BMC Pulmonary Medicine · Apr 15, 2026

Association between frailty and the risks of chronic pulmonary diseases and lung cancer

By Deng Y, Li Z, Lv X et al.

BACKGROUND: Frailty, a multidimensional syndrome of decreased physiological reserve, is associated with adverse health outcomes, but its relationship with a broad spectrum of pulmonary diseases remains incompletely understood. This study aimed to systematically evaluate the associations between frailty and multiple pulmonary diseases and their multimorbidity patterns. METHODS: We analyzed 146,747 participants from the UK Biobank. Frailty was quantified using frailty index (FI) and categorized into non-frail, pre-frail, and frail groups. Outcomes included chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease (ILD), lung cancer, their overlap syndromes, and pulmonary-related mortality. Cox proportional hazards models with inverse probability of treatment weighting estimated hazard ratios (HRs) and 95% confidence intervals, adjusting for demographic, lifestyle, environmental, and clinical covariates with competing risk analyses performed using Fine–Gray models. Non-linear associations were assessed using restricted cubic splines, and E-values evaluated robustness to unmeasured confounding. Mediation analyses based on UK Biobank Pharma Proteomics Project (UKB-PPP) identify protein signatures associated with frailty–disease relationships. RESULTS: Frail individuals showed higher incidence of multiple pulmonary outcomes compared with non-frail and pre-frail participants. Dose-response analyses revealed non-linear associations, with risk elevation evident even at pre-frailty (FI = 0.237) for asthma-COPD overlap. Mediation analyses identified WFDC2 and CXCL17 as proteins associated with both frailty and multiple pulmonary outcomes, including ILD and lung cancer. CONCLUSION: Frailty is associated with a higher incidence of multiple pulmonary diseases and multimorbidity patterns. These associations may be partly accounted for by shared protein signatures. Frailty may serve as a marker for risk stratification in respiratory health.

doi.org/10.1186/s12890-026-04271-6 Open access PubMed 41987142 Biomarkers