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

Abstract

Background: Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.

Methods: Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.

Results: Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.

Conclusions: The results confirm and quantify the causal relationships with smoking.

Figure 1

Forest plot of ever smoking of any product and COPD-part 1. Table 5 presents the results of a main meta-analysis for COPD based on 129 relative risk (RR) and 95% confidence interval (CI) estimates for ever smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale in Figures 1 and 2. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated. Where the RR value falls outside the range, the size of the plotting symbol indicates the weight but the position is not true to the scale.

Figure 2

Forest plot of ever smoking of any product and COPD-part 2. This is a continuation of Figure 1, presenting the remaining individual study data included in the main meta-analysis for COPD shown in Table 5. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 3

Forest plot of ever smoking of any product and CB-part 1. Table 5 presents the results of a main meta-analysis for CB based on 114 relative risk (RR) and 95% confidence interval (CI) estimates for ever smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale in Figures 3 and 4. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated.

Figure 4

Forest plot of ever smoking of any product and CB-part 2. This is a continuation of Figure 3, presenting the remaining individual study data included in the main meta-analysis for CB shown in Table 5. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 5

Forest plot of ever smoking of any product and emphysema. Table 5 presents the results of a main meta-analysis for emphysema based on 28 relative risk (RR) and 95% confidence interval (CI) estimates for ever smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 6

Forest plot of current smoking of any product and COPD-part 1. Table 7 presents the results of a main meta-analysis for COPD based on 120 relative risk (RR) and 95% confidence interval (CI) estimates for current smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale in Figures 6 and 7. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated.

Figure 7

Forest plot of current smoking of any product and COPD-part 2. This is a continuation of Figure 6, presenting the remaining individual study data included in the main meta-analysis for COPD shown in Table 7. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 8

Forest plot of current smoking of any product and CB-part 1. Table 7 presents the results of a main meta-analysis for CB based on 113 relative risk (RR) and 95% confidence interval (CI) estimates for current smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale in Figures 8 and 9. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated.

Figure 9

Forest plot of current smoking of any product and CB-part 2. This is a continuation of Figure 8, presenting the remaining individual study data included in the main meta-analysis for CB shown in Table 7. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 10

Forest plot of current smoking of any product and emphysema. Table 7 presents the results of a main meta-analysis for emphysema based on 22 relative risk (RR) and 95% confidence interval (CI) estimates for current smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated. Where the RR value falls outside the range, the size of the plotting symbol indicates the weight but the position is not true to the scale. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 11

Forest plot of ex smoking of any product and COPD-part 1. Table 10 presents the results of a main meta-analysis for COPD based on 110 relative risk (RR) and 95% confidence interval (CI) estimates for ex smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale in Figures 11 and 12. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated. Where the RR value falls outside the range, the size of the plotting symbol indicates the weight but the position is not true to the scale.

Figure 12

Forest plot of ex smoking of any product and COPD-part 2. This is a continuation of Figure 11, presenting the remaining individual study data included in the main meta-analysis for COPD shown in Table 10. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 13

Forest plot of ex smoking of any product and CB-part 1. Table 10 presents the results of a main meta-analysis for CB based on 105 relative risk (RR) and 95% confidence interval (CI) estimates for ex smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale in Figures 13 and 14. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated. Where the RR value falls outside the range, the size of the plotting symbol indicates the weight but the position is not true to the scale.

Figure 14

Forest plot of ex smoking of any product and CB-part 2. This is a continuation of Figure 13, presenting the remaining individual study data included in the main meta-analysis for CB shown in Table 10. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 15

Forest plot of ex smoking of any product and emphysema. Table 10 presents the results of a main meta-analysis for emphysema based on 17 relative risk (RR) and 95% confidence interval (CI) estimates for ex smoking of any product (or cigarettes if any product not available). The individual study estimates are shown numerically and graphically on a logarithmic scale. The weights (inverse-variance) are also shown numerically, expressed as a percentage of the overall weight. The studies are sorted in order of sex within study reference (REF). In the graphical representation individual RRs are indicated by a solid square, with the area of the square proportional to the weight. Arrows indicate where the CI extends outside the range allocated. Also shown are the combined random-effects estimates. These are represented by a diamond of standard height, with the width indicating the 95% CI.

Figure 16

Funnel plot for ever smoking and COPD. Funnel plot of the 129 relative risk estimates for ever smoking and COPD included in the main meta-analysis in Table 5 against their weight (inverse-variance of log RR). The dotted vertical line indicates the fixed-effect meta-analysis estimate.

Figure 17

Funnel plot for ever smoking and CB. Funnel plot of the 114 relative risk estimates for ever smoking and CB included in the main meta-analysis in Table 5 against their weight (inverse-variance of log RR). The dotted vertical line indicates the fixed-effect meta-analysis estimate.

Figure 18

Funnel plot for ever smoking and emphysema. Funnel plot of the 28 relative risk estimates for ever smoking and emphysema included in the main meta-analysis in Table 5 against their weight (inverse-variance of log RR). The dotted vertical line indicates the fixed-effect meta-analysis estimate.