LAUSR

Rationale: The prevalence of chronic obstructive pulmonary disease (COPD) is increasing faster among women than among men. Objectives: To examine sex differences in the risk of airflow obstruction (a COPD hallmark) in relation to smoking history. Methods: We analyzed 149,075 women and 100,252 men taking part in the UK Biobank who had provided spirometry measurements and information on smoking. The association of airflow obstruction with smoking characteristics was assessed by sex using regression analysis. The shape of this relationship was examined using restricted cubic splines. Measurements and Main Results: The association of airflow obstruction with smoking status was stronger in women (odds ratio for ex‐smokers [ORex], 1.44; ORcurrent, 3.45) than in men (ORex, 1.25; ORcurrent, 3.06) (P for interaction = 5.6 × 10‐4). In both sexes, the association of airflow obstruction with cigarettes per day, smoking duration, and pack‐years did not follow a linear pattern, with the increase in risk at lower doses being steeper among women. For equal doses of exposure, sex differences were present in both ex‐smokers and current smokers for cigarettes per day (P for interactionex = 6.0 × 10‐8; P for interactioncurrent = 1.1 × 10‐5), smoking duration (P for interactionex = 7.9 × 10‐4; P for interactioncurrent = 0.004), and pack‐years (P for interactionex = 6.6 × 10‐18; P for interactioncurrent = 1.3 × 10‐6). Overall, those who started smoking before age 18 years were more likely to have airflow obstruction, but a sex difference in this association was not clear. For equal time since quitting, the reduction in risk among women seemed less marked than among men. Conclusions: Exposed to the same dose of smoking, women showed a higher risk of airflow obstruction than men. This could partly explain the increasingly smaller sex difference in the prevalence of COPD, especially in countries where smoking patterns have become similar between women and men.