Sun Yuming, Kang Jian, Zhang Feng-Ying, Wang Hantao, Lai Peggy S, Washko George R, San Jose Estepar Raul, Christiani David C, Li Yi
Department of Mathematics, College of William & Mary, Williamsburg, VA.
Department of Biostatistics, University of Michigan, Ann Arbor, MI.
Chest. 2025 Jul;168(1):43-55. doi: 10.1016/j.chest.2024.12.037. Epub 2025 Jan 18.
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) and residuals from the linear regression of Exp on the percentage of voxels with attenuation less than -950 HU (Residual) showed the strongest positive correlations. Percent predicted FEV (pp FEV) showed the strongest negative correlation with endotoxin. After adjusting for confounders, the expiratory-to-inspiratory ratio of mean lung attenuation (E/I MLA), RVC, Residual, FEV, and pp FEV yielded a significant association with endotoxin. Workers who were exposed to 1,500 to 2,300 EU/m endotoxin showed a significantly higher RVC by 0.071 (P = .006) and a 8.57% lower pp FEV (P = .007) compared with workers exposed to less than 50 EU/m endotoxin.
We found that occupational endotoxin exposure was significantly associated with SAD and lower FEV. We identified Residual and E/I MLA as the imaging biomarkers for early detection of small airway dysfunction in preclinical individuals (FEV/FVC ≥ 0.70). These findings have important implications for identifying early-stage SAD and airflow obstruction with CT imaging biomarkers.
尽管小气道疾病（SAD）已被认为是阻塞性呼吸道疾病的主要促成因素，但职业性内毒素暴露与以CT扫描为特征的SAD之间的关联仍需进一步研究。
职业性内毒素暴露与SAD之间有何关联，哪些CT成像生物标志物能有效检测临床前期气道功能障碍？
本研究纳入了上海纺织工人队列中的404名患者。我们在2011年和2016年收集了纵向吸气/呼气CT扫描、肺功能测定数据以及内毒素水平。我们通过Pearson相关系数评估内毒素、小气道指标和肺功能测定之间的边缘关联。我们应用线性混合模型和线性回归模型来了解内毒素、小气道指标和肺功能测定之间的校正关联。
我们发现内毒素与SAD以及气流阻塞之间存在显著关联，分别通过小气道指标和肺功能测定进行量化。所有小气道指标与内毒素均存在边缘相关性，其中衰减在-856亨氏单位（HU）至-950 HU之间的体素的相对体积变化（RVC）以及呼气量关于衰减小于-950 HU的体素百分比的线性回归残差（Residual）显示出最强的正相关性。预测FEV百分比（pp FEV）与内毒素显示出最强的负相关性。在调整混杂因素后，平均肺衰减呼气与吸气比（E/I MLA）、RVC、Residual、FEV和pp FEV与内毒素存在显著关联。与暴露于低于50 EU/m内毒素的工人相比，暴露于1500至2300 EU/m内毒素的工人的RVC显著高出0.071（P = 0.006），pp FEV低8.57%（P = 0.007）。
我们发现职业性内毒素暴露与SAD以及较低的FEV显著相关。我们将Residual和E/I MLA确定为在临床前期个体（FEV/FVC≥0.70）中早期检测小气道功能障碍的成像生物标志物。这些发现对于用CT成像生物标志物识别早期SAD和气流阻塞具有重要意义。
