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. 2025 Jul 15;80(8):512-519.
doi: 10.1136/thorax-2024-222682.

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

Yunus Çolak  1   2 , Børge G Nordestgaard  2   3 , Peter Lange  1   2   4 , Shoaib Afzal  5   3
Affiliations

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

Yunus Çolak et al. Thorax. .

Abstract

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.

Keywords: COPD epidemiology; Clinical Epidemiology; Tobacco and the lung.

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Conflict of interest statement

Competing interests: YÇ reports personal fees from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline, and grants and personal fees from Sanofi outside the submitted work. PL reports grants and personal fees from AstraZeneca and Sanofi and personal fees from Boehringer Ingelheim and GlaxoSmithKline outside the submitted work. BGN and SA have nothing to disclose. The views expressed are those of the authors.

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