Moderate-to-vigorous Physical Activity Reduces Mortality, Exacerbation, and Inhaled Corticosteroid Usage in COPD patients Using a LAMA/LABA combination: An Emulated Target Trial Using a Nationwide Cohort

<bold>Background:</bold> Both physical activity (PA) and inhaler therapies constitutes important aspects of COPD management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in COPD patients using a LABA/LAMA combination. <bold>Methods:</bold> We emulated a target trial to estimate the benefit of MVPA in COPD patients using a LABA/LAMA combination. We enrolled COPD patients aged ≥40, diagnosed between 2010 and 2018, who had been using a LABA/LAMA combination and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise >20 minutes per day on ≥3 days/week or moderate aerobic exercise >30 minutes per day on ≥5 days/week. The main outcomes were the future usage of inhaled corticosteroid (ICS), severe exacerbations, and all-cause mortality. <bold>Results:</bold> We identified 1,197 patients initiated MVPA and 3,391 who did not. The median follow-up period was 2.6 years. The adjusted hazard ratio (aHR) for future ICS usage in the MVPA initiation group was 0.81 (95% CI: 0.66, 0.99) compared to the control group. The aHR for severe exacerbation in the MVPA initiation group was 0.74 (95% CI: 0.56, 0.99) compared to the control group. The aHR for all-cause mortality in the MVPA initiation group was 0.63 (95% CI: 0.46, 0.87) compared to the control group. Subgroup analyses by age, sex, body mass index, residence, smoking, drinking, and comorbidity showed a consistent benefit in those outcomes. <bold>Conclusions:</bold> The initiation of regular MVPA could offer additional benefits to patients with COPD using a LABA/LAMA combination.