Gender differences in COPD: are women more susceptible to smoking effects than men?

Background The number of female smokers developing chronic obstructive pulmonary disease (COPD) is rapidly increasing, but whether or not there exists a differential susceptibility by gender remains controversial. Methods How smoking behaviour and subsequent lung function reduction differed by gender was examined in a study including 954 subjects with COPD and 955 subjects without COPD. The study focused on two subgroups: subjects with COPD <60 years of age (early-onset group, n=316) and subjects with COPD with <20 pack-years of smoking (low exposure group, n=241). Results In the low exposure group, female subjects with COPD had lower forced expiratory volume in 1 s (FEV1) % predicted (48.7% vs 55.8%, p=0.001) and more severe disease (50.4% vs 35.6%, p=0.020, in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 3 and 4) than male subjects with COPD. Females also had lower FEV1% predicted (50.6% vs 56.0%, p=0.006) and more severe COPD (41.7% vs 31.1% in GOLD stage 3 and 4, p=0.050) in the early-onset group. Using multivariate regression, female gender was associated with 5.7% lower FEV1% predicted in the low exposure group (p=0.012) and a similar trend was observed in the early-onset group (p=0.057). The number of pack-years was not significantly associated with lung function in female subjects with COPD in this study, and the doseeresponse relationship between smoking and lung function differed by gender at lower levels of smoking exposure. Interaction analysis suggested that the effect of smoking on lung function might be different by gender (p=0.027 in all subjects with COPD). Conclusions Female gender was associated with lung function reduction and more severe disease in subjects with COPD with early onset of disease or low smoking exposure. The findings may suggest a gender difference in susceptibility to the lung-damaging effects of cigarette smoking, but alternative explanations should be considered.