Supplementary Material for: Sex differences in the risk of acute exacerbations among patients with chronic obstructive pulmonary disease treated with long-acting bronchodilators

Introduction: Several post-hoc analyses of clinical trials and observational studies have noticed that women may be at a higher risk of exacerbations than men among patients with chronic obstructive pulmonary disease (COPD), although the findings remain conflicting. These studies, however, did not consider the impact of mainstay treatments over longitudinal follow-up. We examined whether the risk of acute exacerbations differed between women and men in patients with COPD treated with long-acting bronchodilators. Methods: This population-based study included two cohorts of patients with COPD who initiated a single long-acting bronchodilator (mono-bronchodilator cohort) or a dual combination of long-acting bronchodilators (dual-bronchodilator cohort) identified from a nationwide Taiwanese claims database (2017-2022). In each cohort, Cox regression models were executed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of moderate-to-severe exacerbations comparing women to men after 1:10 variable-ratio propensity score (PS) matching. Results: There were 51,945 patients (9,643 women, 42,302 men) in the mono-bronchodilator cohort and 88,271 patients (15,418 women, 72,853 men) in the dual-bronchodilator cohort after PS matching. The HR of moderate-to-severe exacerbations comparing women to men was 0.86 (95% CI, 0.80-0.92) and 0.88 (95% CI, 0.84-0.92) for each cohort, respectively. Results were consistent when analyzing moderate and severe exacerbations separately and did not change materially across pre-specified subgroup and sensitivity analyses. Conclusion: The present study including two sizable COPD cohorts of Asian patients suggests that women may have a lower risk of exacerbations than men when regularly receiving long-acting bronchodilators. The findings highlight the importance of considering maintenance treatments when evaluating sex differences in the risk of acute exacerbations.