Development of the Lung Transplant Frailty Scale (LT-FS)

BACKGROUND: Existing measures of frailty developed in community dwelling older adults may mis-classify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung trans-plantation with improved performance characteristics.METHODS: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate Lung Transplant Frailty Scale (LT-FS) measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. RESULTS: In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre -trans-plant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. CONCLUSIONS: The LT-FS is a disease-specific physical frailty measure with face and construct valid-ity that has superior predictive validity over established measures. J Heart Lung Transplant 2023;42:892-904 & COPY; 2023 International Society for Heart and Lung Transplantation. All rights reserved.

Automated summary

A novel frailty scale specifically designed for lung transplant candidates has been developed in this study, showing better performance in evaluating frailty compared to existing measures. Through a four-step approach, multiple aspects of frailty were identified and measured, and models were built and improved by selectively adding variables. The newly developed lung transplant frailty scale demonstrated superior predictive validity in predicting mortality and functional recovery after lung transplantation.