Dynamic frailty trajectories and risk of chronic obstructive pulmonary disease: a large-scale prospective cohort...

Frailty progression may represent a dynamic clinical marker associated with future chronic obstructive pulmonary disease (COPD) diagnosis, but longitudinal evidence is limited. This study examined the longitudinal association between frailty trajectories and incident COPD.

This prospective cohort study analyzed UK Biobank data. Participants (n = 30,557) aged 40-69 with ≥ 2 valid frailty assessments and no baseline COPD were included. Frailty was assessed longitudinally using a modified Fried phenotype (5 components: weight loss, exhaustion, slow walking, low activity, weak grip). A joint longitudinal-survival model simultaneously analyzed frailty trajectories (linear mixed-effects) and COPD incidence (Cox proportional hazards), linked by shared random effects. Models adjusted for covariates and established COPD risk factors. Sensitivity and subgroup analyses assessed robustness.

Among 30,557 UK Biobank participants, baseline frailty classification revealed 60.8% non-frail, 38.2% pre-frail, and 1.0% frail. Frailty scores increased significantly over time (β = 0.020, P < 0.001). An increasing frailty trajectory was positively associated with the instantaneous hazard of incident COPD (association parameter α = 2.33, 95% CI: 1.64-3.02, P < 0.001). This detrimental association between worsening frailty and COPD incidence remained consistent across all pre-specified subgroups (all P < 0.05) and was robust to multiple sensitivity analyses addressing potential biases, including excluding early events or high-risk groups (all P < 0.001). The joint model showed moderate-to-acceptable discriminative performance (time-dependent AUC 0.63-0.77) for individualized risk assessment.

Our study demonstrates that progressive worsening of frailty is dynamically associated with incident COPD, supporting the potential value of repeated frailty assessment for COPD risk stratification.