
                     RRu     6.10      1.77                          1.79
                      P       +++       +++                           +++
              Random  RR     3.79      2.24                          2.53
                     RRl     2.36      1.64                          1.87
                     RRu     6.10      3.07                          3.43
                      P       +++       +++                           +++
             Between Chi                                            11.44
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2         9        11
                      NS        1         6         7

                      Wt    17.04    967.44    984.48
                 Het Chi     0.45     32.48     44.36
                 Het  df        1         8        10
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.79      1.66      1.68
                     RRl     2.36      1.56      1.58
                     RRu     6.10      1.77      1.79
                      P       +++       +++       +++
              Random  RR     3.79      2.24      2.53
                     RRl     2.36      1.64      1.87
                     RRu     6.10      3.07      3.43
                      P       +++       +++       +++
             Between Chi                        11.44
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

                        Number of adjustment variables
                                0         1        2+     Total

                       N        4         4         3        11
                      NS        3         2         2         7

                      Wt   864.74     21.53     98.22    984.48
                 Het Chi    20.13      3.71      5.85     44.36
                 Het  df        3         3         2        10
                 Het  P       ***      N.S.       (*)       ***
               Fixed  RR     1.69      3.40      1.37      1.68
                     RRl     1.58      2.23      1.13      1.58
                     RRu     1.81      5.18      1.68      1.79
                      P       +++       +++        ++       +++
              Random  RR     3.48      3.37      1.74      2.53
                     RRl     1.65      2.05      1.04      1.87
                     RRu     7.34      5.54      2.93      3.43
                      P        ++       +++         +       +++
             Between Chi                                  14.68
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  18     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  17  24
  ANDER1  26     f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   9  24
  FERRI2  60     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
  FERRI2  74     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
  KOJIMA   8     m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  39
  KOJIMA  13     f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  39
    LIAW  19     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  20  40
    XIAO   5     b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs  20  40
      XU   6 x   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs  14  25
      XU  16 x   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs  14  25
  ZIELI2   9     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  29

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 18  m   1          6       -       2       -      6.61 (  1.22-  35.67)
 ANDER1 26  f   1          5       -      16       -      1.40 (  0.46-   4.21)
 Subtotal ANDER1                                          2.23 (  0.88-   5.64)
 FERRI2 60  m   1         32       -      11       -      4.68 (  2.15-  10.19)
 FERRI2 74  f   1         20       -      54       -      3.35 (  1.84-   6.10)
 Subtotal FERRI2                                          3.79 (  2.36-   6.10)
 KOJIMA 8   m   0         43    1642      19    1871      2.58 (  1.50-   4.44)
 KOJIMA 13  f   0          2      32      20    3545     11.08 (  2.49-  49.38)
 Subtotal KOJIMA                                          3.06 (  1.83-   5.10)
*LIAW   19  b   2          -       -       -       -      2.00 (  1.00-   4.10)
 XIAO   5   b   0         32      12      21      56      7.11 (  3.10-  16.34)
 XU     6   m   0        171    2636     450    5584      0.80 (  0.67-   0.97)
 XU     16  f   0         13      66     647   13773      4.19 (  2.30-   7.64)
 Subtotal XU                                              0.93 (  0.78-   1.10)
 ZIELI2 9   b   0       4412   18809    1262    8933      1.66 (  1.55-   1.78)
Partial Totals          4736   23197    2502   33762
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 18  m   1              1.89     1.35     2.72       0.03
 ANDER1 26  f   1              0.34     3.13     0.05       0.55
 Subtotal ANDER1               0.80     4.48     2.78
 FERRI2 60  m   1              1.54     6.35     7.34       0.00
 FERRI2 74  f   1              1.21    10.70     5.88       0.00
 Subtotal FERRI2               1.33    17.04    13.22
 KOJIMA 8   m   0              0.95    12.98     2.99       0.00
 KOJIMA 13  f   0              2.40     1.72     6.45       0.00
 Subtotal KOJIMA               1.12    14.70     9.44
*LIAW   19  b   2              0.69     7.72     0.39       0.05
 XIAO   5   b   0              1.96     5.55    12.39       0.00
 XU     6   m   0             -0.22   115.89    54.33       0.02
 XU     16  f   0              1.43    10.67     9.95       0.00
 Subtotal XU                  -0.08   126.57    64.28
 ZIELI2 9   b   0              0.51   844.48     1.30       0.00

                       N       11
                      NS        7

                      Wt  1020.55
                 Het Chi   103.81
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.60
                     RRl     1.50
                     RRu     1.70
                      P       +++
              Random  RR     2.70
                     RRl     1.81
                     RRu     4.01
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       11
                      NS        7

                      Wt  1020.55
                 Het Chi   103.81
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.60
                     RRl     1.50
                     RRu     1.70
                      P       +++
              Random  RR     2.70
                     RRl     1.81
                     RRu     4.01
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        3         4         4        11
                      NS        3         4         4        11

                      Wt   857.75    136.57     26.22   1020.55
                 Het Chi    11.91     37.03      5.27    103.81
                 Het  df        2         3         3        10
                 Het  P        **       ***      N.S.       ***
               Fixed  RR     1.68      1.00      3.58      1.60
                     RRl     1.57      0.84      2.44      1.50
                     RRu     1.80      1.18      5.24      1.70
                      P       +++      N.S.       +++       +++
              Random  RR     2.64      2.49      3.55      2.70
                     RRl     1.22      0.88      2.04      1.81
                     RRu     5.73      7.00      6.20      4.01
                      P         +       (+)       +++       +++
             Between Chi                                  49.60
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         1         6                  11
                      NS        2         1         4                   7

                      Wt    21.53    844.48    154.54             1020.55
                 Het Chi     3.71      0.00     70.69              103.81
                 Het  df        3         0         5                  10
                 Het  P      N.S.      N.S.       ***                 ***
               Fixed  RR     3.40      1.66      1.16                1.60
                     RRl     2.23      1.55      0.99                1.50
                     RRu     5.18      1.78      1.36                1.70
                      P       +++       +++       (+)                 +++
              Random  RR     3.37      1.66      3.04                2.70
                     RRl     2.05      1.55      1.28                1.81
                     RRu     5.54      1.78      7.19                4.01
                      P       +++       +++         +                 +++
             Between Chi                                            29.41
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        1         1         9        11
                      NS        1         1         5         7

                      Wt     5.55      7.72   1007.28   1020.55
                 Het Chi     0.00      0.00     90.92    103.81
                 Het  df        0         0         8        10
                 Het  P      N.S.      N.S.       ***       ***
               Fixed  RR     7.11      2.00      1.58      1.60
                     RRl     3.10      0.99      1.49      1.50
                     RRu    16.34      4.05      1.68      1.70
                      P       +++       (+)       +++       +++
              Random  RR     7.11      2.00      2.51      2.70
                     RRl     3.10      0.99      1.63      1.81
                     RRu    16.34      4.05      3.86      4.01
                      P       +++       (+)       +++       +++
             Between Chi                                  12.89
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1         3         7        11
                      NS        1         2         4         7

                      Wt     7.72    859.18    153.65   1020.55
                 Het Chi     0.00      8.62     79.79    103.81
                 Het  df        0         2         6        10
                 Het  P      N.S.         *       ***       ***
               Fixed  RR     2.00      1.68      1.20      1.60
                     RRl     0.99      1.57      1.02      1.50
                     RRu     4.05      1.79      1.40      1.70
                      P       (+)       +++         +       +++
              Random  RR     2.00      2.54      3.06      2.70
                     RRl     0.99      1.32      1.30      1.81
                     RRu     4.05      4.92      7.24      4.01
                      P       (+)        ++         +       +++
             Between Chi                                  15.40
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 11                  11
                      NS                  7                   7

                      Wt            1020.55             1020.55
                 Het Chi             103.81              103.81
                 Het  df                 10                  10
                 Het  P                 ***                 ***
               Fixed  RR               1.60                1.60
                     RRl               1.50                1.50
                     RRu               1.70                1.70
                      P                 +++                 +++
              Random  RR               2.70                2.70
                     RRl               1.81                1.81
                     RRu               4.01                4.01
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2         9                            11
                      NS        1         6                             7

                      Wt    17.04   1003.50                       1020.55
                 Het Chi     0.45     90.37                        103.81
                 Het  df        1         8                            10
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.79      1.57                          1.60
                     RRl     2.36      1.48                          1.50
                     RRu     6.10      1.67                          1.70
                      P       +++       +++                           +++
              Random  RR     3.79      2.46                          2.70
                     RRl     2.36      1.59                          1.81
                     RRu     6.10      3.81                          4.01
                      P       +++       +++                           +++
             Between Chi                                            12.99
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2         9        11
                      NS        1         6         7

                      Wt    17.04   1003.50   1020.55
                 Het Chi     0.45     90.37    103.81
                 Het  df        1         8        10
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.79      1.57      1.60
                     RRl     2.36      1.48      1.50
                     RRu     6.10      1.67      1.70
                      P       +++       +++       +++
              Random  RR     3.79      2.46      2.70
                     RRl     2.36      1.59      1.81
                     RRu     6.10      3.81      4.01
                      P       +++       +++       +++
             Between Chi                        12.99
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC FUKUCH JOHANN    KIM MANNI2 MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 PEREZP   SHIN SPEIZE ZIELI1
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 2 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
    LIAW    WEN     2                     WEN/LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 3 -

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
3) Categorical dose-response data for pack-years
4) vs never smoking base
5) Key value (scheme 1) = 45
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) SMKSTA  : current, ever
8) UNEXP   : never any, never cigarettes
9) PROD    : cigarettes, cigarettes only, any product
10) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  20   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  33   +
  ANDER1  27   f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  25   +
  FERRI2  62   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FERRI2  76   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FUKUCH   5   b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  25  49
  KOJIMA   9   m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
  KOJIMA  14   f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
    LIAW  20   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  41   +
  MANNI2   5   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any   Nev any  30  59
  SPEIZE  15   m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
  SPEIZE  20   f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
    XIAO   6   b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs  40   +
      XU  12   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs  26   +
      XU  22   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs  26   +
  ZIELI2  11   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 20  m   1          6       -       2       -      6.65 (  1.20-  36.88)
 ANDER1 27  f   1          3       -      16       -      3.10 (  0.79-  12.22)
 Subtotal ANDER1                                          4.17 (  1.43-  12.17)
 FERRI2 62  m   1        100       -      11       -      5.82 (  2.92-  11.59)
 FERRI2 76  f   1         12       -      54       -      5.53 (  2.45-  12.47)
 Subtotal FERRI2                                          5.70 (  3.37-   9.64)
 FUKUCH 5   b   0         88     405      64    1039      3.53 (  2.51-   4.97)
 KOJIMA 9   m   0         55     924      19    1871      5.86 (  3.46-   9.93)
 KOJIMA 14  f   0          1       7      20    3545     25.32 (  2.98- 215.41)
 Subtotal KOJIMA                                          6.37 (  3.82-  10.64)
*LIAW   20  b   2          -       -       -       -      1.80 (  0.90-   3.80)
 MANNI2 5   b   1        257       -     202       -      3.43 (  2.80-   4.20)
*SPEIZE 15  m   1         16       -       0       -     22.66 (  1.36- 377.73)
*SPEIZE 20  f   1          3       -       5       -      9.46 (  2.26-  39.59)
 Subtotal SPEIZE                                         11.32 (  3.16-  40.55)
 XIAO   6   b   0         17       7      21      56      6.48 (  2.35-  17.84)
 XU     12  m   13       286       -     450       -      1.43 (  1.17-   1.73)
 XU     22  f   13        17       -     647       -      3.11 (  1.71-   5.65)
 Subtotal XU                                              1.54 (  1.28-   1.86)
 ZIELI2 11  b   0       6784   14529    1262    8933      3.31 (  3.10-   3.53)
Partial Totals          7645   15872    2773   15444
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 20  m   1              1.89     1.31     0.74       0.03
 ANDER1 27  f   1              1.13     2.05     0.00       0.11
 Subtotal ANDER1               1.43     3.36     0.74
 FERRI2 62  m   1              1.76     8.09     3.08       0.00
 FERRI2 76  f   1              1.71     5.80     1.86       0.00
 Subtotal FERRI2               1.74    13.89     4.94
 FUKUCH 5   b   0              1.26    32.87     0.45       0.00
 KOJIMA 9   m   0              1.77    13.81     5.38       0.00
 KOJIMA 14  f   0              3.23     0.84     3.65       0.00
 Subtotal KOJIMA               1.85    14.64     9.03
*LIAW   20  b   2              0.59     7.41     2.29       0.11
 MANNI2 5   b   1              1.23    93.46     0.73       0.00
*SPEIZE 15  m   1              3.12     0.49     1.90       0.03
*SPEIZE 20  f   1              2.25     1.87     2.28       0.00
 Subtotal SPEIZE               2.43     2.36     4.18
 XIAO   6   b   0              1.87     3.74     1.96       0.00
 XU     12  m   13             0.36   100.45    62.13       0.00
 XU     22  f   13             1.13    10.76     0.00       0.00
 Subtotal XU                   0.43   111.21    62.13
 ZIELI2 11  b   0              1.20   892.40     2.35       0.00

                       N       15
                      NS       10

                      Wt  1175.35
                 Het Chi    88.80
                 Het  df       14
                 Het  P       ***
               Fixed  RR     3.14
                     RRl     2.97
                     RRu     3.32
                      P       +++
              Random  RR     3.69
                     RRl     2.79
                     RRu     4.86
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       15
                      NS       10

                      Wt  1175.35
                 Het Chi    88.80
                 Het  df       14
                 Het  P       ***
               Fixed  RR     3.14
                     RRl     2.97
                     RRu     3.32
                      P       +++
              Random  RR     3.69
                     RRl     2.79
                     RRu     4.86
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        5         5         5        15
                      NS        5         5         5        15

                      Wt  1029.89    124.13     21.32   1175.35
                 Het Chi     4.68     40.79      5.51     88.80
                 Het  df        4         4         4        14
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     3.32      1.88      4.35      3.14
                     RRl     3.12      1.58      2.85      2.97
                     RRu     3.53      2.25      6.66      3.32
                      P       +++       +++       +++       +++
              Random  RR     3.33      4.55      4.78      3.69
                     RRl     3.01      1.72      2.75      2.79
                     RRu     3.69     12.07      8.32      4.86
                      P       +++        ++       +++       +++
             Between Chi                                  37.81
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7         1         7                  15
                      NS        4         1         5                  10

                      Wt   113.07    892.40    169.87             1175.35
                 Het Chi     6.86      0.00     49.98               88.80
                 Het  df        6         0         6                  14
                 Het  P      N.S.      N.S.       ***                 ***
               Fixed  RR     3.76      3.31      2.12                3.14
                     RRl     3.13      3.10      1.83                2.97
                     RRu     4.53      3.53      2.47                3.32
                      P       +++       +++       +++                 +++
              Random  RR     4.21      3.31      3.42                3.69
                     RRl     3.15      3.10      1.95                2.79
                     RRu     5.63      3.53      6.00                4.86
                      P       +++       +++       +++                 +++
             Between Chi                                            31.97
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                               (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N        9         2        11
                      NS        6         1         7

                      Wt  1049.63      3.36   1052.99
                 Het Chi    15.64      0.47     16.26
                 Het  df        8         1        10
                 Het  P         *      N.S.       (*)
               Fixed  RR     3.39      4.17      3.39
                     RRl     3.19      1.43      3.19
                     RRu     3.60     12.17      3.60
                      P       +++        ++       +++
              Random  RR     3.96      4.17      3.90
                     RRl     3.26      1.43      3.27
                     RRu     4.79     12.17      4.65
                      P       +++        ++       +++
             Between Chi                         0.15
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        4         3         1                   6         1        15
                      NS        2         2         1                   4         1        10

                      Wt    17.25     95.82      7.41             1051.12      3.74   1175.35
                 Het Chi     0.74      3.58      0.00               73.61      0.00     88.80
                 Het  df        3         2         0                   5         0        14
                 Het  P      N.S.      N.S.      N.S.                 ***      N.S.       ***
               Fixed  RR     5.36      3.53      1.80                3.08      6.48      3.14
                     RRl     3.34      2.89      0.88                2.90      2.35      2.97
                     RRu     8.60      4.32      3.70                3.28     17.84      3.32
                      P       +++       +++      N.S.                 +++       +++       +++
              Random  RR     5.36      5.34      1.80                3.30      6.48      3.69
                     RRl     3.34      2.10      0.88                2.09      2.35      2.79
                     RRu     8.60     13.58      3.70                5.20     17.84      4.86
                      P       +++       +++      N.S.                 +++       +++       +++
             Between Chi                                                                10.87
             Between  df                                                                    4
             Between  P                                                                     *
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        4         2         1         8        15
                      NS        2         1         1         6        10

                      Wt    17.25      2.36      7.41   1148.33   1175.35
                 Het Chi     0.74      0.29      0.00     76.60     88.80
                 Het  df        3         1         0         7        14
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR     5.36     11.32      1.80      3.12      3.14
                     RRl     3.34      3.16      0.88      2.94      2.97
                     RRu     8.60     40.55      3.70      3.30      3.32
                      P       +++       +++      N.S.       +++       +++
              Random  RR     5.36     11.32      1.80      3.39      3.69
                     RRl     3.34      3.16      0.88      2.43      2.79
                     RRu     8.60     40.55      3.70      4.73      4.86
                      P       +++       +++      N.S.       +++       +++
             Between Chi                                            11.17
             Between  df                                                3
             Between  P                                                 *
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        1         3        11        15
                      NS        1         2         7        10

                      Wt     3.74      9.77   1161.84   1175.35
                 Het Chi     0.00      6.35     80.37     88.80
                 Het  df        0         2        10        14
                 Het  P      N.S.         *       ***       ***
               Fixed  RR     6.48      2.81      3.14      3.14
                     RRl     2.35      1.50      2.96      2.97
                     RRu    17.84      5.26      3.32      3.32
                      P       +++        ++       +++       +++
              Random  RR     6.48      5.17      3.59      3.69
                     RRl     2.35      1.14      2.66      2.79
                     RRu    17.84     23.45      4.85      4.86
                      P       +++         +       +++       +++
             Between Chi                                   2.09
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        2        11         2                  15
                      NS        2         6         2                  10

                      Wt   896.15    238.92     40.28             1175.35
                 Het Chi     1.69     72.02      2.74               88.80
                 Het  df        1        10         1                  14
                 Het  P      N.S.       ***       (*)                 ***
               Fixed  RR     3.31      2.57      3.12                3.14
                     RRl     3.10      2.26      2.29                2.97
                     RRu     3.54      2.91      4.24                3.32
                      P       +++       +++       +++                 +++
              Random  RR     3.80      4.40      2.72                3.69
                     RRl     2.23      2.74      1.43                2.79
                     RRu     6.47      7.07      5.17                4.86
                      P       +++       +++        ++                 +++
             Between Chi                                            12.36
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N                  5         2         8                  15
                      NS                  3         1         6                  10

                      Wt             111.47     13.89   1049.99             1175.35
                 Het Chi               7.06      0.01     72.62               88.80
                 Het  df                  4         1         7                  14
                 Het  P                N.S.      N.S.       ***                 ***
               Fixed  RR               3.74      5.70      3.06                3.14
                     RRl               3.11      3.37      2.88                2.97
                     RRu               4.51      9.64      3.25                3.32
                      P                 +++       +++       +++                 +++
              Random  RR               4.55      5.70      3.09                3.69
                     RRl               2.89      3.37      2.03                2.79
                     RRu               7.15      9.64      4.71                4.86
                      P                 +++       +++       +++                 +++
             Between Chi                                                       9.11
             Between  df                                                          2
             Between  P                                                           *
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N                 15        15
                      NS                 10        10

                      Wt            1175.35   1175.35
                 Het Chi              88.80     88.80
                 Het  df                 14        14
                 Het  P                 ***       ***
               Fixed  RR               3.14      3.14
                     RRl               2.97      2.97
                     RRu               3.32      3.32
                      P                 +++       +++
              Random  RR               3.69      3.69
                     RRl               2.79      2.79
                     RRu               4.86      4.86
                      P                 +++       +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         7        15
                      NS        2         4         4        10

                      Wt     9.77   1033.38    132.19   1175.35
                 Het Chi     6.35      8.05     35.65     88.80
                 Het  df        2         4         6        14
                 Het  P         *       (*)       ***       ***
               Fixed  RR     2.81      3.35      1.89      3.14
                     RRl     1.50      3.16      1.59      2.97
                     RRu     5.26      3.57      2.24      3.32
                      P        ++       +++       +++       +++
              Random  RR     5.17      3.60      3.79      3.69
                     RRl     1.14      3.03      1.98      2.79
                     RRu    23.45      4.27      7.24      4.86
                      P         +       +++       +++       +++
             Between Chi                                  38.75
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N        4         3         6         2        15
                      NS        3         2         3         2        10

                      Wt   237.54    907.05     19.61     11.15   1175.35
                 Het Chi    44.40      7.90      2.19      4.08     88.80
                 Het  df        3         2         5         1        14
                 Het  P       ***         *      N.S.         *       ***
               Fixed  RR     2.37      3.34      5.87      2.77      3.14
                     RRl     2.09      3.13      3.77      1.54      2.97
                     RRu     2.69      3.56      9.13      4.98      3.32
                      P       +++       +++       +++       +++       +++
              Random  RR     2.67      4.85      5.87      3.24      3.69
                     RRl     1.56      2.54      3.77      0.93      2.79
                     RRu     4.58      9.26      9.13     11.32      4.86
                      P       +++       +++       +++       (+)       +++
             Between Chi                                            30.22
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        5                   5
                      NS        4                   4

                      Wt  1033.38             1033.38
                 Het Chi     8.05                8.05
                 Het  df        4                   4
                 Het  P       (*)                 (*)
               Fixed  RR     3.35                3.35
                     RRl     3.16                3.16
                     RRu     3.57                3.57
                      P       +++                 +++
              Random  RR     3.60                3.60
                     RRl     3.03                3.03
                     RRu     4.27                4.27
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        2         4         2         7        15
                      NS        1         3         1         5        10

                      Wt     2.36     14.51     14.64   1143.83   1175.35
                 Het Chi     0.29      4.98      1.69     70.45     88.80
                 Het  df        1         3         1         6        14
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR    11.32      3.04      6.37      3.10      3.14
                     RRl     3.16      1.82      3.82      2.93      2.97
                     RRu    40.55      5.09     10.64      3.29      3.32
                      P       +++       +++       +++       +++       +++
              Random  RR    11.32      3.43      8.31      3.19      3.69
                     RRl     3.16      1.67      2.45      2.30      2.79
                     RRu    40.55      7.04     28.19      4.44      4.86
                      P       +++       +++       +++       +++       +++
             Between Chi                                            11.38
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        2         4         2         7        15
                      NS        1         3         1         5        10

                      Wt     2.36     14.51     14.64   1143.83   1175.35
                 Het Chi     0.29      4.98      1.69     70.45     88.80
                 Het  df        1         3         1         6        14
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR    11.32      3.04      6.37      3.10      3.14
                     RRl     3.16      1.82      3.82      2.93      2.97
                     RRu    40.55      5.09     10.64      3.29      3.32
                      P       +++       +++       +++       +++       +++
              Random  RR    11.32      3.43      8.31      3.19      3.69
                     RRl     3.16      1.67      2.45      2.30      2.79
                     RRu    40.55      7.04     28.19      4.44      4.86
                      P       +++       +++       +++       +++       +++
             Between Chi                                            11.38
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       12         3        15
                      NS        8         2        10

                      Wt  1165.58      9.77   1175.35
                 Het Chi    82.33      6.35     88.80
                 Het  df       11         2        14
                 Het  P       ***         *       ***
               Fixed  RR     3.14      2.81      3.14
                     RRl     2.97      1.50      2.97
                     RRu     3.33      5.26      3.32
                      P       +++        ++       +++
              Random  RR     3.70      5.17      3.69
                     RRl     2.77      1.14      2.79
                     RRu     4.96     23.45      4.86
                      P       +++         +       +++
             Between Chi                         0.12
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        14                  15
                      NS        1         9                  10

                      Wt    93.46   1081.88             1175.35
                 Het Chi     0.00     88.01               88.80
                 Het  df        0        13                  14
                 Het  P      N.S.       ***                 ***
               Fixed  RR     3.43      3.12                3.14
                     RRl     2.80      2.94                2.97
                     RRu     4.20      3.31                3.32
                      P       +++       +++                 +++
              Random  RR     3.43      3.86                3.69
                     RRl     2.80      2.76                2.79
                     RRu     4.20      5.39                4.86
                      P       +++       +++                 +++
             Between Chi                                   0.79
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3        12                            15
                      NS        2         8                            10

                      Wt   107.35   1067.99                       1175.35
                 Het Chi     3.12     82.87                         88.80
                 Het  df        2        11                            14
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.66      3.09                          3.14
                     RRl     3.03      2.91                          2.97
                     RRu     4.43      3.28                          3.32
                      P       +++       +++                           +++
              Random  RR     4.13      3.60                          3.69
                     RRl     2.87      2.49                          2.79
                     RRu     5.97      5.21                          4.86
                      P       +++       +++                           +++
             Between Chi                                             2.80
             Between  df                                                1
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3        12        15
                      NS        2         8        10

                      Wt   107.35   1067.99   1175.35
                 Het Chi     3.12     82.87     88.80
                 Het  df        2        11        14
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.66      3.09      3.14
                     RRl     3.03      2.91      2.97
                     RRu     4.43      3.28      3.32
                      P       +++       +++       +++
              Random  RR     4.13      3.60      3.69
                     RRl     2.87      2.49      2.79
                     RRu     5.97      5.21      4.86
                      P       +++       +++       +++
             Between Chi                         2.80
             Between  df                            1
             Between  P                           (*)
             Btwn(F)  P                          N.S.

                        Number of adjustment variables
                                0         1        2+     Total

                       N        5         7         3        15
                      NS        4         4         2        10

                      Wt   943.66    113.07    118.61   1175.35
                 Het Chi     9.62      6.86      6.03     88.80
                 Het  df        4         6         2        14
                 Het  P         *      N.S.         *       ***
               Fixed  RR     3.36      3.76      1.56      3.14
                     RRl     3.15      3.13      1.30      2.97
                     RRu     3.58      4.53      1.86      3.32
                      P       +++       +++       +++       +++
              Random  RR     4.12      4.21      1.89      3.69
                     RRl     3.03      3.15      1.16      2.79
                     RRu     5.61      5.63      3.10      4.86
                      P       +++       +++         +       +++
             Between Chi                                  66.28
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     ***

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  20     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  33   +
  ANDER1  27     f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  25   +
  FERRI2  62     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FERRI2  76     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FUKUCH   5     b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  25  49
  KOJIMA   9     m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
  KOJIMA  14     f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
    LIAW  20     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  41   +
  MANNI2   5     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any   Nev any  30  59
  SPEIZE  15     m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
  SPEIZE  20     f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
    XIAO   6     b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs  40   +
      XU   7 x   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs  26   +
      XU  17 x   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs  26   +
  ZIELI2  11     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 20  m   1          6       -       2       -      6.65 (  1.20-  36.88)
 ANDER1 27  f   1          3       -      16       -      3.10 (  0.79-  12.22)
 Subtotal ANDER1                                          4.17 (  1.43-  12.17)
 FERRI2 62  m   1        100       -      11       -      5.82 (  2.92-  11.59)
 FERRI2 76  f   1         12       -      54       -      5.53 (  2.45-  12.47)
 Subtotal FERRI2                                          5.70 (  3.37-   9.64)
 FUKUCH 5   b   0         88     405      64    1039      3.53 (  2.51-   4.97)
 KOJIMA 9   m   0         55     924      19    1871      5.86 (  3.46-   9.93)
 KOJIMA 14  f   0          1       7      20    3545     25.32 (  2.98- 215.41)
 Subtotal KOJIMA                                          6.37 (  3.82-  10.64)
*LIAW   20  b   2          -       -       -       -      1.80 (  0.90-   3.80)
 MANNI2 5   b   1        257       -     202       -      3.43 (  2.80-   4.20)
*SPEIZE 15  m   1         16       -       0       -     22.66 (  1.36- 377.73)
*SPEIZE 20  f   1          3       -       5       -      9.46 (  2.26-  39.59)
 Subtotal SPEIZE                                         11.32 (  3.16-  40.55)
 XIAO   6   b   0         17       7      21      56      6.48 (  2.35-  17.84)
 XU     7   m   0        286    2634     450    5584      1.35 (  1.15-   1.57)
 XU     17  f   0         17      66     647   13773      5.48 (  3.20-   9.40)
 Subtotal XU                                              1.50 (  1.29-   1.74)
 ZIELI2 11  b   0       6784   14529    1262    8933      3.31 (  3.10-   3.53)
Partial Totals          7645   18572    2773   34801
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 20  m   1              1.89     1.31     0.82       0.03
 ANDER1 27  f   1              1.13     2.05     0.00       0.11
 Subtotal ANDER1               1.43     3.36     0.82
 FERRI2 62  m   1              1.76     8.09     3.48       0.00
 FERRI2 76  f   1              1.71     5.80     2.12       0.00
 Subtotal FERRI2               1.74    13.89     5.61
 FUKUCH 5   b   0              1.26    32.87     0.79       0.00
 KOJIMA 9   m   0              1.77    13.81     6.07       0.00
 KOJIMA 14  f   0              3.23     0.84     3.79       0.00
 Subtotal KOJIMA               1.85    14.64     9.86
*LIAW   20  b   2              0.59     7.41     1.98       0.11
 MANNI2 5   b   1              1.23    93.46     1.52       0.00
*SPEIZE 15  m   1              3.12     0.49     1.97       0.03
*SPEIZE 20  f   1              2.25     1.87     2.44       0.00
 Subtotal SPEIZE               2.43     2.36     4.42
 XIAO   6   b   0              1.87     3.74     2.18       0.00
 XU     7   m   0              0.30   159.30   103.73       0.00
 XU     17  f   0              1.70    13.23     4.71       0.00
 Subtotal XU                   0.41   172.53   108.44
 ZIELI2 11  b   0              1.20   892.40     7.29       0.00

                       N       15
                      NS       10

                      Wt  1236.67
                 Het Chi   142.91
                 Het  df       14
                 Het  P       ***
               Fixed  RR     3.02
                     RRl     2.86
                     RRu     3.19
                      P       +++
              Random  RR     3.97
                     RRl     2.89
                     RRu     5.45
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       15
                      NS       10

                      Wt  1236.67
                 Het Chi   142.91
                 Het  df       14
                 Het  P       ***
               Fixed  RR     3.02
                     RRl     2.86
                     RRu     3.19
                      P       +++
              Random  RR     3.97
                     RRl     2.89
                     RRu     5.45
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        5         5         5        15
                      NS        5         5         5        15

                      Wt  1029.89    182.99     23.79   1236.67
                 Het Chi     4.68     47.44      3.13    142.91
                 Het  df        4         4         4        14
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     3.32      1.64      5.76      3.02
                     RRl     3.12      1.42      3.86      2.86
                     RRu     3.53      1.89      8.61      3.19
                      P       +++       +++       +++       +++
              Random  RR     3.33      4.54      5.76      3.97
                     RRl     3.01      1.63      3.86      2.89
                     RRu     3.69     12.63      8.61      5.45
                      P       +++        ++       +++       +++
             Between Chi                                  87.66
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7         1         7                  15
                      NS        4         1         5                  10

                      Wt   113.07    892.40    231.20             1236.67
                 Het Chi     6.86      0.00     75.05              142.91
                 Het  df        6         0         6                  14
                 Het  P      N.S.      N.S.       ***                 ***
               Fixed  RR     3.76      3.31      1.91                3.02
                     RRl     3.13      3.10      1.68                2.86
                     RRu     4.53      3.53      2.18                3.19
                      P       +++       +++       +++                 +++
              Random  RR     4.21      3.31      3.81                3.97
                     RRl     3.15      3.10      2.00                2.89
                     RRu     5.63      3.53      7.25                5.45
                      P       +++       +++       +++                 +++
             Between Chi                                            61.00
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        1         3        11        15
                      NS        1         2         7        10

                      Wt     3.74      9.77   1223.16   1236.67
                 Het Chi     0.00      6.35    134.33    142.91
                 Het  df        0         2        10        14
                 Het  P      N.S.         *       ***       ***
               Fixed  RR     6.48      2.81      3.01      3.02
                     RRl     2.35      1.50      2.85      2.86
                     RRu    17.84      5.26      3.19      3.19
                      P       +++        ++       +++       +++
              Random  RR     6.48      5.17      3.88      3.97
                     RRl     2.35      1.14      2.74      2.89
                     RRu    17.84     23.45      5.50      5.45
                      P       +++         +       +++       +++
             Between Chi                                   2.24
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         7        15
                      NS        2         4         4        10

                      Wt     9.77   1033.38    193.52   1236.67
                 Het Chi     6.35      8.05     56.89    142.91
                 Het  df        2         4         6        14
                 Het  P         *       (*)       ***       ***
               Fixed  RR     2.81      3.35      1.73      3.02
                     RRl     1.50      3.16      1.50      2.86
                     RRu     5.26      3.57      1.99      3.19
                      P        ++       +++       +++       +++
              Random  RR     5.17      3.60      4.20      3.97
                     RRl     1.14      3.03      1.96      2.89
                     RRu    23.45      4.27      9.01      5.45
                      P         +       +++       +++       +++
             Between Chi                                  71.62
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        14                  15
                      NS        1         9                  10

                      Wt    93.46   1143.20             1236.67
                 Het Chi     0.00    141.27              142.91
                 Het  df        0        13                  14
                 Het  P      N.S.       ***                 ***
               Fixed  RR     3.43      2.99                3.02
                     RRl     2.80      2.82                2.86
                     RRu     4.20      3.17                3.19
                      P       +++       +++                 +++
              Random  RR     3.43      4.16                3.97
                     RRl     2.80      2.87                2.89
                     RRu     4.20      6.03                5.45
                      P       +++       +++                 +++
             Between Chi                                   1.64
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3        12                            15
                      NS        2         8                            10

                      Wt   107.35   1129.32                       1236.67
                 Het Chi     3.12    135.40                        142.91
                 Het  df        2        11                            14
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.66      2.96                          3.02
                     RRl     3.03      2.80                          2.86
                     RRu     4.43      3.14                          3.19
                      P       +++       +++                           +++
              Random  RR     4.13      3.93                          3.97
                     RRl     2.87      2.61                          2.89
                     RRu     5.97      5.91                          5.45
                      P       +++       +++                           +++
             Between Chi                                             4.38
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3        12        15
                      NS        2         8        10

                      Wt   107.35   1129.32   1236.67
                 Het Chi     3.12    135.40    142.91
                 Het  df        2        11        14
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.66      2.96      3.02
                     RRl     3.03      2.80      2.86
                     RRu     4.43      3.14      3.19
                      P       +++       +++       +++
              Random  RR     4.13      3.93      3.97
                     RRl     2.87      2.61      2.89
                     RRu     5.97      5.91      5.45
                      P       +++       +++       +++
             Between Chi                         4.38
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC JOHANN    KIM MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 PEREZP   SHIN ZIELI1
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 3 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (1) 45
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
  MANNI2 MANNI2     1                MANNI2/MANNI3
    LIAW    WEN     2                     WEN/LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 4 -

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 2) = 1
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  16   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  ANDER1  25   f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  FERRI2  58   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  FERRI2  72   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  JOHANN   4   b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ2   7   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ3   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ4   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ5   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ6   4   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
    SHIN  11   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   3    Ever       Cigs  Nev cigs   0   9
  ZIELI1   6   b    0   99     Eu:East  1999  2001    CS  Prev      COPD:LF   1    Ever       Cigs  Nev cigs   1   9
  ZIELI2   7   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 16  m   1          3       -       2       -      2.31 (  0.37-  14.37)
 ANDER1 25  f   1          4       -      16       -      0.66 (  0.20-   2.18)
 Subtotal ANDER1                                          0.96 (  0.35-   2.61)
 FERRI2 58  m   1         20       -      11       -      2.71 (  1.19-   6.16)
 FERRI2 72  f   1         24       -      54       -      1.43 (  0.85-   2.40)
 Subtotal FERRI2                                          1.72 (  1.11-   2.66)
 JOHANN 4   b   0         26     515      22     842      1.93 (  1.08-   3.45)
 MENEZ2 7   b   0         27       -      52       -      1.09 (  0.66-   1.79)
 MENEZ3 4   b   0         48       -      62       -      0.72 (  0.48-   1.08)
 MENEZ4 4   b   0         18       -      34       -      1.05 (  0.58-   1.89)
 MENEZ5 4   b   0         16       -      58       -      0.72 (  0.40-   1.31)
 MENEZ6 4   b   0         34       -      36       -      1.68 (  1.03-   2.74)
 SHIN   11  b   3          9       -      49       -      1.10 (  0.50-   2.60)
 ZIELI1 6   b   1        206       -     316       -      1.26 (  1.03-   1.53)
 ZIELI2 7   b   0       1486    9875    1262    8933      1.07 (  0.98-   1.15)
Partial Totals          1921   10390    1974    9775
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 16  m   1              0.84     1.15     0.63       0.37
 ANDER1 25  f   1             -0.42     2.69     0.70       0.50
 Subtotal ANDER1              -0.04     3.84     1.34
 FERRI2 58  m   1              1.00     5.68     4.61       0.02
 FERRI2 72  f   1              0.36    14.26     0.98       0.18
 Subtotal FERRI2               0.54    19.95     5.59
 JOHANN 4   b   0              0.66    11.49     3.64       0.03
 MENEZ2 7   b   0              0.09    15.44     0.00       0.73
 MENEZ3 4   b   0             -0.33    23.37     4.21       0.11
 MENEZ4 4   b   0              0.05    11.01     0.02       0.87
 MENEZ5 4   b   0             -0.33    10.92     1.97       0.28
 MENEZ6 4   b   0              0.52    16.05     2.87       0.04
 SHIN   11  b   3              0.10     5.65     0.00       0.82
 ZIELI1 6   b   1              0.23    98.13     1.79       0.02
 ZIELI2 7   b   0              0.06   595.75     0.64       0.12

                       N       13
                      NS       11

                      Wt   811.59
                 Het Chi    22.07
                 Het  df       12
                 Het  P         *
               Fixed  RR     1.10
                     RRl     1.03
                     RRu     1.18
                      P        ++
              Random  RR     1.17
                     RRl     0.99
                     RRu     1.37
                      P       (+)
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       13
                      NS       11

                      Wt   811.59
                 Het Chi    22.07
                 Het  df       12
                 Het  P         *
               Fixed  RR     1.10
                     RRl     1.03
                     RRu     1.18
                      P        ++
              Random  RR     1.17
                     RRl     0.99
                     RRu     1.37
                      P       (+)
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        9         2         2        13
                      NS        9         2         2        13

                      Wt   787.81      6.83     16.95    811.59
                 Het Chi    15.06      0.02      1.35     22.07
                 Het  df        8         1         1        12
                 Het  P       (*)      N.S.      N.S.         *
               Fixed  RR     1.09      2.64      1.26      1.10
                     RRl     1.02      1.25      0.79      1.03
                     RRu     1.17      5.58      2.04      1.18
                      P         +         +      N.S.        ++
              Random  RR     1.12      2.64      1.18      1.17
                     RRl     0.95      1.25      0.61      0.99
                     RRu     1.32      5.58      2.27      1.37
                      P      N.S.         +      N.S.       (+)
             Between Chi                                   5.63
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         3         1         5        13
                      NS        2         3         1         5        11

                      Wt    23.79    705.37      5.65     76.78    811.59
                 Het Chi     4.01      6.07      0.00      8.15     22.07
                 Het  df        3         2         0         4        12
                 Het  P      N.S.         *      N.S.       (*)         *
               Fixed  RR     1.56      1.10      1.10      0.99      1.10
                     RRl     1.05      1.02      0.48      0.79      1.03
                     RRu     2.33      1.19      2.51      1.23      1.18
                      P         +         +      N.S.      N.S.        ++
              Random  RR     1.57      1.21      1.10      1.00      1.17
                     RRl     0.93      0.98      0.48      0.72      0.99
                     RRu     2.64      1.50      2.51      1.38      1.37
                      P       (+)       (+)      N.S.      N.S.       (+)
             Between Chi                                             3.84
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                           13        13
                      NS                           11        11

                      Wt                       811.59    811.59
                 Het Chi                        22.07     22.07
                 Het  df                           12        12
                 Het  P                             *         *
               Fixed  RR                         1.10      1.10
                     RRl                         1.03      1.03
                     RRu                         1.18      1.18
                      P                            ++        ++
              Random  RR                         1.17      1.17
                     RRl                         0.99      0.99
                     RRu                         1.37      1.37
                      P                           (+)       (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  9         4        13
                      NS                  9         2        11

                      Wt             787.81     23.79    811.59
                 Het Chi              15.06      4.01     22.07
                 Het  df                  8         3        12
                 Het  P                 (*)      N.S.         *
               Fixed  RR               1.09      1.56      1.10
                     RRl               1.02      1.05      1.03
                     RRu               1.17      2.33      1.18
                      P                   +         +        ++
              Random  RR               1.12      1.57      1.17
                     RRl               0.95      0.93      0.99
                     RRu               1.32      2.64      1.37
                      P                N.S.       (+)       (+)
             Between Chi                                   3.00
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 13                  13
                      NS                 11                  11

                      Wt             811.59              811.59
                 Het Chi              22.07               22.07
                 Het  df                 12                  12
                 Het  P                   *                   *
               Fixed  RR               1.10                1.10
                     RRl               1.03                1.03
                     RRu               1.18                1.18
                      P                  ++                  ++
              Random  RR               1.17                1.17
                     RRl               0.99                0.99
                     RRu               1.37                1.37
                      P                 (+)                 (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2        11                            13
                      NS        1        10                            11

                      Wt    19.95    791.65                        811.59
                 Het Chi     1.66     16.38                         22.07
                 Het  df        1        10                            12
                 Het  P      N.S.       (*)                             *
               Fixed  RR     1.72      1.09                          1.10
                     RRl     1.11      1.02                          1.03
                     RRu     2.66      1.17                          1.18
                      P         +         +                            ++
              Random  RR     1.81      1.11                          1.17
                     RRl     0.99      0.95                          0.99
                     RRu     3.32      1.30                          1.37
                      P       (+)      N.S.                           (+)
             Between Chi                                             4.03
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2        11        13
                      NS        1        10        11

                      Wt    19.95    791.65    811.59
                 Het Chi     1.66     16.38     22.07
                 Het  df        1        10        12
                 Het  P      N.S.       (*)         *
               Fixed  RR     1.72      1.09      1.10
                     RRl     1.11      1.02      1.03
                     RRu     2.66      1.17      1.18
                      P         +         +        ++
              Random  RR     1.81      1.11      1.17
                     RRl     0.99      0.95      0.99
                     RRu     3.32      1.30      1.37
                      P       (+)      N.S.       (+)
             Between Chi                         4.03
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  16     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  ANDER1  25     f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   1   8
  FERRI2  58     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  FERRI2  72     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   0   8
  JOHANN   4     b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ2   7     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ3   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ4   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ5   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  MENEZ6   4     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
    SHIN   6 x   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   0   9
  ZIELI1   3 x   b    0   99     Eu:East  1999  2001    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9
  ZIELI2   7     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 16  m   1          3       -       2       -      2.31 (  0.37-  14.37)
 ANDER1 25  f   1          4       -      16       -      0.66 (  0.20-   2.18)
 Subtotal ANDER1                                          0.96 (  0.35-   2.61)
 FERRI2 58  m   1         20       -      11       -      2.71 (  1.19-   6.16)
 FERRI2 72  f   1         24       -      54       -      1.43 (  0.85-   2.40)
 Subtotal FERRI2                                          1.72 (  1.11-   2.66)
 JOHANN 4   b   0         26     515      22     842      1.93 (  1.08-   3.45)
 MENEZ2 7   b   0         27       -      52       -      1.09 (  0.66-   1.79)
 MENEZ3 4   b   0         48       -      62       -      0.72 (  0.48-   1.08)
 MENEZ4 4   b   0         18       -      34       -      1.05 (  0.58-   1.89)
 MENEZ5 4   b   0         16       -      58       -      0.72 (  0.40-   1.31)
 MENEZ6 4   b   0         34       -      36       -      1.68 (  1.03-   2.74)
 SHIN   6   b   0          9     108      49     730      1.24 (  0.59-   2.60)
 ZIELI1 3   b   0        206    1105     316    1884      1.11 (  0.92-   1.34)
 ZIELI2 7   b   0       1486    9875    1262    8933      1.07 (  0.98-   1.15)
Partial Totals          1921   11603    1974   12389
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 16  m   1              0.84     1.15     0.65       0.37
 ANDER1 25  f   1             -0.42     2.69     0.67       0.50
 Subtotal ANDER1              -0.04     3.84     1.32
 FERRI2 58  m   1              1.00     5.68     4.76       0.02
 FERRI2 72  f   1              0.36    14.26     1.08       0.18
 Subtotal FERRI2               0.54    19.95     5.84
 JOHANN 4   b   0              0.66    11.49     3.82       0.03
 MENEZ2 7   b   0              0.09    15.44     0.00       0.73
 MENEZ3 4   b   0             -0.33    23.37     3.94       0.11
 MENEZ4 4   b   0              0.05    11.01     0.01       0.87
 MENEZ5 4   b   0             -0.33    10.92     1.84       0.28
 MENEZ6 4   b   0              0.52    16.05     3.06       0.04
 SHIN   6   b   0              0.22     7.03     0.13       0.57
 ZIELI1 3   b   0              0.11   105.77     0.06       0.28
 ZIELI2 7   b   0              0.06   595.75     0.22       0.12

                       N       13
                      NS       11

                      Wt   820.61
                 Het Chi    20.23
                 Het  df       12
                 Het  P       (*)
               Fixed  RR     1.09
                     RRl     1.01
                     RRu     1.16
                      P         +
              Random  RR     1.14
                     RRl     0.98
                     RRu     1.33
                      P       (+)
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       13
                      NS       11

                      Wt   820.61
                 Het Chi    20.23
                 Het  df       12
                 Het  P       (*)
               Fixed  RR     1.09
                     RRl     1.01
                     RRu     1.16
                      P         +
              Random  RR     1.14
                     RRl     0.98
                     RRu     1.33
                      P       (+)
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        9         2         2        13
                      NS        9         2         2        13

                      Wt   796.83      6.83     16.95    820.61
                 Het Chi    12.98      0.02      1.35     20.23
                 Het  df        8         1         1        12
                 Het  P      N.S.      N.S.      N.S.       (*)
               Fixed  RR     1.07      2.64      1.26      1.09
                     RRl     1.00      1.25      0.79      1.01
                     RRu     1.15      5.58      2.04      1.16
                      P         +         +      N.S.         +
              Random  RR     1.09      2.64      1.18      1.14
                     RRl     0.94      1.25      0.61      0.98
                     RRu     1.26      5.58      2.27      1.33
                      P      N.S.         +      N.S.       (+)
             Between Chi                                   5.88
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        4         3         1         5        13
                      NS        2         3         1         5        11

                      Wt    23.79    713.01      7.03     76.78    820.61
                 Het Chi     4.01      4.09      0.00      8.15     20.23
                 Het  df        3         2         0         4        12
                 Het  P      N.S.      N.S.      N.S.       (*)       (*)
               Fixed  RR     1.56      1.08      1.24      0.99      1.09
                     RRl     1.05      1.01      0.59      0.79      1.01
                     RRu     2.33      1.16      2.60      1.23      1.16
                      P         +         +      N.S.      N.S.         +
              Random  RR     1.57      1.13      1.24      1.00      1.14
                     RRl     0.93      0.96      0.59      0.72      0.98
                     RRu     2.64      1.33      2.60      1.38      1.33
                      P       (+)      N.S.      N.S.      N.S.       (+)
             Between Chi                                             3.99
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                           13        13
                      NS                           11        11

                      Wt                       820.61    820.61
                 Het Chi                        20.23     20.23
                 Het  df                           12        12
                 Het  P                           (*)       (*)
               Fixed  RR                         1.09      1.09
                     RRl                         1.01      1.01
                     RRu                         1.16      1.16
                      P                             +         +
              Random  RR                         1.14      1.14
                     RRl                         0.98      0.98
                     RRu                         1.33      1.33
                      P                           (+)       (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  9         4        13
                      NS                  9         2        11

                      Wt             796.83     23.79    820.61
                 Het Chi              12.98      4.01     20.23
                 Het  df                  8         3        12
                 Het  P                N.S.      N.S.       (*)
               Fixed  RR               1.07      1.56      1.09
                     RRl               1.00      1.05      1.01
                     RRu               1.15      2.33      1.16
                      P                   +         +         +
              Random  RR               1.09      1.57      1.14
                     RRl               0.94      0.93      0.98
                     RRu               1.26      2.64      1.33
                      P                N.S.       (+)       (+)
             Between Chi                                   3.24
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 13                  13
                      NS                 11                  11

                      Wt             820.61              820.61
                 Het Chi              20.23               20.23
                 Het  df                 12                  12
                 Het  P                 (*)                 (*)
               Fixed  RR               1.09                1.09
                     RRl               1.01                1.01
                     RRu               1.16                1.16
                      P                   +                   +
              Random  RR               1.14                1.14
                     RRl               0.98                0.98
                     RRu               1.33                1.33
                      P                 (+)                 (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2        11                            13
                      NS        1        10                            11

                      Wt    19.95    800.67                        820.61
                 Het Chi     1.66     14.29                         20.23
                 Het  df        1        10                            12
                 Het  P      N.S.      N.S.                           (*)
               Fixed  RR     1.72      1.07                          1.09
                     RRl     1.11      1.00                          1.01
                     RRu     2.66      1.15                          1.16
                      P         +         +                             +
              Random  RR     1.81      1.09                          1.14
                     RRl     0.99      0.95                          0.98
                     RRu     3.32      1.25                          1.33
                      P       (+)      N.S.                           (+)
             Between Chi                                             4.28
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2        11        13
                      NS        1        10        11

                      Wt    19.95    800.67    820.61
                 Het Chi     1.66     14.29     20.23
                 Het  df        1        10        12
                 Het  P      N.S.      N.S.       (*)
               Fixed  RR     1.72      1.07      1.09
                     RRl     1.11      1.00      1.01
                     RRu     2.66      1.15      1.16
                      P         +         +         +
              Random  RR     1.81      1.09      1.14
                     RRl     0.99      0.95      0.98
                     RRu     3.32      1.25      1.33
                      P       (+)      N.S.       (+)
             Between Chi                         4.28
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC FUKUCH    KIM KOJIMA   LIAW MANNI2 PEREZP SPEIZE   XIAO     XU
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 4 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 1
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JOHANN JOHANN     1         HARDIE/JOHANN/BROGGE
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
  MENEZ3 MENEZ3     1                 AMIGO/MENEZ3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 5 -

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 2) = 10
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  17   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   9  16
  FERRI2  59   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   8  16
  FERRI2  73   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   8  16
  JOHANN   5   b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ2   8   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ3   5   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ4   5   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ5   5   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ6   5   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
    SHIN  12   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   3    Ever       Cigs  Nev cigs  10  19
  ZIELI2   8   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 17  m   1          7       -       2       -      4.19 (  0.80-  21.98)
 FERRI2 59  m   1         18       -      11       -      2.00 (  0.87-   4.58)
 FERRI2 73  f   1         24       -      54       -      2.30 (  1.34-   3.96)
 Subtotal FERRI2                                          2.21 (  1.40-   3.47)
 JOHANN 5   b   0         36     372      22     842      3.70 (  2.15-   6.38)
 MENEZ2 8   b   0         19       -      52       -      1.26 (  0.71-   2.24)
 MENEZ3 5   b   0         30       -      62       -      0.97 (  0.60-   1.56)
 MENEZ4 5   b   0         13       -      34       -      2.82 (  1.43-   5.56)
 MENEZ5 5   b   0         15       -      58       -      0.95 (  0.51-   1.77)
 MENEZ6 5   b   0         27       -      36       -      2.56 (  1.50-   4.34)
 SHIN   12  b   3         13       -      49       -      1.60 (  0.70-   3.50)
 ZIELI2 8   b   0       3346   17606    1262    8933      1.35 (  1.25-   1.44)
Partial Totals          3548   17978    1642    9775
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 17  m   1              1.43     1.40     1.70       0.09
 FERRI2 59  m   1              0.69     5.57     0.73       0.10
 FERRI2 73  f   1              0.83    13.09     3.30       0.00
 Subtotal FERRI2               0.79    18.66     4.04
 JOHANN 5   b   0              1.31    12.97    12.43       0.00
 MENEZ2 8   b   0              0.23    11.64     0.11       0.43
 MENEZ3 5   b   0             -0.03    16.83     2.19       0.90
 MENEZ4 5   b   0              1.04     8.33     4.16       0.00
 MENEZ5 5   b   0             -0.05     9.92     1.45       0.87
 MENEZ6 5   b   0              0.94    13.61     5.06       0.00
 SHIN   12  b   3              0.47     5.93     0.12       0.25
 ZIELI2 8   b   0              0.30   793.65     0.91       0.00

                       N       11
                      NS       10

                      Wt   892.95
                 Het Chi    32.16
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.39
                     RRl     1.30
                     RRu     1.49
                      P       +++
              Random  RR     1.77
                     RRl     1.34
                     RRu     2.33
                      P       +++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       11
                      NS       10

                      Wt   892.95
                 Het Chi    32.16
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.39
                     RRl     1.30
                     RRu     1.49
                      P       +++
              Random  RR     1.77
                     RRl     1.34
                     RRu     2.33
                      P       +++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N        8         2         1        11
                      NS        8         2         1        10

                      Wt   872.89      6.97     13.09    892.95
                 Het Chi    26.30      0.61      0.00     32.16
                 Het  df        7         1         0        10
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     1.38      2.32      2.30      1.39
                     RRl     1.29      1.10      1.34      1.30
                     RRu     1.47      4.87      3.95      1.49
                      P       +++         +        ++       +++
              Random  RR     1.65      2.32      2.30      1.77
                     RRl     1.21      1.10      1.34      1.34
                     RRu     2.26      4.87      3.95      2.33
                      P        ++         +        ++       +++
             Between Chi                                   5.24
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         2         1         5        11
                      NS        2         2         1         5        10

                      Wt    20.06    806.62      5.93     60.34    892.95
                 Het Chi     0.61     13.09      0.00     12.80     32.16
                 Het  df        2         1         0         4        10
                 Het  P      N.S.       ***      N.S.         *       ***
               Fixed  RR     2.31      1.37      1.60      1.47      1.39
                     RRl     1.49      1.28      0.72      1.14      1.30
                     RRu     3.57      1.47      3.58      1.89      1.49
                      P       +++       +++      N.S.        ++       +++
              Random  RR     2.31      2.15      1.60      1.51      1.77
                     RRl     1.49      0.80      0.72      0.96      1.34
                     RRu     3.57      5.79      3.58      2.38      2.33
                      P       +++      N.S.      N.S.       (+)       +++
             Between Chi                                             5.66
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                           11        11
                      NS                           10        10

                      Wt                       892.95    892.95
                 Het Chi                        32.16     32.16
                 Het  df                           10        10
                 Het  P                           ***       ***
               Fixed  RR                         1.39      1.39
                     RRl                         1.30      1.30
                     RRu                         1.49      1.49
                      P                           +++       +++
              Random  RR                         1.77      1.77
                     RRl                         1.34      1.34
                     RRu                         2.33      2.33
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  8         3        11
                      NS                  8         2        10

                      Wt             872.89     20.06    892.95
                 Het Chi              26.30      0.61     32.16
                 Het  df                  7         2        10
                 Het  P                 ***      N.S.       ***
               Fixed  RR               1.38      2.31      1.39
                     RRl               1.29      1.49      1.30
                     RRu               1.47      3.57      1.49
                      P                 +++       +++       +++
              Random  RR               1.65      2.31      1.77
                     RRl               1.21      1.49      1.34
                     RRu               2.26      3.57      2.33
                      P                  ++       +++       +++
             Between Chi                                   5.24
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 11                  11
                      NS                 10                  10

                      Wt             892.95              892.95
                 Het Chi              32.16               32.16
                 Het  df                 10                  10
                 Het  P                 ***                 ***
               Fixed  RR               1.39                1.39
                     RRl               1.30                1.30
                     RRu               1.49                1.49
                      P                 +++                 +++
              Random  RR               1.77                1.77
                     RRl               1.34                1.34
                     RRu               2.33                2.33
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2         9                            11
                      NS        1         9                            10

                      Wt    18.66    874.29                        892.95
                 Het Chi     0.08     28.04                         32.16
                 Het  df        1         8                            10
                 Het  P      N.S.       ***                           ***
               Fixed  RR     2.21      1.38                          1.39
                     RRl     1.40      1.29                          1.30
                     RRu     3.47      1.47                          1.49
                      P       +++       +++                           +++
              Random  RR     2.21      1.70                          1.77
                     RRl     1.40      1.25                          1.34
                     RRu     3.47      2.32                          2.33
                      P       +++       +++                           +++
             Between Chi                                             4.05
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2         9        11
                      NS        1         9        10

                      Wt    18.66    874.29    892.95
                 Het Chi     0.08     28.04     32.16
                 Het  df        1         8        10
                 Het  P      N.S.       ***       ***
               Fixed  RR     2.21      1.38      1.39
                     RRl     1.40      1.29      1.30
                     RRu     3.47      1.47      1.49
                      P       +++       +++       +++
              Random  RR     2.21      1.70      1.77
                     RRl     1.40      1.25      1.34
                     RRu     3.47      2.32      2.33
                      P       +++       +++       +++
             Between Chi                         4.05
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  17     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs   9  16
  FERRI2  59     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   8  16
  FERRI2  73     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any   8  16
  JOHANN   5     b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ2   8     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ3   5     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ4   5     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ5   5     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  MENEZ6   5     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
    SHIN   7 x   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19
  ZIELI2   8     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  10  19

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 17  m   1          7       -       2       -      4.19 (  0.80-  21.98)
 FERRI2 59  m   1         18       -      11       -      2.00 (  0.87-   4.58)
 FERRI2 73  f   1         24       -      54       -      2.30 (  1.34-   3.96)
 Subtotal FERRI2                                          2.21 (  1.40-   3.47)
 JOHANN 5   b   0         36     372      22     842      3.70 (  2.15-   6.38)
 MENEZ2 8   b   0         19       -      52       -      1.26 (  0.71-   2.24)
 MENEZ3 5   b   0         30       -      62       -      0.97 (  0.60-   1.56)
 MENEZ4 5   b   0         13       -      34       -      2.82 (  1.43-   5.56)
 MENEZ5 5   b   0         15       -      58       -      0.95 (  0.51-   1.77)
 MENEZ6 5   b   0         27       -      36       -      2.56 (  1.50-   4.34)
 SHIN   7   b   0         13      92      49     730      2.11 (  1.10-   4.03)
 ZIELI2 8   b   0       3346   17606    1262    8933      1.35 (  1.25-   1.44)
Partial Totals          3548   18070    1642   10505
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 17  m   1              1.43     1.40     1.69       0.09
 FERRI2 59  m   1              0.69     5.57     0.72       0.10
 FERRI2 73  f   1              0.83    13.09     3.26       0.00
 Subtotal FERRI2               0.79    18.66     3.98
 JOHANN 5   b   0              1.31    12.97    12.35       0.00
 MENEZ2 8   b   0              0.23    11.64     0.12       0.43
 MENEZ3 5   b   0             -0.03    16.83     2.23       0.90
 MENEZ4 5   b   0              1.04     8.33     4.12       0.00
 MENEZ5 5   b   0             -0.05     9.92     1.47       0.87
 MENEZ6 5   b   0              0.94    13.61     5.00       0.00
 SHIN   7   b   0              0.74     9.13     1.54       0.02
 ZIELI2 8   b   0              0.30   793.65     1.09       0.00

                       N       11
                      NS       10

                      Wt   896.14
                 Het Chi    33.60
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.40
                     RRl     1.31
                     RRu     1.49
                      P       +++
              Random  RR     1.81
                     RRl     1.37
                     RRu     2.38
                      P       +++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       11
                      NS       10

                      Wt   896.14
                 Het Chi    33.60
                 Het  df       10
                 Het  P       ***
               Fixed  RR     1.40
                     RRl     1.31
                     RRu     1.49
                      P       +++
              Random  RR     1.81
                     RRl     1.37
                     RRu     2.38
                      P       +++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N        8         2         1        11
                      NS        8         2         1        10

                      Wt   876.09      6.97     13.09    896.14
                 Het Chi    27.81      0.61      0.00     33.60
                 Het  df        7         1         0        10
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     1.38      2.32      2.30      1.40
                     RRl     1.29      1.10      1.34      1.31
                     RRu     1.47      4.87      3.95      1.49
                      P       +++         +        ++       +++
              Random  RR     1.70      2.32      2.30      1.81
                     RRl     1.24      1.10      1.34      1.37
                     RRu     2.33      4.87      3.95      2.38
                      P       +++         +        ++       +++
             Between Chi                                   5.18
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         2         1         5        11
                      NS        2         2         1         5        10

                      Wt    20.06    806.62      9.13     60.34    896.14
                 Het Chi     0.61     13.09      0.00     12.80     33.60
                 Het  df        2         1         0         4        10
                 Het  P      N.S.       ***      N.S.         *       ***
               Fixed  RR     2.31      1.37      2.11      1.47      1.40
                     RRl     1.49      1.28      1.10      1.14      1.31
                     RRu     3.57      1.47      4.03      1.89      1.49
                      P       +++       +++         +        ++       +++
              Random  RR     2.31      2.15      2.11      1.51      1.81
                     RRl     1.49      0.80      1.10      0.96      1.37
                     RRu     3.57      5.79      4.03      2.38      2.38
                      P       +++      N.S.         +       (+)       +++
             Between Chi                                             7.10
             Between  df                                                3
             Between  P                                               (*)
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                           11        11
                      NS                           10        10

                      Wt                       896.14    896.14
                 Het Chi                        33.60     33.60
                 Het  df                           10        10
                 Het  P                           ***       ***
               Fixed  RR                         1.40      1.40
                     RRl                         1.31      1.31
                     RRu                         1.49      1.49
                      P                           +++       +++
              Random  RR                         1.81      1.81
                     RRl                         1.37      1.37
                     RRu                         2.38      2.38
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  8         3        11
                      NS                  8         2        10

                      Wt             876.09     20.06    896.14
                 Het Chi              27.81      0.61     33.60
                 Het  df                  7         2        10
                 Het  P                 ***      N.S.       ***
               Fixed  RR               1.38      2.31      1.40
                     RRl               1.29      1.49      1.31
                     RRu               1.47      3.57      1.49
                      P                 +++       +++       +++
              Random  RR               1.70      2.31      1.81
                     RRl               1.24      1.49      1.37
                     RRu               2.33      3.57      2.38
                      P                 +++       +++       +++
             Between Chi                                   5.18
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                 11                  11
                      NS                 10                  10

                      Wt             896.14              896.14
                 Het Chi              33.60               33.60
                 Het  df                 10                  10
                 Het  P                 ***                 ***
               Fixed  RR               1.40                1.40
                     RRl               1.31                1.31
                     RRu               1.49                1.49
                      P                 +++                 +++
              Random  RR               1.81                1.81
                     RRl               1.37                1.37
                     RRu               2.38                2.38
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2         9                            11
                      NS        1         9                            10

                      Wt    18.66    877.49                        896.14
                 Het Chi     0.08     29.53                         33.60
                 Het  df        1         8                            10
                 Het  P      N.S.       ***                           ***
               Fixed  RR     2.21      1.38                          1.40
                     RRl     1.40      1.29                          1.31
                     RRu     3.47      1.48                          1.49
                      P       +++       +++                           +++
              Random  RR     2.21      1.75                          1.81
                     RRl     1.40      1.28                          1.37
                     RRu     3.47      2.39                          2.38
                      P       +++       +++                           +++
             Between Chi                                             3.99
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2         9        11
                      NS        1         9        10

                      Wt    18.66    877.49    896.14
                 Het Chi     0.08     29.53     33.60
                 Het  df        1         8        10
                 Het  P      N.S.       ***       ***
               Fixed  RR     2.21      1.38      1.40
                     RRl     1.40      1.29      1.31
                     RRu     3.47      1.48      1.49
                      P       +++       +++       +++
              Random  RR     2.21      1.75      1.81
                     RRl     1.40      1.28      1.37
                     RRu     3.47      2.39      2.38
                      P       +++       +++       +++
             Between Chi                         3.99
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC FUKUCH    KIM KOJIMA   LIAW MANNI2 PEREZP SPEIZE   XIAO     XU ZIELI1
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 5 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 10
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JOHANN JOHANN     1         HARDIE/JOHANN/BROGGE
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
  MENEZ3 MENEZ3     1                 AMIGO/MENEZ3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 6 -

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 2) = 20
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  18   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  17  24
  FERRI2  60   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
  FERRI2  74   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
      XU  11   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs  14  25
      XU  21   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs  Nev cigs  14  25
  ZIELI2   9   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  29

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 18  m   1          6       -       2       -      6.61 (  1.22-  35.67)
 FERRI2 60  m   1         32       -      11       -      4.68 (  2.15-  10.19)
 FERRI2 74  f   1         20       -      54       -      3.35 (  1.84-   6.10)
 Subtotal FERRI2                                          3.79 (  2.36-   6.10)
 XU     11  m   13       171       -     450       -      1.24 (  1.00-   1.54)
 XU     21  f   13        13       -     647       -      2.75 (  1.38-   5.48)
 Subtotal XU                                              1.33 (  1.08-   1.64)
 ZIELI2 9   b   0       4412   18809    1262    8933      1.66 (  1.55-   1.78)
Partial Totals          4654   18809    2426    8933
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 18  m   1              1.89     1.35     2.59       0.03
 FERRI2 60  m   1              1.54     6.35     6.87       0.00
 FERRI2 74  f   1              1.21    10.70     5.33       0.00
 Subtotal FERRI2               1.33    17.04    12.21
 XU     11  m   13             0.22    82.42     6.82       0.05
 XU     21  f   13             1.01     8.08     2.09       0.00
 Subtotal XU                   0.29    90.50     8.91
 ZIELI2 9   b   0              0.51   844.48     0.02       0.00

                       N        6
                      NS        4

                      Wt   953.37
                 Het Chi    23.72
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.65
                     RRl     1.55
                     RRu     1.76
                      P       +++
              Random  RR     2.15
                     RRl     1.55
                     RRu     3.00
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        6
                      NS        4

                      Wt   953.37
                 Het Chi    23.72
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.65
                     RRl     1.55
                     RRu     1.76
                      P       +++
              Random  RR     2.15
                     RRl     1.55
                     RRu     3.00
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         3         2         6
                      NS        1         3         2         6

                      Wt   844.48     90.11     18.78    953.37
                 Het Chi     0.00     13.71      0.18     23.72
                 Het  df        0         2         1         5
                 Het  P      N.S.        **      N.S.       ***
               Fixed  RR     1.66      1.40      3.08      1.65
                     RRl     1.55      1.14      1.96      1.55
                     RRu     1.78      1.72      4.84      1.76
                      P       +++        ++       +++       +++
              Random  RR     1.66      2.90      3.08      2.15
                     RRl     1.55      0.91      1.96      1.55
                     RRu     1.78      9.22      4.84      3.00
                      P       +++       (+)       +++       +++
             Between Chi                                   9.84
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         1         2                   6
                      NS        2         1         1                   4

                      Wt    18.39    844.48     90.50              953.37
                 Het Chi     0.83      0.00      4.67               23.72
                 Het  df        2         0         1                   5
                 Het  P      N.S.      N.S.         *                 ***
               Fixed  RR     3.95      1.66      1.33                1.65
                     RRl     2.50      1.55      1.08                1.55
                     RRu     6.24      1.78      1.64                1.76
                      P       +++       +++        ++                 +++
              Random  RR     3.95      1.66      1.72                2.15
                     RRl     2.50      1.55      0.80                1.55
                     RRu     6.24      1.78      3.71                3.00
                      P       +++       +++      N.S.                 +++
             Between Chi                                            18.23
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                            6         6
                      NS                            4         4

                      Wt                       953.37    953.37
                 Het Chi                        23.72     23.72
                 Het  df                            5         5
                 Het  P                           ***       ***
               Fixed  RR                         1.65      1.65
                     RRl                         1.55      1.55
                     RRu                         1.76      1.76
                      P                           +++       +++
              Random  RR                         2.15      2.15
                     RRl                         1.55      1.55
                     RRu                         3.00      3.00
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  1         5         6
                      NS                  1         3         4

                      Wt             844.48    108.89    953.37
                 Het Chi               0.00     23.59     23.72
                 Het  df                  0         4         5
                 Het  P                N.S.       ***       ***
               Fixed  RR               1.66      1.60      1.65
                     RRl               1.55      1.33      1.55
                     RRu               1.78      1.93      1.76
                      P                 +++       +++       +++
              Random  RR               1.66      2.83      2.15
                     RRl               1.55      1.44      1.55
                     RRu               1.78      5.57      3.00
                      P                 +++        ++       +++
             Between Chi                                   0.13
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  6                   6
                      NS                  4                   4

                      Wt             953.37              953.37
                 Het Chi              23.72               23.72
                 Het  df                  5                   5
                 Het  P                 ***                 ***
               Fixed  RR               1.65                1.65
                     RRl               1.55                1.55
                     RRu               1.76                1.76
                      P                 +++                 +++
              Random  RR               2.15                2.15
                     RRl               1.55                1.55
                     RRu               3.00                3.00
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2         4                             6
                      NS        1         3                             4

                      Wt    17.04    936.33                        953.37
                 Het Chi     0.45     11.30                         23.72
                 Het  df        1         3                             5
                 Het  P      N.S.         *                           ***
               Fixed  RR     3.79      1.63                          1.65
                     RRl     2.36      1.53                          1.55
                     RRu     6.10      1.74                          1.76
                      P       +++       +++                           +++
              Random  RR     3.79      1.66                          2.15
                     RRl     2.36      1.23                          1.55
                     RRu     6.10      2.24                          3.00
                      P       +++       +++                           +++
             Between Chi                                            11.97
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2         4         6
                      NS        1         3         4

                      Wt    17.04    936.33    953.37
                 Het Chi     0.45     11.30     23.72
                 Het  df        1         3         5
                 Het  P      N.S.         *       ***
               Fixed  RR     3.79      1.63      1.65
                     RRl     2.36      1.53      1.55
                     RRu     6.10      1.74      1.76
                      P       +++       +++       +++
              Random  RR     3.79      1.66      2.15
                     RRl     2.36      1.23      1.55
                     RRu     6.10      2.24      3.00
                      P       +++       +++       +++
             Between Chi                        11.97
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  18     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  17  24
  FERRI2  60     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
  FERRI2  74     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  16  24
      XU   6 x   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs  14  25
      XU  16 x   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs  Nev cigs  14  25
  ZIELI2   9     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  20  29

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 18  m   1          6       -       2       -      6.61 (  1.22-  35.67)
 FERRI2 60  m   1         32       -      11       -      4.68 (  2.15-  10.19)
 FERRI2 74  f   1         20       -      54       -      3.35 (  1.84-   6.10)
 Subtotal FERRI2                                          3.79 (  2.36-   6.10)
 XU     6   m   0        171    2636     450    5584      0.80 (  0.67-   0.97)
 XU     16  f   0         13      66     647   13773      4.19 (  2.30-   7.64)
 Subtotal XU                                              0.93 (  0.78-   1.10)
 ZIELI2 9   b   0       4412   18809    1262    8933      1.66 (  1.55-   1.78)
Partial Totals          4654   21511    2426   28290
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 18  m   1              1.89     1.35     2.80       0.03
 FERRI2 60  m   1              1.54     6.35     7.61       0.00
 FERRI2 74  f   1              1.21    10.70     6.19       0.00
 Subtotal FERRI2               1.33    17.04    13.80
 XU     6   m   0             -0.22   115.89    51.30       0.02
 XU     16  f   0              1.43    10.67    10.36       0.00
 Subtotal XU                  -0.08   126.57    61.65
 ZIELI2 9   b   0              0.51   844.48     2.91       0.00

                       N        6
                      NS        4

                      Wt   989.44
                 Het Chi    81.16
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.57
                     RRl     1.47
                     RRu     1.67
                      P       +++
              Random  RR     2.39
                     RRl     1.44
                     RRu     3.97
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        6
                      NS        4

                      Wt   989.44
                 Het Chi    81.16
                 Het  df        5
                 Het  P       ***
               Fixed  RR     1.57
                     RRl     1.47
                     RRu     1.67
                      P       +++
              Random  RR     2.39
                     RRl     1.44
                     RRu     3.97
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         3         2         6
                      NS        1         3         2         6

                      Wt   844.48    123.59     21.37    989.44
                 Het Chi     0.00     24.06      0.27     81.16
                 Het  df        0         2         1         5
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.66      0.90      3.75      1.57
                     RRl     1.55      0.76      2.45      1.47
                     RRu     1.78      1.08      5.73      1.67
                      P       +++      N.S.       +++       +++
              Random  RR     1.66      2.59      3.75      2.39
                     RRl     1.55      0.58      2.45      1.44
                     RRu     1.78     11.66      5.73      3.97
                      P       +++      N.S.       +++       +++
             Between Chi                                  56.83
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         1         2                   6
                      NS        2         1         1                   4

                      Wt    18.39    844.48    126.57              989.44
                 Het Chi     0.83      0.00     26.62               81.16
                 Het  df        2         0         1                   5
                 Het  P      N.S.      N.S.       ***                 ***
               Fixed  RR     3.95      1.66      0.93                1.57
                     RRl     2.50      1.55      0.78                1.47
                     RRu     6.24      1.78      1.10                1.67
                      P       +++       +++      N.S.                 +++
              Random  RR     3.95      1.66      1.79                2.39
                     RRl     2.50      1.55      0.36                1.44
                     RRu     6.24      1.78      9.02                3.97
                      P       +++       +++      N.S.                 +++
             Between Chi                                            53.71
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                            6         6
                      NS                            4         4

                      Wt                       989.44    989.44
                 Het Chi                        81.16     81.16
                 Het  df                            5         5
                 Het  P                           ***       ***
               Fixed  RR                         1.57      1.57
                     RRl                         1.47      1.47
                     RRu                         1.67      1.67
                      P                           +++       +++
              Random  RR                         2.39      2.39
                     RRl                         1.44      1.44
                     RRu                         3.97      3.97
                      P                           +++       +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  1         5         6
                      NS                  1         3         4

                      Wt             844.48    144.96    989.44
                 Het Chi               0.00     61.30     81.16
                 Het  df                  0         4         5
                 Het  P                N.S.       ***       ***
               Fixed  RR               1.66      1.11      1.57
                     RRl               1.55      0.95      1.47
                     RRu               1.78      1.31      1.67
                      P                 +++      N.S.       +++
              Random  RR               1.66      2.98      2.39
                     RRl               1.55      1.09      1.44
                     RRu               1.78      8.14      3.97
                      P                 +++         +       +++
             Between Chi                                  19.85
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  6                   6
                      NS                  4                   4

                      Wt             989.44              989.44
                 Het Chi              81.16               81.16
                 Het  df                  5                   5
                 Het  P                 ***                 ***
               Fixed  RR               1.57                1.57
                     RRl               1.47                1.47
                     RRu               1.67                1.67
                      P                 +++                 +++
              Random  RR               2.39                2.39
                     RRl               1.44                1.44
                     RRu               3.97                3.97
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        2         4                             6
                      NS        1         3                             4

                      Wt    17.04    972.40                        989.44
                 Het Chi     0.45     67.13                         81.16
                 Het  df        1         3                             5
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.79      1.54                          1.57
                     RRl     2.36      1.45                          1.47
                     RRu     6.10      1.64                          1.67
                      P       +++       +++                           +++
              Random  RR     3.79      1.88                          2.39
                     RRl     2.36      1.03                          1.44
                     RRu     6.10      3.45                          3.97
                      P       +++         +                           +++
             Between Chi                                            13.59
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        2         4         6
                      NS        1         3         4

                      Wt    17.04    972.40    989.44
                 Het Chi     0.45     67.13     81.16
                 Het  df        1         3         5
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.79      1.54      1.57
                     RRl     2.36      1.45      1.47
                     RRu     6.10      1.64      1.67
                      P       +++       +++       +++
              Random  RR     3.79      1.88      2.39
                     RRl     2.36      1.03      1.44
                     RRu     6.10      3.45      3.97
                      P       +++         +       +++
             Between Chi                        13.59
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC FUKUCH JOHANN    KIM KOJIMA   LIAW MANNI2 MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 PEREZP   SHIN SPEIZE   XIAO
       ZIELI1
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 6 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 7 -

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 2) = 30
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 1

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  19   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  25  32
  FERRI2  61   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  24  32
  FERRI2  75   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  24  32
  FUKUCH   5   b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  25  49
  MANNI2   5   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any   Nev any  30  59
  SPEIZE  14   m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  21  40
  SPEIZE  19   f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  21  40
  ZIELI2  10   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  30  39

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 2

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 19  m   1          6       -       2       -     11.85 (  2.12-  66.29)
 FERRI2 61  m   1         33       -      11       -      3.95 (  1.83-   8.51)
 FERRI2 75  f   1          6       -      54       -      2.12 (  0.81-   5.53)
 Subtotal FERRI2                                          3.10 (  1.70-   5.65)
 FUKUCH 5   b   0         88     405      64    1039      3.53 (  2.51-   4.97)
 MANNI2 5   b   1        257       -     202       -      3.43 (  2.80-   4.20)
*SPEIZE 14  m   1          7       -       0       -     10.62 (  0.61- 185.90)
*SPEIZE 19  f   1          8       -       5       -     12.62 (  4.13-  38.56)
 Subtotal SPEIZE                                         12.34 (  4.36-  34.91)
 ZIELI2 10  b   0       4232   14120    1262    8933      2.12 (  1.98-   2.27)
Partial Totals          4637   14525    1600    9972
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 19  m   1              2.47     1.30     3.50       0.00
 FERRI2 61  m   1              1.37     6.51     1.93       0.00
 FERRI2 75  f   1              0.75     4.16     0.02       0.13
 Subtotal FERRI2               1.13    10.67     1.96
 FUKUCH 5   b   0              1.26    32.87     6.13       0.00
 MANNI2 5   b   1              1.23    93.46    15.24       0.00
*SPEIZE 14  m   1              2.36     0.47     1.11       0.11
*SPEIZE 19  f   1              2.54     3.08     8.97       0.00
 Subtotal SPEIZE               2.51     3.55    10.07
 ZIELI2 10  b   0              0.75   825.45     4.85       0.00

                       N        8
                      NS        6

                      Wt   967.31
                 Het Chi    41.75
                 Het  df        7
                 Het  P       ***
               Fixed  RR     2.29
                     RRl     2.15
                     RRu     2.44
                      P       +++
              Random  RR     3.50
                     RRl     2.44
                     RRu     5.01
                      P       +++
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        8
                      NS        6

                      Wt   967.31
                 Het Chi    41.75
                 Het  df        7
                 Het  P       ***
               Fixed  RR     2.29
                     RRl     2.15
                     RRu     2.44
                      P       +++
              Random  RR     3.50
                     RRl     2.44
                     RRu     5.01
                      P       +++
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N        3         3         2         8
                      NS        3         3         2         8

                      Wt   951.79      8.27      7.24    967.31
                 Het Chi    26.08      1.59      5.63     41.75
                 Het  df        2         2         1         7
                 Het  P       ***      N.S.         *       ***
               Fixed  RR     2.26      4.96      4.53      2.29
                     RRl     2.12      2.51      2.18      2.15
                     RRu     2.41      9.81      9.37      2.44
                      P       +++       +++       +++       +++
              Random  RR     2.90      4.96      5.05      3.50
                     RRl     1.96      2.51      0.88      2.44
                     RRu     4.28      9.81     29.00      5.01
                      P       +++       +++       (+)       +++
             Between Chi                                   8.44
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        6         1         1                   8
                      NS        4         1         1                   6

                      Wt   108.98    825.45     32.87              967.31
                 Het Chi     8.68      0.00      0.00               41.75
                 Het  df        5         0         0                   7
                 Het  P      N.S.      N.S.      N.S.                 ***
               Fixed  RR     3.59      2.12      3.53                2.29
                     RRl     2.98      1.98      2.51                2.15
                     RRu     4.34      2.27      4.97                2.44
                      P       +++       +++       +++                 +++
              Random  RR     4.32      2.12      3.53                3.50
                     RRl     2.69      1.98      2.51                2.44
                     RRu     6.95      2.27      4.97                5.01
                      P       +++       +++       +++                 +++
             Between Chi                                            33.07
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2         6         8
                      NS                  1         5         6

                      Wt               3.55    963.76    967.31
                 Het Chi               0.01     31.64     41.75
                 Het  df                  1         5         7
                 Het  P                N.S.       ***       ***
               Fixed  RR              12.34      2.28      2.29
                     RRl               4.36      2.14      2.15
                     RRu              34.91      2.42      2.44
                      P                 +++       +++       +++
              Random  RR              12.34      3.07      3.50
                     RRl               4.36      2.18      2.44
                     RRu              34.91      4.33      5.01
                      P                 +++       +++       +++
             Between Chi                                  10.10
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2         3         3         8
                      NS        1         3         2         6

                      Wt     3.55    951.79     11.97    967.31
                 Het Chi     0.01     26.08      3.06     41.75
                 Het  df        1         2         2         7
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR    12.34      2.26      3.58      2.29
                     RRl     4.36      2.12      2.03      2.15
                     RRu    34.91      2.41      6.31      2.44
                      P       +++       +++       +++       +++
              Random  RR    12.34      2.90      3.73      3.50
                     RRl     4.36      1.96      1.76      2.44
                     RRu    34.91      4.28      7.90      5.01
                      P       +++       +++       +++       +++
             Between Chi                                  12.59
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1         7                   8
                      NS        1         5                   6

                      Wt    93.46    873.84              967.31
                 Het Chi     0.00     24.88               41.75
                 Het  df        0         6                   7
                 Het  P      N.S.       ***                 ***
               Fixed  RR     3.43      2.19                2.29
                     RRl     2.80      2.05                2.15
                     RRu     4.20      2.34                2.44
                      P       +++       +++                 +++
              Random  RR     3.43      3.69                3.50
                     RRl     2.80      2.31                2.44
                     RRu     4.20      5.90                5.01
                      P       +++       +++                 +++
             Between Chi                                  16.87
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                     (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 3

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3         5                             8
                      NS        2         4                             6

                      Wt   104.13    863.17                        967.31
                 Het Chi     1.08     22.61                         41.75
                 Het  df        2         4                             7
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.39      2.18                          2.29
                     RRl     2.80      2.04                          2.15
                     RRu     4.11      2.34                          2.44
                      P       +++       +++                           +++
              Random  RR     3.39      4.21                          3.50
                     RRl     2.80      2.30                          2.44
                     RRu     4.11      7.72                          5.01
                      P       +++       +++                           +++
             Between Chi                                            18.06
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                               (*)

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3         5         8
                      NS        2         4         6

                      Wt   104.13    863.17    967.31
                 Het Chi     1.08     22.61     41.75
                 Het  df        2         4         7
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.39      2.18      2.29
                     RRl     2.80      2.04      2.15
                     RRu     4.11      2.34      2.44
                      P       +++       +++       +++
              Random  RR     3.39      4.21      3.50
                     RRl     2.80      2.30      2.44
                     RRu     4.11      7.72      5.01
                      P       +++       +++       +++
             Between Chi                        18.06
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 4

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  19     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  25  32
  FERRI2  61     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  24  32
  FERRI2  75     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  24  32
  FUKUCH   5     b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  25  49
  MANNI2   5     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any   Nev any  30  59
  SPEIZE  14     m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  21  40
  SPEIZE  19     f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  21  40
  ZIELI2  10     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  30  39

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 5

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 19  m   1          6       -       2       -     11.85 (  2.12-  66.29)
 FERRI2 61  m   1         33       -      11       -      3.95 (  1.83-   8.51)
 FERRI2 75  f   1          6       -      54       -      2.12 (  0.81-   5.53)
 Subtotal FERRI2                                          3.10 (  1.70-   5.65)
 FUKUCH 5   b   0         88     405      64    1039      3.53 (  2.51-   4.97)
 MANNI2 5   b   1        257       -     202       -      3.43 (  2.80-   4.20)
*SPEIZE 14  m   1          7       -       0       -     10.62 (  0.61- 185.90)
*SPEIZE 19  f   1          8       -       5       -     12.62 (  4.13-  38.56)
 Subtotal SPEIZE                                         12.34 (  4.36-  34.91)
 ZIELI2 10  b   0       4232   14120    1262    8933      2.12 (  1.98-   2.27)
Partial Totals          4637   14525    1600    9972
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 19  m   1              2.47     1.30     3.50       0.00
 FERRI2 61  m   1              1.37     6.51     1.93       0.00
 FERRI2 75  f   1              0.75     4.16     0.02       0.13
 Subtotal FERRI2               1.13    10.67     1.96
 FUKUCH 5   b   0              1.26    32.87     6.13       0.00
 MANNI2 5   b   1              1.23    93.46    15.24       0.00
*SPEIZE 14  m   1              2.36     0.47     1.11       0.11
*SPEIZE 19  f   1              2.54     3.08     8.97       0.00
 Subtotal SPEIZE               2.51     3.55    10.07
 ZIELI2 10  b   0              0.75   825.45     4.85       0.00

                       N        8
                      NS        6

                      Wt   967.31
                 Het Chi    41.75
                 Het  df        7
                 Het  P       ***
               Fixed  RR     2.29
                     RRl     2.15
                     RRu     2.44
                      P       +++
              Random  RR     3.50
                     RRl     2.44
                     RRu     5.01
                      P       +++
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        8
                      NS        6

                      Wt   967.31
                 Het Chi    41.75
                 Het  df        7
                 Het  P       ***
               Fixed  RR     2.29
                     RRl     2.15
                     RRu     2.44
                      P       +++
              Random  RR     3.50
                     RRl     2.44
                     RRu     5.01
                      P       +++
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N        3         3         2         8
                      NS        3         3         2         8

                      Wt   951.79      8.27      7.24    967.31
                 Het Chi    26.08      1.59      5.63     41.75
                 Het  df        2         2         1         7
                 Het  P       ***      N.S.         *       ***
               Fixed  RR     2.26      4.96      4.53      2.29
                     RRl     2.12      2.51      2.18      2.15
                     RRu     2.41      9.81      9.37      2.44
                      P       +++       +++       +++       +++
              Random  RR     2.90      4.96      5.05      3.50
                     RRl     1.96      2.51      0.88      2.44
                     RRu     4.28      9.81     29.00      5.01
                      P       +++       +++       (+)       +++
             Between Chi                                   8.44
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        6         1         1                   8
                      NS        4         1         1                   6

                      Wt   108.98    825.45     32.87              967.31
                 Het Chi     8.68      0.00      0.00               41.75
                 Het  df        5         0         0                   7
                 Het  P      N.S.      N.S.      N.S.                 ***
               Fixed  RR     3.59      2.12      3.53                2.29
                     RRl     2.98      1.98      2.51                2.15
                     RRu     4.34      2.27      4.97                2.44
                      P       +++       +++       +++                 +++
              Random  RR     4.32      2.12      3.53                3.50
                     RRl     2.69      1.98      2.51                2.44
                     RRu     6.95      2.27      4.97                5.01
                      P       +++       +++       +++                 +++
             Between Chi                                            33.07
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2         6         8
                      NS                  1         5         6

                      Wt               3.55    963.76    967.31
                 Het Chi               0.01     31.64     41.75
                 Het  df                  1         5         7
                 Het  P                N.S.       ***       ***
               Fixed  RR              12.34      2.28      2.29
                     RRl               4.36      2.14      2.15
                     RRu              34.91      2.42      2.44
                      P                 +++       +++       +++
              Random  RR              12.34      3.07      3.50
                     RRl               4.36      2.18      2.44
                     RRu              34.91      4.33      5.01
                      P                 +++       +++       +++
             Between Chi                                  10.10
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2         3         3         8
                      NS        1         3         2         6

                      Wt     3.55    951.79     11.97    967.31
                 Het Chi     0.01     26.08      3.06     41.75
                 Het  df        1         2         2         7
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR    12.34      2.26      3.58      2.29
                     RRl     4.36      2.12      2.03      2.15
                     RRu    34.91      2.41      6.31      2.44
                      P       +++       +++       +++       +++
              Random  RR    12.34      2.90      3.73      3.50
                     RRl     4.36      1.96      1.76      2.44
                     RRu    34.91      4.28      7.90      5.01
                      P       +++       +++       +++       +++
             Between Chi                                  12.59
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1         7                   8
                      NS        1         5                   6

                      Wt    93.46    873.84              967.31
                 Het Chi     0.00     24.88               41.75
                 Het  df        0         6                   7
                 Het  P      N.S.       ***                 ***
               Fixed  RR     3.43      2.19                2.29
                     RRl     2.80      2.05                2.15
                     RRu     4.20      2.34                2.44
                      P       +++       +++                 +++
              Random  RR     3.43      3.69                3.50
                     RRl     2.80      2.31                2.44
                     RRu     4.20      5.90                5.01
                      P       +++       +++                 +++
             Between Chi                                  16.87
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                     (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 6

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3         5                             8
                      NS        2         4                             6

                      Wt   104.13    863.17                        967.31
                 Het Chi     1.08     22.61                         41.75
                 Het  df        2         4                             7
                 Het  P      N.S.       ***                           ***
               Fixed  RR     3.39      2.18                          2.29
                     RRl     2.80      2.04                          2.15
                     RRu     4.11      2.34                          2.44
                      P       +++       +++                           +++
              Random  RR     3.39      4.21                          3.50
                     RRl     2.80      2.30                          2.44
                     RRu     4.11      7.72                          5.01
                      P       +++       +++                           +++
             Between Chi                                            18.06
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                               (*)

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3         5         8
                      NS        2         4         6

                      Wt   104.13    863.17    967.31
                 Het Chi     1.08     22.61     41.75
                 Het  df        2         4         7
                 Het  P      N.S.       ***       ***
               Fixed  RR     3.39      2.18      2.29
                     RRl     2.80      2.04      2.15
                     RRu     4.11      2.34      2.44
                      P       +++       +++       +++
              Random  RR     3.39      4.21      3.50
                     RRl     2.80      2.30      2.44
                     RRu     4.11      7.72      5.01
                      P       +++       +++       +++
             Between Chi                        18.06
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                           (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 7

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC JOHANN    KIM KOJIMA   LIAW MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 PEREZP   SHIN   XIAO     XU ZIELI1
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 7 - 8

                                 IESCOPD - Meta-analysis of pack-years : key value (2) 30
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
  MANNI2 MANNI2     1                MANNI2/MANNI3

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 8 -

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) vs never smoking base
6) Key value (scheme 2) = 999
7) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
8) SMKSTA  : current, ever
9) UNEXP   : never any, never cigarettes
10) PROD    : cigarettes, cigarettes only, any product
11) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 1

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  20   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  33   +
  FERRI2  62   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FERRI2  76   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FUKUCH   6   b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  50   +
  KOJIMA   9   m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
  KOJIMA  14   f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
    LIAW  20   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  41   +
  MANNI2   6   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any   Nev any  60   +
  SPEIZE  15   m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
  SPEIZE  20   f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
    XIAO   6   b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs  40   +
  ZIELI2  11   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 2

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 20  m   1          6       -       2       -      6.65 (  1.20-  36.88)
 FERRI2 62  m   1        100       -      11       -      5.82 (  2.92-  11.59)
 FERRI2 76  f   1         12       -      54       -      5.53 (  2.45-  12.47)
 Subtotal FERRI2                                          5.70 (  3.37-   9.64)
 FUKUCH 6   b   0         68     149      64    1039      7.41 (  5.06-  10.86)
 KOJIMA 9   m   0         55     924      19    1871      5.86 (  3.46-   9.93)
 KOJIMA 14  f   0          1       7      20    3545     25.32 (  2.98- 215.41)
 Subtotal KOJIMA                                          6.37 (  3.82-  10.64)
*LIAW   20  b   2          -       -       -       -      1.80 (  0.90-   3.80)
 MANNI2 6   b   1        167       -     202       -      4.41 (  3.49-   5.57)
*SPEIZE 15  m   1         16       -       0       -     22.66 (  1.36- 377.73)
*SPEIZE 20  f   1          3       -       5       -      9.46 (  2.26-  39.59)
 Subtotal SPEIZE                                         11.32 (  3.16-  40.55)
 XIAO   6   b   0         17       7      21      56      6.48 (  2.35-  17.84)
 ZIELI2 11  b   0       6784   14529    1262    8933      3.31 (  3.10-   3.53)
Partial Totals          7229   15616    1660   15444
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 20  m   1              1.89     1.31     0.54       0.03
 FERRI2 62  m   1              1.76     8.09     2.08       0.00
 FERRI2 76  f   1              1.71     5.80     1.21       0.00
 Subtotal FERRI2               1.74    13.89     3.29
 FUKUCH 6   b   0              2.00    26.31    14.74       0.00
 KOJIMA 9   m   0              1.77    13.81     3.65       0.00
 KOJIMA 14  f   0              3.23     0.84     3.28       0.00
 Subtotal KOJIMA               1.85    14.64     6.93
*LIAW   20  b   2              0.59     7.41     3.29       0.11
 MANNI2 6   b   1              1.48    70.31     3.71       0.00
*SPEIZE 15  m   1              3.12     0.49     1.69       0.03
*SPEIZE 20  f   1              2.25     1.87     1.85       0.00
 Subtotal SPEIZE               2.43     2.36     3.54
 XIAO   6   b   0              1.87     3.74     1.41       0.00
 ZIELI2 11  b   0              1.20   892.40     3.07       0.00

                       N       12
                      NS        9

                      Wt  1032.37
                 Het Chi    40.52
                 Het  df       11
                 Het  P       ***
               Fixed  RR     3.50
                     RRl     3.30
                     RRu     3.73
                      P       +++
              Random  RR     4.97
                     RRl     3.73
                     RRu     6.63
                      P       +++
               Asymm  P        **

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 3

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       12
                      NS        9

                      Wt  1032.37
                 Het Chi    40.52
                 Het  df       11
                 Het  P       ***
               Fixed  RR     3.50
                     RRl     3.30
                     RRu     3.73
                      P       +++
              Random  RR     4.97
                     RRl     3.73
                     RRu     6.63
                      P       +++
               Asymm  P        **

                                   Sex
                             both      male    female     Total

                       N        5         4         3        12
                      NS        5         4         3        12

                      Wt  1000.17     23.69      8.52   1032.37
                 Het Chi    25.86      0.88      1.87     40.52
                 Het  df        4         3         2        11
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     3.44      6.05      7.23      3.50
                     RRl     3.23      4.05      3.69      3.30
                     RRu     3.66      9.06     14.15      3.73
                      P       +++       +++       +++       +++
              Random  RR     4.17      6.05      7.23      4.97
                     RRl     2.92      4.05      3.69      3.73
                     RRu     5.94      9.06     14.15      6.63
                      P       +++       +++       +++       +++
             Between Chi                                  11.90
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        6         1         5                  12
                      NS        4         1         4                   9

                      Wt    87.87    892.40     52.11             1032.37
                 Het Chi     3.08      0.00     13.58               40.52
                 Het  df        5         0         4                  11
                 Het  P      N.S.      N.S.        **                 ***
               Fixed  RR     4.74      3.31      5.75                3.50
                     RRl     3.84      3.10      4.38                3.30
                     RRu     5.84      3.53      7.55                3.73
                      P       +++       +++       +++                 +++
              Random  RR     4.74      3.31      5.38                4.97
                     RRl     3.84      3.10      2.97                3.73
                     RRu     5.84      3.53      9.77                6.63
                      P       +++       +++       +++                 +++
             Between Chi                                            23.86
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 3

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        1         3         8        12
                      NS        1         2         6         9

                      Wt     3.74      9.77   1018.87   1032.37
                 Het Chi     0.00      6.35     32.28     40.52
                 Het  df        0         2         7        11
                 Het  P      N.S.         *       ***       ***
               Fixed  RR     6.48      2.81      3.50      3.50
                     RRl     2.35      1.50      3.30      3.30
                     RRu    17.84      5.26      3.73      3.73
                      P       +++        ++       +++       +++
              Random  RR     6.48      5.17      5.18      4.97
                     RRl     2.35      1.14      3.79      3.73
                     RRu    17.84     23.45      7.08      6.63
                      P       +++         +       +++       +++
             Between Chi                                   1.89
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         4        12
                      NS        2         4         3         9

                      Wt     9.77   1003.67     18.94   1032.37
                 Het Chi     6.35     28.39      0.08     40.52
                 Het  df        2         4         3        11
                 Het  P         *       ***      N.S.       ***
               Fixed  RR     2.81      3.48      5.91      3.50
                     RRl     1.50      3.27      3.76      3.30
                     RRu     5.26      3.70      9.27      3.73
                      P        ++       +++       +++       +++
              Random  RR     5.17      5.03      5.91      4.97
                     RRl     1.14      3.48      3.76      3.73
                     RRu    23.45      7.28      9.27      6.63
                      P         +       +++       +++       +++
             Between Chi                                   5.70
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        11                  12
                      NS        1         8                   9

                      Wt    70.31    962.07             1032.37
                 Het Chi     0.00     36.53               40.52
                 Het  df        0        10                  11
                 Het  P      N.S.       ***                 ***
               Fixed  RR     4.41      3.45                3.50
                     RRl     3.49      3.24                3.30
                     RRu     5.57      3.67                3.73
                      P       +++       +++                 +++
              Random  RR     4.41      5.27                4.97
                     RRl     3.49      3.62                3.73
                     RRu     5.57      7.66                6.63
                      P       +++       +++                 +++
             Between Chi                                   3.98
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 3

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3         9                            12
                      NS        2         7                             9

                      Wt    84.20    948.18                       1032.37
                 Het Chi     0.77     32.97                         40.52
                 Het  df        2         8                            11
                 Het  P      N.S.       ***                           ***
               Fixed  RR     4.60      3.42                          3.50
                     RRl     3.72      3.21                          3.30
                     RRu     5.70      3.65                          3.73
                      P       +++       +++                           +++
              Random  RR     4.60      5.23                          4.97
                     RRl     3.72      3.35                          3.73
                     RRu     5.70      8.15                          6.63
                      P       +++       +++                           +++
             Between Chi                                             6.78
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3         9        12
                      NS        2         7         9

                      Wt    84.20    948.18   1032.37
                 Het Chi     0.77     32.97     40.52
                 Het  df        2         8        11
                 Het  P      N.S.       ***       ***
               Fixed  RR     4.60      3.42      3.50
                     RRl     3.72      3.21      3.30
                     RRu     5.70      3.65      3.73
                      P       +++       +++       +++
              Random  RR     4.60      5.23      4.97
                     RRl     3.72      3.35      3.73
                     RRu     5.70      8.15      6.63
                      P       +++       +++       +++
             Between Chi                         6.78
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 4

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  ANDER1  20     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs  Nev cigs  33   +
  FERRI2  62     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FERRI2  76     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs   Nev any  33   +
  FUKUCH   6     b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  50   +
  KOJIMA   9     m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
  KOJIMA  14     f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +
    LIAW  20     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs  Nev cigs  41   +
  MANNI2   6     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any   Nev any  60   +
  SPEIZE  15     m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
  SPEIZE  20     f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs  Nev cigs  41   +
    XIAO   6     b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs  Nev cigs  40   +
  ZIELI2  11     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs  Nev cigs  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 5

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 20  m   1          6       -       2       -      6.65 (  1.20-  36.88)
 FERRI2 62  m   1        100       -      11       -      5.82 (  2.92-  11.59)
 FERRI2 76  f   1         12       -      54       -      5.53 (  2.45-  12.47)
 Subtotal FERRI2                                          5.70 (  3.37-   9.64)
 FUKUCH 6   b   0         68     149      64    1039      7.41 (  5.06-  10.86)
 KOJIMA 9   m   0         55     924      19    1871      5.86 (  3.46-   9.93)
 KOJIMA 14  f   0          1       7      20    3545     25.32 (  2.98- 215.41)
 Subtotal KOJIMA                                          6.37 (  3.82-  10.64)
*LIAW   20  b   2          -       -       -       -      1.80 (  0.90-   3.80)
 MANNI2 6   b   1        167       -     202       -      4.41 (  3.49-   5.57)
*SPEIZE 15  m   1         16       -       0       -     22.66 (  1.36- 377.73)
*SPEIZE 20  f   1          3       -       5       -      9.46 (  2.26-  39.59)
 Subtotal SPEIZE                                         11.32 (  3.16-  40.55)
 XIAO   6   b   0         17       7      21      56      6.48 (  2.35-  17.84)
 ZIELI2 11  b   0       6784   14529    1262    8933      3.31 (  3.10-   3.53)
Partial Totals          7229   15616    1660   15444
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 20  m   1              1.89     1.31     0.54       0.03
 FERRI2 62  m   1              1.76     8.09     2.08       0.00
 FERRI2 76  f   1              1.71     5.80     1.21       0.00
 Subtotal FERRI2               1.74    13.89     3.29
 FUKUCH 6   b   0              2.00    26.31    14.74       0.00
 KOJIMA 9   m   0              1.77    13.81     3.65       0.00
 KOJIMA 14  f   0              3.23     0.84     3.28       0.00
 Subtotal KOJIMA               1.85    14.64     6.93
*LIAW   20  b   2              0.59     7.41     3.29       0.11
 MANNI2 6   b   1              1.48    70.31     3.71       0.00
*SPEIZE 15  m   1              3.12     0.49     1.69       0.03
*SPEIZE 20  f   1              2.25     1.87     1.85       0.00
 Subtotal SPEIZE               2.43     2.36     3.54
 XIAO   6   b   0              1.87     3.74     1.41       0.00
 ZIELI2 11  b   0              1.20   892.40     3.07       0.00

                       N       12
                      NS        9

                      Wt  1032.37
                 Het Chi    40.52
                 Het  df       11
                 Het  P       ***
               Fixed  RR     3.50
                     RRl     3.30
                     RRu     3.73
                      P       +++
              Random  RR     4.97
                     RRl     3.73
                     RRu     6.63
                      P       +++
               Asymm  P        **

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 6

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       12
                      NS        9

                      Wt  1032.37
                 Het Chi    40.52
                 Het  df       11
                 Het  P       ***
               Fixed  RR     3.50
                     RRl     3.30
                     RRu     3.73
                      P       +++
              Random  RR     4.97
                     RRl     3.73
                     RRu     6.63
                      P       +++
               Asymm  P        **

                                   Sex
                             both      male    female     Total

                       N        5         4         3        12
                      NS        5         4         3        12

                      Wt  1000.17     23.69      8.52   1032.37
                 Het Chi    25.86      0.88      1.87     40.52
                 Het  df        4         3         2        11
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     3.44      6.05      7.23      3.50
                     RRl     3.23      4.05      3.69      3.30
                     RRu     3.66      9.06     14.15      3.73
                      P       +++       +++       +++       +++
              Random  RR     4.17      6.05      7.23      4.97
                     RRl     2.92      4.05      3.69      3.73
                     RRu     5.94      9.06     14.15      6.63
                      P       +++       +++       +++       +++
             Between Chi                                  11.90
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        6         1         5                  12
                      NS        4         1         4                   9

                      Wt    87.87    892.40     52.11             1032.37
                 Het Chi     3.08      0.00     13.58               40.52
                 Het  df        5         0         4                  11
                 Het  P      N.S.      N.S.        **                 ***
               Fixed  RR     4.74      3.31      5.75                3.50
                     RRl     3.84      3.10      4.38                3.30
                     RRu     5.84      3.53      7.55                3.73
                      P       +++       +++       +++                 +++
              Random  RR     4.74      3.31      5.38                4.97
                     RRl     3.84      3.10      2.97                3.73
                     RRu     5.84      3.53      9.77                6.63
                      P       +++       +++       +++                 +++
             Between Chi                                            23.86
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                                 *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 6

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        1         3         8        12
                      NS        1         2         6         9

                      Wt     3.74      9.77   1018.87   1032.37
                 Het Chi     0.00      6.35     32.28     40.52
                 Het  df        0         2         7        11
                 Het  P      N.S.         *       ***       ***
               Fixed  RR     6.48      2.81      3.50      3.50
                     RRl     2.35      1.50      3.30      3.30
                     RRu    17.84      5.26      3.73      3.73
                      P       +++        ++       +++       +++
              Random  RR     6.48      5.17      5.18      4.97
                     RRl     2.35      1.14      3.79      3.73
                     RRu    17.84     23.45      7.08      6.63
                      P       +++         +       +++       +++
             Between Chi                                   1.89
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         4        12
                      NS        2         4         3         9

                      Wt     9.77   1003.67     18.94   1032.37
                 Het Chi     6.35     28.39      0.08     40.52
                 Het  df        2         4         3        11
                 Het  P         *       ***      N.S.       ***
               Fixed  RR     2.81      3.48      5.91      3.50
                     RRl     1.50      3.27      3.76      3.30
                     RRu     5.26      3.70      9.27      3.73
                      P        ++       +++       +++       +++
              Random  RR     5.17      5.03      5.91      4.97
                     RRl     1.14      3.48      3.76      3.73
                     RRu    23.45      7.28      9.27      6.63
                      P         +       +++       +++       +++
             Between Chi                                   5.70
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        1        11                  12
                      NS        1         8                   9

                      Wt    70.31    962.07             1032.37
                 Het Chi     0.00     36.53               40.52
                 Het  df        0        10                  11
                 Het  P      N.S.       ***                 ***
               Fixed  RR     4.41      3.45                3.50
                     RRl     3.49      3.24                3.30
                     RRu     5.57      3.67                3.73
                      P       +++       +++                 +++
              Random  RR     4.41      5.27                4.97
                     RRl     3.49      3.62                3.73
                     RRu     5.57      7.66                6.63
                      P       +++       +++                 +++
             Between Chi                                   3.98
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 6

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3         9                            12
                      NS        2         7                             9

                      Wt    84.20    948.18                       1032.37
                 Het Chi     0.77     32.97                         40.52
                 Het  df        2         8                            11
                 Het  P      N.S.       ***                           ***
               Fixed  RR     4.60      3.42                          3.50
                     RRl     3.72      3.21                          3.30
                     RRu     5.70      3.65                          3.73
                      P       +++       +++                           +++
              Random  RR     4.60      5.23                          4.97
                     RRl     3.72      3.35                          3.73
                     RRu     5.70      8.15                          6.63
                      P       +++       +++                           +++
             Between Chi                                             6.78
             Between  df                                                1
             Between  P                                                **
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3         9        12
                      NS        2         7         9

                      Wt    84.20    948.18   1032.37
                 Het Chi     0.77     32.97     40.52
                 Het  df        2         8        11
                 Het  P      N.S.       ***       ***
               Fixed  RR     4.60      3.42      3.50
                     RRl     3.72      3.21      3.30
                     RRu     5.70      3.65      3.73
                      P       +++       +++       +++
              Random  RR     4.60      5.23      4.97
                     RRl     3.72      3.35      3.73
                     RRu     5.70      8.15      6.63
                      P       +++       +++       +++
             Between Chi                         6.78
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 7

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG DETORR GEIJER HEDMAN KOTAN2   LIU2  PRICE WATSON
6      DEMARC JOHANN    KIM MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 PEREZP   SHIN     XU ZIELI1
11     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 8 - 8

                                IESCOPD - Meta-analysis of pack-years : key value (2) 999
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
  MANNI2 MANNI2     1                MANNI2/MANNI3
    LIAW    WEN     2                     WEN/LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - G - 9 -

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for pack-years
5) High vs low base
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) SMKSTA  : current, ever
8) PROD    : cigarettes, cigarettes only, any product
9) The highest vs lowest category
10) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 1

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

  ANDER1  24   m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs       8  33   +
  ANDER1  29   f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs       8  25   +
  DEMARC  14   b   20   44       Multi  1991  2004    CS  Prev      COPD:LF   4 Current       Cigs      14  15   +
  DETORR   3   m    0   99     Eu:West  2001  2006    CS  Prev      COPD:LF   0    Ever       Cigs      20  61   +
  DETORR   6   f    0   99     Eu:West  2001  2006    CS  Prev      COPD:LF   0    Ever       Cigs      20  61   +
  FERRI2  66   m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs       8  33   +
  FERRI2  80   f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs       8  33   +
  FUKUCH   8   b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs      24  50   +
  GEIJER   2   m   40   70     Eu:West  1998  2006    Pr   Inc      COPD:LF   0 Current       Cigs      19  30   +
  JOHANN   8   b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
     KIM  12   m   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs      10  20   +
     KIM  17   f   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs      10  20   +
  KOJIMA  11   m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs      19  40   +
  KOJIMA  16   f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs      19  40   +
    LIAW  22   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs      19  41   +
  MANNI2   8   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any      29  60   +
  MENEZ2  11   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ3   8   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ4   8   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ5   8   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ6   8   b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  PEREZP   4   f   40   99 Am:Sth/Cent  1992  1996    CC  Prev      COPD:LF   0    Ever       Cigs      10  11   +
   PRICE   3   b   40   99       Multi     *  2006    CS  Prev      COPD:LF   0    Ever        Any      14  50   +
    SHIN  15   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   3    Ever       Cigs       9  20   +
  SPEIZE  17   m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs      20  41   +
  SPEIZE  22   f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs      20  41   +
    XIAO   8   b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs      19  40   +
      XU  14   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs      14  26   +
      XU  24   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM  13    Ever       Cigs      14  26   +
  ZIELI1   8   b    0   99     Eu:East  1999  2001    CS  Prev      COPD:LF   1    Ever       Cigs       9  10   +
  ZIELI2  15   b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs       9  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 2

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 24  m   1          6       -       3       -      2.88 (  0.69-  12.09)
 ANDER1 29  f   1          3       -       4       -      4.67 (  0.88-  24.66)
 Subtotal ANDER1                                          3.54 (  1.19-  10.48)
 DEMARC 14  b   4        180       -      77       -      2.99 (  2.22-   4.01)
 DETORR 3   m   0         35      50      33      81      1.72 (  0.95-   3.11)
 DETORR 6   f   0          8      28       4      67      4.79 (  1.33-  17.19)
 Subtotal DETORR                                          2.06 (  1.20-   3.52)
 FERRI2 66  m   1        100       -      20       -      2.14 (  1.20-   3.84)
 FERRI2 80  f   1         12       -      24       -      3.88 (  1.62-   9.32)
 Subtotal FERRI2                                          2.57 (  1.58-   4.17)
 FUKUCH 8   b   0         68     149      36     494      6.26 (  4.02-   9.76)
*GEIJER 2   m   0         14      92       4     109      4.15 (  1.41-  12.16)
 JOHANN 8   b   0         65     309      26     515      4.17 (  2.59-   6.71)
 KIM    12  m   1        144       -      17       -      3.12 (  1.78-   5.47)
 KIM    17  f   1          6       -       1       -     11.58 (  1.61-  83.38)
 Subtotal KIM                                             3.44 (  2.01-   5.91)
 KOJIMA 11  m   0         55     924      20     880      2.62 (  1.56-   4.41)
 KOJIMA 16  f   0          1       7       2     159     11.36 (  0.92- 140.73)
 Subtotal KOJIMA                                          2.78 (  1.67-   4.63)
*LIAW   22  b   2          -       -       -       -      1.13 (  0.48-   2.66)
 MANNI2 8   b   1        167       -     282       -      2.76 (  2.21-   3.45)
 MENEZ2 11  b   0         54       -      27       -      2.10 (  1.26-   3.50)
 MENEZ3 8   b   0         57       -      48       -      3.28 (  2.12-   5.06)
 MENEZ4 8   b   0         12       -      18       -      2.62 (  1.20-   5.72)
 MENEZ5 8   b   0         85       -      16       -      3.61 (  2.01-   6.46)
 MENEZ6 8   b   0         58       -      34       -      2.77 (  1.75-   4.40)
 PEREZP 4   f   0          7       8      12      39      2.84 (  0.85-   9.47)
 PRICE  3   b   0         66      60      61     274      4.94 (  3.16-   7.72)
 SHIN   15  b   3         49       -       9       -      2.91 (  1.14-   7.46)
*SPEIZE 17  m   1         16       -       3       -      6.53 (  1.90-  22.40)
*SPEIZE 22  f   1          3       -       3       -      3.33 (  0.67-  16.52)
 Subtotal SPEIZE                                          5.08 (  1.91-  13.51)
 XIAO   8   b   0         17       7      30      25      2.02 (  0.72-   5.66)
 XU     14  m   13       286       -     139       -      1.34 (  1.05-   1.70)
 XU     24  f   13        17       -      21       -      1.37 (  0.63-   2.98)
 Subtotal XU                                              1.34 (  1.07-   1.69)
 ZIELI1 8   b   1       2158       -     206       -      1.73 (  1.47-   2.04)
 ZIELI2 15  b   0       6784   14529    1486    9875      3.10 (  2.92-   3.30)
Partial Totals         10533   16163    2666   12518
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 24  m   1              1.06     1.87     0.00       0.15
 ANDER1 29  f   1              1.54     1.38     0.35       0.07
 Subtotal ANDER1               1.26     3.26     0.35
 DEMARC 14  b   4              1.10    43.95     0.14       0.00
 DETORR 3   m   0              0.54    10.96     2.71       0.07
 DETORR 6   f   0              1.57     2.35     0.65       0.02
 Subtotal DETORR               0.72    13.31     3.36
 FERRI2 66  m   1              0.76    11.36     0.88       0.01
 FERRI2 80  f   1              1.36     5.02     0.51       0.00
 Subtotal FERRI2               0.94    16.38     1.38
 FUKUCH 8   b   0              1.83    19.52    12.38       0.00
*GEIJER 2   m   0              1.42     3.32     0.49       0.01
 JOHANN 8   b   0              1.43    16.94     2.56       0.00
 KIM    12  m   1              1.14    12.19     0.12       0.00
 KIM    17  f   1              2.45     0.99     1.96       0.02
 Subtotal KIM                  1.24    13.18     2.08
 KOJIMA 11  m   0              0.96    14.20     0.08       0.00
 KOJIMA 16  f   0              2.43     0.61     1.17       0.06
 Subtotal KOJIMA               1.02    14.81     1.26
*LIAW   22  b   2              0.12     5.24     4.40       0.78
 MANNI2 8   b   1              1.02    77.46     0.04       0.00
 MENEZ2 11  b   0              0.74    14.72     1.29       0.00
 MENEZ3 8   b   0              1.19    20.30     0.45       0.00
 MENEZ4 8   b   0              0.96     6.30     0.04       0.02
 MENEZ5 8   b   0              1.28    11.27     0.68       0.00
 MENEZ6 8   b   0              1.02    18.08     0.01       0.00
 PEREZP 4   f   0              1.05     2.65     0.00       0.09
 PRICE  3   b   0              1.60    19.28     6.03       0.00
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 2

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 SHIN   15  b   3              1.07     4.35     0.00       0.03
*SPEIZE 17  m   1              1.88     2.52     1.77       0.00
*SPEIZE 22  f   1              1.20     1.50     0.04       0.14
 Subtotal SPEIZE               1.63     4.02     1.81
 XIAO   8   b   0              0.70     3.64     0.40       0.18
 XU     14  m   13             0.29    66.18    36.81       0.02
 XU     24  f   13             0.31     6.36     3.33       0.43
 Subtotal XU                   0.29    72.55    40.14
 ZIELI1 8   b   1              0.55   143.10    34.40       0.00
 ZIELI2 15  b   0              1.13  1009.65     8.90       0.00

                       N       31
                      NS       24

                      Wt  1557.28
                 Het Chi   122.60
                 Het  df       30
                 Het  P       ***
               Fixed  RR     2.82
                     RRl     2.69
                     RRu     2.97
                      P       +++
              Random  RR     2.80
                     RRl     2.37
                     RRu     3.30
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 3

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       31
                      NS       24

                      Wt  1557.28
                 Het Chi   122.60
                 Het  df       30
                 Het  P       ***
               Fixed  RR     2.82
                     RRl     2.69
                     RRu     2.97
                      P       +++
              Random  RR     2.80
                     RRl     2.37
                     RRu     3.30
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N       15         8         8        31
                      NS       15         8         8        31

                      Wt  1413.81    122.62     20.86   1557.28
                 Het Chi    69.74     18.72      7.92    122.60
                 Het  df       14         7         7        30
                 Het  P       ***        **      N.S.       ***
               Fixed  RR     2.93      1.81      3.02      2.82
                     RRl     2.78      1.52      1.97      2.69
                     RRu     3.09      2.16      4.64      2.97
                      P       +++       +++       +++       +++
              Random  RR     2.95      2.35      3.16      2.80
                     RRl     2.44      1.64      1.97      2.37
                     RRu     3.57      3.36      5.07      3.30
                      P       +++       +++       +++       +++
             Between Chi                                  26.22
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7         6        10         8        31
                      NS        4         5         7         8        24

                      Wt   101.12   1186.32    133.29    136.56   1557.28
                 Het Chi     3.59     49.04     47.47      7.22    122.60
                 Het  df        6         5         9         7        30
                 Het  P      N.S.       ***       ***      N.S.       ***
               Fixed  RR     2.82      2.89      2.06      3.13      2.82
                     RRl     2.32      2.73      1.74      2.64      2.69
                     RRu     3.42      3.06      2.44      3.70      2.97
                      P       +++       +++       +++       +++       +++
              Random  RR     2.82      2.72      2.57      3.13      2.80
                     RRl     2.32      1.86      1.58      2.63      2.37
                     RRu     3.42      3.97      4.17      3.71      3.30
                      P       +++       +++       +++       +++       +++
             Between Chi                                            15.28
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 3

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N       23         2        25
                      NS       18         1        19

                      Wt  1409.37      3.26   1412.63
                 Het Chi    69.64      0.19     69.94
                 Het  df       22         1        24
                 Het  P       ***      N.S.       ***
               Fixed  RR     2.92      3.54      2.92
                     RRl     2.77      1.19      2.77
                     RRu     3.07     10.48      3.08
                      P       +++         +       +++
              Random  RR     2.98      3.54      2.99
                     RRl     2.52      1.19      2.53
                     RRu     3.54     10.48      3.53
                      P       +++         +       +++
             Between Chi                         0.12
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        4         3         1         6        15         2        31
                      NS        2         2         1         6        11         2        24

                      Wt    19.63     81.48      5.24    214.32   1213.69     22.92   1557.28
                 Het Chi     1.70      1.85      0.00     20.99     68.08      2.44    122.60
                 Het  df        3         2         0         5        14         1        30
                 Het  P      N.S.      N.S.      N.S.       ***       ***      N.S.       ***
               Fixed  RR     2.71      2.84      1.13      2.14      2.96      4.29      2.82
                     RRl     1.74      2.29      0.48      1.87      2.79      2.85      2.69
                     RRu     4.21      3.53      2.66      2.44      3.13      6.46      2.97
                      P       +++       +++      N.S.       +++       +++       +++       +++
              Random  RR     2.71      2.84      1.13      2.82      2.76      3.58      2.80
                     RRl     1.74      2.29      0.48      1.89      2.14      1.55      2.37
                     RRu     4.21      3.53      2.66      4.21      3.56      8.30      3.30
                      P       +++       +++      N.S.       +++       +++        ++       +++
             Between Chi                                                                27.55
             Between  df                                                                    5
             Between  P                                                                   ***
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        4         2         2        23        31
                      NS        2         1         2        19        24

                      Wt    19.63      4.02      7.89   1525.74   1557.28
                 Het Chi     1.70      0.43      1.50    114.65    122.60
                 Het  df        3         1         1        22        30
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR     2.71      5.08      1.54      2.83      2.82
                     RRl     1.74      1.91      0.77      2.69      2.69
                     RRu     4.21     13.51      3.10      2.98      2.97
                      P       +++        ++      N.S.       +++       +++
              Random  RR     2.71      5.08      1.62      2.82      2.80
                     RRl     1.74      1.91      0.67      2.35      2.37
                     RRu     4.21     13.51      3.92      3.38      3.30
                      P       +++        ++      N.S.       +++       +++
             Between Chi                                             4.33
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 3

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4        25        31
                      NS        2         3        19        24

                      Wt     6.29     12.58   1538.42   1557.28
                 Het Chi     0.18      6.59    115.49    122.60
                 Het  df        1         3        24        30
                 Het  P      N.S.       (*)       ***       ***
               Fixed  RR     2.34      2.57      2.83      2.82
                     RRl     1.07      1.48      2.69      2.69
                     RRu     5.10      4.47      2.97      2.97
                      P         +       +++       +++       +++
              Random  RR     2.34      2.94      2.82      2.80
                     RRl     1.07      1.25      2.37      2.37
                     RRu     5.10      6.90      3.36      3.30
                      P         +         +       +++       +++
             Between Chi                                   0.34
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        7        12        12                  31
                      NS        6         7        11                  24

                      Wt  1218.00    205.42    133.87             1557.28
                 Het Chi    46.83     36.39     22.78              122.60
                 Het  df        6        11        11                  30
                 Het  P       ***       ***         *                 ***
               Fixed  RR     2.88      2.24      3.43                2.82
                     RRl     2.72      1.95      2.90                2.69
                     RRu     3.04      2.57      4.06                2.97
                      P       +++       +++       +++                 +++
              Random  RR     2.46      2.65      3.30                2.80
                     RRl     1.78      1.91      2.54                2.37
                     RRu     3.40      3.69      4.29                3.30
                      P       +++       +++       +++                 +++
             Between Chi                                            16.61
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N        1         6         3        21                  31
                      NS        1         4         2        17                  24

                      Wt    43.95     98.85     33.32   1381.17             1557.28
                 Het Chi     0.00      2.14      3.18    116.34              122.60
                 Het  df        0         5         2        20                  30
                 Het  P      N.S.      N.S.      N.S.       ***                 ***
               Fixed  RR     2.99      2.82      3.28      2.81                2.82
                     RRl     2.22      2.32      2.34      2.67                2.69
                     RRu     4.02      3.44      4.61      2.96                2.97
                      P       +++       +++       +++       +++                 +++
              Random  RR     2.99      2.82      3.24      2.69                2.80
                     RRl     2.22      2.32      2.07      2.15                2.37
                     RRu     4.02      3.44      5.07      3.37                3.30
                      P       +++       +++       +++       +++                 +++
             Between Chi                                                       0.94
             Between  df                                                          3
             Between  P                                                        N.S.
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 3

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        2        29        31
                      NS        1        23        24

                      Wt    13.31   1543.97   1557.28
                 Het Chi     2.03    119.23    122.60
                 Het  df        1        28        30
                 Het  P      N.S.       ***       ***
               Fixed  RR     2.06      2.83      2.82
                     RRl     1.20      2.69      2.69
                     RRu     3.52      2.98      2.97
                      P        ++       +++       +++
              Random  RR     2.44      2.83      2.80
                     RRl     0.94      2.39      2.37
                     RRu     6.31      3.36      3.30
                      P       (+)       +++       +++
             Between Chi                         1.34
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3        21         7        31
                      NS        2        18         4        24

                      Wt     9.26   1452.21     95.82   1557.28
                 Het Chi     5.57     71.76      9.54    122.60
                 Het  df        2        20         6        30
                 Het  P       (*)       ***      N.S.       ***
               Fixed  RR     2.17      2.94      1.57      2.82
                     RRl     1.14      2.79      1.29      2.69
                     RRu     4.13      3.10      1.92      2.97
                      P         +       +++       +++       +++
              Random  RR     2.67      3.06      1.90      2.80
                     RRl     0.84      2.59      1.34      2.37
                     RRu     8.52      3.61      2.70      3.30
                      P       (+)       +++       +++       +++
             Between Chi                                  35.73
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N       16         7         6         2        31
                      NS       14         5         3         2        24

                      Wt   481.01   1043.74     23.65      8.88   1557.28
                 Het Chi    84.45      5.96      3.45      0.73    122.60
                 Het  df       15         6         5         1        30
                 Het  P       ***      N.S.      N.S.      N.S.       ***
               Fixed  RR     2.36      3.08      3.01      1.43      2.82
                     RRl     2.16      2.90      2.01      0.74      2.69
                     RRu     2.58      3.28      4.51      2.77      2.97
                      P       +++       +++       +++      N.S.       +++
              Random  RR     2.86      3.08      3.01      1.43      2.80
                     RRl     2.24      2.90      2.01      0.74      2.37
                     RRu     3.64      3.28      4.51      2.77      3.30
                      P       +++       +++       +++      N.S.       +++
             Between Chi                                            28.02
             Between  df                                                3
             Between  P                                               ***
             Btwn(F)  P                                               (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 3

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N       11        10        21
                      NS        9         9        18

                      Wt  1328.68    123.53   1452.21
                 Het Chi    57.79     13.08     71.76
                 Het  df       10         9        20
                 Het  P       ***      N.S.       ***
               Fixed  RR     2.92      3.19      2.94
                     RRl     2.77      2.67      2.79
                     RRu     3.08      3.81      3.10
                      P       +++       +++       +++
              Random  RR     3.01      3.16      3.06
                     RRl     2.37      2.54      2.59
                     RRu     3.83      3.94      3.61
                      P       +++       +++       +++
             Between Chi                         0.90
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        3         6         8        14        31
                      NS        2         5         7        10        24

                      Wt     7.34     21.09    100.48   1428.38   1557.28
                 Het Chi     0.50      3.63      5.68    108.84    122.60
                 Het  df        2         5         7        13        30
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR     4.64      2.15      3.05      2.81      2.82
                     RRl     2.25      1.40      2.50      2.67      2.69
                     RRu     9.56      3.30      3.70      2.96      2.97
                      P       +++       +++       +++       +++       +++
              Random  RR     4.64      2.15      3.05      2.72      2.80
                     RRl     2.25      1.40      2.50      2.14      2.37
                     RRu     9.56      3.30      3.70      3.46      3.30
                      P       +++       +++       +++       +++       +++
             Between Chi                                             3.95
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        3         6         8        14        31
                      NS        2         5         7        10        24

                      Wt     7.34     21.09    100.48   1428.38   1557.28
                 Het Chi     0.50      3.63      5.68    108.84    122.60
                 Het  df        2         5         7        13        30
                 Het  P      N.S.      N.S.      N.S.       ***       ***
               Fixed  RR     4.64      2.15      3.05      2.81      2.82
                     RRl     2.25      1.40      2.50      2.67      2.69
                     RRu     9.56      3.30      3.70      2.96      2.97
                      P       +++       +++       +++       +++       +++
              Random  RR     4.64      2.15      3.05      2.72      2.80
                     RRl     2.25      1.40      2.50      2.14      2.37
                     RRu     9.56      3.30      3.70      3.46      3.30
                      P       +++       +++       +++       +++       +++
             Between Chi                                             3.95
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 3

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N       27         4        31
                      NS       21         3        24

                      Wt  1544.71     12.58   1557.28
                 Het Chi   115.90      6.59    122.60
                 Het  df       26         3        30
                 Het  P       ***       (*)       ***
               Fixed  RR     2.83      2.57      2.82
                     RRl     2.69      1.48      2.69
                     RRu     2.97      4.47      2.97
                      P       +++       +++       +++
              Random  RR     2.80      2.94      2.80
                     RRl     2.36      1.25      2.37
                     RRu     3.32      6.90      3.30
                      P       +++         +       +++
             Between Chi                         0.11
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        2        29                  31
                      NS        2        22                  24

                      Wt    96.74   1460.54             1557.28
                 Het Chi     5.24    116.48              122.60
                 Het  df        1        28                  30
                 Het  P         *       ***                 ***
               Fixed  RR     3.10      2.81                2.82
                     RRl     2.54      2.67                2.69
                     RRu     3.78      2.96                2.97
                      P       +++       +++                 +++
              Random  RR     3.57      2.73                2.80
                     RRl     2.03      2.28                2.37
                     RRu     6.30      3.28                3.30
                      P       +++       +++                 +++
             Between Chi                                   0.89
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                        Number of adjustment variables
                                0         1        2+     Total

                       N       16        10         5        31
                      NS       14         6         4        24

                      Wt  1173.80    257.39    126.09   1557.28
                 Het Chi    24.75     22.20     19.69    122.60
                 Het  df       15         9         4        30
                 Het  P       (*)        **       ***       ***
               Fixed  RR     3.14      2.17      1.81      2.82
                     RRl     2.96      1.92      1.52      2.69
                     RRu     3.32      2.45      2.15      2.97
                      P       +++       +++       +++       +++
              Random  RR     3.27      2.73      1.81      2.80
                     RRl     2.78      2.02      1.11      2.37
                     RRu     3.86      3.68      2.93      3.30
                      P       +++       +++         +       +++
             Between Chi                                  55.96
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     ***
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 4

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

  ANDER1  24     m   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs       8  33   +
  ANDER1  29     f   25   74   Am:Canada  1963  1965    CS  Prev     COPD:oth   1    Ever       Cigs       8  25   +
  DEMARC  11 x   b   20   44       Multi  1991  2004    CS  Prev      COPD:LF   0 Current       Cigs      14  15   +
  DETORR   3     m    0   99     Eu:West  2001  2006    CS  Prev      COPD:LF   0    Ever       Cigs      20  61   +
  DETORR   6     f    0   99     Eu:West  2001  2006    CS  Prev      COPD:LF   0    Ever       Cigs      20  61   +
  FERRI2  66     m   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs       8  33   +
  FERRI2  80     f   25   80      Am:USA  1967  1971    CS  Prev     COPD:oth   1    Ever       Cigs       8  33   +
  FUKUCH   8     b   40   99   Asia:FarE  2000  2004    CS  Prev      COPD:LF   0    Ever       Cigs      24  50   +
  GEIJER   2     m   40   70     Eu:West  1998  2006    Pr   Inc      COPD:LF   0 Current       Cigs      19  30   +
  JOHANN   8     b   26   82    Eu:Scand  1996  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
     KIM  12     m   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs      10  20   +
     KIM  17     f   45   99   Asia:FarE  2001  2005    CS  Prev      COPD:LF   1    Ever       Cigs      10  20   +
  KOJIMA  11     m   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs      19  40   +
  KOJIMA  16     f   25   74   Asia:FarE  2001  2005    CS  Prev      COPD:LF   0    Ever       Cigs      19  40   +
    LIAW  22     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs      19  41   +
  MANNI2   8     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1    Ever        Any      29  60   +
  MENEZ2  11     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ3   8     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ4   8     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ5   8     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  MENEZ6   8     b   40   99 Am:Sth/Cent  2003  2005    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  PEREZP   4     f   40   99 Am:Sth/Cent  1992  1996    CC  Prev      COPD:LF   0    Ever       Cigs      10  11   +
   PRICE   3     b   40   99       Multi     *  2006    CS  Prev      COPD:LF   0    Ever        Any      14  50   +
    SHIN  10 x   b   18   99   Asia:FarE  1999  2003    CS  Prev      COPD:LF   0    Ever       Cigs       9  20   +
  SPEIZE  17     m   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs      20  41   +
  SPEIZE  22     f   25   86      Am:USA  1974  1989    Pr   Inc    COPD:mort   1    Ever       Cigs      20  41   +
    XIAO   8     b    0   99   Asia:FarE     *  2004    CC  Prev   COPD:undef   0    Ever       Cigs      19  40   +
      XU   9 x   m   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs      14  26   +
      XU  19 x   f   35   99   Asia:FarE  2000  2005    CS  Prev        CB/EM   0    Ever       Cigs      14  26   +
  ZIELI1   5 x   b    0   99     Eu:East  1999  2001    CS  Prev      COPD:LF   0    Ever       Cigs       9  10   +
  ZIELI2  15     b    0   99     Eu:East  2000  2006    CS  Prev      COPD:LF   0    Ever       Cigs       9  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 5

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 ANDER1 24  m   1          6       -       3       -      2.88 (  0.69-  12.09)
 ANDER1 29  f   1          3       -       4       -      4.67 (  0.88-  24.66)
 Subtotal ANDER1                                          3.54 (  1.19-  10.48)
 DEMARC 11  b   0        180    1972      77    3000      3.56 (  2.71-   4.67)
 DETORR 3   m   0         35      50      33      81      1.72 (  0.95-   3.11)
 DETORR 6   f   0          8      28       4      67      4.79 (  1.33-  17.19)
 Subtotal DETORR                                          2.06 (  1.20-   3.52)
 FERRI2 66  m   1        100       -      20       -      2.14 (  1.20-   3.84)
 FERRI2 80  f   1         12       -      24       -      3.88 (  1.62-   9.32)
 Subtotal FERRI2                                          2.57 (  1.58-   4.17)
 FUKUCH 8   b   0         68     149      36     494      6.26 (  4.02-   9.76)
*GEIJER 2   m   0         14      92       4     109      4.15 (  1.41-  12.16)
 JOHANN 8   b   0         65     309      26     515      4.17 (  2.59-   6.71)
 KIM    12  m   1        144       -      17       -      3.12 (  1.78-   5.47)
 KIM    17  f   1          6       -       1       -     11.58 (  1.61-  83.38)
 Subtotal KIM                                             3.44 (  2.01-   5.91)
 KOJIMA 11  m   0         55     924      20     880      2.62 (  1.56-   4.41)
 KOJIMA 16  f   0          1       7       2     159     11.36 (  0.92- 140.73)
 Subtotal KOJIMA                                          2.78 (  1.67-   4.63)
*LIAW   22  b   2          -       -       -       -      1.13 (  0.48-   2.66)
 MANNI2 8   b   1        167       -     282       -      2.76 (  2.21-   3.45)
 MENEZ2 11  b   0         54       -      27       -      2.10 (  1.26-   3.50)
 MENEZ3 8   b   0         57       -      48       -      3.28 (  2.12-   5.06)
 MENEZ4 8   b   0         12       -      18       -      2.62 (  1.20-   5.72)
 MENEZ5 8   b   0         85       -      16       -      3.61 (  2.01-   6.46)
 MENEZ6 8   b   0         58       -      34       -      2.77 (  1.75-   4.40)
 PEREZP 4   f   0          7       8      12      39      2.84 (  0.85-   9.47)
 PRICE  3   b   0         66      60      61     274      4.94 (  3.16-   7.72)
 SHIN   10  b   0         49     110       9     108      5.35 (  2.50-  11.42)
*SPEIZE 17  m   1         16       -       3       -      6.53 (  1.90-  22.40)
*SPEIZE 22  f   1          3       -       3       -      3.33 (  0.67-  16.52)
 Subtotal SPEIZE                                          5.08 (  1.91-  13.51)
 XIAO   8   b   0         17       7      30      25      2.02 (  0.72-   5.66)
 XU     9   m   0        286    2634     139    2675      2.09 (  1.69-   2.58)
 XU     19  f   0         17      66      21     141      1.73 (  0.86-   3.49)
 Subtotal XU                                              2.06 (  1.68-   2.52)
 ZIELI1 5   b   0       2158    5341     206    1105      2.17 (  1.85-   2.54)
 ZIELI2 15  b   0       6784   14529    1486    9875      3.10 (  2.92-   3.30)
Partial Totals         10533   26286    2666   19547
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 ANDER1 24  m   1              1.06     1.87     0.00       0.15
 ANDER1 29  f   1              1.54     1.38     0.29       0.07
 Subtotal ANDER1               1.26     3.26     0.30
 DEMARC 11  b   0              1.27    51.59     1.84       0.00
 DETORR 3   m   0              0.54    10.96     3.18       0.07
 DETORR 6   f   0              1.57     2.35     0.55       0.02
 Subtotal DETORR               0.72    13.31     3.73
 FERRI2 66  m   1              0.76    11.36     1.16       0.01
 FERRI2 80  f   1              1.36     5.02     0.38       0.00
 Subtotal FERRI2               0.94    16.38     1.54
 FUKUCH 8   b   0              1.83    19.52    11.13       0.00
*GEIJER 2   m   0              1.42     3.32     0.39       0.01
 JOHANN 8   b   0              1.43    16.94     2.04       0.00
 KIM    12  m   1              1.14    12.19     0.04       0.00
 KIM    17  f   1              2.45     0.99     1.85       0.02
 Subtotal KIM                  1.24    13.18     1.89
 KOJIMA 11  m   0              0.96    14.20     0.19       0.00
 KOJIMA 16  f   0              2.43     0.61     1.11       0.06
 Subtotal KOJIMA               1.02    14.81     1.30
*LIAW   22  b   2              0.12     5.24     4.80       0.78
 MANNI2 8   b   1              1.02    77.46     0.32       0.00
 MENEZ2 11  b   0              0.74    14.72     1.68       0.00
 MENEZ3 8   b   0              1.19    20.30     0.24       0.00
 MENEZ4 8   b   0              0.96     6.30     0.09       0.02
 MENEZ5 8   b   0              1.28    11.27     0.47       0.00
 MENEZ6 8   b   0              1.02    18.08     0.07       0.00
 PEREZP 4   f   0              1.05     2.65     0.00       0.09
 PRICE  3   b   0              1.60    19.28     5.17       0.00
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 5

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 SHIN   10  b   0              1.68     6.67     2.37       0.00
*SPEIZE 17  m   1              1.88     2.52     1.60       0.00
*SPEIZE 22  f   1              1.20     1.50     0.02       0.14
 Subtotal SPEIZE               1.63     4.02     1.62
 XIAO   8   b   0              0.70     3.64     0.51       0.18
 XU     9   m   0              0.74    87.38    10.26       0.00
 XU     19  f   0              0.55     7.77     2.20       0.13
 Subtotal XU                   0.72    95.15    12.46
 ZIELI1 5   b   0              0.77   156.01    14.63       0.00
 ZIELI2 15  b   0              1.13  1009.65     2.80       0.00

                       N       31
                      NS       24

                      Wt  1602.76
                 Het Chi    71.40
                 Het  df       30
                 Het  P       ***
               Fixed  RR     2.94
                     RRl     2.80
                     RRu     3.09
                      P       +++
              Random  RR     2.96
                     RRl     2.61
                     RRu     3.37
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 6

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       31
                      NS       24

                      Wt  1602.76
                 Het Chi    71.40
                 Het  df       30
                 Het  P       ***
               Fixed  RR     2.94
                     RRl     2.80
                     RRu     3.09
                      P       +++
              Random  RR     2.96
                     RRl     2.61
                     RRu     3.37
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N       15         8         8        31
                      NS       15         8         8        31

                      Wt  1436.68    143.81     22.26   1602.76
                 Het Chi    47.26      7.14      6.34     71.40
                 Het  df       14         7         7        30
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     3.02      2.27      3.12      2.94
                     RRl     2.87      1.93      2.06      2.80
                     RRu     3.18      2.67      4.73      3.09
                      P       +++       +++       +++       +++
              Random  RR     3.13      2.29      3.12      2.96
                     RRl     2.68      1.93      2.06      2.61
                     RRu     3.67      2.71      4.73      3.37
                      P       +++       +++       +++       +++
             Between Chi                                  10.66
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        7         6        10         8        31
                      NS        4         5         7         8        24

                      Wt   101.12   1199.22    158.21    144.20   1602.76
                 Het Chi     3.59     23.54     31.81      7.47     71.40
                 Het  df        6         5         9         7        30
                 Het  P      N.S.       ***       ***      N.S.       ***
               Fixed  RR     2.82      2.96      2.59      3.32      2.94
                     RRl     2.32      2.80      2.21      2.82      2.80
                     RRu     3.42      3.14      3.02      3.91      3.09
                      P       +++       +++       +++       +++       +++
              Random  RR     2.82      2.80      2.93      3.31      2.96
                     RRl     2.32      2.14      2.00      2.78      2.61
                     RRu     3.42      3.66      4.30      3.93      3.37
                      P       +++       +++       +++       +++       +++
             Between Chi                                             4.99
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 6

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4        25        31
                      NS        2         3        19        24

                      Wt     6.29     12.58   1583.89   1602.76
                 Het Chi     0.18      6.59     64.06     71.40
                 Het  df        1         3        24        30
                 Het  P      N.S.       (*)       ***       ***
               Fixed  RR     2.34      2.57      2.95      2.94
                     RRl     1.07      1.48      2.81      2.80
                     RRu     5.10      4.47      3.10      3.09
                      P         +       +++       +++       +++
              Random  RR     2.34      2.94      3.00      2.96
                     RRl     1.07      1.25      2.62      2.61
                     RRu     5.10      6.90      3.42      3.37
                      P         +         +       +++       +++
             Between Chi                                   0.57
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3        21         7        31
                      NS        2        18         4        24

                      Wt     9.26   1475.07    118.42   1602.76
                 Het Chi     5.57     49.08      3.19     71.40
                 Het  df        2        20         6        30
                 Het  P       (*)       ***      N.S.       ***
               Fixed  RR     2.17      3.02      2.15      2.94
                     RRl     1.14      2.87      1.80      2.80
                     RRu     4.13      3.18      2.58      3.09
                      P         +       +++       +++       +++
              Random  RR     2.67      3.17      2.15      2.96
                     RRl     0.84      2.76      1.80      2.61
                     RRu     8.52      3.64      2.58      3.37
                      P       (+)       +++       +++       +++
             Between Chi                                  13.55
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                     (*)

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        2        29                  31
                      NS        2        22                  24

                      Wt    96.74   1506.01             1602.76
                 Het Chi     5.24     65.89               71.40
                 Het  df        1        28                  30
                 Het  P         *       ***                 ***
               Fixed  RR     3.10      2.93                2.94
                     RRl     2.54      2.79                2.80
                     RRu     3.78      3.09                3.09
                      P       +++       +++                 +++
              Random  RR     3.57      2.91                2.96
                     RRl     2.03      2.53                2.61
                     RRu     6.30      3.34                3.37
                      P       +++       +++                 +++
             Between Chi                                   0.27
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 7

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3 CLEMEN  COCCI  DEAN1 DEJONG DICKIN  DOLL1  DOLL2
       DONTA1 EKBERG ENSTRO FERRI3  FIDAN FORAST GODTFR GULSVI HAMMO2 HARDIE HARIKK HAWTHO HIGGI4     HO HOZAWA HUHTI1
       HUHTI2 HUHTI3 ITABAS JACOBS JAENDI KACHEL   KAHN  KAHN2 KARAKA KATANC KHOURY  KIRAZ KLAYTO KRZYZA KULLER    LAI
         LAM1   LAM2   LAM3  LANGE LEBOWI    LEE LINDBE LINDST   LIU1 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS
       MATHES MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON   PETO RENWIC RICCIO SARGEA SAWICK SHAHAB SICHLE  SILVA
       STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD  WEISS
          WEN WILSO1 WOJTYN YAMAGU   YUAN ZIETKO
5       CHENG HEDMAN KOTAN2 WATSON
6        LIU2
10     FERRI1

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - G - 9 - 8

                                IESCOPD - Meta-analysis of pack-years : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  DEMARC DEMARC     1         DEMARC/URRUTI/DEMEER
  JOHANN JOHANN     1         HARDIE/JOHANN/BROGGE
  FERRI2 FERRIS     1         FERRI1/FERRI2/FERRI3
  MANNI2 MANNI2     1                MANNI2/MANNI3
    LIAW    WEN     2                     WEN/LIAW
  MENEZ3 MENEZ3     1                 AMIGO/MENEZ3

                                    Most-adjusted - insufficient data for meta-analysis
     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

    LIU2   2   b   40   99   Asia:FarE  2002  2005    CS  Prev      COPD:LF   0 Current       Cigs      10  21   +
          RR|SIG|

        1.14   ?

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - H - 1 -

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Current or ever smoking
4) Categorical dose-response data for duration of smoking
5) High vs low base
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) SMKSTA  : current, ever
8) PROD    : cigarettes, cigarettes only, any product
9) The highest vs lowest category
10) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 1

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

    BEST  51   m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only       9  40   +
    LIAW  12   b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs      20  31   +
   WEISS  13   m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only      39  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 2

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*BEST   51  m   1         55       -       4       -      0.79 (  0.30-   2.10)
*LIAW   12  b   2          -       -       -       -      1.00 (  0.38-   2.64)
 WEISS  13  m   0         16      51       6      36      1.88 (  0.67-   5.28)
Partial Totals            71      51      10      36
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*BEST   51  m   1             -0.24     4.06     0.49       0.63
*LIAW   12  b   2              0.00     4.09     0.05       1.00
 WEISS  13  m   0              0.63     3.62     0.98       0.23

                       N        3
                      NS        3

                      Wt    11.76
                 Het Chi     1.52
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
              Random  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 3

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        3
                      NS        3

                      Wt    11.76
                 Het Chi     1.52
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
              Random  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         2                   3
                      NS        1         2                   3

                      Wt     4.09      7.67               11.76
                 Het Chi     0.00      1.44                1.52
                 Het  df        0         1                   2
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     1.00      1.19                1.12
                     RRl     0.38      0.59                0.63
                     RRu     2.64      2.41                1.98
                      P      N.S.      N.S.                N.S.
              Random  RR     1.00      1.20                1.12
                     RRl     0.38      0.51                0.63
                     RRu     2.64      2.80                1.98
                      P      N.S.      N.S.                N.S.
             Between Chi                                   0.08
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2                   1                   3
                      NS        2                   1                   3

                      Wt     7.67                4.09               11.76
                 Het Chi     1.44                0.00                1.52
                 Het  df        1                   0                   2
                 Het  P      N.S.                N.S.                N.S.
               Fixed  RR     1.19                1.00                1.12
                     RRl     0.59                0.38                0.63
                     RRu     2.41                2.64                1.98
                      P      N.S.                N.S.                N.S.
              Random  RR     1.20                1.00                1.12
                     RRl     0.51                0.38                0.63
                     RRu     2.80                2.64                1.98
                      P      N.S.                N.S.                N.S.
             Between Chi                                             0.08
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 3

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N        1         1         2
                      NS        1         1         2

                      Wt     3.62      4.06      7.67
                 Het Chi     0.00      0.00      1.44
                 Het  df        0         0         1
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     1.88      0.79      1.19
                     RRl     0.67      0.30      0.59
                     RRu     5.28      2.09      2.41
                      P      N.S.      N.S.      N.S.
              Random  RR     1.88      0.79      1.20
                     RRl     0.67      0.30      0.51
                     RRu     5.28      2.09      2.80
                      P      N.S.      N.S.      N.S.
             Between Chi                         1.44
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        2                   1                                       3
                      NS        2                   1                                       3

                      Wt     7.67                4.09                                   11.76
                 Het Chi     1.44                0.00                                    1.52
                 Het  df        1                   0                                       2
                 Het  P      N.S.                N.S.                                    N.S.
               Fixed  RR     1.19                1.00                                    1.12
                     RRl     0.59                0.38                                    0.63
                     RRu     2.41                2.64                                    1.98
                      P      N.S.                N.S.                                    N.S.
              Random  RR     1.20                1.00                                    1.12
                     RRl     0.51                0.38                                    0.63
                     RRu     2.80                2.64                                    1.98
                      P      N.S.                N.S.                                    N.S.
             Between Chi                                                                 0.08
             Between  df                                                                    1
             Between  P                                                                  N.S.
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        2                   1                   3
                      NS        2                   1                   3

                      Wt     7.67                4.09               11.76
                 Het Chi     1.44                0.00                1.52
                 Het  df        1                   0                   2
                 Het  P      N.S.                N.S.                N.S.
               Fixed  RR     1.19                1.00                1.12
                     RRl     0.59                0.38                0.63
                     RRu     2.41                2.64                1.98
                      P      N.S.                N.S.                N.S.
              Random  RR     1.20                1.00                1.12
                     RRl     0.51                0.38                0.63
                     RRu     2.80                2.64                1.98
                      P      N.S.                N.S.                N.S.
             Between Chi                                             0.08
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 3

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2         1         3
                      NS                  2         1         3

                      Wt               8.15      3.62     11.76
                 Het Chi               0.11      0.00      1.52
                 Het  df                  1         0         2
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.89      1.88      1.12
                     RRl               0.45      0.67      0.63
                     RRu               1.77      5.28      1.98
                      P                N.S.      N.S.      N.S.
              Random  RR               0.89      1.88      1.12
                     RRl               0.45      0.67      0.63
                     RRu               1.77      5.28      1.98
                      P                N.S.      N.S.      N.S.
             Between Chi                                   1.41
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N                  1         2                   3
                      NS                  1         2                   3

                      Wt               4.06      7.71               11.76
                 Het Chi               0.00      0.77                1.52
                 Het  df                  0         1                   2
                 Het  P                N.S.      N.S.                N.S.
               Fixed  RR               0.79      1.35                1.12
                     RRl               0.30      0.66                0.63
                     RRu               2.09      2.73                1.98
                      P                N.S.      N.S.                N.S.
              Random  RR               0.79      1.35                1.12
                     RRl               0.30      0.66                0.63
                     RRu               2.09      2.73                1.98
                      P                N.S.      N.S.                N.S.
             Between Chi                                             0.75
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N                  1                   2                   3
                      NS                  1                   2                   3

                      Wt               3.62                8.15               11.76
                 Het Chi               0.00                0.11                1.52
                 Het  df                  0                   1                   2
                 Het  P                N.S.                N.S.                N.S.
               Fixed  RR               1.88                0.89                1.12
                     RRl               0.67                0.45                0.63
                     RRu               5.28                1.77                1.98
                      P                N.S.                N.S.                N.S.
              Random  RR               1.88                0.89                1.12
                     RRl               0.67                0.45                0.63
                     RRu               5.28                1.77                1.98
                      P                N.S.                N.S.                N.S.
             Between Chi                                                       1.41
             Between  df                                                          1
             Between  P                                                        N.S.
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 3

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N                  3         3
                      NS                  3         3

                      Wt              11.76     11.76
                 Het Chi               1.52      1.52
                 Het  df                  2         2
                 Het  P                N.S.      N.S.
               Fixed  RR               1.12      1.12
                     RRl               0.63      0.63
                     RRu               1.98      1.98
                      P                N.S.      N.S.
              Random  RR               1.12      1.12
                     RRl               0.63      0.63
                     RRu               1.98      1.98
                      P                N.S.      N.S.
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2         1                   3
                      NS        2         1                   3

                      Wt     8.15      3.62               11.76
                 Het Chi     0.11      0.00                1.52
                 Het  df        1         0                   2
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     0.89      1.88                1.12
                     RRl     0.45      0.67                0.63
                     RRu     1.77      5.28                1.98
                      P      N.S.      N.S.                N.S.
              Random  RR     0.89      1.88                1.12
                     RRl     0.45      0.67                0.63
                     RRu     1.77      5.28                1.98
                      P      N.S.      N.S.                N.S.
             Between Chi                                   1.41
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N        2                             1         3
                      NS        2                             1         3

                      Wt     7.67                          4.09     11.76
                 Het Chi     1.44                          0.00      1.52
                 Het  df        1                             0         2
                 Het  P      N.S.                          N.S.      N.S.
               Fixed  RR     1.19                          1.00      1.12
                     RRl     0.59                          0.38      0.63
                     RRu     2.41                          2.64      1.98
                      P      N.S.                          N.S.      N.S.
              Random  RR     1.20                          1.00      1.12
                     RRl     0.51                          0.38      0.63
                     RRu     2.80                          2.64      1.98
                      P      N.S.                          N.S.      N.S.
             Between Chi                                             0.08
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 3

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        1                   1
                      NS        1                   1

                      Wt     3.62                3.62
                 Het Chi     0.00                0.00
                 Het  df        0                   0
                 Het  P      N.S.                N.S.
               Fixed  RR     1.88                1.88
                     RRl     0.67                0.67
                     RRu     5.28                5.28
                      P      N.S.                N.S.
              Random  RR     1.88                1.88
                     RRl     0.67                0.67
                     RRu     5.28                5.28
                      P      N.S.                N.S.
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N        1         1         1                   3
                      NS        1         1         1                   3

                      Wt     3.62      4.09      4.06               11.76
                 Het Chi     0.00      0.00      0.00                1.52
                 Het  df        0         0         0                   2
                 Het  P      N.S.      N.S.      N.S.                N.S.
               Fixed  RR     1.88      1.00      0.79                1.12
                     RRl     0.67      0.38      0.30                0.63
                     RRu     5.28      2.64      2.09                1.98
                      P      N.S.      N.S.      N.S.                N.S.
              Random  RR     1.88      1.00      0.79                1.12
                     RRl     0.67      0.38      0.30                0.63
                     RRu     5.28      2.64      2.09                1.98
                      P      N.S.      N.S.      N.S.                N.S.
             Between Chi                                             1.52
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N        1         1         1                   3
                      NS        1         1         1                   3

                      Wt     3.62      4.09      4.06               11.76
                 Het Chi     0.00      0.00      0.00                1.52
                 Het  df        0         0         0                   2
                 Het  P      N.S.      N.S.      N.S.                N.S.
               Fixed  RR     1.88      1.00      0.79                1.12
                     RRl     0.67      0.38      0.30                0.63
                     RRu     5.28      2.64      2.09                1.98
                      P      N.S.      N.S.      N.S.                N.S.
              Random  RR     1.88      1.00      0.79                1.12
                     RRl     0.67      0.38      0.30                0.63
                     RRu     5.28      2.64      2.09                1.98
                      P      N.S.      N.S.      N.S.                N.S.
             Between Chi                                             1.52
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 3

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N        1         2         3
                      NS        1         2         3

                      Wt     3.62      8.15     11.76
                 Het Chi     0.00      0.11      1.52
                 Het  df        0         1         2
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     1.88      0.89      1.12
                     RRl     0.67      0.45      0.63
                     RRu     5.28      1.77      1.98
                      P      N.S.      N.S.      N.S.
              Random  RR     1.88      0.89      1.12
                     RRl     0.67      0.45      0.63
                     RRu     5.28      1.77      1.98
                      P      N.S.      N.S.      N.S.
             Between Chi                         1.41
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         2         3
                      NS                  1         2         3

                      Wt               4.09      7.67     11.76
                 Het Chi               0.00      1.44      1.52
                 Het  df                  0         1         2
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               1.00      1.19      1.12
                     RRl               0.38      0.59      0.63
                     RRu               2.64      2.41      1.98
                      P                N.S.      N.S.      N.S.
              Random  RR               1.00      1.20      1.12
                     RRl               0.38      0.51      0.63
                     RRu               2.64      2.80      1.98
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.08
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                        Number of adjustment variables
                                0         1        2+     Total

                       N        1         1         1         3
                      NS        1         1         1         3

                      Wt     3.62      4.06      4.09     11.76
                 Het Chi     0.00      0.00      0.00      1.52
                 Het  df        0         0         0         2
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     1.88      0.79      1.00      1.12
                     RRl     0.67      0.30      0.38      0.63
                     RRu     5.28      2.09      2.64      1.98
                      P      N.S.      N.S.      N.S.      N.S.
              Random  RR     1.88      0.79      1.00      1.12
                     RRl     0.67      0.30      0.38      0.63
                     RRu     5.28      2.09      2.64      1.98
                      P      N.S.      N.S.      N.S.      N.S.
             Between Chi                                   1.52
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 4

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

    BEST  51     m   30   97   Am:Canada  1955  1967    Pr   Inc    COPD:mort   1 Current  Cigs only       9  40   +
    LIAW  12     b   40   99   Asia:FarE  1982  1998    Pr   Inc    COPD:mort   2 Current       Cigs      20  31   +
   WEISS  13     m   50   69      Am:USA  1961  1963    CS  Prev      COPD:LF   0 Current  Cigs only      39  40   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 5

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*BEST   51  m   1         55       -       4       -      0.79 (  0.30-   2.10)
*LIAW   12  b   2          -       -       -       -      1.00 (  0.38-   2.64)
 WEISS  13  m   0         16      51       6      36      1.88 (  0.67-   5.28)
Partial Totals            71      51      10      36
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*BEST   51  m   1             -0.24     4.06     0.49       0.63
*LIAW   12  b   2              0.00     4.09     0.05       1.00
 WEISS  13  m   0              0.63     3.62     0.98       0.23

                       N        3
                      NS        3

                      Wt    11.76
                 Het Chi     1.52
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
              Random  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 6

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        3
                      NS        3

                      Wt    11.76
                 Het Chi     1.52
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
              Random  RR     1.12
                     RRl     0.63
                     RRu     1.98
                      P      N.S.
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         2                   3
                      NS        1         2                   3

                      Wt     4.09      7.67               11.76
                 Het Chi     0.00      1.44                1.52
                 Het  df        0         1                   2
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     1.00      1.19                1.12
                     RRl     0.38      0.59                0.63
                     RRu     2.64      2.41                1.98
                      P      N.S.      N.S.                N.S.
              Random  RR     1.00      1.20                1.12
                     RRl     0.38      0.51                0.63
                     RRu     2.64      2.80                1.98
                      P      N.S.      N.S.                N.S.
             Between Chi                                   0.08
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2                   1                   3
                      NS        2                   1                   3

                      Wt     7.67                4.09               11.76
                 Het Chi     1.44                0.00                1.52
                 Het  df        1                   0                   2
                 Het  P      N.S.                N.S.                N.S.
               Fixed  RR     1.19                1.00                1.12
                     RRl     0.59                0.38                0.63
                     RRu     2.41                2.64                1.98
                      P      N.S.                N.S.                N.S.
              Random  RR     1.20                1.00                1.12
                     RRl     0.51                0.38                0.63
                     RRu     2.80                2.64                1.98
                      P      N.S.                N.S.                N.S.
             Between Chi                                             0.08
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 6

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2         1         3
                      NS                  2         1         3

                      Wt               8.15      3.62     11.76
                 Het Chi               0.11      0.00      1.52
                 Het  df                  1         0         2
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.89      1.88      1.12
                     RRl               0.45      0.67      0.63
                     RRu               1.77      5.28      1.98
                      P                N.S.      N.S.      N.S.
              Random  RR               0.89      1.88      1.12
                     RRl               0.45      0.67      0.63
                     RRu               1.77      5.28      1.98
                      P                N.S.      N.S.      N.S.
             Between Chi                                   1.41
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2         1                   3
                      NS        2         1                   3

                      Wt     8.15      3.62               11.76
                 Het Chi     0.11      0.00                1.52
                 Het  df        1         0                   2
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     0.89      1.88                1.12
                     RRl     0.45      0.67                0.63
                     RRu     1.77      5.28                1.98
                      P      N.S.      N.S.                N.S.
              Random  RR     0.89      1.88                1.12
                     RRl     0.45      0.67                0.63
                     RRu     1.77      5.28                1.98
                      P      N.S.      N.S.                N.S.
             Between Chi                                   1.41
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         2         3
                      NS                  1         2         3

                      Wt               4.09      7.67     11.76
                 Het Chi               0.00      1.44      1.52
                 Het  df                  0         1         2
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               1.00      1.19      1.12
                     RRl               0.38      0.59      0.63
                     RRu               2.64      2.41      1.98
                      P                N.S.      N.S.      N.S.
              Random  RR               1.00      1.20      1.12
                     RRl               0.38      0.51      0.63
                     RRu               2.64      2.80      1.98
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.08
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 7

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      VINEIS
4      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI  DEAN1 DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FORAST FUKUCH GEIJER GODTFR GULSVI HAMMO2
       HARDIE HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI2 HUHTI3 ITABAS JACOBS JAENDI JOHANN KACHEL   KAHN
        KAHN2 KARAKA KATANC KHOURY    KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KRZYZA KULLER    LAI   LAM1   LAM2   LAM3  LANGE
       LEBOWI    LEE LINDBE LINDST   LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI2 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2
       MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO
       SARGEA SAWICK SHAHAB   SHIN SICHLE  SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA
       VESTBO VIEGI2 VOLLM1 VOLLM2 VONHER   WALD WATSON    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2
       ZIETKO

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - H - 1 - 8

                            IESCOPD - Meta-analysis of duration of smoking : highest vs lowest
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    LIAW    WEN     2                     WEN/LIAW

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 1 -

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) vs never smoking base
5) Key value = 12
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) UNEXP   : never any, never cigarettes
8) PROD    : cigarettes, cigarettes only, any product
9) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 1

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  49   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   9   +
   DEAN1  84   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   9   +
  FORAST  10   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   1      Ex       Cigs  Nev cigs  11   +
  HUHTI2   7   m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any  10   +
  HUHTI2  10   f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any  10   +
  JACOBS   7   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Nev cigs  10   +
    KAHN  27   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any  10  19
  KRZYZA  14   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13
  KRZYZA  19   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13
  MANNI2   9   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Nev any  10   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 2

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  49  m   1         42       -      47       -      1.82 (  1.16-   2.86)
 DEAN1  84  f   1         15       -     120       -      1.99 (  1.13-   3.52)
 Subtotal DEAN1                                           1.88 (  1.32-   2.68)
 FORAST 10  f   1         23       -      28       -      1.41 (  0.80-   2.48)
 HUHTI2 7   m   0          6      90       0      76     10.99~(  0.61- 198.22)
 HUHTI2 10  f   0          1      21      15     477      1.51 (  0.19-  12.01)
 Subtotal HUHTI2                                          2.96 (  0.55-  15.97)
*JACOBS 7   m   2          8       -      28       -      1.43 (  0.58-   3.50)
*KAHN   27  m   2        224       -     243       -      7.80 (  6.30-   9.70)
*KRZYZA 14  m   1          4       -       5       -      2.57 (  0.70-   9.41)
*KRZYZA 19  f   1          0       -      32       -      0.74 (  0.05-  11.54)
 Subtotal KRZYZA                                          2.04 (  0.63-   6.59)
 MANNI2 9   b   1         44       -     202       -      1.26 (  0.89-   1.78)
Partial Totals           367     111     720     553
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  49  m   1              0.60    18.87     7.70       0.01
 DEAN1  84  f   1              0.69    11.90     3.59       0.02
 Subtotal DEAN1                0.63    30.77    11.29
 FORAST 10  f   1              0.34    12.00     9.59       0.23
 HUHTI2 7   m   0              2.40     0.46     0.62       0.10
 HUHTI2 10  f   0              0.41     0.90     0.61       0.69
 Subtotal HUHTI2               1.09     1.35     1.22
*JACOBS 7   m   2              0.36     4.76     3.68       0.44
*KAHN   27  m   2              2.05    82.50    55.01       0.00
*KRZYZA 14  m   1              0.94     2.28     0.20       0.15
*KRZYZA 19  f   1             -0.30     0.52     1.23       0.83
 Subtotal KRZYZA               0.71     2.79     1.42
 MANNI2 9   b   1              0.23    31.98    32.39       0.19

                       N       10
                      NS        7

                      Wt   166.16
                 Het Chi   114.62
                 Het  df        9
                 Het  P       ***
               Fixed  RR     3.45
                     RRl     2.96
                     RRu     4.01
                      P       +++
              Random  RR     2.12
                     RRl     1.06
                     RRu     4.26
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       10
                      NS        7

                      Wt   166.16
                 Het Chi   114.62
                 Het  df        9
                 Het  P       ***
               Fixed  RR     3.45
                     RRl     2.96
                     RRu     4.01
                      P       +++
              Random  RR     2.12
                     RRl     1.06
                     RRu     4.26
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    31.98    108.86     25.32    166.16
                 Het Chi     0.00     43.31      1.05    114.62
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.26      5.51      1.64      3.45
                     RRl     0.89      4.56      1.11      2.96
                     RRu     1.78      6.64      2.42      4.01
                      P      N.S.       +++         +       +++
              Random  RR     1.26      3.12      1.64      2.12
                     RRl     0.89      1.18      1.11      1.06
                     RRu     1.78      8.27      2.42      4.26
                      P      N.S.         +         +         +
             Between Chi                                  70.25
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt   126.48     34.92                4.76    166.16
                 Het Chi    92.27      2.18                0.00    114.62
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     4.18      1.93                1.43      3.45
                     RRl     3.51      1.38                0.58      2.96
                     RRu     4.98      2.69                3.51      4.01
                      P       +++       +++                N.S.       +++
              Random  RR     2.43      1.93                1.43      2.12
                     RRl     0.62      1.38                0.58      1.06
                     RRu     9.56      2.69                3.51      4.26
                      P      N.S.       +++                N.S.         +
             Between Chi                                            20.16
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    30.77     90.05     45.34    166.16
                 Het Chi     0.06     17.82      2.20    114.62
                 Het  df        1         3         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.88      6.84      1.33      3.45
                     RRl     1.32      5.56      1.00      2.96
                     RRu     2.68      8.41      1.78      4.01
                      P       +++       +++       (+)       +++
              Random  RR     1.88      2.73      1.33      2.12
                     RRl     1.32      0.84      1.00      1.06
                     RRu     2.68      8.90      1.78      4.26
                      P       +++       (+)       (+)         +
             Between Chi                                  94.54
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt   118.02     36.13     12.00    166.16
                 Het Chi    53.14      3.31      0.00    114.62
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     5.03      1.35      1.41      3.45
                     RRl     4.20      0.97      0.80      2.96
                     RRu     6.02      1.87      2.48      4.01
                      P       +++       (+)      N.S.       +++
              Random  RR     2.61      1.35      1.41      2.12
                     RRl     0.99      0.97      0.80      1.06
                     RRu     6.90      1.87      2.48      4.26
                      P       (+)       (+)      N.S.         +
             Between Chi                                  58.17
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    33.34    102.05     30.77    166.16
                 Het Chi     2.14     44.24      0.06    114.62
                 Het  df        2         4         1         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.30      5.68      1.88      3.45
                     RRl     0.93      4.68      1.32      2.96
                     RRu     1.83      6.90      2.68      4.01
                      P      N.S.       +++       +++       +++
              Random  RR     1.37      2.30      1.88      2.12
                     RRl     0.80      0.77      1.32      1.06
                     RRu     2.37      6.81      2.68      4.26
                      P      N.S.      N.S.       +++         +
             Between Chi                                  68.18
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        6         4                            10
                      NS        4         3                             7

                      Wt   146.61     19.55                        166.16
                 Het Chi    98.09      0.98                        114.62
                 Het  df        5         3                             9
                 Het  P       ***      N.S.                           ***
               Fixed  RR     3.85      1.49                          3.45
                     RRl     3.28      0.96                          2.96
                     RRu     4.53      2.32                          4.01
                      P       +++       (+)                           +++
              Random  RR     2.60      1.49                          2.12
                     RRl     1.03      0.96                          1.06
                     RRu     6.57      2.32                          4.26
                      P         +       (+)                             +
             Between Chi                                            15.56
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        6         4        10
                      NS        4         3         7

                      Wt   146.61     19.55    166.16
                 Het Chi    98.09      0.98    114.62
                 Het  df        5         3         9
                 Het  P       ***      N.S.       ***
               Fixed  RR     3.85      1.49      3.45
                     RRl     3.28      0.96      2.96
                     RRu     4.53      2.32      4.01
                      P       +++       (+)       +++
              Random  RR     2.60      1.49      2.12
                     RRl     1.03      0.96      1.06
                     RRu     6.57      2.32      4.26
                      P         +       (+)         +
             Between Chi                        15.56
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 4

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  39 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   9   +
   DEAN1  79 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   9   +
  FORAST   7 x   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   0      Ex       Cigs  Nev cigs  11   +
  HUHTI2   7     m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any  10   +
  HUHTI2  10     f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any  10   +
  JACOBS   7     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Nev cigs  10   +
    KAHN  27     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any  10  19
  KRZYZA  14     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13
  KRZYZA  19     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13
  MANNI2   9     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Nev any  10   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 5

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  39  m   0         42     152      47     510      3.00 (  1.90-   4.72)
 DEAN1  79  f   0         15     114     120    1538      1.69 (  0.95-   2.98)
 Subtotal DEAN1                                           2.40 (  1.68-   3.42)
 FORAST 7   f   0         23     325      28     531      1.34 (  0.76-   2.37)
 HUHTI2 7   m   0          6      90       0      76     10.99~(  0.61- 198.22)
 HUHTI2 10  f   0          1      21      15     477      1.51 (  0.19-  12.01)
 Subtotal HUHTI2                                          2.96 (  0.55-  15.97)
*JACOBS 7   m   2          8       -      28       -      1.43 (  0.58-   3.50)
*KAHN   27  m   2        224       -     243       -      7.80 (  6.30-   9.70)
*KRZYZA 14  m   1          4       -       5       -      2.57 (  0.70-   9.41)
*KRZYZA 19  f   1          0       -      32       -      0.74 (  0.05-  11.54)
 Subtotal KRZYZA                                          2.04 (  0.63-   6.59)
 MANNI2 9   b   1         44       -     202       -      1.26 (  0.89-   1.78)
Partial Totals           367     702     720    3132
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  39  m   0              1.10    18.65     0.62       0.00
 DEAN1  79  f   0              0.52    11.85     6.80       0.07
 Subtotal DEAN1                0.87    30.49     7.41
 FORAST 7   f   0              0.29    11.88    11.55       0.31
 HUHTI2 7   m   0              2.40     0.46     0.57       0.10
 HUHTI2 10  f   0              0.41     0.90     0.67       0.69
 Subtotal HUHTI2               1.09     1.35     1.24
*JACOBS 7   m   2              0.36     4.76     4.05       0.44
*KAHN   27  m   2              2.05    82.50    49.43       0.00
*KRZYZA 14  m   1              0.94     2.28     0.26       0.15
*KRZYZA 19  f   1             -0.30     0.52     1.30       0.83
 Subtotal KRZYZA               0.71     2.79     1.55
 MANNI2 9   b   1              0.23    31.98    35.19       0.19

                       N       10
                      NS        7

                      Wt   165.76
                 Het Chi   110.43
                 Het  df        9
                 Het  P       ***
               Fixed  RR     3.60
                     RRl     3.09
                     RRu     4.19
                      P       +++
              Random  RR     2.21
                     RRl     1.11
                     RRu     4.38
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       10
                      NS        7

                      Wt   165.76
                 Het Chi   110.43
                 Het  df        9
                 Het  P       ***
               Fixed  RR     3.60
                     RRl     3.09
                     RRu     4.19
                      P       +++
              Random  RR     2.21
                     RRl     1.11
                     RRu     4.38
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    31.98    108.64     25.14    165.76
                 Het Chi     0.00     26.24      0.57    110.43
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.26      6.01      1.48      3.60
                     RRl     0.89      4.98      1.00      3.09
                     RRu     1.78      7.26      2.19      4.19
                      P      N.S.       +++         +       +++
              Random  RR     1.26      3.56      1.48      2.21
                     RRl     0.89      1.64      1.00      1.11
                     RRu     1.78      7.74      2.19      4.38
                      P      N.S.        ++         +         +
             Between Chi                                  83.62
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt   126.36     34.64                4.76    165.76
                 Het Chi    93.43      4.38                0.00    110.43
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     4.17      2.39                1.43      3.60
                     RRl     3.50      1.71                0.58      3.09
                     RRu     4.96      3.33                3.51      4.19
                      P       +++       +++                N.S.       +++
              Random  RR     2.39      2.39                1.43      2.21
                     RRl     0.60      1.71                0.58      1.11
                     RRu     9.50      3.33                3.51      4.38
                      P      N.S.       +++                N.S.         +
             Between Chi                                            12.61
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    30.49     90.05     45.22    165.76
                 Het Chi     2.40     17.82      2.15    110.43
                 Het  df        1         3         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     2.40      6.84      1.31      3.60
                     RRl     1.68      5.56      0.98      3.09
                     RRu     3.42      8.41      1.76      4.19
                      P       +++       +++       (+)       +++
              Random  RR     2.31      2.73      1.31      2.21
                     RRl     1.32      0.84      0.98      1.11
                     RRu     4.05      8.90      1.76      4.38
                      P        ++       (+)       (+)         +
             Between Chi                                  88.06
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt   117.75     36.13     11.88    165.76
                 Het Chi    42.05      3.31      0.00    110.43
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     5.37      1.35      1.34      3.60
                     RRl     4.48      0.97      0.76      3.09
                     RRu     6.43      1.87      2.37      4.19
                      P       +++       (+)      N.S.       +++
              Random  RR     2.88      1.35      1.34      2.21
                     RRl     1.21      0.97      0.76      1.11
                     RRu     6.87      1.87      2.37      4.38
                      P         +       (+)      N.S.         +
             Between Chi                                  65.07
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    33.34    101.93     30.49    165.76
                 Het Chi     2.14     45.67      2.40    110.43
                 Het  df        2         4         1         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.30      5.66      2.40      3.60
                     RRl     0.93      4.66      1.68      3.09
                     RRu     1.83      6.87      3.42      4.19
                      P      N.S.       +++       +++       +++
              Random  RR     1.37      2.26      2.31      2.21
                     RRl     0.80      0.75      1.32      1.11
                     RRu     2.37      6.83      4.05      4.38
                      P      N.S.      N.S.        ++         +
             Between Chi                                  60.22
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        6         4                            10
                      NS        4         3                             7

                      Wt   146.33     19.43                        165.76
                 Het Chi    91.14      1.05                        110.43
                 Het  df        5         3                             9
                 Het  P       ***      N.S.                           ***
               Fixed  RR     4.06      1.45                          3.60
                     RRl     3.45      0.93                          3.09
                     RRu     4.77      2.26                          4.19
                      P       +++      N.S.                           +++
              Random  RR     2.78      1.45                          2.21
                     RRl     1.13      0.93                          1.11
                     RRu     6.83      2.26                          4.38
                      P         +      N.S.                             +
             Between Chi                                            18.23
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        6         4        10
                      NS        4         3         7

                      Wt   146.33     19.43    165.76
                 Het Chi    91.14      1.05    110.43
                 Het  df        5         3         9
                 Het  P       ***      N.S.       ***
               Fixed  RR     4.06      1.45      3.60
                     RRl     3.45      0.93      3.09
                     RRu     4.77      2.26      4.19
                      P       +++      N.S.       +++
              Random  RR     2.78      1.45      2.21
                     RRl     1.13      0.93      1.11
                     RRu     6.83      2.26      4.38
                      P         +      N.S.         +
             Between Chi                        18.23
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 7

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 1 - 8

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI2 HUHTI1     2                HUHTI1/HUHTI2
  MANNI2 MANNI2     1                MANNI2/MANNI3
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 2 -

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) vs never smoking base
5) Key value = 7
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) UNEXP   : never any, never cigarettes
8) PROD    : cigarettes, cigarettes only, any product
9) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 1

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  50   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   5   8
   DEAN1  85   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   5   8
    KAHN  28   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any   5   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 2

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  50  m   1         15       -      47       -      2.52 (  1.30-   4.87)
 DEAN1  85  f   1          6       -     120       -      2.64 (  1.09-   6.37)
 Subtotal DEAN1                                           2.56 (  1.51-   4.35)
*KAHN   28  m   2         71       -     243       -     16.50 ( 10.90-  24.90)
Partial Totals            92       0     410       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  50  m   1              0.92     8.81    12.13       0.01
 DEAN1  85  f   1              0.97     4.93     6.26       0.03
 Subtotal DEAN1                0.94    13.74    18.39
*KAHN   28  m   2              2.80    22.52    11.22       0.00

                       N        3
                      NS        2

                      Wt    36.25
                 Het Chi    29.60
                 Het  df        2
                 Het  P       ***
               Fixed  RR     8.15
                     RRl     5.88
                     RRu    11.28
                      P       +++
              Random  RR     4.94
                     RRl     1.21
                     RRu    20.07
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        3
                      NS        2

                      Wt    36.25
                 Het Chi    29.60
                 Het  df        2
                 Het  P       ***
               Fixed  RR     8.15
                     RRl     5.88
                     RRu    11.28
                      P       +++
              Random  RR     4.94
                     RRl     1.21
                     RRu    20.07
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         3

                      Wt              31.32      4.93     36.25
                 Het Chi              22.36      0.00     29.60
                 Het  df                  1         0         2
                 Het  P                 ***      N.S.       ***
               Fixed  RR               9.73      2.64      8.15
                     RRl               6.85      1.09      5.88
                     RRu              13.81      6.38     11.28
                      P                 +++         +       +++
              Random  RR               6.57      2.64      4.94
                     RRl               1.04      1.09      1.21
                     RRu              41.40      6.38     20.07
                      P                   +         +         +
             Between Chi                                   7.24
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    22.52     13.74                         36.25
                 Het Chi     0.00      0.01                         29.60
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           ***
               Fixed  RR    16.50      2.56                          8.15
                     RRl    10.92      1.51                          5.88
                     RRu    24.94      4.35                         11.28
                      P       +++       +++                           +++
              Random  RR    16.50      2.56                          4.94
                     RRl    10.92      1.51                          1.21
                     RRu    24.94      4.35                         20.07
                      P       +++       +++                             +
             Between Chi                                            29.60
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                                **

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         1                   3
                      NS        1         1                   2

                      Wt    13.74     22.52               36.25
                 Het Chi     0.01      0.00               29.60
                 Het  df        1         0                   2
                 Het  P      N.S.      N.S.                 ***
               Fixed  RR     2.56     16.50                8.15
                     RRl     1.51     10.92                5.88
                     RRu     4.35     24.94               11.28
                      P       +++       +++                 +++
              Random  RR     2.56     16.50                4.94
                     RRl     1.51     10.92                1.21
                     RRu     4.35     24.94               20.07
                      P       +++       +++                   +
             Between Chi                                  29.60
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N        3                             3
                      NS        2                             2

                      Wt    36.25                         36.25
                 Het Chi    29.60                         29.60
                 Het  df        2                             2
                 Het  P       ***                           ***
               Fixed  RR     8.15                          8.15
                     RRl     5.88                          5.88
                     RRu    11.28                         11.28
                      P       +++                           +++
              Random  RR     4.94                          4.94
                     RRl     1.21                          1.21
                     RRu    20.07                         20.07
                      P         +                             +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         2         3
                      NS                  1         1         2

                      Wt              22.52     13.74     36.25
                 Het Chi               0.00      0.01     29.60
                 Het  df                  0         1         2
                 Het  P                N.S.      N.S.       ***
               Fixed  RR              16.50      2.56      8.15
                     RRl              10.92      1.51      5.88
                     RRu              24.94      4.35     11.28
                      P                 +++       +++       +++
              Random  RR              16.50      2.56      4.94
                     RRl              10.92      1.51      1.21
                     RRu              24.94      4.35     20.07
                      P                 +++       +++         +
             Between Chi                                  29.60
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                      **
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3                                       3
                      NS        2                                       2

                      Wt    36.25                                   36.25
                 Het Chi    29.60                                   29.60
                 Het  df        2                                       2
                 Het  P       ***                                     ***
               Fixed  RR     8.15                                    8.15
                     RRl     5.88                                    5.88
                     RRu    11.28                                   11.28
                      P       +++                                     +++
              Random  RR     4.94                                    4.94
                     RRl     1.21                                    1.21
                     RRu    20.07                                   20.07
                      P         +                                       +
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3                   3
                      NS        2                   2

                      Wt    36.25               36.25
                 Het Chi    29.60               29.60
                 Het  df        2                   2
                 Het  P       ***                 ***
               Fixed  RR     8.15                8.15
                     RRl     5.88                5.88
                     RRu    11.28               11.28
                      P       +++                 +++
              Random  RR     4.94                4.94
                     RRl     1.21                1.21
                     RRu    20.07               20.07
                      P         +                   +
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 4

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  40 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   5   8
   DEAN1  80 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   5   8
    KAHN  28     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any   5   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 5

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  40  m   0         15      43      47     510      3.79 (  1.96-   7.32)
 DEAN1  80  f   0          6      38     120    1538      2.02 (  0.84-   4.88)
 Subtotal DEAN1                                           3.02 (  1.78-   5.12)
*KAHN   28  m   2         71       -     243       -     16.50 ( 10.90-  24.90)
Partial Totals            92      81     410    2048
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  40  m   0              1.33     8.84     6.05       0.00
 DEAN1  80  f   0              0.70     4.95    10.47       0.12
 Subtotal DEAN1                1.11    13.79    16.52
*KAHN   28  m   2              2.80    22.52     9.35       0.00

                       N        3
                      NS        2

                      Wt    36.30
                 Het Chi    25.87
                 Het  df        2
                 Het  P       ***
               Fixed  RR     8.66
                     RRl     6.26
                     RRu    11.99
                      P       +++
              Random  RR     5.23
                     RRl     1.41
                     RRu    19.37
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        3
                      NS        2

                      Wt    36.30
                 Het Chi    25.87
                 Het  df        2
                 Het  P       ***
               Fixed  RR     8.66
                     RRl     6.26
                     RRu    11.99
                      P       +++
              Random  RR     5.23
                     RRl     1.41
                     RRu    19.37
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         3

                      Wt              31.35      4.95     36.30
                 Het Chi              13.76      0.00     25.87
                 Het  df                  1         0         2
                 Het  P                 ***      N.S.       ***
               Fixed  RR              10.90      2.02      8.66
                     RRl               7.68      0.84      6.26
                     RRu              15.46      4.88     11.99
                      P                 +++      N.S.       +++
              Random  RR               8.09      2.02      5.23
                     RRl               1.91      0.84      1.41
                     RRu              34.21      4.88     19.37
                      P                  ++      N.S.         +
             Between Chi                                  12.12
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    22.52     13.79                         36.30
                 Het Chi     0.00      1.24                         25.87
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           ***
               Fixed  RR    16.50      3.02                          8.66
                     RRl    10.92      1.78                          6.26
                     RRu    24.94      5.12                         11.99
                      P       +++       +++                           +++
              Random  RR    16.50      2.97                          5.23
                     RRl    10.92      1.63                          1.41
                     RRu    24.94      5.40                         19.37
                      P       +++       +++                             +
             Between Chi                                            24.63
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         1                   3
                      NS        1         1                   2

                      Wt    13.79     22.52               36.30
                 Het Chi     1.24      0.00               25.87
                 Het  df        1         0                   2
                 Het  P      N.S.      N.S.                 ***
               Fixed  RR     3.02     16.50                8.66
                     RRl     1.78     10.92                6.26
                     RRu     5.12     24.94               11.99
                      P       +++       +++                 +++
              Random  RR     2.97     16.50                5.23
                     RRl     1.63     10.92                1.41
                     RRu     5.40     24.94               19.37
                      P       +++       +++                   +
             Between Chi                                  24.63
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3                             3
                      NS        2                             2

                      Wt    36.30                         36.30
                 Het Chi    25.87                         25.87
                 Het  df        2                             2
                 Het  P       ***                           ***
               Fixed  RR     8.66                          8.66
                     RRl     6.26                          6.26
                     RRu    11.99                         11.99
                      P       +++                           +++
              Random  RR     5.23                          5.23
                     RRl     1.41                          1.41
                     RRu    19.37                         19.37
                      P         +                             +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         2         3
                      NS                  1         1         2

                      Wt              22.52     13.79     36.30
                 Het Chi               0.00      1.24     25.87
                 Het  df                  0         1         2
                 Het  P                N.S.      N.S.       ***
               Fixed  RR              16.50      3.02      8.66
                     RRl              10.92      1.78      6.26
                     RRu              24.94      5.12     11.99
                      P                 +++       +++       +++
              Random  RR              16.50      2.97      5.23
                     RRl              10.92      1.63      1.41
                     RRu              24.94      5.40     19.37
                      P                 +++       +++         +
             Between Chi                                  24.63
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3                                       3
                      NS        2                                       2

                      Wt    36.30                                   36.30
                 Het Chi    25.87                                   25.87
                 Het  df        2                                       2
                 Het  P       ***                                     ***
               Fixed  RR     8.66                                    8.66
                     RRl     6.26                                    6.26
                     RRu    11.99                                   11.99
                      P       +++                                     +++
              Random  RR     5.23                                    5.23
                     RRl     1.41                                    1.41
                     RRu    19.37                                   19.37
                      P         +                                       +
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3                   3
                      NS        2                   2

                      Wt    36.30               36.30
                 Het Chi    25.87               25.87
                 Het  df        2                   2
                 Het  P       ***                 ***
               Fixed  RR     8.66                8.66
                     RRl     6.26                6.26
                     RRu    11.99               11.99
                      P       +++                 +++
              Random  RR     5.23                5.23
                     RRl     1.41                1.41
                     RRu    19.37               19.37
                      P         +                   +
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 7

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
5      FORAST HUHTI2 JACOBS KRZYZA MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 2 - 8

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 3 -

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) vs never smoking base
5) Key value = 3
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) UNEXP   : never any, never cigarettes
8) PROD    : cigarettes, cigarettes only, any product
9) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 1

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  51   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   1   4
   DEAN1  86   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   1   4
    KAHN  29   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any   1   4

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 2

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  51  m   1         24       -      47       -      2.27 (  1.33-   3.88)
 DEAN1  86  f   1          7       -     120       -      1.26 (  0.57-   2.77)
 Subtotal DEAN1                                           1.89 (  1.21-   2.94)
*KAHN   29  m   2         20       -     243       -     24.10 ( 11.20-  51.80)
Partial Totals            51       0     410       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  51  m   1              0.82    13.40     2.77       0.00
 DEAN1  86  f   1              0.23     6.15     6.69       0.57
 Subtotal DEAN1                0.63    19.55     9.45
*KAHN   29  m   2              3.18     6.55    23.85       0.00

                       N        3
                      NS        2

                      Wt    26.10
                 Het Chi    33.31
                 Het  df        2
                 Het  P       ***
               Fixed  RR     3.58
                     RRl     2.44
                     RRu     5.25
                      P       +++
              Random  RR     4.08
                     RRl     0.80
                     RRu    20.77
                      P       (+)
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        3
                      NS        2

                      Wt    26.10
                 Het Chi    33.31
                 Het  df        2
                 Het  P       ***
               Fixed  RR     3.58
                     RRl     2.44
                     RRu     5.25
                      P       +++
              Random  RR     4.08
                     RRl     0.80
                     RRu    20.77
                      P       (+)
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         3

                      Wt              19.96      6.15     26.10
                 Het Chi              24.56      0.00     33.31
                 Het  df                  1         0         2
                 Het  P                 ***      N.S.       ***
               Fixed  RR               4.93      1.26      3.58
                     RRl               3.18      0.57      2.44
                     RRu               7.65      2.78      5.25
                      P                 +++      N.S.       +++
              Random  RR               7.28      1.26      4.08
                     RRl               0.72      0.57      0.80
                     RRu              73.66      2.78     20.77
                      P                 (+)      N.S.       (+)
             Between Chi                                   8.75
             Between  df                                      1
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt     6.55     19.55                         26.10
                 Het Chi     0.00      1.46                         33.31
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           ***
               Fixed  RR    24.10      1.89                          3.58
                     RRl    11.21      1.21                          2.44
                     RRu    51.83      2.94                          5.25
                      P       +++        ++                           +++
              Random  RR    24.10      1.82                          4.08
                     RRl    11.21      1.04                          0.80
                     RRu    51.83      3.18                         20.77
                      P       +++         +                           (+)
             Between Chi                                            31.85
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         1                   3
                      NS        1         1                   2

                      Wt    19.55      6.55               26.10
                 Het Chi     1.46      0.00               33.31
                 Het  df        1         0                   2
                 Het  P      N.S.      N.S.                 ***
               Fixed  RR     1.89     24.10                3.58
                     RRl     1.21     11.21                2.44
                     RRu     2.94     51.83                5.25
                      P        ++       +++                 +++
              Random  RR     1.82     24.10                4.08
                     RRl     1.04     11.21                0.80
                     RRu     3.18     51.83               20.77
                      P         +       +++                 (+)
             Between Chi                                  31.85
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3                             3
                      NS        2                             2

                      Wt    26.10                         26.10
                 Het Chi    33.31                         33.31
                 Het  df        2                             2
                 Het  P       ***                           ***
               Fixed  RR     3.58                          3.58
                     RRl     2.44                          2.44
                     RRu     5.25                          5.25
                      P       +++                           +++
              Random  RR     4.08                          4.08
                     RRl     0.80                          0.80
                     RRu    20.77                         20.77
                      P       (+)                           (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         2         3
                      NS                  1         1         2

                      Wt               6.55     19.55     26.10
                 Het Chi               0.00      1.46     33.31
                 Het  df                  0         1         2
                 Het  P                N.S.      N.S.       ***
               Fixed  RR              24.10      1.89      3.58
                     RRl              11.21      1.21      2.44
                     RRu              51.83      2.94      5.25
                      P                 +++        ++       +++
              Random  RR              24.10      1.82      4.08
                     RRl              11.21      1.04      0.80
                     RRu              51.83      3.18     20.77
                      P                 +++         +       (+)
             Between Chi                                  31.85
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3                                       3
                      NS        2                                       2

                      Wt    26.10                                   26.10
                 Het Chi    33.31                                   33.31
                 Het  df        2                                       2
                 Het  P       ***                                     ***
               Fixed  RR     3.58                                    3.58
                     RRl     2.44                                    2.44
                     RRu     5.25                                    5.25
                      P       +++                                     +++
              Random  RR     4.08                                    4.08
                     RRl     0.80                                    0.80
                     RRu    20.77                                   20.77
                      P       (+)                                     (+)
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3                   3
                      NS        2                   2

                      Wt    26.10               26.10
                 Het Chi    33.31               33.31
                 Het  df        2                   2
                 Het  P       ***                 ***
               Fixed  RR     3.58                3.58
                     RRl     2.44                2.44
                     RRu     5.25                5.25
                      P       +++                 +++
              Random  RR     4.08                4.08
                     RRl     0.80                0.80
                     RRu    20.77               20.77
                      P       (+)                 (+)
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 4

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  41 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   1   4
   DEAN1  81 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   1   4
    KAHN  29     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any   1   4

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 5

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  41  m   0         24     102      47     510      2.55 (  1.49-   4.36)
 DEAN1  81  f   0          7     110     120    1538      0.82 (  0.37-   1.79)
 Subtotal DEAN1                                           1.78 (  1.14-   2.77)
*KAHN   29  m   2         20       -     243       -     24.10 ( 11.20-  51.80)
Partial Totals            51     212     410    2048
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  41  m   0              0.94    13.39     1.14       0.00
 DEAN1  81  f   0             -0.20     6.21    12.75       0.61
 Subtotal DEAN1                0.58    19.60    13.88
*KAHN   29  m   2              3.18     6.55    25.00       0.00

                       N        3
                      NS        2

                      Wt    26.15
                 Het Chi    38.89
                 Het  df        2
                 Het  P       ***
               Fixed  RR     3.42
                     RRl     2.33
                     RRu     5.01
                      P       +++
              Random  RR     3.68
                     RRl     0.64
                     RRu    21.31
                      P      N.S.
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        3
                      NS        2

                      Wt    26.15
                 Het Chi    38.89
                 Het  df        2
                 Het  P       ***
               Fixed  RR     3.42
                     RRl     2.33
                     RRu     5.01
                      P       +++
              Random  RR     3.68
                     RRl     0.64
                     RRu    21.31
                      P      N.S.
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         3

                      Wt              19.94      6.21     26.15
                 Het Chi              22.17      0.00     38.89
                 Het  df                  1         0         2
                 Het  P                 ***      N.S.       ***
               Fixed  RR               5.34      0.82      3.42
                     RRl               3.44      0.37      2.33
                     RRu               8.28      1.79      5.01
                      P                 +++      N.S.       +++
              Random  RR               7.71      0.82      3.68
                     RRl               0.85      0.37      0.64
                     RRu              69.55      1.79     21.31
                      P                 (+)      N.S.      N.S.
             Between Chi                                  16.72
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt     6.55     19.60                         26.15
                 Het Chi     0.00      5.53                         38.89
                 Het  df        0         1                             2
                 Het  P      N.S.         *                           ***
               Fixed  RR    24.10      1.78                          3.42
                     RRl    11.21      1.14                          2.33
                     RRu    51.83      2.77                          5.01
                      P       +++         +                           +++
              Random  RR    24.10      1.50                          3.68
                     RRl    11.21      0.49                          0.64
                     RRu    51.83      4.57                         21.31
                      P       +++      N.S.                          N.S.
             Between Chi                                            33.36
             Between  df                                                1
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         1                   3
                      NS        1         1                   2

                      Wt    19.60      6.55               26.15
                 Het Chi     5.53      0.00               38.89
                 Het  df        1         0                   2
                 Het  P         *      N.S.                 ***
               Fixed  RR     1.78     24.10                3.42
                     RRl     1.14     11.21                2.33
                     RRu     2.77     51.83                5.01
                      P         +       +++                 +++
              Random  RR     1.50     24.10                3.68
                     RRl     0.49     11.21                0.64
                     RRu     4.57     51.83               21.31
                      P      N.S.       +++                N.S.
             Between Chi                                  33.36
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3                             3
                      NS        2                             2

                      Wt    26.15                         26.15
                 Het Chi    38.89                         38.89
                 Het  df        2                             2
                 Het  P       ***                           ***
               Fixed  RR     3.42                          3.42
                     RRl     2.33                          2.33
                     RRu     5.01                          5.01
                      P       +++                           +++
              Random  RR     3.68                          3.68
                     RRl     0.64                          0.64
                     RRu    21.31                         21.31
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  1         2         3
                      NS                  1         1         2

                      Wt               6.55     19.60     26.15
                 Het Chi               0.00      5.53     38.89
                 Het  df                  0         1         2
                 Het  P                N.S.         *       ***
               Fixed  RR              24.10      1.78      3.42
                     RRl              11.21      1.14      2.33
                     RRu              51.83      2.77      5.01
                      P                 +++         +       +++
              Random  RR              24.10      1.50      3.68
                     RRl              11.21      0.49      0.64
                     RRu              51.83      4.57     21.31
                      P                 +++      N.S.      N.S.
             Between Chi                                  33.36
             Between  df                                      1
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        3                                       3
                      NS        2                                       2

                      Wt    26.15                                   26.15
                 Het Chi    38.89                                   38.89
                 Het  df        2                                       2
                 Het  P       ***                                     ***
               Fixed  RR     3.42                                    3.42
                     RRl     2.33                                    2.33
                     RRu     5.01                                    5.01
                      P       +++                                     +++
              Random  RR     3.68                                    3.68
                     RRl     0.64                                    0.64
                     RRu    21.31                                   21.31
                      P      N.S.                                    N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        3                   3
                      NS        2                   2

                      Wt    26.15               26.15
                 Het Chi    38.89               38.89
                 Het  df        2                   2
                 Het  P       ***                 ***
               Fixed  RR     3.42                3.42
                     RRl     2.33                2.33
                     RRu     5.01                5.01
                      P       +++                 +++
              Random  RR     3.68                3.68
                     RRl     0.64                0.64
                     RRu    21.31               21.31
                      P      N.S.                N.S.
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 7

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
5      FORAST HUHTI2 JACOBS KRZYZA MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 3 - 8

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 4 -

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) vs never smoking base
5) Key value = 12
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) UNEXP   : never any, never cigarettes
8) PROD    : cigarettes, cigarettes only, any product
9) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 1

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN  26   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any  20  29
  KRZYZA  13   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs  14   +
  KRZYZA  18   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs  14   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 2

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KAHN   26  m   2        174       -     243       -      3.50 (  2.80-   4.20)
*KRZYZA 13  m   1          8       -       5       -      2.03 (  0.65-   6.35)
*KRZYZA 18  f   1          1       -      32       -      0.67 (  0.06-   7.02)
 Subtotal KRZYZA                                          1.65 (  0.59-   4.62)
Partial Totals           183       0     280       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KAHN   26  m   2              1.25    93.46     0.07       0.00
*KRZYZA 13  m   1              0.71     2.96     0.79       0.22
*KRZYZA 18  f   1             -0.40     0.68     1.79       0.74
 Subtotal KRZYZA               0.50     3.64     2.58

                       N        3
                      NS        2

                      Wt    97.10
                 Het Chi     2.65
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     3.40
                     RRl     2.79
                     RRu     4.15
                      P       +++
              Random  RR     2.91
                     RRl     1.68
                     RRu     5.06
                      P       +++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        3
                      NS        2

                      Wt    97.10
                 Het Chi     2.65
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     3.40
                     RRl     2.79
                     RRu     4.15
                      P       +++
              Random  RR     2.91
                     RRl     1.68
                     RRu     5.06
                      P       +++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         2

                      Wt              96.42      0.68     97.10
                 Het Chi               0.85      0.00      2.65
                 Het  df                  1         0         2
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               3.44      0.67      3.40
                     RRl               2.82      0.06      2.79
                     RRu               4.20      7.25      4.15
                      P                 +++      N.S.       +++
              Random  RR               3.44      0.67      2.91
                     RRl               2.82      0.06      1.68
                     RRu               4.20      7.25      5.06
                      P                 +++      N.S.       +++
             Between Chi                                   1.80
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    93.46      3.64                         97.10
                 Het Chi     0.00      0.68                          2.65
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                          N.S.
               Fixed  RR     3.50      1.65                          3.40
                     RRl     2.86      0.59                          2.79
                     RRu     4.29      4.62                          4.15
                      P       +++      N.S.                           +++
              Random  RR     3.50      1.65                          2.91
                     RRl     2.86      0.59                          1.68
                     RRu     4.29      4.62                          5.06
                      P       +++      N.S.                           +++
             Between Chi                                             1.98
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              97.10               97.10
                 Het Chi               2.65                2.65
                 Het  df                  2                   2
                 Het  P                N.S.                N.S.
               Fixed  RR               3.40                3.40
                     RRl               2.79                2.79
                     RRu               4.15                4.15
                      P                 +++                 +++
              Random  RR               2.91                2.91
                     RRl               1.68                1.68
                     RRu               5.06                5.06
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1         2                   3
                      NS        1         1                   2

                      Wt    93.46      3.64               97.10
                 Het Chi     0.00      0.68                2.65
                 Het  df        0         1                   2
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     3.50      1.65                3.40
                     RRl     2.86      0.59                2.79
                     RRu     4.29      4.62                4.15
                      P       +++      N.S.                 +++
              Random  RR     3.50      1.65                2.91
                     RRl     2.86      0.59                1.68
                     RRu     4.29      4.62                5.06
                      P       +++      N.S.                 +++
             Between Chi                                   1.98
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              97.10               97.10
                 Het Chi               2.65                2.65
                 Het  df                  2                   2
                 Het  P                N.S.                N.S.
               Fixed  RR               3.40                3.40
                     RRl               2.79                2.79
                     RRu               4.15                4.15
                      P                 +++                 +++
              Random  RR               2.91                2.91
                     RRl               1.68                1.68
                     RRu               5.06                5.06
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    93.46      3.64                         97.10
                 Het Chi     0.00      0.68                          2.65
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                          N.S.
               Fixed  RR     3.50      1.65                          3.40
                     RRl     2.86      0.59                          2.79
                     RRu     4.29      4.62                          4.15
                      P       +++      N.S.                           +++
              Random  RR     3.50      1.65                          2.91
                     RRl     2.86      0.59                          1.68
                     RRu     4.29      4.62                          5.06
                      P       +++      N.S.                           +++
             Between Chi                                             1.98
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        1         2         3
                      NS        1         1         2

                      Wt    93.46      3.64     97.10
                 Het Chi     0.00      0.68      2.65
                 Het  df        0         1         2
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     3.50      1.65      3.40
                     RRl     2.86      0.59      2.79
                     RRu     4.29      4.62      4.15
                      P       +++      N.S.       +++
              Random  RR     3.50      1.65      2.91
                     RRl     2.86      0.59      1.68
                     RRu     4.29      4.62      5.06
                      P       +++      N.S.       +++
             Between Chi                         1.98
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 4

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN  26     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any  20  29
  KRZYZA  13     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs  14   +
  KRZYZA  18     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs  14   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 5

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KAHN   26  m   2        174       -     243       -      3.50 (  2.80-   4.20)
*KRZYZA 13  m   1          8       -       5       -      2.03 (  0.65-   6.35)
*KRZYZA 18  f   1          1       -      32       -      0.67 (  0.06-   7.02)
 Subtotal KRZYZA                                          1.65 (  0.59-   4.62)
Partial Totals           183       0     280       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KAHN   26  m   2              1.25    93.46     0.07       0.00
*KRZYZA 13  m   1              0.71     2.96     0.79       0.22
*KRZYZA 18  f   1             -0.40     0.68     1.79       0.74
 Subtotal KRZYZA               0.50     3.64     2.58

                       N        3
                      NS        2

                      Wt    97.10
                 Het Chi     2.65
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     3.40
                     RRl     2.79
                     RRu     4.15
                      P       +++
              Random  RR     2.91
                     RRl     1.68
                     RRu     5.06
                      P       +++
               Asymm  P       (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        3
                      NS        2

                      Wt    97.10
                 Het Chi     2.65
                 Het  df        2
                 Het  P      N.S.
               Fixed  RR     3.40
                     RRl     2.79
                     RRu     4.15
                      P       +++
              Random  RR     2.91
                     RRl     1.68
                     RRu     5.06
                      P       +++
               Asymm  P       (*)

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         2

                      Wt              96.42      0.68     97.10
                 Het Chi               0.85      0.00      2.65
                 Het  df                  1         0         2
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               3.44      0.67      3.40
                     RRl               2.82      0.06      2.79
                     RRu               4.20      7.25      4.15
                      P                 +++      N.S.       +++
              Random  RR               3.44      0.67      2.91
                     RRl               2.82      0.06      1.68
                     RRu               4.20      7.25      5.06
                      P                 +++      N.S.       +++
             Between Chi                                   1.80
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    93.46      3.64                         97.10
                 Het Chi     0.00      0.68                          2.65
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                          N.S.
               Fixed  RR     3.50      1.65                          3.40
                     RRl     2.86      0.59                          2.79
                     RRu     4.29      4.62                          4.15
                      P       +++      N.S.                           +++
              Random  RR     3.50      1.65                          2.91
                     RRl     2.86      0.59                          1.68
                     RRu     4.29      4.62                          5.06
                      P       +++      N.S.                           +++
             Between Chi                                             1.98
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              97.10               97.10
                 Het Chi               2.65                2.65
                 Het  df                  2                   2
                 Het  P                N.S.                N.S.
               Fixed  RR               3.40                3.40
                     RRl               2.79                2.79
                     RRu               4.15                4.15
                      P                 +++                 +++
              Random  RR               2.91                2.91
                     RRl               1.68                1.68
                     RRu               5.06                5.06
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1         2                   3
                      NS        1         1                   2

                      Wt    93.46      3.64               97.10
                 Het Chi     0.00      0.68                2.65
                 Het  df        0         1                   2
                 Het  P      N.S.      N.S.                N.S.
               Fixed  RR     3.50      1.65                3.40
                     RRl     2.86      0.59                2.79
                     RRu     4.29      4.62                4.15
                      P       +++      N.S.                 +++
              Random  RR     3.50      1.65                2.91
                     RRl     2.86      0.59                1.68
                     RRu     4.29      4.62                5.06
                      P       +++      N.S.                 +++
             Between Chi                                   1.98
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              97.10               97.10
                 Het Chi               2.65                2.65
                 Het  df                  2                   2
                 Het  P                N.S.                N.S.
               Fixed  RR               3.40                3.40
                     RRl               2.79                2.79
                     RRu               4.15                4.15
                      P                 +++                 +++
              Random  RR               2.91                2.91
                     RRl               1.68                1.68
                     RRu               5.06                5.06
                      P                 +++                 +++
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    93.46      3.64                         97.10
                 Het Chi     0.00      0.68                          2.65
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                          N.S.
               Fixed  RR     3.50      1.65                          3.40
                     RRl     2.86      0.59                          2.79
                     RRu     4.29      4.62                          4.15
                      P       +++      N.S.                           +++
              Random  RR     3.50      1.65                          2.91
                     RRl     2.86      0.59                          1.68
                     RRu     4.29      4.62                          5.06
                      P       +++      N.S.                           +++
             Between Chi                                             1.98
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        1         2         3
                      NS        1         1         2

                      Wt    93.46      3.64     97.10
                 Het Chi     0.00      0.68      2.65
                 Het  df        0         1         2
                 Het  P      N.S.      N.S.      N.S.
               Fixed  RR     3.50      1.65      3.40
                     RRl     2.86      0.59      2.79
                     RRu     4.29      4.62      4.15
                      P       +++      N.S.       +++
              Random  RR     3.50      1.65      2.91
                     RRl     2.86      0.59      1.68
                     RRu     4.29      4.62      5.06
                      P       +++      N.S.       +++
             Between Chi                         1.98
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 7

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
5       DEAN1 FORAST HUHTI2 JACOBS MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 4 - 8

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 5 -

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) vs never smoking base
5) Key value = 7
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) UNEXP   : never any, never cigarettes
8) PROD    : cigarettes, cigarettes only, any product
9) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 1

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN  27   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any  10  19
  KRZYZA  14   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13
  KRZYZA  19   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 2

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KAHN   27  m   2        224       -     243       -      7.80 (  6.30-   9.70)
*KRZYZA 14  m   1          4       -       5       -      2.57 (  0.70-   9.41)
*KRZYZA 19  f   1          0       -      32       -      0.74 (  0.05-  11.54)
 Subtotal KRZYZA                                          2.04 (  0.63-   6.59)
Partial Totals           228       0     280       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KAHN   27  m   2              2.05    82.50     0.16       0.00
*KRZYZA 14  m   1              0.94     2.28     2.59       0.15
*KRZYZA 19  f   1             -0.30     0.52     2.77       0.83
 Subtotal KRZYZA               0.71     2.79     5.36

                       N        3
                      NS        2

                      Wt    85.29
                 Het Chi     5.52
                 Het  df        2
                 Het  P       (*)
               Fixed  RR     7.46
                     RRl     6.04
                     RRu     9.23
                      P       +++
              Random  RR     3.93
                     RRl     1.22
                     RRu    12.61
                      P         +
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        3
                      NS        2

                      Wt    85.29
                 Het Chi     5.52
                 Het  df        2
                 Het  P       (*)
               Fixed  RR     7.46
                     RRl     6.04
                     RRu     9.23
                      P       +++
              Random  RR     3.93
                     RRl     1.22
                     RRu    12.61
                      P         +
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         2

                      Wt              84.77      0.52     85.29
                 Het Chi               2.73      0.00      5.52
                 Het  df                  1         0         2
                 Het  P                 (*)      N.S.       (*)
               Fixed  RR               7.57      0.74      7.46
                     RRl               6.12      0.05      6.04
                     RRu               9.37     11.24      9.23
                      P                 +++      N.S.       +++
              Random  RR               5.43      0.74      3.93
                     RRl               1.96      0.05      1.22
                     RRu              15.06     11.24     12.61
                      P                  ++      N.S.         +
             Between Chi                                   2.79
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    82.50      2.79                         85.29
                 Het Chi     0.00      0.66                          5.52
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           (*)
               Fixed  RR     7.80      2.04                          7.46
                     RRl     6.29      0.63                          6.04
                     RRu     9.68      6.59                          9.23
                      P       +++      N.S.                           +++
              Random  RR     7.80      2.04                          3.93
                     RRl     6.29      0.63                          1.22
                     RRu     9.68      6.59                         12.61
                      P       +++      N.S.                             +
             Between Chi                                             4.86
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              85.29               85.29
                 Het Chi               5.52                5.52
                 Het  df                  2                   2
                 Het  P                 (*)                 (*)
               Fixed  RR               7.46                7.46
                     RRl               6.04                6.04
                     RRu               9.23                9.23
                      P                 +++                 +++
              Random  RR               3.93                3.93
                     RRl               1.22                1.22
                     RRu              12.61               12.61
                      P                   +                   +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1         2                   3
                      NS        1         1                   2

                      Wt    82.50      2.79               85.29
                 Het Chi     0.00      0.66                5.52
                 Het  df        0         1                   2
                 Het  P      N.S.      N.S.                 (*)
               Fixed  RR     7.80      2.04                7.46
                     RRl     6.29      0.63                6.04
                     RRu     9.68      6.59                9.23
                      P       +++      N.S.                 +++
              Random  RR     7.80      2.04                3.93
                     RRl     6.29      0.63                1.22
                     RRu     9.68      6.59               12.61
                      P       +++      N.S.                   +
             Between Chi                                   4.86
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              85.29               85.29
                 Het Chi               5.52                5.52
                 Het  df                  2                   2
                 Het  P                 (*)                 (*)
               Fixed  RR               7.46                7.46
                     RRl               6.04                6.04
                     RRu               9.23                9.23
                      P                 +++                 +++
              Random  RR               3.93                3.93
                     RRl               1.22                1.22
                     RRu              12.61               12.61
                      P                   +                   +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 3

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    82.50      2.79                         85.29
                 Het Chi     0.00      0.66                          5.52
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           (*)
               Fixed  RR     7.80      2.04                          7.46
                     RRl     6.29      0.63                          6.04
                     RRu     9.68      6.59                          9.23
                      P       +++      N.S.                           +++
              Random  RR     7.80      2.04                          3.93
                     RRl     6.29      0.63                          1.22
                     RRu     9.68      6.59                         12.61
                      P       +++      N.S.                             +
             Between Chi                                             4.86
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        1         2         3
                      NS        1         1         2

                      Wt    82.50      2.79     85.29
                 Het Chi     0.00      0.66      5.52
                 Het  df        0         1         2
                 Het  P      N.S.      N.S.       (*)
               Fixed  RR     7.80      2.04      7.46
                     RRl     6.29      0.63      6.04
                     RRu     9.68      6.59      9.23
                      P       +++      N.S.       +++
              Random  RR     7.80      2.04      3.93
                     RRl     6.29      0.63      1.22
                     RRu     9.68      6.59     12.61
                      P       +++      N.S.         +
             Between Chi                         4.86
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 4

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

    KAHN  27     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any  10  19
  KRZYZA  14     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13
  KRZYZA  19     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   9  13

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 5

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KAHN   27  m   2        224       -     243       -      7.80 (  6.30-   9.70)
*KRZYZA 14  m   1          4       -       5       -      2.57 (  0.70-   9.41)
*KRZYZA 19  f   1          0       -      32       -      0.74 (  0.05-  11.54)
 Subtotal KRZYZA                                          2.04 (  0.63-   6.59)
Partial Totals           228       0     280       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KAHN   27  m   2              2.05    82.50     0.16       0.00
*KRZYZA 14  m   1              0.94     2.28     2.59       0.15
*KRZYZA 19  f   1             -0.30     0.52     2.77       0.83
 Subtotal KRZYZA               0.71     2.79     5.36

                       N        3
                      NS        2

                      Wt    85.29
                 Het Chi     5.52
                 Het  df        2
                 Het  P       (*)
               Fixed  RR     7.46
                     RRl     6.04
                     RRu     9.23
                      P       +++
              Random  RR     3.93
                     RRl     1.22
                     RRu    12.61
                      P         +
               Asymm  P         *

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        3
                      NS        2

                      Wt    85.29
                 Het Chi     5.52
                 Het  df        2
                 Het  P       (*)
               Fixed  RR     7.46
                     RRl     6.04
                     RRu     9.23
                      P       +++
              Random  RR     3.93
                     RRl     1.22
                     RRu    12.61
                      P         +
               Asymm  P         *

                                   Sex
                             both      male    female     Total

                       N                  2         1         3
                      NS                  2         1         2

                      Wt              84.77      0.52     85.29
                 Het Chi               2.73      0.00      5.52
                 Het  df                  1         0         2
                 Het  P                 (*)      N.S.       (*)
               Fixed  RR               7.57      0.74      7.46
                     RRl               6.12      0.05      6.04
                     RRu               9.37     11.24      9.23
                      P                 +++      N.S.       +++
              Random  RR               5.43      0.74      3.93
                     RRl               1.96      0.05      1.22
                     RRu              15.06     11.24     12.61
                      P                  ++      N.S.         +
             Between Chi                                   2.79
             Between  df                                      1
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    82.50      2.79                         85.29
                 Het Chi     0.00      0.66                          5.52
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           (*)
               Fixed  RR     7.80      2.04                          7.46
                     RRl     6.29      0.63                          6.04
                     RRu     9.68      6.59                          9.23
                      P       +++      N.S.                           +++
              Random  RR     7.80      2.04                          3.93
                     RRl     6.29      0.63                          1.22
                     RRu     9.68      6.59                         12.61
                      P       +++      N.S.                             +
             Between Chi                                             4.86
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              85.29               85.29
                 Het Chi               5.52                5.52
                 Het  df                  2                   2
                 Het  P                 (*)                 (*)
               Fixed  RR               7.46                7.46
                     RRl               6.04                6.04
                     RRu               9.23                9.23
                      P                 +++                 +++
              Random  RR               3.93                3.93
                     RRl               1.22                1.22
                     RRu              12.61               12.61
                      P                   +                   +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        1         2                   3
                      NS        1         1                   2

                      Wt    82.50      2.79               85.29
                 Het Chi     0.00      0.66                5.52
                 Het  df        0         1                   2
                 Het  P      N.S.      N.S.                 (*)
               Fixed  RR     7.80      2.04                7.46
                     RRl     6.29      0.63                6.04
                     RRu     9.68      6.59                9.23
                      P       +++      N.S.                 +++
              Random  RR     7.80      2.04                3.93
                     RRl     6.29      0.63                1.22
                     RRu     9.68      6.59               12.61
                      P       +++      N.S.                   +
             Between Chi                                   4.86
             Between  df                                      1
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  3                   3
                      NS                  2                   2

                      Wt              85.29               85.29
                 Het Chi               5.52                5.52
                 Het  df                  2                   2
                 Het  P                 (*)                 (*)
               Fixed  RR               7.46                7.46
                     RRl               6.04                6.04
                     RRu               9.23                9.23
                      P                 +++                 +++
              Random  RR               3.93                3.93
                     RRl               1.22                1.22
                     RRu              12.61               12.61
                      P                   +                   +
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 6

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        1         2                             3
                      NS        1         1                             2

                      Wt    82.50      2.79                         85.29
                 Het Chi     0.00      0.66                          5.52
                 Het  df        0         1                             2
                 Het  P      N.S.      N.S.                           (*)
               Fixed  RR     7.80      2.04                          7.46
                     RRl     6.29      0.63                          6.04
                     RRu     9.68      6.59                          9.23
                      P       +++      N.S.                           +++
              Random  RR     7.80      2.04                          3.93
                     RRl     6.29      0.63                          1.22
                     RRu     9.68      6.59                         12.61
                      P       +++      N.S.                             +
             Between Chi                                             4.86
             Between  df                                                1
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        1         2         3
                      NS        1         1         2

                      Wt    82.50      2.79     85.29
                 Het Chi     0.00      0.66      5.52
                 Het  df        0         1         2
                 Het  P      N.S.      N.S.       (*)
               Fixed  RR     7.80      2.04      7.46
                     RRl     6.29      0.63      6.04
                     RRu     9.68      6.59      9.23
                      P       +++      N.S.       +++
              Random  RR     7.80      2.04      3.93
                     RRl     6.29      0.63      1.22
                     RRu     9.68      6.59     12.61
                      P       +++      N.S.         +
             Between Chi                         4.86
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 7

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
5       DEAN1 FORAST HUHTI2 JACOBS MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 5 - 8

                        IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 6 -

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) vs never smoking base
5) Key value = 3
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) UNEXP   : never any, never cigarettes
8) PROD    : cigarettes, cigarettes only, any product
9) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 1

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  51   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   1   4
   DEAN1  86   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only   Nev any   1   4
  FORAST  11   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   1      Ex       Cigs  Nev cigs   1  10
  HUHTI2   8   m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any   1   9
  HUHTI2  11   f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any   1   9
  JACOBS   8   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Nev cigs   1   9
    KAHN  29   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any   1   4
  KRZYZA  15   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   1   8
  KRZYZA  20   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   1   8
  MANNI2  10   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Nev any   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 2

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  51  m   1         24       -      47       -      2.27 (  1.33-   3.88)
 DEAN1  86  f   1          7       -     120       -      1.26 (  0.57-   2.77)
 Subtotal DEAN1                                           1.89 (  1.21-   2.94)
 FORAST 11  f   1         21       -      28       -      3.99 (  2.16-   7.34)
 HUHTI2 8   m   0          6      58       0      76     17.00~(  0.94- 307.88)
 HUHTI2 11  f   0          1      12      15     477      2.65 (  0.32-  21.72)
 Subtotal HUHTI2                                          5.04 (  0.92-  27.62)
*JACOBS 8   m   2         24       -      28       -      3.43 (  1.92-   6.12)
*KAHN   29  m   2         20       -     243       -     24.10 ( 11.20-  51.80)
*KRZYZA 15  m   1         12       -       5       -      3.38 (  1.21-   9.41)
*KRZYZA 20  f   1          4       -      32       -      2.30 (  0.79-   6.74)
 Subtotal KRZYZA                                          2.81 (  1.34-   5.90)
 MANNI2 10  b   1        125       -     202       -      2.32 (  1.82-   2.97)
Partial Totals           244      70     720     553
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  51  m   1              0.82    13.40     0.64       0.00
 DEAN1  86  f   1              0.23     6.15     4.01       0.57
 Subtotal DEAN1                0.63    19.55     4.65
 FORAST 11  f   1              1.38    10.27     1.22       0.00
 HUHTI2 8   m   0              2.83     0.46     1.47       0.06
 HUHTI2 11  f   0              0.97     0.87     0.00       0.36
 Subtotal HUHTI2               1.62     1.33     1.48
*JACOBS 8   m   2              1.23    11.43     0.43       0.00
*KAHN   29  m   2              3.18     6.55    30.10       0.00
*KRZYZA 15  m   1              1.22     3.65     0.12       0.02
*KRZYZA 20  f   1              0.83     3.34     0.14       0.13
 Subtotal KRZYZA               1.03     7.00     0.26
 MANNI2 10  b   1              0.84    64.07     2.49       0.00

                       N       10
                      NS        7

                      Wt   120.20
                 Het Chi    40.63
                 Het  df        9
                 Het  P       ***
               Fixed  RR     2.83
                     RRl     2.36
                     RRu     3.38
                      P       +++
              Random  RR     3.45
                     RRl     2.13
                     RRu     5.59
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       10
                      NS        7

                      Wt   120.20
                 Het Chi    40.63
                 Het  df        9
                 Het  P       ***
               Fixed  RR     2.83
                     RRl     2.36
                     RRu     3.38
                      P       +++
              Random  RR     3.45
                     RRl     2.13
                     RRu     5.59
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    64.07     35.50     20.63    120.20
                 Het Chi     0.00     26.59      5.15     40.63
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     2.32      4.29      2.54      2.83
                     RRl     1.82      3.09      1.65      2.36
                     RRu     2.96      5.96      3.92      3.38
                      P       +++       +++       +++       +++
              Random  RR     2.32      5.46      2.39      3.45
                     RRl     1.82      2.09      1.28      2.13
                     RRu     2.96     14.25      4.47      5.59
                      P       +++       +++        ++       +++
             Between Chi                                   8.89
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt    80.89     27.87               11.43    120.20
                 Het Chi    33.51      4.55                0.00     40.63
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     3.00      2.18                3.43      2.83
                     RRl     2.42      1.51                1.92      2.36
                     RRu     3.74      3.17                6.12      3.38
                      P       +++       +++                 +++       +++
              Random  RR     5.81      2.18                3.43      3.45
                     RRl     1.68      1.51                1.92      2.13
                     RRu    20.06      3.17                6.12      5.59
                      P        ++       +++                 +++       +++
             Between Chi                                             2.58
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    19.55     24.98     75.66    120.20
                 Het Chi     1.46     20.25      4.28     40.63
                 Het  df        1         3         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.89      5.41      2.53      2.83
                     RRl     1.21      3.65      2.02      2.36
                     RRu     2.94      8.01      3.17      3.38
                      P        ++       +++       +++       +++
              Random  RR     1.82      5.17      2.88      3.45
                     RRl     1.04      1.76      1.86      2.13
                     RRu     3.18     15.19      4.47      5.59
                      P         +        ++       +++       +++
             Between Chi                                  14.65
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt    37.54     72.39     10.27    120.20
                 Het Chi    33.32      2.27      0.00     40.63
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     3.53      2.40      3.99      2.83
                     RRl     2.56      1.90      2.16      2.36
                     RRu     4.86      3.02      7.36      3.38
                      P       +++       +++       +++       +++
              Random  RR     3.89      2.40      3.99      3.45
                     RRl     1.31      1.90      2.16      2.13
                     RRu    11.56      3.02      7.36      5.59
                      P         +       +++       +++       +++
             Between Chi                                   5.04
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    65.40     35.25     19.55    120.20
                 Het Chi     1.82     20.93      1.46     40.63
                 Het  df        2         4         1         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     2.36      4.95      1.89      2.83
                     RRl     1.85      3.56      1.21      2.36
                     RRu     3.00      6.89      2.94      3.38
                      P       +++       +++        ++       +++
              Random  RR     2.36      4.92      1.82      3.45
                     RRl     1.85      2.24      1.04      2.13
                     RRu     3.00     10.83      3.18      5.59
                      P       +++       +++         +       +++
             Between Chi                                  16.43
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 3

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        6         4                            10
                      NS        4         3                             7

                      Wt    91.50     28.70                        120.20
                 Het Chi    38.36      0.77                         40.63
                 Het  df        5         3                             9
                 Het  P       ***      N.S.                           ***
               Fixed  RR     2.65      3.45                          2.83
                     RRl     2.16      2.39                          2.36
                     RRu     3.26      4.97                          3.38
                      P       +++       +++                           +++
              Random  RR     3.73      3.45                          3.45
                     RRl     1.62      2.39                          2.13
                     RRu     8.59      4.97                          5.59
                      P        ++       +++                           +++
             Between Chi                                             1.50
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        6         4        10
                      NS        4         3         7

                      Wt    91.50     28.70    120.20
                 Het Chi    38.36      0.77     40.63
                 Het  df        5         3         9
                 Het  P       ***      N.S.       ***
               Fixed  RR     2.65      3.45      2.83
                     RRl     2.16      2.39      2.36
                     RRu     3.26      4.97      3.38
                      P       +++       +++       +++
              Random  RR     3.73      3.45      3.45
                     RRl     1.62      2.39      2.13
                     RRu     8.59      4.97      5.59
                      P        ++       +++       +++
             Between Chi                         1.50
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 4

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  41 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   1   4
   DEAN1  81 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only   Nev any   1   4
  FORAST   8 x   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   0      Ex       Cigs  Nev cigs   1  10
  HUHTI2   8     m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any   1   9
  HUHTI2  11     f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Nev any   1   9
  JACOBS   8     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Nev cigs   1   9
    KAHN  29     m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs   Nev any   1   4
  KRZYZA  15     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   1   8
  KRZYZA  20     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Nev cigs   1   8
  MANNI2  10     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Nev any   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 5

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  41  m   0         24     102      47     510      2.55 (  1.49-   4.36)
 DEAN1  81  f   0          7     110     120    1538      0.82 (  0.37-   1.79)
 Subtotal DEAN1                                           1.78 (  1.14-   2.77)
 FORAST 8   f   0         21     114      28     531      3.49 (  1.92-   6.37)
 HUHTI2 8   m   0          6      58       0      76     17.00~(  0.94- 307.88)
 HUHTI2 11  f   0          1      12      15     477      2.65 (  0.32-  21.72)
 Subtotal HUHTI2                                          5.04 (  0.92-  27.62)
*JACOBS 8   m   2         24       -      28       -      3.43 (  1.92-   6.12)
*KAHN   29  m   2         20       -     243       -     24.10 ( 11.20-  51.80)
*KRZYZA 15  m   1         12       -       5       -      3.38 (  1.21-   9.41)
*KRZYZA 20  f   1          4       -      32       -      2.30 (  0.79-   6.74)
 Subtotal KRZYZA                                          2.81 (  1.34-   5.90)
 MANNI2 10  b   1        125       -     202       -      2.32 (  1.82-   2.97)
Partial Totals           244     396     720    3132
*prospective study                                        ~ With 0.5 adjustment for zero

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  41  m   0              0.94    13.39     0.09       0.00
 DEAN1  81  f   0             -0.20     6.21     9.28       0.61
 Subtotal DEAN1                0.58    19.60     9.37
 FORAST 8   f   0              1.25    10.64     0.58       0.00
 HUHTI2 8   m   0              2.83     0.46     1.51       0.06
 HUHTI2 11  f   0              0.97     0.87     0.00       0.36
 Subtotal HUHTI2               1.62     1.33     1.51
*JACOBS 8   m   2              1.23    11.43     0.52       0.00
*KAHN   29  m   2              3.18     6.55    30.68       0.00
*KRZYZA 15  m   1              1.22     3.65     0.15       0.02
*KRZYZA 20  f   1              0.83     3.34     0.11       0.13
 Subtotal KRZYZA               1.03     7.00     0.26
 MANNI2 10  b   1              0.84    64.07     2.00       0.00

                       N       10
                      NS        7

                      Wt   120.62
                 Het Chi    44.92
                 Het  df        9
                 Het  P       ***
               Fixed  RR     2.77
                     RRl     2.32
                     RRu     3.31
                      P       +++
              Random  RR     3.29
                     RRl     1.99
                     RRu     5.45
                      P       +++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       10
                      NS        7

                      Wt   120.62
                 Het Chi    44.92
                 Het  df        9
                 Het  P       ***
               Fixed  RR     2.77
                     RRl     2.32
                     RRu     3.31
                      P       +++
              Random  RR     3.29
                     RRl     1.99
                     RRu     5.45
                      P       +++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    64.07     35.48     21.06    120.62
                 Het Chi     0.00     24.70      8.39     44.92
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***         *       ***
               Fixed  RR     2.32      4.48      2.10      2.77
                     RRl     1.82      3.23      1.37      2.32
                     RRu     2.96      6.23      3.23      3.31
                      P       +++       +++       +++       +++
              Random  RR     2.32      5.59      1.97      3.29
                     RRl     1.82      2.21      0.87      1.99
                     RRu     2.96     14.11      4.44      5.45
                      P       +++       +++      N.S.       +++
             Between Chi                                  11.83
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt    81.26     27.92               11.43    120.62
                 Het Chi    32.90      8.97                0.00     44.92
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     2.96      2.10                3.43      2.77
                     RRl     2.38      1.45                1.92      2.32
                     RRu     3.67      3.04                6.12      3.31
                      P       +++       +++                 +++       +++
              Random  RR     5.55      2.16                3.43      3.29
                     RRl     1.64      1.21                1.92      1.99
                     RRu    18.75      3.86                6.12      5.45
                      P        ++        ++                 +++       +++
             Between Chi                                             3.04
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    19.60     24.98     76.03    120.62
                 Het Chi     5.53     20.25      3.23     44.92
                 Het  df        1         3         3         9
                 Het  P         *       ***      N.S.       ***
               Fixed  RR     1.78      5.41      2.49      2.77
                     RRl     1.14      3.65      1.99      2.32
                     RRu     2.77      8.01      3.12      3.31
                      P         +       +++       +++       +++
              Random  RR     1.50      5.17      2.57      3.29
                     RRl     0.49      1.76      1.94      1.99
                     RRu     4.57     15.19      3.41      5.45
                      P      N.S.        ++       +++       +++
             Between Chi                                  15.91
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt    37.59     72.39     10.64    120.62
                 Het Chi    38.89      2.27      0.00     44.92
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     3.42      2.40      3.49      2.77
                     RRl     2.48      1.90      1.92      2.32
                     RRu     4.71      3.02      6.37      3.31
                      P       +++       +++       +++       +++
              Random  RR     3.61      2.40      3.49      3.29
                     RRl     1.11      1.90      1.92      1.99
                     RRu    11.70      3.02      6.37      5.45
                      P         +       +++       +++       +++
             Between Chi                                   3.76
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    65.40     35.62     19.60    120.62
                 Het Chi     1.82     21.68      5.53     44.92
                 Het  df        2         4         1         9
                 Het  P      N.S.       ***         *       ***
               Fixed  RR     2.36      4.75      1.78      2.77
                     RRl     1.85      3.42      1.14      2.32
                     RRu     3.00      6.59      2.77      3.31
                      P       +++       +++         +       +++
              Random  RR     2.36      4.78      1.50      3.29
                     RRl     1.85      2.15      0.49      1.99
                     RRu     3.00     10.62      4.57      5.45
                      P       +++       +++      N.S.       +++
             Between Chi                                  15.90
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 6

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                                     Unexposed group
                          nev any   nev cig  nev+ any  nev+ cig     Total

                       N        6         4                            10
                      NS        4         3                             7

                      Wt    91.55     29.07                        120.62
                 Het Chi    43.28      0.49                         44.92
                 Het  df        5         3                             9
                 Het  P       ***      N.S.                           ***
               Fixed  RR     2.62      3.29                          2.77
                     RRl     2.14      2.29                          2.32
                     RRu     3.22      4.73                          3.31
                      P       +++       +++                           +++
              Random  RR     3.54      3.29                          3.29
                     RRl     1.47      2.29                          1.99
                     RRu     8.55      4.73                          5.45
                      P        ++       +++                           +++
             Between Chi                                             1.15
             Between  df                                                1
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Unexposed group (combining nev+ with main levels)
                          nev any   nev cig     Total

                       N        6         4        10
                      NS        4         3         7

                      Wt    91.55     29.07    120.62
                 Het Chi    43.28      0.49     44.92
                 Het  df        5         3         9
                 Het  P       ***      N.S.       ***
               Fixed  RR     2.62      3.29      2.77
                     RRl     2.14      2.29      2.32
                     RRu     3.22      4.73      3.31
                      P       +++       +++       +++
              Random  RR     3.54      3.29      3.29
                     RRl     1.47      2.29      1.99
                     RRu     8.55      4.73      5.45
                      P        ++       +++       +++
             Between Chi                         1.15
             Between  df                            1
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 7

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 6 - 8

                         IESCOPD - Meta-analysis of years since quit (vs never) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI2 HUHTI1     2                HUHTI1/HUHTI2
  MANNI2 MANNI2     1                MANNI2/MANNI3
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - I - 7 -

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs never/long-term)
4) Recent vs long term base
5) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
6) PROD    : cigarettes, cigarettes only, any product
7) The most recent vs longest ago category
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 1

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-LO|LOW| HI|

   DEAN1  53   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only       9   1   4
   DEAN1  88   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only       9   1   4
  FORAST  12   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   1      Ex       Cigs      11   1  10
  HUHTI2   9   m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any      10   1   9
  HUHTI2  12   f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any      10   1   9
  JACOBS  11   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs      10   0   0
    KAHN  48   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   3      Ex       Cigs      40   1   4
  KRZYZA  17   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs      14   1   8
  KRZYZA  22   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs      14   1   8
  MANNI2  11   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any      10   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 2

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  53  m   1         24       -      42       -      1.25 (  0.71-   2.19)
 DEAN1  88  f   1          7       -      15       -      0.63 (  0.25-   1.57)
 Subtotal DEAN1                                           1.04 (  0.64-   1.68)
 FORAST 12  f   1         21       -      23       -      2.84 (  1.52-   5.30)
 HUHTI2 9   m   0          6      58       6      90      1.55 (  0.48-   5.04)
 HUHTI2 12  f   0          1      12       1      21      1.75 (  0.10-  30.59)
 Subtotal HUHTI2                                          1.58 (  0.53-   4.70)
*JACOBS 11  m   2          9       -       8       -      2.70 (  0.98-   7.46)
*KAHN   48  m   3         20       -      49       -     14.59 (  7.46-  28.56)
*KRZYZA 17  m   1         12       -       8       -      1.67 (  0.64-   4.31)
*KRZYZA 22  f   1          4       -       1       -      3.41 (  0.27-  42.74)
 Subtotal KRZYZA                                          1.82 (  0.75-   4.45)
 MANNI2 11  b   1        125       -      44       -      1.85 (  1.27-   2.67)
Partial Totals           229      70     197     111
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  53  m   1              0.22    12.11     3.88       0.44
 DEAN1  88  f   1             -0.46     4.55     7.13       0.32
 Subtotal DEAN1                0.04    16.66    11.01
 FORAST 12  f   1              1.04     9.85     0.64       0.00
 HUHTI2 9   m   0              0.44     2.76     0.34       0.47
 HUHTI2 12  f   0              0.56     0.47     0.02       0.70
 Subtotal HUHTI2               0.46     3.23     0.36
*JACOBS 11  m   2              0.99     3.73     0.15       0.06
*KAHN   48  m   3              2.68     8.53    30.48       0.00
*KRZYZA 17  m   1              0.51     4.22     0.32       0.29
*KRZYZA 22  f   1              1.23     0.60     0.11       0.34
 Subtotal KRZYZA               0.60     4.82     0.44
 MANNI2 11  b   1              0.62    27.83     0.85       0.00

                       N       10
                      NS        7

                      Wt    74.66
                 Het Chi    43.94
                 Het  df        9
                 Het  P       ***
               Fixed  RR     2.20
                     RRl     1.76
                     RRu     2.76
                      P       +++
              Random  RR     2.21
                     RRl     1.24
                     RRu     3.94
                      P        ++
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 3

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       10
                      NS        7

                      Wt    74.66
                 Het Chi    43.94
                 Het  df        9
                 Het  P       ***
               Fixed  RR     2.20
                     RRl     1.76
                     RRu     2.76
                      P       +++
              Random  RR     2.21
                     RRl     1.24
                     RRu     3.94
                      P        ++
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    27.83     31.36     15.47     74.66
                 Het Chi     0.00     33.20      7.31     43.94
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***       (*)       ***
               Fixed  RR     1.85      2.83      1.81      2.20
                     RRl     1.28      2.00      1.10      1.76
                     RRu     2.68      4.02      2.98      2.76
                      P        ++       +++         +       +++
              Random  RR     1.85      2.69      1.62      2.21
                     RRl     1.28      0.93      0.58      1.24
                     RRu     2.68      7.79      4.52      3.94
                      P        ++       (+)      N.S.        ++
             Between Chi                                   3.43
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt    46.21     24.72                3.73     74.66
                 Het Chi    27.86      3.27                0.00     43.94
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     2.97      1.22                2.70      2.20
                     RRl     2.22      0.82                0.98      1.76
                     RRu     3.96      1.81                7.45      2.76
                      P       +++      N.S.                 (+)       +++
              Random  RR     4.15      1.22                2.70      2.21
                     RRl     1.28      0.82                0.98      1.24
                     RRu    13.51      1.81                7.45      3.94
                      P         +      N.S.                 (+)        ++
             Between Chi                                            12.81
             Between  df                                                2
             Between  P                                                **
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 3

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N        8         2        10
                      NS        6         1         7

                      Wt    57.99     16.66     74.66
                 Het Chi    30.21      1.55     43.94
                 Het  df        7         1         9
                 Het  P       ***      N.S.       ***
               Fixed  RR     2.73      1.04      2.20
                     RRl     2.11      0.64      1.76
                     RRu     3.54      1.68      2.76
                      P       +++      N.S.       +++
              Random  RR     2.91      0.98      2.21
                     RRl     1.51      0.52      1.24
                     RRu     5.60      1.86      3.94
                      P        ++      N.S.        ++
             Between Chi                        12.18
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        6         3                   1                            10
                      NS        4         2                   1                             7

                      Wt    33.74     31.06                9.85                         74.66
                 Het Chi    41.74      0.08                0.00                         43.94
                 Het  df        5         2                   0                             9
                 Het  P       ***      N.S.                N.S.                           ***
               Fixed  RR     2.44      1.82                2.84                          2.20
                     RRl     1.74      1.28                1.52                          1.76
                     RRu     3.42      2.59                5.30                          2.76
                      P       +++       +++                  ++                           +++
              Random  RR     2.32      1.82                2.84                          2.21
                     RRl     0.81      1.28                1.52                          1.24
                     RRu     6.70      2.59                5.30                          3.94
                      P      N.S.       +++                  ++                            ++
             Between Chi                                                                 2.11
             Between  df                                                                    2
             Between  P                                                                  N.S.
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        3         4         2         1        10
                      NS        2         2         2         1         7

                      Wt    25.19      8.06     13.58     27.83     74.66
                 Het Chi    40.99      0.31      0.01      0.00     43.94
                 Het  df        2         3         1         0         9
                 Het  P       ***      N.S.      N.S.      N.S.       ***
               Fixed  RR     2.54      1.72      2.80      1.85      2.20
                     RRl     1.72      0.86      1.65      1.28      1.76
                     RRu     3.75      3.43      4.77      2.68      2.76
                      P       +++      N.S.       +++        ++       +++
              Random  RR     2.29      1.72      2.80      1.85      2.21
                     RRl     0.37      0.86      1.65      1.28      1.24
                     RRu    14.33      3.43      4.77      2.68      3.94
                      P      N.S.      N.S.       +++        ++        ++
             Between Chi                                             2.62
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 3

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    16.66     17.08     40.91     74.66
                 Het Chi     1.55     16.13      1.56     43.94
                 Het  df        1         3         3         9
                 Het  P      N.S.        **      N.S.       ***
               Fixed  RR     1.04      5.61      2.03      2.20
                     RRl     0.64      3.49      1.49      1.76
                     RRu     1.68      9.02      2.75      2.76
                      P      N.S.       +++       +++       +++
              Random  RR     0.98      4.08      2.03      2.21
                     RRl     0.52      1.18      1.49      1.24
                     RRu     1.86     14.16      2.75      3.94
                      P      N.S.         +       +++        ++
             Between Chi                                  24.69
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        2         4         4                  10
                      NS        1         3         3                   7

                      Wt     4.82     53.02     16.81               74.66
                 Het Chi     0.27     42.31      0.87               43.94
                 Het  df        1         3         3                   9
                 Het  P      N.S.       ***      N.S.                 ***
               Fixed  RR     1.82      2.15      2.51                2.20
                     RRl     0.75      1.64      1.56                1.76
                     RRu     4.45      2.81      4.05                2.76
                      P      N.S.       +++       +++                 +++
              Random  RR     1.82      2.18      2.51                2.21
                     RRl     0.75      0.72      1.56                1.24
                     RRu     4.45      6.59      4.05                3.94
                      P      N.S.      N.S.       +++                  ++
             Between Chi                                             0.49
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N                  3         3         4                  10
                      NS                  2         2         3                   7

                      Wt              31.06      8.55     35.04               74.66
                 Het Chi               0.08      0.59     41.08               43.94
                 Het  df                  2         2         3                   9
                 Het  P                N.S.      N.S.       ***                 ***
               Fixed  RR               1.82      2.16      2.62                2.20
                     RRl               1.28      1.11      1.88                1.76
                     RRu               2.59      4.23      3.65                2.76
                      P                 +++         +       +++                 +++
              Random  RR               1.82      2.16      2.43                2.21
                     RRl               1.28      1.11      0.70                1.24
                     RRu               2.59      4.23      8.48                3.94
                      P                 +++         +      N.S.                  ++
             Between Chi                                                       2.19
             Between  df                                                          2
             Between  P                                                        N.S.
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 3

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        3         7        10
                      NS        2         5         7

                      Wt    26.51     48.14     74.66
                 Het Chi     7.84     30.19     43.94
                 Het  df        2         6         9
                 Het  P         *       ***       ***
               Fixed  RR     1.51      2.71      2.20
                     RRl     1.03      2.05      1.76
                     RRu     2.21      3.60      2.76
                      P         +       +++       +++
              Random  RR     1.38      2.89      2.21
                     RRl     0.63      1.27      1.24
                     RRu     3.02      6.55      3.94
                      P      N.S.         +        ++
             Between Chi                         5.91
             Between  df                            1
             Between  P                             *
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt    28.92     35.89      9.85     74.66
                 Het Chi    41.01      0.35      0.00     43.94
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     2.56      1.82      2.84      2.20
                     RRl     1.78      1.31      1.52      1.76
                     RRu     3.68      2.53      5.30      2.76
                      P       +++       +++        ++       +++
              Random  RR     2.39      1.82      2.84      2.21
                     RRl     0.59      1.31      1.52      1.24
                     RRu     9.73      2.53      5.30      3.94
                      P      N.S.       +++        ++        ++
             Between Chi                                   2.59
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N        6         1         2         1        10
                      NS        4         1         1         1         7

                      Wt    44.41      9.85     16.66      3.73     74.66
                 Het Chi    30.19      0.00      1.55      0.00     43.94
                 Het  df        5         0         1         0         9
                 Het  P       ***      N.S.      N.S.      N.S.       ***
               Fixed  RR     2.71      2.84      1.04      2.70      2.20
                     RRl     2.02      1.52      0.64      0.98      1.76
                     RRu     3.64      5.30      1.68      7.45      2.76
                      P       +++        ++      N.S.       (+)       +++
              Random  RR     2.90      2.84      0.98      2.70      2.21
                     RRl     1.09      1.52      0.52      0.98      1.24
                     RRu     7.69      5.30      1.86      7.45      3.94
                      P         +        ++      N.S.       (+)        ++
             Between Chi                                            12.20
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 3

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        5                   5
                      NS        3                   3

                      Wt    35.89               35.89
                 Het Chi     0.35                0.35
                 Het  df        4                   4
                 Het  P      N.S.                N.S.
               Fixed  RR     1.82                1.82
                     RRl     1.31                1.31
                     RRu     2.53                2.53
                      P       +++                 +++
              Random  RR     1.82                1.82
                     RRl     1.31                1.31
                     RRu     2.53                2.53
                      P       +++                 +++
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N                  3         2         5        10
                      NS                  2         1         4         7

                      Wt              13.08      4.82     56.75     74.66
                 Het Chi               0.84      0.27     42.49     43.94
                 Het  df                  2         1         4         9
                 Het  P                N.S.      N.S.       ***       ***
               Fixed  RR               2.46      1.82      2.18      2.20
                     RRl               1.43      0.75      1.68      1.76
                     RRu               4.22      4.45      2.83      2.76
                      P                  ++      N.S.       +++       +++
              Random  RR               2.46      1.82      2.27      2.21
                     RRl               1.43      0.75      0.89      1.24
                     RRu               4.22      4.45      5.78      3.94
                      P                  ++      N.S.       (+)        ++
             Between Chi                                             0.33
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N                  3         2         5        10
                      NS                  2         1         4         7

                      Wt              13.08      4.82     56.75     74.66
                 Het Chi               0.84      0.27     42.49     43.94
                 Het  df                  2         1         4         9
                 Het  P                N.S.      N.S.       ***       ***
               Fixed  RR               2.46      1.82      2.18      2.20
                     RRl               1.43      0.75      1.68      1.76
                     RRu               4.22      4.45      2.83      2.76
                      P                  ++      N.S.       +++       +++
              Random  RR               2.46      1.82      2.27      2.21
                     RRl               1.43      0.75      0.89      1.24
                     RRu               4.22      4.45      5.78      3.94
                      P                  ++      N.S.       (+)        ++
             Between Chi                                             0.33
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 3

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N        6         4        10
                      NS        4         3         7

                      Wt    57.58     17.08     74.66
                 Het Chi     8.43     16.13     43.94
                 Het  df        5         3         9
                 Het  P      N.S.        **       ***
               Fixed  RR     1.67      5.61      2.20
                     RRl     1.29      3.49      1.76
                     RRu     2.16      9.02      2.76
                      P       +++       +++       +++
              Random  RR     1.58      4.08      2.21
                     RRl     1.07      1.18      1.24
                     RRu     2.34     14.16      3.94
                      P         +         +        ++
             Between Chi                        19.38
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    31.06     26.93     16.66     74.66
                 Het Chi     0.08     19.03      1.55     43.94
                 Het  df        2         4         1         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     1.82      4.37      1.04      2.20
                     RRl     1.28      3.00      0.64      1.76
                     RRu     2.59      6.38      1.68      2.76
                      P       +++       +++      N.S.       +++
              Random  RR     1.82      3.79      0.98      2.21
                     RRl     1.28      1.52      0.52      1.24
                     RRu     2.59      9.44      1.86      3.94
                      P       +++        ++      N.S.        ++
             Between Chi                                  23.27
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                        Number of adjustment variables
                                0         1        2+     Total

                       N        2         6         2        10
                      NS        1         4         2         7

                      Wt     3.23     59.17     12.26     74.66
                 Het Chi     0.01      8.71      7.39     43.94
                 Het  df        1         5         1         9
                 Het  P      N.S.      N.S.        **       ***
               Fixed  RR     1.58      1.69      8.73      2.20
                     RRl     0.53      1.31      4.99      1.76
                     RRu     4.70      2.18     15.28      2.76
                      P      N.S.       +++       +++       +++
              Random  RR     1.58      1.62      6.56      2.21
                     RRl     0.53      1.10      1.26      1.24
                     RRu     4.70      2.38     34.21      3.94
                      P      N.S.         +         +        ++
             Between Chi                                  27.84
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 4

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-LO|LOW| HI|

   DEAN1  43 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only       9   1   4
   DEAN1  83 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only       9   1   4
  FORAST   9 x   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   0      Ex       Cigs      11   1  10
  HUHTI2   9     m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any      10   1   9
  HUHTI2  12     f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any      10   1   9
  JACOBS  11     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs      10   0   0
    KAHN  34 x   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs      40   1   4
  KRZYZA  17     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs      14   1   8
  KRZYZA  22     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs      14   1   8
  MANNI2  11     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any      10   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 5

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  43  m   0         24     102      42     152      0.85 (  0.49-   1.49)
 DEAN1  83  f   0          7     110      15     114      0.48 (  0.19-   1.23)
 Subtotal DEAN1                                           0.73 (  0.45-   1.19)
 FORAST 9   f   0         21     114      23     325      2.60 (  1.39-   4.88)
 HUHTI2 9   m   0          6      58       6      90      1.55 (  0.48-   5.04)
 HUHTI2 12  f   0          1      12       1      21      1.75 (  0.10-  30.59)
 Subtotal HUHTI2                                          1.58 (  0.53-   4.70)
*JACOBS 11  m   2          9       -       8       -      2.70 (  0.98-   7.46)
*KAHN   34  m   2         20       -      49       -     15.06 (  6.73-  33.72)
*KRZYZA 17  m   1         12       -       8       -      1.67 (  0.64-   4.31)
*KRZYZA 22  f   1          4       -       1       -      3.41 (  0.27-  42.74)
 Subtotal KRZYZA                                          1.82 (  0.75-   4.45)
 MANNI2 11  b   1        125       -      44       -      1.85 (  1.27-   2.67)
Partial Totals           229     396     197     702
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  43  m   0             -0.16    12.22     7.67       0.57
 DEAN1  83  f   0             -0.73     4.40     8.11       0.13
 Subtotal DEAN1               -0.31    16.61    15.78
 FORAST 9   f   0              0.96     9.71     1.03       0.00
 HUHTI2 9   m   0              0.44     2.76     0.10       0.47
 HUHTI2 12  f   0              0.56     0.47     0.00       0.70
 Subtotal HUHTI2               0.46     3.23     0.10
*JACOBS 11  m   2              0.99     3.73     0.49       0.06
*KAHN   34  m   2              2.71     5.92    25.61       0.00
*KRZYZA 17  m   1              0.51     4.22     0.06       0.29
*KRZYZA 22  f   1              1.23     0.60     0.21       0.34
 Subtotal KRZYZA               0.60     4.82     0.27
 MANNI2 11  b   1              0.62    27.83     0.01       0.00

                       N       10
                      NS        7

                      Wt    71.86
                 Het Chi    43.29
                 Het  df        9
                 Het  P       ***
               Fixed  RR     1.88
                     RRl     1.49
                     RRu     2.37
                      P       +++
              Random  RR     1.99
                     RRl     1.11
                     RRu     3.59
                      P         +
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 6

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       10
                      NS        7

                      Wt    71.86
                 Het Chi    43.29
                 Het  df        9
                 Het  P       ***
               Fixed  RR     1.88
                     RRl     1.49
                     RRu     2.37
                      P       +++
              Random  RR     1.99
                     RRl     1.11
                     RRu     3.59
                      P         +
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    27.83     28.85     15.18     71.86
                 Het Chi     0.00     33.63      8.94     43.29
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***         *       ***
               Fixed  RR     1.85      2.08      1.60      1.88
                     RRl     1.28      1.45      0.97      1.49
                     RRu     2.68      3.00      2.64      2.37
                      P        ++       +++       (+)       +++
              Random  RR     1.85      2.46      1.44      1.99
                     RRl     1.28      0.80      0.46      1.11
                     RRu     2.68      7.50      4.57      3.59
                      P        ++      N.S.      N.S.         +
             Between Chi                                   0.72
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt    43.46     24.67                3.73     71.86
                 Het Chi    21.46      5.30                0.00     43.29
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     2.66      0.97                2.70      1.88
                     RRl     1.97      0.65                0.98      1.49
                     RRu     3.58      1.44                7.45      2.37
                      P       +++      N.S.                 (+)       +++
              Random  RR     3.98      0.98                2.70      1.99
                     RRl     1.31      0.64                0.98      1.11
                     RRu    12.04      1.49                7.45      3.59
                      P         +      N.S.                 (+)         +
             Between Chi                                            16.52
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 6

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    16.61     14.47     40.78     71.86
                 Het Chi     1.03     13.75      1.03     43.29
                 Het  df        1         3         3         9
                 Het  P      N.S.        **      N.S.       ***
               Fixed  RR     0.73      4.79      1.98      1.88
                     RRl     0.45      2.86      1.46      1.49
                     RRu     1.19      8.01      2.69      2.37
                      P      N.S.       +++       +++       +++
              Random  RR     0.73      4.07      1.98      1.99
                     RRl     0.45      1.22      1.46      1.11
                     RRu     1.20     13.60      2.69      3.59
                      P      N.S.         +       +++         +
             Between Chi                                  27.48
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt    26.26     35.89      9.71     71.86
                 Het Chi    41.73      0.35      0.00     43.29
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     1.74      1.82      2.60      1.88
                     RRl     1.19      1.31      1.39      1.49
                     RRu     2.56      2.53      4.88      2.37
                      P        ++       +++        ++       +++
              Random  RR     2.02      1.82      2.60      1.99
                     RRl     0.45      1.31      1.39      1.11
                     RRu     9.03      2.53      4.88      3.59
                      P      N.S.       +++        ++         +
             Between Chi                                   1.22
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    31.06     24.18     16.61     71.86
                 Het Chi     0.08     15.90      1.03     43.29
                 Het  df        2         4         1         9
                 Het  P      N.S.        **      N.S.       ***
               Fixed  RR     1.82      3.75      0.73      1.88
                     RRl     1.28      2.52      0.45      1.49
                     RRu     2.59      5.58      1.19      2.37
                      P       +++       +++      N.S.       +++
              Random  RR     1.82      3.68      0.73      1.99
                     RRl     1.28      1.53      0.45      1.11
                     RRu     2.59      8.81      1.20      3.59
                      P       +++        ++      N.S.         +
             Between Chi                                  26.27
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 7

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - I - 7 - 8

         IESCOPD - Meta-analysis of years since quit (vs never) : highest (=most recent) vs lowest (=longest ago)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI2 HUHTI1     2                HUHTI1/HUHTI2
  MANNI2 MANNI2     1                MANNI2/MANNI3
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 1 -

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) vs current smoking base
5) Key value = 3
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) PROD    : cigarettes, cigarettes only, any product
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 1

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  99   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   1   4
   DEAN1 114   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   1   4

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 2

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  99  m   1         24       -     238       -      0.82 (  0.51-   1.31)
 DEAN1  114 f   1          7       -      70       -      0.64 (  0.29-   1.40)
 Subtotal DEAN1                                           0.77 (  0.51-   1.15)
Partial Totals            31       0     308       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  99  m   1             -0.20    17.27     0.07       0.41
 DEAN1  114 f   1             -0.45     6.20     0.21       0.27
 Subtotal DEAN1               -0.26    23.47     0.28

                       N        2
                      NS        1

                      Wt    23.47
                 Het Chi     0.28
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.77
                     RRl     0.51
                     RRu     1.15
                      P      N.S.
              Random  RR     0.77
                     RRl     0.51
                     RRu     1.15
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 3

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        2
                      NS        1

                      Wt    23.47
                 Het Chi     0.28
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.77
                     RRl     0.51
                     RRu     1.15
                      P      N.S.
              Random  RR     0.77
                     RRl     0.51
                     RRu     1.15
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt              17.27      6.20     23.47
                 Het Chi               0.00      0.00      0.28
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.82      0.64      0.77
                     RRl               0.51      0.29      0.51
                     RRu               1.31      1.41      1.15
                      P                N.S.      N.S.      N.S.
              Random  RR               0.82      0.64      0.77
                     RRl               0.51      0.29      0.51
                     RRu               1.31      1.41      1.15
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.28
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt              23.47                         23.47
                 Het Chi               0.28                          0.28
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               0.77                          0.77
                     RRl               0.51                          0.51
                     RRu               1.15                          1.15
                      P                N.S.                          N.S.
              Random  RR               0.77                          0.77
                     RRl               0.51                          0.51
                     RRu               1.15                          1.15
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 3

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2                             2
                      NS        1                             1

                      Wt    23.47                         23.47
                 Het Chi     0.28                          0.28
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     0.77                          0.77
                     RRl     0.51                          0.51
                     RRu     1.15                          1.15
                      P      N.S.                          N.S.
              Random  RR     0.77                          0.77
                     RRl     0.51                          0.51
                     RRu     1.15                          1.15
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2                             2
                      NS        1                             1

                      Wt    23.47                         23.47
                 Het Chi     0.28                          0.28
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     0.77                          0.77
                     RRl     0.51                          0.51
                     RRu     1.15                          1.15
                      P      N.S.                          N.S.
              Random  RR     0.77                          0.77
                     RRl     0.51                          0.51
                     RRu     1.15                          1.15
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                            2         2
                      NS                            1         1

                      Wt                        23.47     23.47
                 Het Chi                         0.28      0.28
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                         0.77      0.77
                     RRl                         0.51      0.51
                     RRu                         1.15      1.15
                      P                          N.S.      N.S.
              Random  RR                         0.77      0.77
                     RRl                         0.51      0.51
                     RRu                         1.15      1.15
                      P                          N.S.      N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 4

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  89 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   1   4
   DEAN1 109 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   1   4

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 5

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  89  m   0         24     102     238     930      0.92 (  0.58-   1.47)
 DEAN1  109 f   0          7     110      70    1158      1.05 (  0.47-   2.35)
 Subtotal DEAN1                                           0.95 (  0.64-   1.42)
Totals                    31     212     308    2088
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  89  m   0             -0.08    17.62     0.02       0.72
 DEAN1  109 f   0              0.05     5.98     0.06       0.90
 Subtotal DEAN1               -0.05    23.61     0.08

                       N        2
                      NS        1

                      Wt    23.61
                 Het Chi     0.08
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.95
                     RRl     0.64
                     RRu     1.42
                      P      N.S.
              Random  RR     0.95
                     RRl     0.64
                     RRu     1.42
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 6

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        2
                      NS        1

                      Wt    23.61
                 Het Chi     0.08
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.95
                     RRl     0.64
                     RRu     1.42
                      P      N.S.
              Random  RR     0.95
                     RRl     0.64
                     RRu     1.42
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt              17.62      5.98     23.61
                 Het Chi               0.00      0.00      0.08
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.92      1.05      0.95
                     RRl               0.58      0.47      0.64
                     RRu               1.47      2.35      1.42
                      P                N.S.      N.S.      N.S.
              Random  RR               0.92      1.05      0.95
                     RRl               0.58      0.47      0.64
                     RRu               1.47      2.35      1.42
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.08
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt              23.61                         23.61
                 Het Chi               0.08                          0.08
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               0.95                          0.95
                     RRl               0.64                          0.64
                     RRu               1.42                          1.42
                      P                N.S.                          N.S.
              Random  RR               0.95                          0.95
                     RRl               0.64                          0.64
                     RRu               1.42                          1.42
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 6

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2                             2
                      NS        1                             1

                      Wt    23.61                         23.61
                 Het Chi     0.08                          0.08
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     0.95                          0.95
                     RRl     0.64                          0.64
                     RRu     1.42                          1.42
                      P      N.S.                          N.S.
              Random  RR     0.95                          0.95
                     RRl     0.64                          0.64
                     RRu     1.42                          1.42
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2                             2
                      NS        1                             1

                      Wt    23.61                         23.61
                 Het Chi     0.08                          0.08
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     0.95                          0.95
                     RRl     0.64                          0.64
                     RRu     1.42                          1.42
                      P      N.S.                          N.S.
              Random  RR     0.95                          0.95
                     RRl     0.64                          0.64
                     RRu     1.42                          1.42
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                            2         2
                      NS                            1         1

                      Wt                        23.61     23.61
                 Het Chi                         0.08      0.08
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                         0.95      0.95
                     RRl                         0.64      0.64
                     RRu                         1.42      1.42
                      P                          N.S.      N.S.
              Random  RR                         0.95      0.95
                     RRl                         0.64      0.64
                     RRu                         1.42      1.42
                      P                          N.S.      N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 1 - 7

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
4        KAHN
5      FORAST HUHTI2 JACOBS KRZYZA MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 2 -

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) vs current smoking base
5) Key value = 7
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) PROD    : cigarettes, cigarettes only, any product
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 1

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1 100   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   5   8
   DEAN1 115   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   5   8

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 2

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  100 m   1         15       -     238       -      0.90 (  0.49-   1.67)
 DEAN1  115 f   1          6       -      70       -      1.34 (  0.56-   3.22)
 Subtotal DEAN1                                           1.03 (  0.62-   1.70)
Partial Totals            21       0     308       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  100 m   1             -0.11    10.22     0.18       0.74
 DEAN1  115 f   1              0.29     5.02     0.36       0.51
 Subtotal DEAN1                0.03    15.24     0.53

                       N        2
                      NS        1

                      Wt    15.24
                 Het Chi     0.53
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     1.03
                     RRl     0.62
                     RRu     1.70
                      P      N.S.
              Random  RR     1.03
                     RRl     0.62
                     RRu     1.70
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 3

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        2
                      NS        1

                      Wt    15.24
                 Het Chi     0.53
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     1.03
                     RRl     0.62
                     RRu     1.70
                      P      N.S.
              Random  RR     1.03
                     RRl     0.62
                     RRu     1.70
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt              10.22      5.02     15.24
                 Het Chi               0.00      0.00      0.53
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.90      1.34      1.03
                     RRl               0.49      0.56      0.62
                     RRu               1.66      3.21      1.70
                      P                N.S.      N.S.      N.S.
              Random  RR               0.90      1.34      1.03
                     RRl               0.49      0.56      0.62
                     RRu               1.66      3.21      1.70
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.53
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt              15.24                         15.24
                 Het Chi               0.53                          0.53
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               1.03                          1.03
                     RRl               0.62                          0.62
                     RRu               1.70                          1.70
                      P                N.S.                          N.S.
              Random  RR               1.03                          1.03
                     RRl               0.62                          0.62
                     RRu               1.70                          1.70
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 3

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2                             2
                      NS        1                             1

                      Wt    15.24                         15.24
                 Het Chi     0.53                          0.53
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     1.03                          1.03
                     RRl     0.62                          0.62
                     RRu     1.70                          1.70
                      P      N.S.                          N.S.
              Random  RR     1.03                          1.03
                     RRl     0.62                          0.62
                     RRu     1.70                          1.70
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2                             2
                      NS        1                             1

                      Wt    15.24                         15.24
                 Het Chi     0.53                          0.53
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     1.03                          1.03
                     RRl     0.62                          0.62
                     RRu     1.70                          1.70
                      P      N.S.                          N.S.
              Random  RR     1.03                          1.03
                     RRl     0.62                          0.62
                     RRu     1.70                          1.70
                      P      N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                            2         2
                      NS                            1         1

                      Wt                        15.24     15.24
                 Het Chi                         0.53      0.53
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                         1.03      1.03
                     RRl                         0.62      0.62
                     RRu                         1.70      1.70
                      P                          N.S.      N.S.
              Random  RR                         1.03      1.03
                     RRl                         0.62      0.62
                     RRu                         1.70      1.70
                      P                          N.S.      N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 4

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  90 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   5   8
   DEAN1 110 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   5   8

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 5

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  90  m   0         15      43     238     930      1.36 (  0.74-   2.50)
 DEAN1  110 f   0          6      38      70    1158      2.61 (  1.07-   6.39)
 Subtotal DEAN1                                           1.67 (  1.01-   2.76)
Totals                    21      81     308    2088
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  90  m   0              0.31    10.50     0.44       0.32
 DEAN1  110 f   0              0.96     4.80     0.96       0.04
 Subtotal DEAN1                0.51    15.31     1.39

                       N        2
                      NS        1

                      Wt    15.31
                 Het Chi     1.39
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     1.67
                     RRl     1.01
                     RRu     2.76
                      P         +
              Random  RR     1.73
                     RRl     0.94
                     RRu     3.20
                      P       (+)
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 6

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        2
                      NS        1

                      Wt    15.31
                 Het Chi     1.39
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     1.67
                     RRl     1.01
                     RRu     2.76
                      P         +
              Random  RR     1.73
                     RRl     0.94
                     RRu     3.20
                      P       (+)
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt              10.50      4.80     15.31
                 Het Chi               0.00      0.00      1.39
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               1.36      2.61      1.67
                     RRl               0.74      1.07      1.01
                     RRu               2.50      6.39      2.76
                      P                N.S.         +         +
              Random  RR               1.36      2.61      1.73
                     RRl               0.74      1.07      0.94
                     RRu               2.50      6.39      3.20
                      P                N.S.         +       (+)
             Between Chi                                   1.39
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt              15.31                         15.31
                 Het Chi               1.39                          1.39
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               1.67                          1.67
                     RRl               1.01                          1.01
                     RRu               2.76                          2.76
                      P                   +                             +
              Random  RR               1.73                          1.73
                     RRl               0.94                          0.94
                     RRu               3.20                          3.20
                      P                 (+)                           (+)
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 6

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2                             2
                      NS        1                             1

                      Wt    15.31                         15.31
                 Het Chi     1.39                          1.39
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     1.67                          1.67
                     RRl     1.01                          1.01
                     RRu     2.76                          2.76
                      P         +                             +
              Random  RR     1.73                          1.73
                     RRl     0.94                          0.94
                     RRu     3.20                          3.20
                      P       (+)                           (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        2                             2
                      NS        1                             1

                      Wt    15.31                         15.31
                 Het Chi     1.39                          1.39
                 Het  df        1                             1
                 Het  P      N.S.                          N.S.
               Fixed  RR     1.67                          1.67
                     RRl     1.01                          1.01
                     RRu     2.76                          2.76
                      P         +                             +
              Random  RR     1.73                          1.73
                     RRl     0.94                          0.94
                     RRu     3.20                          3.20
                      P       (+)                           (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                            2         2
                      NS                            1         1

                      Wt                        15.31     15.31
                 Het Chi                         1.39      1.39
                 Het  df                            1         1
                 Het  P                          N.S.      N.S.
               Fixed  RR                         1.67      1.67
                     RRl                         1.01      1.01
                     RRu                         2.76      2.76
                      P                             +         +
              Random  RR                         1.73      1.73
                     RRl                         0.94      0.94
                     RRu                         3.20      3.20
                      P                           (+)       (+)
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 2 - 7

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 7
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
4        KAHN
5      FORAST HUHTI2 JACOBS KRZYZA MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 3 -

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) vs current smoking base
5) Key value = 12
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) PROD    : cigarettes, cigarettes only, any product
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 1

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1 101   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   9   +
   DEAN1 116   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   9   +
  FORAST  17   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   1      Ex       Cigs  Cur cigs  11   +
  HUHTI2  14   m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any  10   +
  HUHTI2  17   f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any  10   +
  JACOBS  14   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Cur cigs  10   +
  KRZYZA  24   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13
  KRZYZA  29   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13
  MANNI2  13   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Cur any  10   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 2

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  101 m   1         42       -     238       -      0.65 (  0.45-   0.95)
 DEAN1  116 f   1         15       -      70       -      1.01 (  0.58-   1.76)
 Subtotal DEAN1                                           0.75 (  0.55-   1.02)
 FORAST 17  f   1         23       -      17       -      0.30 (  0.15-   0.59)
 HUHTI2 14  m   0          6      90      36     151      0.28 (  0.11-   0.69)
 HUHTI2 17  f   0          1      21       1      41      1.95 (  0.12-  32.80)
 Subtotal HUHTI2                                          0.33 (  0.14-   0.79)
*JACOBS 14  m   2          8       -     216       -      0.35 (  0.16-   0.76)
*KRZYZA 24  m   1          4       -      31       -      0.90 (  0.32-   2.54)
*KRZYZA 29  f   1          0       -      12       -      0.40 (  0.02-   6.31)
 Subtotal KRZYZA                                          0.82 (  0.31-   2.17)
 MANNI2 13  b   1         44       -     581       -      0.43 (  0.31-   0.59)
Partial Totals           143     111    1202     192
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  101 m   1             -0.43    27.52     1.38       0.02
 DEAN1  116 f   1              0.01    12.47     5.51       0.97
 Subtotal DEAN1               -0.29    39.99     6.89
 FORAST 17  f   1             -1.20     8.19     2.47       0.00
 HUHTI2 14  m   0             -1.27     4.71     1.81       0.01
 HUHTI2 17  f   0              0.67     0.48     0.85       0.64
 Subtotal HUHTI2              -1.09     5.20     2.65
*JACOBS 14  m   2             -1.05     6.33     0.99       0.01
*KRZYZA 24  m   1             -0.11     3.58     1.08       0.84
*KRZYZA 29  f   1             -0.92     0.46     0.03       0.53
 Subtotal KRZYZA              -0.20     4.04     1.11
 MANNI2 13  b   1             -0.84    37.10     1.33       0.00

                       N        9
                      NS        6

                      Wt   100.86
                 Het Chi    15.45
                 Het  df        8
                 Het  P       (*)
               Fixed  RR     0.52
                     RRl     0.43
                     RRu     0.63
                      P       ---
              Random  RR     0.52
                     RRl     0.37
                     RRu     0.71
                      P       ---
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 3

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        9
                      NS        6

                      Wt   100.86
                 Het Chi    15.45
                 Het  df        8
                 Het  P       (*)
               Fixed  RR     0.52
                     RRl     0.43
                     RRu     0.63
                      P       ---
              Random  RR     0.52
                     RRl     0.37
                     RRu     0.71
                      P       ---
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         4         4         9
                      NS        1         4         4         9

                      Wt    37.10     42.14     21.61    100.86
                 Het Chi     0.00      5.08      8.00     15.45
                 Het  df        0         3         3         8
                 Het  P      N.S.      N.S.         *       (*)
               Fixed  RR     0.43      0.55      0.63      0.52
                     RRl     0.31      0.41      0.42      0.43
                     RRu     0.59      0.75      0.97      0.63
                      P       ---       ---         -       ---
              Random  RR     0.43      0.51      0.61      0.52
                     RRl     0.31      0.32      0.24      0.37
                     RRu     0.59      0.81      1.55      0.71
                      P       ---        --      N.S.       ---
             Between Chi                                   2.36
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2         6                   1         9
                      NS        2         3                   1         6

                      Wt    45.29     49.23                6.33    100.86
                 Het Chi     0.87      6.67                0.00     15.45
                 Het  df        1         5                   0         8
                 Het  P      N.S.      N.S.                N.S.       (*)
               Fixed  RR     0.40      0.69                0.35      0.52
                     RRl     0.30      0.52                0.16      0.43
                     RRu     0.54      0.91                0.76      0.63
                      P       ---        --                  --       ---
              Random  RR     0.40      0.69                0.35      0.52
                     RRl     0.30      0.47                0.16      0.37
                     RRu     0.54      1.01                0.76      0.71
                      P       ---       (-)                  --       ---
             Between Chi                                             7.91
             Between  df                                                2
             Between  P                                                 *
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 3

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         3         4         9
                      NS        1         2         3         6

                      Wt    39.99     10.37     50.49    100.86
                 Het Chi     1.67      2.06      2.68     15.45
                 Het  df        1         2         3         8
                 Het  P      N.S.      N.S.      N.S.       (*)
               Fixed  RR     0.75      0.49      0.40      0.52
                     RRl     0.55      0.27      0.30      0.43
                     RRu     1.02      0.90      0.52      0.63
                      P       (-)         -       ---       ---
              Random  RR     0.77      0.49      0.40      0.52
                     RRl     0.51      0.26      0.30      0.37
                     RRu     1.17      0.92      0.52      0.71
                      P      N.S.         -       ---       ---
             Between Chi                                   9.04
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                     (*)

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         1         9
                      NS        2         3         1         6

                      Wt    46.32     46.34      8.19    100.86
                 Het Chi     4.79      3.90      0.00     15.45
                 Het  df        2         4         0         8
                 Het  P       (*)      N.S.      N.S.       (*)
               Fixed  RR     0.67      0.44      0.30      0.52
                     RRl     0.50      0.33      0.15      0.43
                     RRu     0.90      0.59      0.59      0.63
                      P        --       ---       ---       ---
              Random  RR     0.65      0.44      0.30      0.52
                     RRl     0.40      0.33      0.15      0.37
                     RRu     1.06      0.59      0.59      0.71
                      P       (-)       ---       ---       ---
             Between Chi                                   6.76
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         4         2         9
                      NS        2         3         1         6

                      Wt    42.30     18.57     39.99    100.86
                 Het Chi     1.94      3.14      1.67     15.45
                 Het  df        2         3         1         8
                 Het  P      N.S.      N.S.      N.S.       (*)
               Fixed  RR     0.42      0.39      0.75      0.52
                     RRl     0.31      0.25      0.55      0.43
                     RRu     0.56      0.62      1.02      0.63
                      P       ---       ---       (-)       ---
              Random  RR     0.42      0.40      0.77      0.52
                     RRl     0.31      0.25      0.51      0.37
                     RRu     0.56      0.64      1.17      0.71
                      P       ---       ---      N.S.       ---
             Between Chi                                   8.70
             Between  df                                      2
             Between  P                                       *
             Btwn(F)  P                                     (*)
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 4

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  91 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   9   +
   DEAN1 111 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   9   +
  FORAST  14 x   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   0      Ex       Cigs  Cur cigs  11   +
  HUHTI2  14     m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any  10   +
  HUHTI2  17     f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any  10   +
  JACOBS  14     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Cur cigs  10   +
  KRZYZA  24     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13
  KRZYZA  29     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13
  MANNI2  13     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Cur any  10   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 5

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  91  m   0         42     152     238     930      1.08 (  0.75-   1.56)
 DEAN1  111 f   0         15     114      70    1158      2.18 (  1.21-   3.93)
 Subtotal DEAN1                                           1.32 (  0.96-   1.80)
 FORAST 14  f   0         23     325      17      81      0.34 (  0.17-   0.66)
 HUHTI2 14  m   0          6      90      36     151      0.28 (  0.11-   0.69)
 HUHTI2 17  f   0          1      21       1      41      1.95 (  0.12-  32.80)
 Subtotal HUHTI2                                          0.33 (  0.14-   0.79)
*JACOBS 14  m   2          8       -     216       -      0.35 (  0.16-   0.76)
*KRZYZA 24  m   1          4       -      31       -      0.90 (  0.32-   2.54)
*KRZYZA 29  f   1          0       -      12       -      0.40 (  0.02-   6.31)
 Subtotal KRZYZA                                          0.82 (  0.31-   2.17)
 MANNI2 13  b   1         44       -     581       -      0.43 (  0.31-   0.59)
Partial Totals           143     702    1202    2361
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  91  m   0              0.08    28.04     7.15       0.68
 DEAN1  111 f   0              0.78    11.04    16.06       0.01
 Subtotal DEAN1                0.27    39.08    23.21
 FORAST 14  f   0             -1.09     8.49     3.69       0.00
 HUHTI2 14  m   0             -1.27     4.71     3.37       0.01
 HUHTI2 17  f   0              0.67     0.48     0.58       0.64
 Subtotal HUHTI2              -1.09     5.20     3.95
*JACOBS 14  m   2             -1.05     6.33     2.44       0.01
*KRZYZA 24  m   1             -0.11     3.58     0.37       0.84
*KRZYZA 29  f   1             -0.92     0.46     0.11       0.53
 Subtotal KRZYZA              -0.20     4.04     0.48
 MANNI2 13  b   1             -0.84    37.10     6.41       0.00

                       N        9
                      NS        6

                      Wt   100.24
                 Het Chi    40.19
                 Het  df        8
                 Het  P       ***
               Fixed  RR     0.65
                     RRl     0.54
                     RRu     0.79
                      P       ---
              Random  RR     0.63
                     RRl     0.37
                     RRu     1.08
                      P       (-)
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 6

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        9
                      NS        6

                      Wt   100.24
                 Het Chi    40.19
                 Het  df        8
                 Het  P       ***
               Fixed  RR     0.65
                     RRl     0.54
                     RRu     0.79
                      P       ---
              Random  RR     0.63
                     RRl     0.37
                     RRu     1.08
                      P       (-)
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         4         4         9
                      NS        1         4         4         9

                      Wt    37.10     42.66     20.48    100.24
                 Het Chi     0.00     12.06     17.30     40.19
                 Het  df        0         3         3         8
                 Het  P      N.S.        **       ***       ***
               Fixed  RR     0.43      0.77      0.96      0.65
                     RRl     0.31      0.57      0.63      0.54
                     RRu     0.59      1.05      1.49      0.79
                      P       ---       (-)      N.S.       ---
              Random  RR     0.43      0.58      0.87      0.63
                     RRl     0.31      0.28      0.22      0.37
                     RRu     0.59      1.20      3.48      1.08
                      P       ---      N.S.      N.S.       (-)
             Between Chi                                  10.83
             Between  df                                      2
             Between  P                                      **
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2         6                   1         9
                      NS        2         3                   1         6

                      Wt    45.60     48.32                6.33    100.24
                 Het Chi     0.41     14.77                0.00     40.19
                 Het  df        1         5                   0         8
                 Het  P      N.S.         *                N.S.       ***
               Fixed  RR     0.41      1.09                0.35      0.65
                     RRl     0.31      0.82                0.16      0.54
                     RRu     0.55      1.45                0.76      0.79
                      P       ---      N.S.                  --       ---
              Random  RR     0.41      0.94                0.35      0.63
                     RRl     0.31      0.49                0.16      0.37
                     RRu     0.55      1.79                0.76      1.08
                      P       ---      N.S.                  --       (-)
             Between Chi                                            25.01
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                               (*)

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 6

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         3         4         9
                      NS        1         2         3         6

                      Wt    39.08     10.37     50.79    100.24
                 Het Chi     3.89      2.06      2.26     40.19
                 Het  df        1         2         3         8
                 Het  P         *      N.S.      N.S.       ***
               Fixed  RR     1.32      0.49      0.40      0.65
                     RRl     0.96      0.27      0.31      0.54
                     RRu     1.80      0.90      0.53      0.79
                      P       (+)         -       ---       ---
              Random  RR     1.47      0.49      0.40      0.63
                     RRl     0.74      0.26      0.31      0.37
                     RRu     2.92      0.92      0.53      1.08
                      P      N.S.         -       ---       (-)
             Between Chi                                  31.98
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         1         9
                      NS        2         3         1         6

                      Wt    45.41     46.34      8.49    100.24
                 Het Chi    13.45      3.90      0.00     40.19
                 Het  df        2         4         0         8
                 Het  P        **      N.S.      N.S.       ***
               Fixed  RR     1.09      0.44      0.34      0.65
                     RRl     0.82      0.33      0.17      0.54
                     RRu     1.46      0.59      0.66      0.79
                      P      N.S.       ---        --       ---
              Random  RR     0.98      0.44      0.34      0.63
                     RRl     0.42      0.33      0.17      0.37
                     RRu     2.27      0.59      0.66      1.08
                      P      N.S.       ---        --       (-)
             Between Chi                                  22.84
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         4         2         9
                      NS        2         3         1         6

                      Wt    42.30     18.87     39.08    100.24
                 Het Chi     1.94      2.70      3.89     40.19
                 Het  df        2         3         1         8
                 Het  P      N.S.      N.S.         *       ***
               Fixed  RR     0.42      0.41      1.32      0.65
                     RRl     0.31      0.26      0.96      0.54
                     RRu     0.56      0.65      1.80      0.79
                      P       ---       ---       (+)       ---
              Random  RR     0.42      0.41      1.47      0.63
                     RRl     0.31      0.26      0.74      0.37
                     RRu     0.56      0.65      2.92      1.08
                      P       ---       ---      N.S.       (-)
             Between Chi                                  31.66
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                      **
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 7

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
4        KAHN

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 3 - 8

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (1) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI2 HUHTI1     2                HUHTI1/HUHTI2
  MANNI2 MANNI2     1                MANNI2/MANNI3
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 4 -

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) vs current smoking base
5) Key value = 3
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
6) PROD    : cigarettes, cigarettes only, any product
7) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 1

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  99   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   1   4
   DEAN1 114   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only  Cur cigs   1   4
  FORAST  16   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   1      Ex       Cigs  Cur cigs   1  10
  HUHTI2  13   m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any   1   9
  HUHTI2  16   f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any   1   9
  JACOBS  13   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Cur cigs   1   9
  KRZYZA  23   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   1   8
  KRZYZA  28   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   1   8
  MANNI2  12   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Cur any   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 2

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  99  m   1         24       -     238       -      0.82 (  0.51-   1.31)
 DEAN1  114 f   1          7       -      70       -      0.64 (  0.29-   1.40)
 Subtotal DEAN1                                           0.77 (  0.51-   1.15)
 FORAST 16  f   1         21       -      17       -      0.86 (  0.42-   1.75)
 HUHTI2 13  m   0          6      58      36     151      0.43 (  0.17-   1.08)
 HUHTI2 16  f   0          1      12       1      41      3.42 (  0.20-  58.80)
 Subtotal HUHTI2                                          0.53 (  0.22-   1.26)
*JACOBS 13  m   2         24       -     216       -      0.83 (  0.56-   1.24)
*KRZYZA 23  m   1         12       -      31       -      1.19 (  0.62-   2.28)
*KRZYZA 28  f   1          4       -      12       -      1.25 (  0.41-   3.87)
 Subtotal KRZYZA                                          1.20 (  0.69-   2.12)
 MANNI2 12  b   1        125       -     581       -      0.79 (  0.63-   0.98)
Partial Totals           224      70    1202     192
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  99  m   1             -0.20    17.27     0.00       0.41
 DEAN1  114 f   1             -0.45     6.20     0.35       0.27
 Subtotal DEAN1               -0.26    23.47     0.35
 FORAST 16  f   1             -0.15     7.54     0.02       0.68
 HUHTI2 13  m   0             -0.83     4.58     1.80       0.07
 HUHTI2 16  f   0              1.23     0.47     0.98       0.40
 Subtotal HUHTI2              -0.64     5.06     2.78
*JACOBS 13  m   2             -0.19    24.32     0.01       0.36
*KRZYZA 23  m   1              0.17     9.06     1.32       0.60
*KRZYZA 28  f   1              0.22     3.05     0.57       0.70
 Subtotal KRZYZA               0.19    12.11     1.89
 MANNI2 12  b   1             -0.24    78.71     0.06       0.04

                       N        9
                      NS        6

                      Wt   151.20
                 Het Chi     5.12
                 Het  df        8
                 Het  P      N.S.
               Fixed  RR     0.81
                     RRl     0.69
                     RRu     0.95
                      P         -
              Random  RR     0.81
                     RRl     0.69
                     RRu     0.95
                      P         -
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 3

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        9
                      NS        6

                      Wt   151.20
                 Het Chi     5.12
                 Het  df        8
                 Het  P      N.S.
               Fixed  RR     0.81
                     RRl     0.69
                     RRu     0.95
                      P         -
              Random  RR     0.81
                     RRl     0.69
                     RRu     0.95
                      P         -
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         4         4         9
                      NS        1         4         4         9

                      Wt    78.71     55.22     17.27    151.20
                 Het Chi     0.00      3.11      1.87      5.12
                 Het  df        0         3         3         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.79      0.83      0.86      0.81
                     RRl     0.63      0.64      0.54      0.69
                     RRu     0.99      1.08      1.38      0.95
                      P         -      N.S.      N.S.         -
              Random  RR     0.79      0.83      0.86      0.81
                     RRl     0.63      0.63      0.54      0.69
                     RRu     0.99      1.09      1.38      0.95
                      P         -      N.S.      N.S.         -
             Between Chi                                   0.14
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2         6                   1         9
                      NS        2         3                   1         6

                      Wt    86.26     40.63               24.32    151.20
                 Het Chi     0.05      4.98                0.00      5.12
                 Het  df        1         5                   0         8
                 Het  P      N.S.      N.S.                N.S.      N.S.
               Fixed  RR     0.80      0.84                0.83      0.81
                     RRl     0.64      0.62                0.56      0.69
                     RRu     0.98      1.14                1.24      0.95
                      P         -      N.S.                N.S.         -
              Random  RR     0.80      0.84                0.83      0.81
                     RRl     0.64      0.62                0.56      0.69
                     RRu     0.98      1.14                1.24      0.95
                      P         -      N.S.                N.S.         -
             Between Chi                                             0.09
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 3

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         3         4         9
                      NS        1         2         3         6

                      Wt    23.47     36.43     91.31    151.20
                 Het Chi     0.28      1.13      2.69      5.12
                 Het  df        1         2         3         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.77      0.94      0.78      0.81
                     RRl     0.51      0.68      0.63      0.69
                     RRu     1.15      1.30      0.95      0.95
                      P      N.S.      N.S.         -         -
              Random  RR     0.77      0.94      0.78      0.81
                     RRl     0.51      0.68      0.63      0.69
                     RRu     1.15      1.30      0.95      0.95
                      P      N.S.      N.S.         -         -
             Between Chi                                   1.02
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         1         9
                      NS        2         3         1         6

                      Wt    47.78     95.88      7.54    151.20
                 Het Chi     0.35      4.73      0.00      5.12
                 Het  df        2         4         0         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.80      0.82      0.86      0.81
                     RRl     0.60      0.67      0.42      0.69
                     RRu     1.06      1.00      1.76      0.95
                      P      N.S.         -      N.S.         -
              Random  RR     0.80      0.84      0.86      0.81
                     RRl     0.60      0.62      0.42      0.69
                     RRu     1.06      1.14      1.76      0.95
                      P      N.S.      N.S.      N.S.         -
             Between Chi                                   0.04
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         4         2         9
                      NS        2         3         1         6

                      Wt    83.77     43.97     23.47    151.20
                 Het Chi     2.61      1.18      0.28      5.12
                 Het  df        2         3         1         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.77      0.93      0.77      0.81
                     RRl     0.62      0.69      0.51      0.69
                     RRu     0.95      1.24      1.15      0.95
                      P         -      N.S.      N.S.         -
              Random  RR     0.73      0.93      0.77      0.81
                     RRl     0.45      0.69      0.51      0.69
                     RRu     1.17      1.24      1.15      0.95
                      P      N.S.      N.S.      N.S.         -
             Between Chi                                   1.05
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 4

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

   DEAN1  89 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   1   4
   DEAN1 109 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only  Cur cigs   1   4
  FORAST  13 x   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   0      Ex       Cigs  Cur cigs   1  10
  HUHTI2  13     m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any   1   9
  HUHTI2  16     f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any   Cur any   1   9
  JACOBS  13     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs  Cur cigs   1   9
  KRZYZA  23     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   1   8
  KRZYZA  28     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   1   8
  MANNI2  12     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any   Cur any   1   9

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 5

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  89  m   0         24     102     238     930      0.92 (  0.58-   1.47)
 DEAN1  109 f   0          7     110      70    1158      1.05 (  0.47-   2.35)
 Subtotal DEAN1                                           0.95 (  0.64-   1.42)
 FORAST 13  f   0         21     114      17      81      0.88 (  0.44-   1.77)
 HUHTI2 13  m   0          6      58      36     151      0.43 (  0.17-   1.08)
 HUHTI2 16  f   0          1      12       1      41      3.42 (  0.20-  58.80)
 Subtotal HUHTI2                                          0.53 (  0.22-   1.26)
*JACOBS 13  m   2         24       -     216       -      0.83 (  0.56-   1.24)
*KRZYZA 23  m   1         12       -      31       -      1.19 (  0.62-   2.28)
*KRZYZA 28  f   1          4       -      12       -      1.25 (  0.41-   3.87)
 Subtotal KRZYZA                                          1.20 (  0.69-   2.12)
 MANNI2 12  b   1        125       -     581       -      0.79 (  0.63-   0.98)
Partial Totals           224     396    1202    2361
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  89  m   0             -0.08    17.62     0.14       0.72
 DEAN1  109 f   0              0.05     5.98     0.30       0.90
 Subtotal DEAN1               -0.05    23.61     0.44
 FORAST 13  f   0             -0.13     7.84     0.01       0.71
 HUHTI2 13  m   0             -0.83     4.58     2.01       0.07
 HUHTI2 16  f   0              1.23     0.47     0.93       0.40
 Subtotal HUHTI2              -0.64     5.06     2.94
*JACOBS 13  m   2             -0.19    24.32     0.00       0.36
*KRZYZA 23  m   1              0.17     9.06     1.09       0.60
*KRZYZA 28  f   1              0.22     3.05     0.48       0.70
 Subtotal KRZYZA               0.19    12.11     1.57
 MANNI2 12  b   1             -0.24    78.71     0.31       0.04

                       N        9
                      NS        6

                      Wt   151.64
                 Het Chi     5.28
                 Het  df        8
                 Het  P      N.S.
               Fixed  RR     0.84
                     RRl     0.72
                     RRu     0.99
                      P         -
              Random  RR     0.84
                     RRl     0.72
                     RRu     0.99
                      P         -
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 6

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        9
                      NS        6

                      Wt   151.64
                 Het Chi     5.28
                 Het  df        8
                 Het  P      N.S.
               Fixed  RR     0.84
                     RRl     0.72
                     RRu     0.99
                      P         -
              Random  RR     0.84
                     RRl     0.72
                     RRu     0.99
                      P         -
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         4         4         9
                      NS        1         4         4         9

                      Wt    78.71     55.58     17.35    151.64
                 Het Chi     0.00      3.21      1.00      5.28
                 Het  df        0         3         3         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.79      0.86      1.03      0.84
                     RRl     0.63      0.66      0.64      0.72
                     RRu     0.99      1.12      1.65      0.99
                      P         -      N.S.      N.S.         -
              Random  RR     0.79      0.86      1.03      0.84
                     RRl     0.63      0.65      0.64      0.72
                     RRu     0.99      1.13      1.65      0.99
                      P         -      N.S.      N.S.         -
             Between Chi                                   1.07
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        2         6                   1         9
                      NS        2         3                   1         6

                      Wt    86.55     40.77               24.32    151.64
                 Het Chi     0.08      4.36                0.00      5.28
                 Het  df        1         5                   0         8
                 Het  P      N.S.      N.S.                N.S.      N.S.
               Fixed  RR     0.80      0.95                0.83      0.84
                     RRl     0.65      0.70                0.56      0.72
                     RRu     0.98      1.29                1.24      0.99
                      P         -      N.S.                N.S.         -
              Random  RR     0.80      0.95                0.83      0.84
                     RRl     0.65      0.70                0.56      0.72
                     RRu     0.98      1.29                1.24      0.99
                      P         -      N.S.                N.S.         -
             Between Chi                                             0.84
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 6

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         3         4         9
                      NS        1         2         3         6

                      Wt    23.61     36.43     91.61    151.64
                 Het Chi     0.08      1.13      2.73      5.28
                 Het  df        1         2         3         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.95      0.94      0.78      0.84
                     RRl     0.64      0.68      0.64      0.72
                     RRu     1.42      1.30      0.96      0.99
                      P      N.S.      N.S.         -         -
              Random  RR     0.95      0.94      0.78      0.84
                     RRl     0.64      0.68      0.64      0.72
                     RRu     1.42      1.30      0.96      0.99
                      P      N.S.      N.S.         -         -
             Between Chi                                   1.33
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        3         5         1         9
                      NS        2         3         1         6

                      Wt    47.92     95.88      7.84    151.64
                 Het Chi     0.31      4.73      0.00      5.28
                 Het  df        2         4         0         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.89      0.82      0.88      0.84
                     RRl     0.67      0.67      0.44      0.72
                     RRu     1.18      1.00      1.77      0.99
                      P      N.S.         -      N.S.         -
              Random  RR     0.89      0.84      0.88      0.84
                     RRl     0.67      0.62      0.44      0.72
                     RRu     1.18      1.14      1.77      0.99
                      P      N.S.      N.S.      N.S.         -
             Between Chi                                   0.24
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         4         2         9
                      NS        2         3         1         6

                      Wt    83.77     44.27     23.61    151.64
                 Het Chi     2.61      1.16      0.08      5.28
                 Het  df        2         3         1         8
                 Het  P      N.S.      N.S.      N.S.      N.S.
               Fixed  RR     0.77      0.93      0.95      0.84
                     RRl     0.62      0.69      0.64      0.72
                     RRu     0.95      1.25      1.42      0.99
                      P         -      N.S.      N.S.         -
              Random  RR     0.73      0.93      0.95      0.84
                     RRl     0.45      0.69      0.64      0.72
                     RRu     1.17      1.25      1.42      0.99
                      P      N.S.      N.S.      N.S.         -
             Between Chi                                   1.43
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 7

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
4        KAHN

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 4 - 8

                        IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 3
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI2 HUHTI1     2                HUHTI1/HUHTI2
  MANNI2 MANNI2     1                MANNI2/MANNI3
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 5 -

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) vs current smoking base
5) Key value = 7
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) PROD    : cigarettes, cigarettes only, any product
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 1

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  KRZYZA  24   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13
  KRZYZA  29   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 2

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KRZYZA 24  m   1          4       -      31       -      0.90 (  0.32-   2.54)
*KRZYZA 29  f   1          0       -      12       -      0.40 (  0.02-   6.31)
 Subtotal KRZYZA                                          0.82 (  0.31-   2.17)
Partial Totals             4       0      43       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KRZYZA 24  m   1             -0.11     3.58     0.03       0.84
*KRZYZA 29  f   1             -0.92     0.46     0.24       0.53
 Subtotal KRZYZA              -0.20     4.04     0.27

                       N        2
                      NS        1

                      Wt     4.04
                 Het Chi     0.27
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
              Random  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 3

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        2
                      NS        1

                      Wt     4.04
                 Het Chi     0.27
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
              Random  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt               3.58      0.46      4.04
                 Het Chi               0.00      0.00      0.27
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.90      0.40      0.82
                     RRl               0.32      0.02      0.31
                     RRu               2.54      7.10      2.17
                      P                N.S.      N.S.      N.S.
              Random  RR               0.90      0.40      0.82
                     RRl               0.32      0.02      0.31
                     RRu               2.54      7.10      2.17
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.27
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt               4.04                          4.04
                 Het Chi               0.27                          0.27
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               0.82                          0.82
                     RRl               0.31                          0.31
                     RRu               2.17                          2.17
                      P                N.S.                          N.S.
              Random  RR               0.82                          0.82
                     RRl               0.31                          0.31
                     RRu               2.17                          2.17
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 3

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               4.04                4.04
                 Het Chi               0.27                0.27
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
              Random  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               4.04                4.04
                 Het Chi               0.27                0.27
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
              Random  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               4.04                4.04
                 Het Chi               0.27                0.27
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
              Random  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 4

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  KRZYZA  24     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13
  KRZYZA  29     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs   9  13

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 5

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KRZYZA 24  m   1          4       -      31       -      0.90 (  0.32-   2.54)
*KRZYZA 29  f   1          0       -      12       -      0.40 (  0.02-   6.31)
 Subtotal KRZYZA                                          0.82 (  0.31-   2.17)
Partial Totals             4       0      43       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KRZYZA 24  m   1             -0.11     3.58     0.03       0.84
*KRZYZA 29  f   1             -0.92     0.46     0.24       0.53
 Subtotal KRZYZA              -0.20     4.04     0.27

                       N        2
                      NS        1

                      Wt     4.04
                 Het Chi     0.27
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
              Random  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 6

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        2
                      NS        1

                      Wt     4.04
                 Het Chi     0.27
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
              Random  RR     0.82
                     RRl     0.31
                     RRu     2.17
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt               3.58      0.46      4.04
                 Het Chi               0.00      0.00      0.27
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.90      0.40      0.82
                     RRl               0.32      0.02      0.31
                     RRu               2.54      7.10      2.17
                      P                N.S.      N.S.      N.S.
              Random  RR               0.90      0.40      0.82
                     RRl               0.32      0.02      0.31
                     RRu               2.54      7.10      2.17
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.27
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt               4.04                          4.04
                 Het Chi               0.27                          0.27
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               0.82                          0.82
                     RRl               0.31                          0.31
                     RRu               2.17                          2.17
                      P                N.S.                          N.S.
              Random  RR               0.82                          0.82
                     RRl               0.31                          0.31
                     RRu               2.17                          2.17
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 6

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               4.04                4.04
                 Het Chi               0.27                0.27
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
              Random  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               4.04                4.04
                 Het Chi               0.27                0.27
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
              Random  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               4.04                4.04
                 Het Chi               0.27                0.27
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
              Random  RR               0.82                0.82
                     RRl               0.31                0.31
                     RRu               2.17                2.17
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 7

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
4        KAHN
5       DEAN1 FORAST HUHTI2 JACOBS MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 5 - 8

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 12
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 6 -

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) vs current smoking base
5) Key value = 12
6) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
7) PROD    : cigarettes, cigarettes only, any product
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 1

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  KRZYZA  25   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs  14   +
  KRZYZA  30   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs  14   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 2

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KRZYZA 25  m   1          8       -      31       -      0.71 (  0.31-   1.63)
*KRZYZA 30  f   1          1       -      12       -      0.37 (  0.03-   3.92)
 Subtotal KRZYZA                                          0.66 (  0.30-   1.46)
Partial Totals             9       0      43       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KRZYZA 25  m   1             -0.34     5.58     0.03       0.42
*KRZYZA 30  f   1             -0.99     0.65     0.22       0.42
 Subtotal KRZYZA              -0.41     6.22     0.25

                       N        2
                      NS        1

                      Wt     6.22
                 Het Chi     0.25
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
              Random  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 3

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N        2
                      NS        1

                      Wt     6.22
                 Het Chi     0.25
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
              Random  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt               5.58      0.65      6.22
                 Het Chi               0.00      0.00      0.25
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.71      0.37      0.66
                     RRl               0.31      0.03      0.30
                     RRu               1.63      4.23      1.46
                      P                N.S.      N.S.      N.S.
              Random  RR               0.71      0.37      0.66
                     RRl               0.31      0.03      0.30
                     RRu               1.63      4.23      1.46
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.25
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt               6.22                          6.22
                 Het Chi               0.25                          0.25
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               0.66                          0.66
                     RRl               0.30                          0.30
                     RRu               1.46                          1.46
                      P                N.S.                          N.S.
              Random  RR               0.66                          0.66
                     RRl               0.30                          0.30
                     RRu               1.46                          1.46
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 3

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               6.22                6.22
                 Het Chi               0.25                0.25
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
              Random  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               6.22                6.22
                 Het Chi               0.25                0.25
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
              Random  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               6.22                6.22
                 Het Chi               0.25                0.25
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
              Random  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 4

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|    UNEXP|LOW| HI|

  KRZYZA  25     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs  14   +
  KRZYZA  30     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs  Cur cigs  14   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 5

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
*KRZYZA 25  m   1          8       -      31       -      0.71 (  0.31-   1.63)
*KRZYZA 30  f   1          1       -      12       -      0.37 (  0.03-   3.92)
 Subtotal KRZYZA                                          0.66 (  0.30-   1.46)
Partial Totals             9       0      43       0
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
*KRZYZA 25  m   1             -0.34     5.58     0.03       0.42
*KRZYZA 30  f   1             -0.99     0.65     0.22       0.42
 Subtotal KRZYZA              -0.41     6.22     0.25

                       N        2
                      NS        1

                      Wt     6.22
                 Het Chi     0.25
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
              Random  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
               Asymm  P

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 6

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N        2
                      NS        1

                      Wt     6.22
                 Het Chi     0.25
                 Het  df        1
                 Het  P      N.S.
               Fixed  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
              Random  RR     0.66
                     RRl     0.30
                     RRu     1.46
                      P      N.S.
               Asymm  P

                                   Sex
                             both      male    female     Total

                       N                  1         1         2
                      NS                  1         1         1

                      Wt               5.58      0.65      6.22
                 Het Chi               0.00      0.00      0.25
                 Het  df                  0         0         1
                 Het  P                N.S.      N.S.      N.S.
               Fixed  RR               0.71      0.37      0.66
                     RRl               0.31      0.03      0.30
                     RRu               1.63      4.23      1.46
                      P                N.S.      N.S.      N.S.
              Random  RR               0.71      0.37      0.66
                     RRl               0.31      0.03      0.30
                     RRu               1.63      4.23      1.46
                      P                N.S.      N.S.      N.S.
             Between Chi                                   0.25
             Between  df                                      1
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N                  2                             2
                      NS                  1                             1

                      Wt               6.22                          6.22
                 Het Chi               0.25                          0.25
                 Het  df                  1                             1
                 Het  P                N.S.                          N.S.
               Fixed  RR               0.66                          0.66
                     RRl               0.30                          0.30
                     RRu               1.46                          1.46
                      P                N.S.                          N.S.
              Random  RR               0.66                          0.66
                     RRl               0.30                          0.30
                     RRu               1.46                          1.46
                      P                N.S.                          N.S.
             Between Chi
             Between  df
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 6

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               6.22                6.22
                 Het Chi               0.25                0.25
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
              Random  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               6.22                6.22
                 Het Chi               0.25                0.25
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
              Random  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N                  2                   2
                      NS                  1                   1

                      Wt               6.22                6.22
                 Het Chi               0.25                0.25
                 Het  df                  1                   1
                 Het  P                N.S.                N.S.
               Fixed  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
              Random  RR               0.66                0.66
                     RRl               0.30                0.30
                     RRu               1.46                1.46
                      P                N.S.                N.S.
             Between Chi
             Between  df
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 7

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO
4        KAHN
5       DEAN1 FORAST HUHTI2 JACOBS MANNI2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 6 - 8

                       IESCOPD - Meta-analysis of years since quit (vs current) : key value (2) 20
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                    Table 1 - J - 7 -

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)

This analysis is restricted to results for:
1) Eligible study on database
2) Outcome COPD
3) Categorical dose-response data for years since quit (vs current/recent)
4) Long-term vs recent base
5) Results complete enough for use in meta-analysis

Within each study, results are then selected (in the following order of preference, within each sex) for:
6) PROD    : cigarettes, cigarettes only, any product
7) The longest vs most recent category
8) For overlapping studies: principal rather than subsidiary studies
and then for single sex results (m, f) in preference to results for both sexes combined (b).

Results adjusted for the most potential confounders are then chosen in Sections -1 to -3
and results adjusted for the least confounders in Sections -4 to -6. (Those least-adjusted results which
actually differ from the most-adjusted are marked 'x' in column X in Section -4)

Section -7 shows excluded studies, together with the stage (as above) at which no qualifying
results were found.

Section -8 lists the potentially overlapping studies which have been included (1=principal, 2=subsidiary),
and any results which would have been included in preference except that they had data not complete enough
for use in meta-analysis. It also lists their significance (yes/no), if known.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 1

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

     REF|NRR|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

   DEAN1 103   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only       4   9   +
   DEAN1 118   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   1      Ex MCigs only       4   9   +
  FORAST  18   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   1      Ex       Cigs      10  11   +
  HUHTI2  15   m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any       9  10   +
  HUHTI2  18   f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any       9  10   +
  JACOBS  16   m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs       0  10   +
    KAHN  53   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   3      Ex       Cigs       4  40   +
  KRZYZA  27   m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs       8  14   +
  KRZYZA  32   f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs       8  14   +
  MANNI2  14   b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any       9  10   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 2

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  103 m   1         42       -      24       -      0.80 (  0.46-   1.41)
 DEAN1  118 f   1         15       -       7       -      1.58 (  0.64-   3.93)
 Subtotal DEAN1                                           0.97 (  0.60-   1.55)
 FORAST 18  f   1         23       -      21       -      0.35 (  0.19-   0.66)
 HUHTI2 15  m   0          6      90       6      58      0.64 (  0.20-   2.09)
 HUHTI2 18  f   0          1      21       1      12      0.57 (  0.03-   9.99)
 Subtotal HUHTI2                                          0.63 (  0.21-   1.88)
*JACOBS 16  m   2          8       -       9       -      0.37 (  0.13-   1.02)
*KAHN   53  m   3         49       -      20       -      0.07 (  0.04-   0.13)
*KRZYZA 27  m   1          8       -      12       -      0.60 (  0.23-   1.55)
*KRZYZA 32  f   1          1       -       4       -      0.29 (  0.02-   3.67)
 Subtotal KRZYZA                                          0.55 (  0.22-   1.35)
 MANNI2 14  b   1         44       -     125       -      0.54 (  0.37-   0.79)
Partial Totals           197     111     229      70
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  103 m   1             -0.22    12.25     4.81       0.43
 DEAN1  118 f   1              0.46     4.66     7.98       0.32
 Subtotal DEAN1               -0.04    16.91    12.79
 FORAST 18  f   1             -1.05     9.91     0.40       0.00
 HUHTI2 15  m   0             -0.44     2.76     0.47       0.47
 HUHTI2 18  f   0             -0.56     0.47     0.04       0.70
 Subtotal HUHTI2              -0.46     3.23     0.51
*JACOBS 16  m   2             -0.99     3.62     0.08       0.06
*KAHN   53  m   3             -2.66    11.06    36.20       0.00
*KRZYZA 27  m   1             -0.51     4.22     0.49       0.29
*KRZYZA 32  f   1             -1.24     0.57     0.09       0.35
 Subtotal KRZYZA              -0.60     4.79     0.57
 MANNI2 14  b   1             -0.62    26.71     1.46       0.00

                       N       10
                      NS        7

                      Wt    76.23
                 Het Chi    52.00
                 Het  df        9
                 Het  P       ***
               Fixed  RR     0.43
                     RRl     0.34
                     RRu     0.53
                      P       ---
              Random  RR     0.45
                     RRl     0.24
                     RRu     0.84
                      P         -
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 3

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted

                       N       10
                      NS        7

                      Wt    76.23
                 Het Chi    52.00
                 Het  df        9
                 Het  P       ***
               Fixed  RR     0.43
                     RRl     0.34
                     RRu     0.53
                      P       ---
              Random  RR     0.45
                     RRl     0.24
                     RRu     0.84
                      P         -
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    26.71     33.91     15.61     76.23
                 Het Chi     0.00     38.92      7.45     52.00
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***       (*)       ***
               Fixed  RR     0.54      0.32      0.55      0.43
                     RRl     0.37      0.23      0.34      0.34
                     RRu     0.79      0.44      0.91      0.53
                      P        --       ---         -       ---
              Random  RR     0.54      0.37      0.62      0.45
                     RRl     0.37      0.12      0.22      0.24
                     RRu     0.79      1.13      1.74      0.84
                      P        --       (-)      N.S.         -
             Between Chi                                   5.63
             Between  df                                      2
             Between  P                                     (*)
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt    47.68     24.93                3.62     76.23
                 Het Chi    32.86      3.26                0.00     52.00
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     0.31      0.82                0.37      0.43
                     RRl     0.23      0.55                0.13      0.34
                     RRu     0.41      1.21                1.04      0.53
                      P       ---      N.S.                 (-)       ---
              Random  RR     0.24      0.82                0.37      0.45
                     RRl     0.07      0.55                0.13      0.24
                     RRu     0.82      1.21                1.04      0.84
                      P         -      N.S.                 (-)         -
             Between Chi                                            15.88
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 3

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        National cigarette tobacco type (excluding mixed/unkown)
                          blended  virginia     Total

                       N        8         2        10
                      NS        6         1         7

                      Wt    59.32     16.91     76.23
                 Het Chi    36.01      1.56     52.00
                 Het  df        7         1         9
                 Het  P       ***      N.S.       ***
               Fixed  RR     0.34      0.97      0.43
                     RRl     0.26      0.60      0.34
                     RRu     0.44      1.55      0.53
                      P       ---      N.S.       ---
              Random  RR     0.34      1.02      0.45
                     RRl     0.17      0.54      0.24
                     RRu     0.69      1.93      0.84
                      P        --      N.S.         -
             Between Chi                        14.43
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                          N.S.

                                        Start year of study
                            <1970   1970-79   1980-89   1990-99     2000+   unknown     Total

                       N        6         3                   1                            10
                      NS        4         2                   1                             7

                      Wt    36.38     29.94                9.91                         76.23
                 Het Chi    48.79      0.08                0.00                         52.00
                 Het  df        5         2                   0                             9
                 Het  P       ***      N.S.                N.S.                           ***
               Fixed  RR     0.37      0.55                0.35                          0.43
                     RRl     0.27      0.38                0.19                          0.34
                     RRu     0.51      0.79                0.65                          0.53
                      P       ---        --                 ---                           ---
              Random  RR     0.43      0.55                0.35                          0.45
                     RRl     0.14      0.38                0.19                          0.24
                     RRu     1.30      0.79                0.65                          0.84
                      P      N.S.        --                 ---                             -
             Between Chi                                                                 3.13
             Between  df                                                                    2
             Between  P                                                                  N.S.
             Btwn(F)  P                                                                  N.S.

                                Publication year
                            <1980   1980-89   1990-99     2000+     Total

                       N        3         4         2         1        10
                      NS        2         2         2         1         7

                      Wt    27.97      8.02     13.53     26.71     76.23
                 Het Chi    47.60      0.31      0.01      0.00     52.00
                 Het  df        2         3         1         0         9
                 Het  P       ***      N.S.      N.S.      N.S.       ***
               Fixed  RR     0.34      0.58      0.36      0.54      0.43
                     RRl     0.24      0.29      0.21      0.37      0.34
                     RRu     0.50      1.16      0.61      0.79      0.53
                      P       ---      N.S.       ---        --       ---
              Random  RR     0.44      0.58      0.36      0.54      0.45
                     RRl     0.07      0.29      0.21      0.37      0.24
                     RRu     2.85      1.16      0.61      0.79      0.84
                      P      N.S.      N.S.       ---        --         -
             Between Chi                                             4.08
             Between  df                                                3
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 3

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    16.91     19.47     39.85     76.23
                 Het Chi     1.56     17.68      1.59     52.00
                 Het  df        1         3         3         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     0.97      0.16      0.49      0.43
                     RRl     0.60      0.10      0.36      0.34
                     RRu     1.55      0.25      0.67      0.53
                      P      N.S.       ---       ---       ---
              Random  RR     1.02      0.24      0.49      0.45
                     RRl     0.54      0.07      0.36      0.24
                     RRu     1.93      0.87      0.67      0.84
                      P      N.S.         -       ---         -
             Between Chi                                  31.17
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                                    Lowest age in RR
                        <25/unlim     25-39       40+   unknown     Total

                       N        2         4         4                  10
                      NS        1         3         3                   7

                      Wt     4.79     54.68     16.76               76.23
                 Het Chi     0.26     50.45      0.89               52.00
                 Het  df        1         3         3                   9
                 Het  P      N.S.       ***      N.S.                 ***
               Fixed  RR     0.55      0.43      0.40                0.43
                     RRl     0.22      0.33      0.25                0.34
                     RRu     1.35      0.56      0.64                0.53
                      P      N.S.       ---       ---                 ---
              Random  RR     0.55      0.46      0.40                0.45
                     RRl     0.22      0.14      0.25                0.24
                     RRu     1.35      1.46      0.64                0.84
                      P      N.S.      N.S.       ---                   -
             Between Chi                                             0.40
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                                         Highest age in RR
                              <65     65-74     75-84 85+/unlim   unknown     Total

                       N                  3         3         4                  10
                      NS                  2         2         3                   7

                      Wt              29.94      8.41     37.88               76.23
                 Het Chi               0.08      0.59     47.61               52.00
                 Het  df                  2         2         3                   9
                 Het  P                N.S.      N.S.       ***                 ***
               Fixed  RR               0.55      0.46      0.34                0.43
                     RRl               0.38      0.24      0.25                0.34
                     RRu               0.79      0.91      0.47                0.53
                      P                  --         -       ---                 ---
              Random  RR               0.55      0.46      0.41                0.45
                     RRl               0.38      0.24      0.11                0.24
                     RRu               0.79      0.91      1.50                0.84
                      P                  --         -      N.S.                   -
             Between Chi                                                       3.73
             Between  df                                                          2
             Between  P                                                        N.S.
             Btwn(F)  P                                                        N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 3

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                           Study weakness
                              Yes        No     Total

                       N        3         7        10
                      NS        2         5         7

                      Wt    26.82     49.41     76.23
                 Het Chi     7.99     36.00     52.00
                 Het  df        2         6         9
                 Het  P         *       ***       ***
               Fixed  RR     0.66      0.34      0.43
                     RRl     0.45      0.25      0.34
                     RRu     0.97      0.44      0.53
                      P         -       ---       ---
              Random  RR     0.72      0.35      0.45
                     RRl     0.33      0.15      0.24
                     RRu     1.59      0.82      0.84
                      P      N.S.         -         -
             Between Chi                         8.01
             Between  df                            1
             Between  P                            **
             Btwn(F)  P                          N.S.

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt    31.59     34.73      9.91     76.23
                 Het Chi    47.62      0.34      0.00     52.00
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     0.35      0.55      0.35      0.43
                     RRl     0.24      0.39      0.19      0.34
                     RRu     0.49      0.77      0.65      0.53
                      P       ---       ---       ---       ---
              Random  RR     0.42      0.55      0.35      0.45
                     RRl     0.10      0.39      0.19      0.24
                     RRu     1.79      0.77      0.65      0.84
                      P      N.S.       ---       ---         -
             Between Chi                                   4.03
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                               Asthma analysis type (COPD)
                        inc-irres  excl-all defn-incl     other     Total

                       N        6         1         2         1        10
                      NS        4         1         1         1         7

                      Wt    45.79      9.91     16.91      3.62     76.23
                 Het Chi    35.96      0.00      1.56      0.00     52.00
                 Het  df        5         0         1         0         9
                 Het  P       ***      N.S.      N.S.      N.S.       ***
               Fixed  RR     0.33      0.35      0.97      0.37      0.43
                     RRl     0.25      0.19      0.60      0.13      0.34
                     RRu     0.45      0.65      1.55      1.04      0.53
                      P       ---       ---      N.S.       (-)       ---
              Random  RR     0.34      0.35      1.02      0.37      0.45
                     RRl     0.12      0.19      0.54      0.13      0.24
                     RRu     0.96      0.65      1.93      1.04      0.84
                      P         -       ---      N.S.       (-)         -
             Between Chi                                            14.47
             Between  df                                                3
             Between  P                                                **
             Btwn(F)  P                                              N.S.
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 3

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                        Bronchodilator/reversibility (LF only)
                          no/unkn  yes/revs     Total

                       N        5                   5
                      NS        3                   3

                      Wt    34.73               34.73
                 Het Chi     0.34                0.34
                 Het  df        4                   4
                 Het  P      N.S.                N.S.
               Fixed  RR     0.55                0.55
                     RRl     0.39                0.39
                     RRu     0.77                0.77
                      P       ---                 ---
              Random  RR     0.55                0.55
                     RRl     0.39                0.39
                     RRu     0.77                0.77
                      P       ---                 ---
             Between Chi
             Between  df
             Between  P                          N.S.
             Btwn(F)  P                          N.S.

                                  Number of COPD cases
                             1-50    51-100   101-200      201+     Total

                       N                  3         2         5        10
                      NS                  2         1         4         7

                      Wt              13.14      4.79     58.30     76.23
                 Het Chi               0.86      0.26     50.52     52.00
                 Het  df                  2         1         4         9
                 Het  P                N.S.      N.S.       ***       ***
               Fixed  RR               0.40      0.55      0.42      0.43
                     RRl               0.24      0.22      0.33      0.34
                     RRu               0.70      1.35      0.55      0.53
                      P                  --      N.S.       ---       ---
              Random  RR               0.40      0.55      0.44      0.45
                     RRl               0.24      0.22      0.16      0.24
                     RRu               0.70      1.35      1.18      0.84
                      P                  --      N.S.      N.S.         -
             Between Chi                                             0.35
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

                        Number of COPD cases (excluding unknown)

                       N                  3         2         5        10
                      NS                  2         1         4         7

                      Wt              13.14      4.79     58.30     76.23
                 Het Chi               0.86      0.26     50.52     52.00
                 Het  df                  2         1         4         9
                 Het  P                N.S.      N.S.       ***       ***
               Fixed  RR               0.40      0.55      0.42      0.43
                     RRl               0.24      0.22      0.33      0.34
                     RRu               0.70      1.35      0.55      0.53
                      P                  --      N.S.       ---       ---
              Random  RR               0.40      0.55      0.44      0.45
                     RRl               0.24      0.22      0.16      0.24
                     RRu               0.70      1.35      1.18      0.84
                      P                  --      N.S.      N.S.         -
             Between Chi                                             0.35
             Between  df                                                2
             Between  P                                              N.S.
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 3

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Most-adjusted
                            Analysis type
                         prevlnce     onset     Total

                       N        6         4        10
                      NS        4         3         7

                      Wt    56.76     19.47     76.23
                 Het Chi     8.58     17.68     52.00
                 Het  df        5         3         9
                 Het  P      N.S.       ***       ***
               Fixed  RR     0.60      0.16      0.43
                     RRl     0.46      0.10      0.34
                     RRu     0.78      0.25      0.53
                      P       ---       ---       ---
              Random  RR     0.63      0.24      0.45
                     RRl     0.43      0.07      0.24
                     RRu     0.94      0.87      0.84
                      P         -         -         -
             Between Chi                        25.75
             Between  df                            1
             Between  P                           ***
             Btwn(F)  P                             *

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    29.94     29.38     16.91     76.23
                 Het Chi     0.08     21.80      1.56     52.00
                 Het  df        2         4         1         9
                 Het  P      N.S.       ***      N.S.       ***
               Fixed  RR     0.55      0.21      0.97      0.43
                     RRl     0.38      0.14      0.60      0.34
                     RRu     0.79      0.30      1.55      0.53
                      P        --       ---      N.S.       ---
              Random  RR     0.55      0.26      1.02      0.45
                     RRl     0.38      0.10      0.54      0.24
                     RRu     0.79      0.68      1.93      0.84
                      P        --        --      N.S.         -
             Between Chi                                  28.55
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                     (*)

                        Number of adjustment variables
                                0         1        2+     Total

                       N        2         6         2        10
                      NS        1         4         2         7

                      Wt     3.23     58.31     14.68     76.23
                 Het Chi     0.01      8.86      7.56     52.00
                 Het  df        1         5         1         9
                 Het  P      N.S.      N.S.        **       ***
               Fixed  RR     0.63      0.59      0.11      0.43
                     RRl     0.21      0.46      0.06      0.34
                     RRu     1.88      0.77      0.18      0.53
                      P      N.S.       ---       ---       ---
              Random  RR     0.63      0.62      0.15      0.45
                     RRl     0.21      0.42      0.03      0.24
                     RRu     1.88      0.92      0.78      0.84
                      P      N.S.         -         -         -
             Between Chi                                  35.58
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 4

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

     REF|NRR|X|SEX|AGEL|AGEH|     REGION|BEGYR|PUBYR|STTYP|ONSET|      DISEAS|ADJ|SMOKSTA|   PRODUCT|BASE-HI|LOW| HI|

   DEAN1  93 x   m   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only       4   9   +
   DEAN1 113 x   f   35   99       Eu:UK  1969  1977    CC  Prev    COPD:mort   0      Ex MCigs only       4   9   +
  FORAST  15 x   f   55   99      Am:USA  1993  1998    CS  Prev        CB/EM   0      Ex       Cigs      10  11   +
  HUHTI2  15     m   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any       9  10   +
  HUHTI2  18     f   50   74    Eu:Scand  1971  1980    CS  Prev      COPD:LF   0      Ex        Any       9  10   +
  JACOBS  16     m   40   84       Multi  1957  1999    Pr   Inc    COPD:mort   2      Ex       Cigs       0  10   +
    KAHN  39 x   m   31   99      Am:USA  1954  1966    Pr   Inc    COPD:mort   2      Ex       Cigs       4  40   +
  KRZYZA  27     m   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs       8  14   +
  KRZYZA  32     f   19   83     Eu:East  1968  1986    Pr   Inc      COPD:LF   1      Ex       Cigs       8  14   +
  MANNI2  14     b   25   74      Am:USA  1971  2003    CS  Prev      COPD:LF   1      Ex        Any       9  10   +

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 5

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                        Number Exposed  Non-exposed
 REF    NRR SEX ADJ     Case    Cont    Case    Cont      RR        95.00%CI
 DEAN1  93  m   0         42     152      24     102      1.17 (  0.67-   2.06)
 DEAN1  113 f   0         15     114       7     110      2.07 (  0.81-   5.26)
 Subtotal DEAN1                                           1.36 (  0.84-   2.21)
 FORAST 15  f   0         23     325      21     114      0.38 (  0.20-   0.72)
 HUHTI2 15  m   0          6      90       6      58      0.64 (  0.20-   2.09)
 HUHTI2 18  f   0          1      21       1      12      0.57 (  0.03-   9.99)
 Subtotal HUHTI2                                          0.63 (  0.21-   1.88)
*JACOBS 16  m   2          8       -       9       -      0.37 (  0.13-   1.02)
*KAHN   39  m   2         49       -      20       -      0.07 (  0.03-   0.15)
*KRZYZA 27  m   1          8       -      12       -      0.60 (  0.23-   1.55)
*KRZYZA 32  f   1          1       -       4       -      0.29 (  0.02-   3.67)
 Subtotal KRZYZA                                          0.55 (  0.22-   1.35)
 MANNI2 14  b   1         44       -     125       -      0.54 (  0.37-   0.79)
Partial Totals           197     702     229     396
*prospective study

 REF    NRR SEX ADJ             Ys       Ws       Qs       Ps
 DEAN1  93  m   0              0.16    12.22     7.59       0.57
 DEAN1  113 f   0              0.73     4.40     8.06       0.13
 Subtotal DEAN1                0.31    16.61    15.65
 FORAST 15  f   0             -0.96     9.71     1.05       0.00
 HUHTI2 15  m   0             -0.44     2.76     0.10       0.47
 HUHTI2 18  f   0             -0.56     0.47     0.00       0.70
 Subtotal HUHTI2              -0.46     3.23     0.10
*JACOBS 16  m   2             -0.99     3.62     0.49       0.06
*KAHN   39  m   2             -2.66     5.93    24.49       0.00
*KRZYZA 27  m   1             -0.51     4.22     0.06       0.29
*KRZYZA 32  f   1             -1.24     0.57     0.21       0.35
 Subtotal KRZYZA              -0.60     4.79     0.27
 MANNI2 14  b   1             -0.62    26.71     0.00       0.00

                       N       10
                      NS        7

                      Wt    70.61
                 Het Chi    42.05
                 Het  df        9
                 Het  P       ***
               Fixed  RR     0.53
                     RRl     0.42
                     RRu     0.67
                      P       ---
              Random  RR     0.51
                     RRl     0.28
                     RRu     0.91
                      P         -
               Asymm  P      N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 6

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted

                       N       10
                      NS        7

                      Wt    70.61
                 Het Chi    42.05
                 Het  df        9
                 Het  P       ***
               Fixed  RR     0.53
                     RRl     0.42
                     RRu     0.67
                      P       ---
              Random  RR     0.51
                     RRl     0.28
                     RRu     0.91
                      P         -
               Asymm  P      N.S.

                                   Sex
                             both      male    female     Total

                       N        1         5         4        10
                      NS        1         5         4        10

                      Wt    26.71     28.76     15.15     70.61
                 Het Chi     0.00     32.46      8.93     42.05
                 Het  df        0         4         3         9
                 Het  P      N.S.       ***         *       ***
               Fixed  RR     0.54      0.49      0.63      0.53
                     RRl     0.37      0.34      0.38      0.42
                     RRu     0.79      0.70      1.04      0.67
                      P        --       ---       (-)       ---
              Random  RR     0.54      0.41      0.70      0.51
                     RRl     0.37      0.14      0.22      0.28
                     RRu     0.79      1.24      2.21      0.91
                      P        --      N.S.      N.S.         -
             Between Chi                                   0.66
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                                        Continent
                            NAmer    Europe      Asia  oth/mult     Total

                       N        3         6                   1        10
                      NS        3         3                   1         7

                      Wt    42.35     24.63                3.62     70.61
                 Het Chi    20.27      5.26                0.00     42.05
                 Het  df        2         5                   0         9
                 Het  P       ***      N.S.                N.S.       ***
               Fixed  RR     0.38      1.03                0.37      0.53
                     RRl     0.28      0.70                0.13      0.42
                     RRu     0.51      1.53                1.04      0.67
                      P       ---      N.S.                 (-)       ---
              Random  RR     0.26      1.02                0.37      0.51
                     RRl     0.09      0.67                0.13      0.28
                     RRu     0.75      1.55                1.04      0.91
                      P         -      N.S.                 (-)         -
             Between Chi                                            16.52
             Between  df                                                2
             Between  P                                               ***
             Btwn(F)  P                                              N.S.

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 6

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                                      Least-adjusted
                               Study type
                               CC        Pr        CS     Total

                       N        2         4         4        10
                      NS        1         3         3         7

                      Wt    16.61     14.34     39.65     70.61
                 Het Chi     1.03     13.03      1.02     42.05
                 Het  df        1         3         3         9
                 Het  P      N.S.        **      N.S.       ***
               Fixed  RR     1.36      0.21      0.50      0.53
                     RRl     0.84      0.13      0.37      0.42
                     RRu     2.21      0.36      0.69      0.67
                      P      N.S.       ---       ---       ---
              Random  RR     1.37      0.25      0.50      0.51
                     RRl     0.84      0.08      0.37      0.28
                     RRu     2.24      0.81      0.69      0.91
                      P      N.S.         -       ---         -
             Between Chi                                  26.97
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *

                          COPD subtype
                             mort        LF     other     Total

                       N        4         5         1        10
                      NS        3         3         1         7

                      Wt    26.17     34.73      9.71     70.61
                 Het Chi    40.44      0.34      0.00     42.05
                 Het  df        3         4         0         9
                 Het  P       ***      N.S.      N.S.       ***
               Fixed  RR     0.58      0.55      0.38      0.53
                     RRl     0.40      0.39      0.20      0.42
                     RRu     0.85      0.77      0.72      0.67
                      P        --       ---        --       ---
              Random  RR     0.50      0.55      0.38      0.51
                     RRl     0.11      0.39      0.20      0.28
                     RRu     2.21      0.77      0.72      0.91
                      P      N.S.       ---        --         -
             Between Chi                                   1.27
             Between  df                                      2
             Between  P                                    N.S.
             Btwn(F)  P                                    N.S.

                             Smoking product
                              any      cigs  cigsonly     Total

                       N        3         5         2        10
                      NS        2         4         1         7

                      Wt    29.94     24.05     16.61     70.61
                 Het Chi     0.08     15.07      1.03     42.05
                 Het  df        2         4         1         9
                 Het  P      N.S.        **      N.S.       ***
               Fixed  RR     0.55      0.27      1.36      0.53
                     RRl     0.38      0.18      0.84      0.42
                     RRu     0.79      0.40      2.21      0.67
                      P        --       ---      N.S.       ---
              Random  RR     0.55      0.27      1.37      0.51
                     RRl     0.38      0.12      0.84      0.28
                     RRu     0.79      0.65      2.24      0.91
                      P        --        --      N.S.         -
             Between Chi                                  25.86
             Between  df                                      2
             Between  P                                     ***
             Btwn(F)  P                                       *
  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 7

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                 Excluded studies (and stage at which they were excluded)

1       CLARK COTTON  MEYER REMYJA RUTGER SNYDER SOBRAX     SU TAKEMU  WANG4   WEIR WHICKE ZALACA
2      ALDERS ANDER2 AUERBA   BANG  BECK1  BECK2 BJORNS  BROWN CERVER CHAPMA COATES COLLEG  DEAN2  DEANE DONTA2 DOPICO
       EHRLIC ENRIGH FINKLE FLETCH FOXMAN GOLDBE HAENSZ HARRIS  HAYES HIGGI2 HIGGI3 HIGGI6 HIRAYA HOLLA2 HOLLNA  HOUSE
       HRUBEC HUCHON JENSEN JINDA2  JOSHI JOUSI1   KATO KOTAN1  KUBIK LAMBER LANGE2 LANGHA LAVECC LUNDB2 MAGNUS MANFRE
       MELLST MENEZ1  MEREN MILLER  MILNE MOLLER   NAWA NEJJAR OGILVI  OMORI OSWAL1 OSWAL2 PANDEY  PRATT   REID RIMING
        RYDER SCHWAR  SHARP SHIMUR SOBRAD STJERN SUADIC SUTINE TAGER2 TROISI URRUTI VIEGI1 VIKGRE WAGEN2  WANG2    WIG
       WILHEL WILSO2  WOODS  WOOLF   ZOIA
3      ALESSA  AMIGO ANDER1 ANDER3 BEDNAR   BEST BROGGE  CHEN1  CHEN2  CHEN3  CHENG CLEMEN  COCCI DEJONG DEMARC DETORR
       DICKIN  DOLL1  DOLL2 DONTA1 EKBERG ENSTRO FERRI1 FERRI2 FERRI3  FIDAN FUKUCH GEIJER GODTFR GULSVI HAMMO2 HARDIE
       HARIKK HAWTHO HEDMAN HIGGI4     HO HOZAWA HUHTI1 HUHTI3 ITABAS JAENDI JOHANN KACHEL  KAHN2 KARAKA KATANC KHOURY
          KIM  KIRAZ KLAYTO KOJIMA KOTAN2 KULLER    LAI   LAM1   LAM2   LAM3  LANGE LEBOWI    LEE   LIAW LINDBE LINDST
         LIU1   LIU2 LUNDB1  MADOR MANNI1 MANNI3 MARAN1 MARAN2 MARCUS MATHES MENEZ2 MENEZ3 MENEZ4 MENEZ5 MENEZ6 MONTNE
       MUELLE NIEPSU NIHLEN NILSSO   PEAT PELKON PEREZP   PETO  PRICE RENWIC RICCIO SARGEA SAWICK SHAHAB   SHIN SICHLE
        SILVA SPEIZE STERLI  STROM  TAGER   TANG   THUN   TODD TRUPIN TSUSHI TVERDA VESTBO VIEGI2 VINEIS VOLLM1 VOLLM2
       VONHER   WALD WATSON  WEISS    WEN WILSO1 WOJTYN   XIAO     XU YAMAGU   YUAN ZIELI1 ZIELI2 ZIETKO

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10

                                                   Table 1 - J - 7 - 8

        IESCOPD - Meta-analysis of years since quit (vs current) : highest (=longest ago) vs lowest (=most recent)
                            Any COPD, cigarettes (or any product if cigarettes not available)
                                             Potentially overlapping studies

     REF| REFGP|PRINC|                     OVERLAP|

  JACOBS JACOBS     1  JACOBS/DONTA1/DONTA2/PELKON
  HUHTI2 HUHTI1     2                HUHTI1/HUHTI2
  MANNI2 MANNI2     1                MANNI2/MANNI3
  KRZYZA KRZYZA     1         SAWICK/KRZYZA/WOJTYN
    KAHN   KAHN     1                   KAHN/KAHN2

  ________________________________________________________________________________________________________________________
                                            International Evidence on Smoking and COPD, Phase 3, Analysis run on 28-SEP-10