title: Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug-induced lung injury.
abstract: 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.
  
  
  
  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.
  
  
  
  At the time of diagnosis, 39 patients (57%) had respiratory failure (partial pressure of oxygen/inspiratory oxygen fraction ratio, PaO2/FiO2ratio < 300). There was a significant negative linear correlation between the PaO2/FiO2ratio 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 PaO2/FiO2ratio. 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 (PaO2/FiO2ratio < 300).
  
  
  
  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.
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kondoh
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018893:Bronchoalveolar Lavage / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D055370:Lung Injury / Q000139:chemically induced / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018180:Thrombomodulin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018180:Thrombomodulin
keywords: acute respiratory distress syndrome; drug-induced lung injury; interstitial lung disease; thrombomodulin