Background: Many lung transplant recipients fail to derive substantial improvements in functioning, health-related quality of life (HRQL), or long-term survival. Identifying modifiable factors that drive poor clinical outcomes after lung transplant is key to advancing the field. Sleep may represent one key, though rarely examined behavioral factor. Methods: As part of a larger longitudinal cohort study, 141 lung transplant recipients completed the 6-item Medical Outcomes Study (MOS) Sleep Scale at a single point in time concurrent with a broader survey of patient reported outcomes, including measures of functioning/disability, cognitive function depressive symptoms, generic and respiratory-specific HRQL, and health utilities. Participants also completed frailty assessments by the Short Physical Performance Battery and Fried Frailty Phenotype (FFP). Time to onset of chronic lung allograft dysfunction (CLAD) and death were derived from pulmonary function and medical record review. The MOS Sleep Scale yields a summary Sleep Problems Index (SPI); we also derived a 2-item insomnia-specific subscale. We tested associations between SPI and Insomnia on PROs and frailty by linear regression and analysis of covariance (ANCOVA) adjusting for age, sex, transplant indication and lung function. We fit Cox proportional hazards models to test the associations between SPI and Insomnia on time to CLAD and death adjusted for age, sex, and transplant indication. Results: We found that worse sleep by either SPI or our insomnia subscale was associated with worse depressive symptoms, cognitive function, generic and respiratory specific HRQL, physical disability, and health utilities (all p < 0.01). Poorer SPI sleep and insomnia were associated with FFP defined frailty. Notably, after adjusting for age, sex, and transplant indication, those in the worst quartile of SPI and insomnia were at markedly increased risk of CLAD (HR 2.18; 95%CI: 1.22, 3.89; p=0.01 for SPI and HR 1.96; 95%CI 1.09, 3.53; p=0.03 for insomnia). Worsening in SPI was also associated with mortality (HR: 1.29; 95%CI: 1.05, 1.58; p=0.01). Conclusion: Poor self-reported sleep after lung transplant appears to be a novel predictor of a range of key patient reported outcomes, physical frailty, CLAD, and death. Further research investigating the prevalence and changes in sleep during transplant is warranted as this data may inform intervention strategies to improve sleep and lung transplant outcomes.

JPS: Consulting fees from XVIVO; Scientific Advisory Board: Mallinckrodt Pharmaceuticals; DSMB: Krystal Biotech SRH: Consulting fees from AI Therapeutics and CareDx; Scientific Advisory Board: CareDx JK: DSMB Lung Bioengineering JRG: Scientific Advisory Board and Research Funding: Theravance Biopharma

JPS: NHLBI K23HL111115, U01HL163242, U01HL145435. JRG: R01 HL151552 VA CDA IK2CX002011; CYH: U01HL163242

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