Each standard deviation increase in CT-derived muscle-associated fat was associated with increased mortality risk (HR 1.236, p<0.001) and worse respiratory impairment in patients with COPD.
Cohort (n=9,254)
Are CT-derived intrathoracic muscle-associated fat and skeletal muscle associated with COPD severity, function, and mortality?
CT-derived intrathoracic muscle-associated fat and skeletal muscle are significant predictors of COPD severity, disease progression, and mortality, identifying high-risk phenotypes even in normal-BMI individuals.
Effect estimate: HR 1.236
p-value: p=<0.001
Abstract Rationale Muscle-associated fat, including intermuscular and intramuscular fat — adipose tissue infiltrating within and between skeletal muscles—represents a novel composition phenotype. Quantitative intrathoracic composition measures such as muscle-associated fat and skeletal muscle may better represent soft tissue pathology as compared with body mass index and weight. This study tested whether how muscle-associated fat and skeletal muscle are associated with COPD severity, function, and mortality. Methods Quantitative CT analysis was performed on 9,254 COPDGene participants at Phase1. Composition percentages were derived from a deep learning-based segmentation algorithm that quantifies thoracic volumes of subcutaneous fat, visceral fat, muscle-associated fat, skeletal muscle, and lungs. Fat and muscle segmentations were constrained to a standardized z-axis range to lung segmented boundaries. Multivariable analyses adjusted for age, sex, race, BMI, smoking status, pack-years, emphysema, Pi10, and scanner type tested for associations with cross-sectional outcomes (FEV₁, FEV₁/FVC, SGRQ, dyspnea) and longitudinal outcomes (FEV₁ decline, adjusted lung density and emphysema progression, all-cause mortality). Additional adjustment with baseline FEV1 was performed for morbidity and mortality metrics. We stratified participants into tertiles of skeletal muscle and intermuscular fat percentage, creating 9 composite phenotypes, calculated model-adjusted least squares means, and performed multivariable analysis for each outcome. Results Muscle-associated fat percentage increased significantly across GOLD stages (Jonckheere-Terpstra p 0.001).Each SD increase in fat (2.5%) was independently associated with lower FEV₁ (β=-0.143 L, p 0.001), reduced FEV₁/FVC ratio (β=-0.015, p 0.001), shorter 6MWD (β=-10.7 m, p 0.001), worse SGRQ score (β = 2.1, p 0.001), greater dyspnea severity (β = 1.1, p 0.001), accelerated lung density loss (β = 0.104g/L/year, p = 0.01), and increased mortality risk (HR = 1.236, p 0.001). Each SD decrease in skeletal muscle percentage (15.4%) was associated with accelerated FEV₁ decline (β=-3.0 mL/year, p = 0.02), faster adjusted lung density loss (β=-0.260 g/L/year, p 0.001), increased emphysema progression (β = 0.450%/year, p 0.001), and increased risk for mortality (HR = 1.079, p = 0.03). With respect to the optimal phenotype of high skeletal muscle/low muscle-associated fat, low skeletal muscle/high muscle-associated fat exhibited the largest deficits across all outcomes: FEV₁ (β=-0.287 L, p 0.001), SGRQ (β = 4.81, p 0.001), dyspnea (β = 1.333, p 0.001) and mortality (HR = 1.766, p 0.001). Composite phenotypes were distributed unevenly across BMI categories, with 20% of normal-BMI individuals possessing high-risk phenotypes based on their body composition. Conclusions CT-derived muscle-associated fat and skeletal muscle are associated with COPD outcomes. Muscle-associated fat accumulation demonstrates stronger associations with respiratory impairment and mortality, while skeletal muscle loss predicts accelerated longitudinal disease progression. This abstract is funded by: This work was supported by NHLBI K01HL163249 (SB), NHLBI R01 HL151421 (SPB & AN), R01HL153460 (MKL). The COPDGene study (NCT00608764) is supported by grants from the NHLBI (U01HL089897 and U01HL089856), by NIH contract 75N92023D00011, and by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion.
Aguilera et al. (Fri,) conducted a cohort in Chronic Obstructive Pulmonary Disease (COPD) (n=9,254). CT-derived muscle-associated fat and skeletal muscle percentage vs. Lower muscle-associated fat and higher skeletal muscle percentage was evaluated on COPD severity, function, and all-cause mortality (HR 1.236, p=<0.001). Each standard deviation increase in CT-derived muscle-associated fat was associated with increased mortality risk (HR 1.236, p<0.001) and worse respiratory impairment in patients with COPD.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: