# Frailty and patient centered outcomes in candidates for lung transplantation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $720,039

## Abstract

PROJECT ABSTRACT/SUMMARY
For adults suffering from from end-stage lung disease, lung transplantation aims to extend survival, relieve
disability, and improve health-related quality of life (HRQL). An overhaul in organ allocation policy in 2005
prioritized lung transplant for sicker and older adults without impacting one-year survival – the primary measure
of transplant efficacy. This overhaul has come at substantial cost, however, including recent trends towards
increased disability, poorer HRQL, and increased longer-term mortality. There is an urgent need to discriminate
candidates likely to survive after surgery with improved disability and HRQL and to identify new informative pre-
transplant factors to aid in candidacy decision-making. Recently, we found that frailty was prevalent and
associated with disability. In contrast to other solid organ transplant populations, only one of two well-established
measures of frailty predicted risk of waitlist death/delisting in lung transplant candidates. Additionally, our early
data suggests that established measures of frailty may be confounded by lung disease, resulting in
misclassification. We also showed that protein biomarkers representing putative pathways of frailty (i.e., systemic
inflammation, aging, and cachexia) are important in lung transplant candidates. Whether the pathways causing
frailty are universal across heterogeneous lung diseases or whether sub-phenotypes of frailty (so called
“endotypes”) with distinct pathobiology, outcome risks, and treatment responses exist are unknown. Herein, we
propose a prospective cohort study in three large U.S. lung transplant centers to address three fundamental and
new areas in which frailty may inform the field of lung transplantation. In 624 lung transplant candidates, we will
assess existing frailty measures as well as performance, biomarker, and anthropomorphic measures (including
sarcopenia) relevant in lung disease. Of these candidates, 480 will ultimately undergo transplantation in whom
we will evaluate survival, disability, and HRQL one year after transplant. In Aim 1, we will use operational
measures of frailty domains relevant in lung disease to design a novel frailty index for lung transplantation. We
hypothesize that this index will better quantify frailty-attributable vulnerability to stressors than existing measures
developed in community-dwelling older adult populations. In Aim 2, we will utilize latent class analysis (LCA) to
identify endotypes of frailty. We hypothesize that LCA that considers clinical and biomarker measures of
mechanisms driving frailty will identify distinct endotypes in lung disease. In Aim 3, we will develop a clinical
prediction model to identify those at risk for disability, poor HRQL, and death after lung transplant. We hypothesize
that a model that includes frailty will better predict survival with improved disability and HRQL than a model without.
In sum, this proposal will yield a novel measure of frailty relev...

## Key facts

- **NIH application ID:** 9948710
- **Project number:** 5R01HL134851-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jonathan Paul Singer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $720,039
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948710

## Citation

> US National Institutes of Health, RePORTER application 9948710, Frailty and patient centered outcomes in candidates for lung transplantation (5R01HL134851-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9948710. Licensed CC0.

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