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

ABSTRACT 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.