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Research Paper|Volume 17, Issue 7|pp 1590—1623

Frailty associates with respiratory exacerbations and mortality in the COPDGene cohort

Eleanor Kate Phillips1,2, Yichen Huang1, Elizabeth Regan3, Barry Make4, Matthew Strand5, Abebaw Mengistu Yohannes6, Nicola A. Hanania7, Jessica Bon8, Karin F. Hoth9, James D. Crapo4, Edwin K. Silverman1,2,10, Dawn L. DeMeo1,2,10
  • 1Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
  • 2Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
  • 3Division of Rheumatology, National Jewish Health, Denver, CO 80206, USA
  • 4Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO 80206, USA
  • 5Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, CO 80206, USA
  • 6Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL 35294, USA
  • 7Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX 77030, USA
  • 8Section of Pulmonary, Critical Care, Allergy, and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
  • 9Department of Psychiatry, University of Iowa Carver College of Medicine, Lowa City, IA 52242, USA
  • 10Harvard Medical School, Boston, MA 02115, USA
Received: February 26, 2025Accepted: June 2, 2025Published: July 3, 2025
https://doi.org/10.18632/aging.206275

Copyright: © 2025 Phillips et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.