Characterization of Occupational Endotoxin-Related Small Airway Disease With Longitudinal Paired Inspiratory/Expiratory CT Scans.

Abstract

Although small airway disease (SAD) has been recognized as a major contributor to obstructive respiratory diseases, the association between occupational endotoxin exposure and SAD, as characterized by CT scans, requires further investigation. What is the association between occupational endotoxin exposure and SAD, and which CT imaging biomarkers effectively detect preclinical airway dysfunction? This study included 404 patients from the Shanghai Textile Workers Cohort. We collected longitudinal inspiratory/expiratory CT scans, spirometry data, and endotoxin levels in 2011 and 2016. We evaluated the marginal association among endotoxin, small airway measures, and spirometry by Pearson correlation coefficient. We applied linear mixed models and linear regression models to understand the adjusted association among endotoxin, small airway measures, and spirometry. We found significant association between endotoxin and SAD and airflow obstruction, as quantified by small airway measures and spirometry, respectively. All small airway measures were marginally correlated with endotoxin, among which relative volume change in voxels with attenuation between -856 Hounsfield units (HU) and -950 HU (RVC_{-856 to -950}) and residuals from the linear regression of Exp_-856 on the percentage of voxels with attenuation less than -950 HU (Residual_-856) showed the strongest positive correlations. Percent predicted FEV₁ (pp FEV₁) showed the strongest negative correlation with endotoxin. After adjusting for confounders, the expiratory-to-inspiratory ratio of mean lung attenuation (E/I MLA), RVC_{-856 to -950}, Residual_-856, FEV₁, and pp FEV₁ yielded a significant association with endotoxin. Workers who were exposed to 1,500 to 2,300 EU/m³ endotoxin showed a significantly higher RVC_{-856 to -950} by 0.071 (P = .006) and a 8.57% lower pp FEV₁ (P = .007) compared with workers exposed to less than 50 EU/m³ endotoxin. We found that occupational endotoxin exposure was significantly associated with SAD and lower FEV₁. We identified Residual_-856 and E/I MLA as the imaging biomarkers for early detection of small airway dysfunction in preclinical individuals (FEV₁/FVC ≥ 0.70). These findings have important implications for identifying early-stage SAD and airflow obstruction with CT imaging biomarkers.