Sex differences in COPD in relation to smoking exposure: a population-based cohort study

Background Sex discrepancies in the association between smoking and development and prognosis of chronic obstructive pulmonary disease (COPD) are controversial. We tested the hypothesis that females compared with males are more susceptible to the detrimental effects of smoking in relation to COPD. Methods We identified 47 231 males and 57 806 females from the Copenhagen General Population Study. Smoking amount was assessed with sex interaction against COPD-related outcomes, including the cross-sectional association with airway obstruction, chronic bronchitis and dyspnoea, assessed using logistic regression analyses, and longitudinal association with exacerbation and mortality, assessed using Cox proportional hazard regression adjusted for potential confounders. Results The increase in risk of airway obstruction (N=7367), chronic bronchitis (N=9206) and dyspnoea (N=8541) with higher smoking amount was greater in females compared with males. During 15 years’ follow-up (median 9.3 years), the increase in risk of exacerbation (events=2756), respiratory mortality (events=711) and all-cause mortality (events=10 658) with higher smoking was greater for females compared with males. Compared with never-smokers, adjusted HRs for exacerbation increased from 4.64 (95% CI 2.83 to 7.61) in females with 10 pack-years to 41.6 (95% CI 28.8 to 60.2) in females with ≥50 pack-years, and from 2.21 (95% CI 0.92 to 5.32) in males with 10 pack-years to 23.7 (95% CI 12.9 to 43.5) in males with ≥50 pack-years. Corresponding HR increases for respiratory mortality were 2.04 (95% CI 1.27 to 3.26) to 11.1 (95% CI 7.39 to 16.8) in females and 1.09 (95% CI 0.62 to 1.92) to 5.66 (95% CI 3.96 to 8.11) in males, and for all-cause mortality, HR increases were 1.50 (95% CI 1.34 to 1.67) to 3.53 (95% CI 3.11 to 4.00) in females and 1.62 (1.45–1.81) to 2.94 (2.69–3.21) in males, respectively. Conclusions Females seem more susceptible to the detrimental effects of smoking in development and prognosis of COPD compared with males.