Peri-transplant frailty changes impact survival in interstitial lung diseases

Frailty is a dynamic state of vulnerability resulting from progressive functional decline and multimorbidity in patients with interstitial lung disease (ILD). The effect of lung transplantation (LTx) on frailty and its prognostic significance remains insufficiently understood.

This single-centre cohort study aimed to characterise peri-transplant frailty trajectories, measured by the clinical frailty scale (CFS), and determine their impact on long-term survival in patients with ILD undergoing LTx. CFS was assessed pre-operatively, at 4-months and 5-years post-transplant. Patients were categorised as fit (CFS 1-3), vulnerable (CFS 4) or frail (CFS 5-9). Frailty change (ΔCFS) was classified as improved (ΔCFS ≤-1), unchanged (ΔCFS 0) or worsened (ΔCFS ≥+1). Survival was analysed using Kaplan-Meier estimates and Cox proportional hazards models.

The proportion of fit patients increased from 22.2% before to 87.5% 4 months and 75.0% 5 years post-transplant. Frailty improved in 93.1%, remained unchanged in 2.8% and worsened in 4.1% of patients. Median ΔCFS was -3 in frail, -1 in vulnerable and 0 in pre-LTx fit patients. Prolonged intensive care unit/hospital stay/ventilation was associated with reduced CFS recovery. Each one-point increase in ΔCFS was associated with a 1.76-fold higher mortality hazard (95% CI 1.34-2.31, p<0.001). Compared to those with improvement, patients with worsened frailty had a 43.9-fold higher mortality hazard (95% CI 10.1-173.2, p<0.001).

Peri-transplant CFS trajectory is associated with long-term survival in ILD, underscoring frailty as a modifiable risk factor and highlighting the need for systematic assessment and targeted interventions to optimise outcomes throughout the transplant course.