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

The National Heart, Lung, and Blood Institute awarded The Regents of the University of California, San Francisco $363,556 on February 23, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct secondary cross-sectional analyses examining the association between body composition and patient-centered outcomes in advanced interstitial lung disease.

The funded research will analyze data from two prospective cohort studies to define how obesity and sarcopenia—characterized as pathologic states of elevated fat mass and low muscle mass and function respectively—associate with quality of life, functional status, exercise capacity, and disability in patients with interstitial lung disease. The study addresses a gap in ILD research by investigating extrapulmonary drivers of poor outcomes beyond respiratory function, with particular relevance to aging populations where body mass index alone fails to capture age-related shifts in adiposity and muscle mass. The analyses will leverage completed and ongoing cohort data (R01 HL134851 and U01 HL163242) to examine whether sarcopenic obesity—the concurrent presence of high adiposity and low muscle function—carries multiplicative health impacts in ILD comparable to associations better established in chronic obstructive pulmonary disease.

Work is performed in San Francisco, California. The award has a period of performance through August 31, 2028.

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.