Novel QCT textures are associated with sRAGE and IL-6 in SPIROMICS

Abstract

Background: Two newly identified quantitative computed tomography (QCT) textures, found in association with bronchovascular bundles and lobar fissures, predict exacerbation risk in chronic obstructive pulmonary disease (COPD). To better understand disease mechanisms, it is imperative to investigate relationships between such structural QCT phenotypes and underlying blood biomarkers. Inflammatory blood markers such as sRAGE and IL–6, were recently shown to be associated with % emphysema on QCT.

Objectives: We hypothesized that the QCT-based lung parenchymal textures, increased CT density (ICTD) and CT density gradients (CTDG), are associated with sRAGE and IL–6.

Methods: We analyzed the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort to extract the two texture biomarkers using the adaptive multiple feature method (AMFM). Mult­iple linear regression models were used to independently associate plasma concentrations of sRAGE (n=824) and IL–6 (n=642) (Meso Scale Discovery; Rockville, MD) with texture biomarkers, ICTD and CTDG, which were adjusted for age, sex, BODE, FEV₁, FEV₁/FVC, smoking status, pack years, and BMI. As add­itional covariates, we adjusted for QCT biomarkers including Pi10, wall area %, airway fractal dimension, parametric response mapping (PRM)-based emphysema and functional small airways disease (fSAD), disease probability mapping (DPM)-based emphysema and fSAD, density-based emphysema, and air trapping.

Results: sRAGE was inversely correlated with ICTD (b=-0.0078; p=0.0026) and CTDG (b=-0.0195; p=0.0053), whereas IL-6 was positively associated with ICTD (b=0.0074; p=0.0057).

Conclusion: QCT textures have a strong correlation with inflammatory blood markers.