Background Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown.
Methods Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes.
Results Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant.
Conclusions Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.
- lung transplantation
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AV and NAK are joint first authors.
Funding This work was supported by grants from the National Heart, Lung and Blood Institute (K23 HL111115 and R01 HL134851) to JPS, and the Clinical Sciences Research and Development Service of the VA Office of Research and Development (career development award IK2CX001034 to JRG).
Competing interests JRG reports grants and personal fees from Thermo Fisher, Genentech, Atara Biotherapeutics, and BioMérieux, outside the submitted work. PJW reports grants from MedImmune, grants from Genentech, personal fees from Roche, personal fees from Blade Therapeutics, grants and personal fees from Boehringer Ingelheim, personal fees from Pliant, outside the submitted work.
Patient consent for publication Not required.
Ethics approval Breathe Again was approved by our local Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. The deidentified data are available on reasonable request directed to JPS, ORCID ID 0000-0003-0224-7472.
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