Characterization of occupational endotoxin-related small airway disease with longitudinal paired inspiratory/expiratory CT scans

Background: Although small airway disease has been recognized as a major contributor to obstructive respiratory diseases, the association between occupational endotoxin exposure and small airway disease, as characterized by CT scans, requires further investigation.

Research question: What is the association between occupational endotoxin exposure and small airway disease, and which CT imaging biomarkers effectively detect pre-clinical airway dysfunction?

Study design and methods: This study includes 404 subjects from the Shanghai Textile Worker 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.

Results: We found significant association between endotoxin and small airway disease and airflow obstruction, as quantified by small airway measures and spirometry, respectively. All small airway measures were marginally correlated with endotoxin, among which RVC_-856to-950 and Residual_-856 showed the strongest positive correlations. pp FEV₁ showed the strongest negative correlation with endotoxin. Adjusting for the confounders, E/I MLA, RVC_-856to-950, Residual_-856, FEV₁, and pp FEV₁ reported significant association with endotoxin. Workers who were exposed to 1,500 - 2,300 EU/m³ endotoxin showed a significantly higher RVC_-856to-950 by 0.071 (p = 0.006) and a 8.57% lower pp FEV₁ (p = 0.007) compared to workers exposed to less than 50 EU/m³ endotoxin.

Interpretation: We found that occupational endotoxin exposure was significantly associated with small airway disease and lower FEV₁. We identified Residual_-856 and E/I MLA as the imaging biomarkers for early detection of small airway dysfunction in pre-clinical individuals (FEV₁/FVC ≥ 0.70). These findings have important implications for identifying early-stage SAD and airflow obstruction with CT imaging biomarkers.