Sexually dimorphic response to tobacco exposure in COPD: a systematic review and meta-analysis

Chronic obstructive pulmonary disease (COPD) is a heterogeneous, progressive pulmonary disorder with persistent respiratory symptoms resulting from abnormalities in the airways and/or alveoli and was prevalent globally in 10.3% of people aged 30–79 years in 2019. The prevalence of COPD has increased rapidly in women in the past decade. This may be due to increased tobacco use, but may also involve sex-specific factors. To evaluate the prevalence of COPD in the context of sex and tobacco exposure. Comprehensive searches of MEDLINE (OVID), EMBASE and CENTRAL were conducted for articles published from inception to July 22, 2022. We independently evaluated titles, abstracts and full-text articles in a duplicated two-staged process. Studies were included if they reported the prevalence of COPD as a primary outcome in the context of sex and tobacco exposure. Pooled analysis was conducted with Review Manager 5, and heterogeneity was assessed with the I 2 statistic. For 163, 450 individuals the prevalence of COPD was 3.5–20.7% in males and 6.3–18.5% in females, and we observed a non-statistically significant difference of 1.53% [95% CI: -5.83, 8.89] ( p = 0.68) in females compared to males with tobacco exposure (Tau 2 = 54.02; Chi 2 = 53.15; df = 4 ( P < 0.00001); I 2 = 92%). Females with COPD had earlier mortality, greater co-morbidities involving cardiovascular disease and others, and decreased FEV 1 % predicted, as compared to males with COPD. Estrogen and androgens may protect against COPD, but smoking-induced hypogonadism may diminish these effects. Menopause could also be a contributor to worse COPD outcomes. Included articles are limited by the quality of data on tobacco smoke exposure, primarily reported as a binary risk factor, with lack of availability on duration and intensity of exposure. There was earlier mortality and reduced FEV 1 in females with COPD, as compared to males with COPD. Thus, sex-specific considerations are important in understanding the pathophysiology of COPD and should be a focus of further research.