Background
Existing measures of frailty developed in community dwelling older adults may misclassify
frailty in lung transplant candidates. We aimed to develop a novel frailty scale for
lung transplantation 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-transplant 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 validity
that has superior predictive validity over established measures.
KEYWORDS
Abbreviations:
SPPB (short physical performance battery), FFP (fried frailty phenotype), FFP-DASI (fried frailty phenotype with duke activity status index modification), LT-FS (lung transplant frailty scale), UCSF (University of California San Francisco), CUMC (Columbia University Medical Center), Penn (University of Pennsylvania), DXA (dual x-ray absorptiometry), LTBC (Lung Transplant Body Composition Study), ASMI (appendicular skeletal muscle index), LAS (lung allocation score), HRQL (Health-related quality of life), SF12-PCS (medical outcomes study short form-12 physical component summary scale), LOS (length of stay), ROC (receiver operating curve), AIC (akaiki information criteria), AUC (area under the curve), IL-6 (Interleukin 6), IP-10 (interferon-inducible protein 10), TNFa (tumor necrosis factor alpha), TNF-R1 (TNF receptor-1), IL-1Ra (Interleukin-1 receptor antagonist), PTX-3 (Pentraxin-3), CRP (C-reactive protein), GDF-15 (Growth differentiation factor 15 vimentin), FGF-21 (Fibroblast growth factor 21), FGF-23 (Fibroblast growth factor-23), IGF-1 (Insulin like Growth Factor-1)To read this article in full you will need to make a payment
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Published online: February 20, 2023
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