title: 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.
authors.affiliation: P N Lee Statistics and Computing Ltd, Sutton, Surrey, UK. BarbaraForey@pnlee.co.uk
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Forey
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Thornton
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lee
mesh_terms: D000367:Age Factors; D029481:Bronchitis, Chronic / Q000453:epidemiology* / Q000401:mortality; D004646:Emphysema / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology* / Q000401:mortality; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate