C34-20 Systemic Interleukin-6 Levels in Adults With Asthma Are Associated With Adverse Quantitative Thoracic Computed Tomography Body Composition Metrics: The Severe Asthma Research Program (sarp)

Rationale Asthma is increasingly recognized as a systemic inflammatory disease with links to metabolic dysfunction and multi-organ impacts. Elevated circulating IL-6 levels in the Severe Asthma Research Program (SARP) have been associated with worse clinical outcomes, including more exacerbations and greater comorbidity. However, the extra-pulmonary body composition profile of individuals with high IL-6 asthma remains undefined. This study examined CT-based quantitative thoracic body composition metrics in relation to systemic IL-6 levels among SARP participants, hypothesizing that high IL-6 asthma would be associated with more adverse body composition features than low IL-6 asthma. Methods The SARP is a longitudinal asthma cohort. All SARP III and IV participants with chest CT imaging and IL-6 data were included (N = 183; [268 person-visits]. CT derived body composition metrics (T12 skeletal muscle density [SMD], intramuscular adipose tissue [IMAT], liver density, and coronary calcium) were calculated from CT images using a fully automated, artificial intelligence (AI) based pipeline for body composition. SMD and liver density measured in Hounsfield units (HU), while IMAT measured as square root transformed area and total aortic and CAC measured in Agatston units ln(CAC+ 1) transformed. Participants were stratified by blood IL-6 concentration into “IL6-low” (≤3.1 pg/mL) and “IL6-high” (>3.1 pg/mL) consistent with prior definitions in SARP. To account for the repeated measures design, generalized estimating equations (GEE) characterized the body composition metrics by IL-6 category in unadjusted and age-and-sex adjusted models. Results The N = 183 participants were a mean (SD) 51.1 (14.8) years, 64% female, mean (SD) BMI of 31.3 (8.2) kg/m2 and 55% had severe asthma. In unadjusted models, IL6-high participants demonstrated significantly worse (lower) total T12 SMD compared with IL6-low participants (11.1 HU, 95% CI [7.2–15.0] vs. 20.0 HU, 95% CI [18.1–22.0]; p < 0.0001), and greater IMAT area (p < 0.0001). Liver density was also lower in IL-6-high vs IL-6-low participants (48.5 HU [95% CI 44.7-52.3] vs 52.9 HU [95% CI 50.9-55.0], p = 0.04), Figure. Age-and-sex adjustment yielded similar results. CAC showed a non-significant trend toward higher values in the IL-6-low vs IL-6-high participants (ln[CAC +1] transformed Agatston unit difference 0.62 [95% CI -0.15, 1.38], p = 0.11. Conclusions Participants in SARP with IL-6-high asthma had a more adverse body composition profile compared to those with IL-6-low asthma, characterized by lower (worse) T12 paraspinal muscle density (PSMD), greater intramuscular adipose tissue (IMAT), and lower (worse) liver density. These findings underscore the systemic, multi-organ associations present in participants with IL-6-high asthma.