Citation

Veress LA, O'Neill HC, Hendry-Hofer TB, Loader JE, Rancourt RC, White CW. Am. J. Respir. Crit. Care Med. 2010; 182(11): 1352-1361.

Affiliation

Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, United States; Department of Pediatrics, National Jewish Health, Denver, Colorado, United States.

Copyright

(Copyright © 2010, American Thoracic Society)

DOI

10.1164/rccm.200910-1618OC

PMID

20639443

PMCID

PMC3029928

Abstract

RATIONALE: Sulfur mustard (SM) is a frequently used chemical warfare agent, even in modern history. SM inhalation causes significant respiratory tract injury, with early complications due to airway obstructive bronchial casts, akin to those seen after smoke inhalation and in single ventricle physiology. This process with SM is poorly understood because animal models are unavailable. OBJECTIVES: To develop a rat inhalation model for airway obstruction due to SM analog, 2-chloroethyl ethyl sulfide (CEES), and investigate the pathogenesis of bronchial cast formation. METHODS: Adult rats were exposed to 0, 5 or 7.5% CEES in ethanol via nose-only aerosol inhalation (15 min). Airway microdissection and confocal microscopy were used to assess cast formation (4 and 18 h postexposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were used to evaluate vascular permeability. MEASUREMENTS AND MAIN RESULTS: Bronchial casts, composed mainly of fibrin and lacking mucus, occluded dependent lobar bronchi within 18 h after CEES exposure. BALF contained elevated concentrations of IgM, protein, and fibrin. Accumulation of fibrin-rich fluid in peribronchovascular regions (4 h) preceded cast formation. Monastral blue dye leakage identified bronchial vessels as the site of leakage. CONCLUSION: Following CEES inhalation, increased permeability from damaged bronchial vessels underlying damaged airway epithelium leads to the appearance of plasma proteins in both peribronchovascular regions and BALF. The subsequent formation of fibrin-rich casts within the airways then leads to airways obstruction, causing significant morbidity and mortality acutely after exposure.

Language: en