C47-31 A Refined Lung Transplant Frailty Scale Incorporating Serum Albumin Is Associated With Risk of Mortality in Lung Transplant Candidates

In lung transplant candidates, the Lung Transplant Frailty Scale (LTFS) Base and Body Composition models have superior construct and predictive validity for poor outcomes compared to other frailty measures. Real-world implementation of the LTFS identified day-to-day variations in C-reactive protein (CRP), a biomarker included in the LTFS, raising concerns about its reliability. Further, the binary categorization of LTFS frailty (frail vs. not-frail) lacks granularity. Therefore, we sought to refine the LTFS, substituting CRP with serum albumin as a frailty biomarker and creating a three-category scoring system (“frail”, “pre-frail”, and “not-frail”) to improve discrimination. In an analysis of two multicenter cohort studies of lung transplant candidates, we explored substituting high serum C-reactive protein (≥10 mg/L) with low albumin (≤3.5 g/dL) as the LTFS biomarker. Other LTFS components, including skeletal muscle mass, grip strength, and gait speed, were not changed (Fig. A). We evaluated potential cut-points to establish LTFS “frail”, “pre-frail”, and “not-frail” categories using machine learning metrics, including Macro-Area Under the Curve, Brier Score, Max-rescaled R², and Spiegelhalter’s Z test. We applied multivariable Cox models to evaluate the associations of LTFS-Albumin as a continuous and categorical measure with a composite outcome of waitlist death or delisting or post-transplant mortality, preoperative delisting/death, and post-transplant mortality. Models were adjusted for age, sex, and transplant center. Among 419 participants, 48% were women, with a median age of 61 (interquartile range 51-66). The new LTFS-Base model score ranged from 9.1-24.6; mean 14.5 ±4.6. The new LTFS-Body Composition score ranged from 9-30.7; mean 15.6 ±5.8. Each 1 point-worsening in LTFS-Base and LTFS Body Composition was associated with an 11% increased risk of composite death (Base OR: 1.11, 95% CI: 1.05 to 1.16, Body Composition OR: 1.11, 95% CI: 1.06 to 1.15). Pre-frail and frail candidates had increased mortality risk by both LTFS measures, with pre-frailty capturing an intermediate risk between non-frailty and frailty (Fig. B). For example, using LTFS-Body Composition, compared to non-frailty, pre-frailty conferred a 2.5-fold increased risk of composite mortality and frailty conferred a nearly 6-fold increased risk (pre-frail HR: 2.53, 95% CI: 1.49 to 4.28, frail HR: 5.86, 95% CI: 2.93 to 11.69). We developed a three-category Lung Transplant Frailty Scale incorporating serum albumin instead of CRP. This development cohort refinement demonstrates strong associations with waitlist and post-transplant mortality. The addition of a “pre-frail” category better represents the spectrum of frailty and, if validated, may allow more nuanced assessments of potential transplant candidates.