Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug‐induced lung injury

Background and objective Drug‐induced lung injury ( DLI ) can result from a vast number of agents, and sometimes presents findings similar to those of acute respiratory distress syndrome ( ARDS ). Previous studies have reported that circulating levels of soluble thrombomodulin ( TM ) reflect endothelial injuries, which play key roles in the development of ARDS . We hypothesized that endothelial injuries are an important aspect of pathogenesis in severe DLI . The primary aim of this study was to examine the associations between soluble TM and disease severity in DLI patients. Methods Of the 2580 patients who underwent a bronchoalveolar lavage ( BAL ) procedure at Tosei General Hospital between May 2007 and February 2015, we retrospectively analysed the data of 68 DLI patients. Soluble TM in plasma and BAL fluid ( BALF ), and other biomarkers were included in our analysis. Results At the time of diagnosis, 39 patients (57%) had respiratory failure (partial pressure of oxygen/inspiratory oxygen fraction ratio, PaO 2 / FiO 2 ratio < 300). There was a significant negative linear correlation between the PaO 2 / FiO 2 ratio and soluble TM in BALF (r = −0.448, P  < 0.001). In a stepwise multiple regression analysis, soluble TM in BALF and surfactant protein D ( SP ‐D) were the only independent determinants of the PaO 2 / FiO 2 ratio. Additionally, in a multivariate logistic regression model, soluble TM in BALF (adjusted OR ( aOR ): 7.48, 95% CI : 1.60–34.98) and SP ‐D ( aOR : 5.31, 95% CI : 1.40–20.15) was an independent predictor of respiratory failure ( PaO 2 / FiO 2 ratio < 300). Conclusion Soluble TM in BALF is an independent predictor of severe DLI . These findings underscore the importance of pulmonary endothelial injuries in the pathogenesis of severe DLI .