Frailty associates with respiratory exacerbations and mortality in the COPDGene cohort

Abstract

Frailty is associated with respiratory exacerbations and mortality in individuals with Chronic Obstructive Pulmonary Disease (COPD). Among those with a smoking history and normal spirometry, frailty’s association with respiratory outcomes is less defined. COPDGene is a cohort study of individuals aged 45–80 with a minimum 10 pack-year smoking history. A modified Fried Frailty Phenotype was performed at 10-year follow-up; participants were categorized as frail, prefrail, or robust. Primary outcomes were respiratory exacerbations, epigenetic pace of aging, and all-cause mortality. Among 2665 participants, 401 (15%) were frail and 1352 (51%) were prefrail. Adjusting for smoking and lung function, frailty was associated with prospective respiratory exacerbation rate (IRR 3.4, 95% CI 2.4–4.8), severe exacerbations (OR 2.8(1.8–4.2)), and frequent exacerbations (OR 5.5(3.2–9.3)). Prefrailty was also associated with exacerbation outcomes (rate IRR 1.8(1.4–2.3); severe OR 1.6(1.1–2.2); frequent OR 2.6(1.7–4.1)). Frailty and prefrailty were associated with increased all-cause mortality (AHR: frailty 4.5(2.4–8.5); prefrailty 2.5(1.5–4.2)). All frailty (and most prefrailty) findings persisted in those with normal spirometry. Baseline DunedinPACE of aging was associated with prospective frailty at 10-year follow-up. Frailty associated with respiratory exacerbations and mortality; findings persisted among individuals with normal spirometry, highlighting the relevance of evaluating for frailty in people with a history of smoking.