Frailty, Chronological Age, and Clinical Outcomes in COPD : A Nationwide Cohort Study

BACKGROUND AND OBJECTIVES: Frailty and chronological age are major prognostic factors in chronic obstructive pulmonary disease (COPD), yet their combined effects have not been fully examined in large population-based cohorts. We investigated whether low frailty attenuates the adverse impact of aging on COPD outcomes. METHODS: We conducted a nationwide retrospective cohort study using the Korean National Health Insurance Service database. Patients aged ≥ 40 years diagnosed with COPD between 2010 and 2021 were included. Frailty was assessed using a claims-based frailty index and categorized as low, intermediate, or high. The primary outcome was all-cause mortality, and the secondary outcome was severe exacerbation. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs). RESULTS: Among 1,505,638 patients with COPD, 784,962 were aged < 70 years and 720,676 were aged ≥ 70 years. Over a median follow-up of 7.0 years (interquartile range, 3.0-10.3), 500,097 deaths and 169,102 severe exacerbations occurred. Compared with older patients (≥ 70 years) with low frailty, intermediate frailty was associated with higher mortality risk in both younger (HR 1.19; 95% CI 1.17-1.21) and older patients (HR 1.21; 95% CI 1.20-1.21). High frailty showed highest risk (HR 2.66; 95% CI 2.54-2.78 in < 70 years; HR 1.90; 95% CI 1.87-1.93 in ≥ 70 years). Similar graded associations were observed for severe exacerbations. CONCLUSION: In patients with COPD, frailty risk provided prognostic information beyond chronological age, highlighting the importance of biological vulnerability in determining outcomes in COPD.