Association Between Regular Moderate to Vigorous Physical Activity Initiation Following COPD Diagnosis and Mortality: An Emulated Target Trial Using Nationwide Cohort Data

Background: Moderate to vigorous physical activity (MVPA) in patients with COPD affects their overall health outcomes, including symptom relief and improved quality of life. However, the magnitude of the effect of MVPA initiation on real-world clinical outcomes has not been well investigated. Research Question: How does MVPA initiation affect mortality and severe exacerbation in patients who have not engaged in MVPA prior to COPD diagnosis? Study Design and Methods: This study included patients with COPD aged ≥ 40 years who were not performing MVPA prior to COPD diagnosis and who had at least one health screening visit prior to and following their COPD diagnosis between January 1, 2010, and December 31, 2018. The main exposure was MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days per week or moderate aerobic exercise > 30 min per day on ≥ 5 days per week. The primary end point was all-cause mortality, and the secondary end point was initial severe exacerbation as the time to event following COPD diagnosis. Results: In total, 110,097 person-trials were included (27,564 MVPA increases and 82,533 control groups). No differences were observed between the covariates following matching. The adjusted hazards ratio of all-cause mortality for the MVPA group compared with the control group was 0.84 (95% CI, 0.79-0.89). In the subgroup analysis, patients aged > 65 years, female patients, those who had never smoked, and patients with a higher Charlson Comorbidity Index score displayed a stronger effect of MVPA on reducing mortality than younger male patients, those who had ever smoked, and patients with a lower Charlson Comorbidity Index score (P_interaction < .05). The fully adjusted hazards ratio for the risk of severe exacerbation (MVPA group vs control) was 0.90 (95% CI, 0.87-0.94). Interpretation: Initiation of MVPA can potentially reduce mortality and severe exacerbations in patients with COPD, although personalized interventions and further clinical trials are necessary.