The effect of body composition on patient-centered outcomes in advanced interstitial lung disease

/Abstract Interstitial lung diseases (ILD) are a group of chronic lung diseases characterized by progressive fibrosis and loss of lung function over time. Prior research has appropriately focused on respiratory function and attenuation of disease progression; however, the myriad impacts of ILD on health beyond the respiratory system are less well studied. Reflecting these insights, the American Thoracic Society has emphasized the need to incorporate patient-centered outcomes (PCOs) in ILD research. Patients with ILD suffer from lower quality of life, increased functional limitation, and increased frailty, but the extrapulmonary drivers of the impacts are not well defined. My early findings have identified body composition as a novel risk factor for poor outcomes in advanced ILD. Obesity – a pathologic state of elevated fat mass – and sarcopenia – a pathologic state of low muscle mass and function, have been associated with worse functional status, reduced quality of life, and increased disability. As age increases, for a given body mass index (BMI), people experience an increase in adiposity and decrease in muscle mass and function. At their extremes, this parallel change is termed sarcopenic obesity, which appears to have multiplicative impacts on health. These aging-related changes in body composition, and the limitation of BMI to identify them, are relevant in ILD which increases in prevalence with age. The study of body composition in ILD is nascent, and limited evidence suggests both sarcopenia and obesity are associated with reduced quality of life and exercise capacity, akin to the associations better established in chronic obstructive pulmonary disease. Secondary cross-sectional analyses of two prospective cohort studies (R01 HL134851 [completed]; U01 HL163242 [ongoing]) are proposed to define the association between body composition and PCOs in adults with advanced ILD undergoing lung transplantation evaluation. My central hypotheses are that abnormalities in body composition will be associated with worse PCOs, that the magnitudes of association will be largest in participants with sarcopenic obesity, and that these associations will not be apparent when using BMI as a primary exposure variable. A projected 872 participants with baseline pre-transplantation visits will meet inclusion and exclusion criteria and will be categorized by bioelectrical impedance as non-obese/non-sarcopenic, obese by fat mass, sarcopenic, and sarcopenic obese. The outcomes of interest will be frailty by the Short Physical Performance Battery and Fried Frailty Phenotype, exercise capacity by six-minute walk distance, disability by the Lung- Transplant Valued Life Activities Scale, and general and respiratory-specific health-related quality of life by the Short Form 12 and Airways Questionnaire 20-Revised, respectively. This proposal is significant by exploring a novel and potentially intervenable risk factor for poor PCOs in a population already vulnerable to significant morbidity, while also supporting my growth as an early-stage investigator through strong cross-disciplinary mentorship alongside didactic and experiential training. Project Number: 1F32HL182143-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Andrew Curnow | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $89,860 | Activity Code: F32 | Study Section: Special Emphasis Panel[ZRG1 F18-E (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1F32HL18214301