Abstract

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 (COPD hallmark) in relation to smoking history. Methods: We analysed 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 (ORex=1.44; ORcurrent=3.45) than in men (ORex=1.25; ORcurrent=3.06) (P-interaction=5.6x10(-4)). In both sexes, the association of airflow obstruction with cigarettes/day, 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- and current smokers for cigarettes/day (P-interactionex=6.0x10(-8); P-interactioncurrent=1.1x10(-5)), duration (P-interactionex=7.9x10(-4); P-interactioncurrent=0.004) and pack-years (P-interactionex=6.6x10(-18); P-interactioncurrent=1.3x10(-6)). Overall those who started smoking before 18 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. Conclusion: Exposed to the same dose of smoking, women show 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.