Airway Obstruction Due to Bronchial Vascular Injury after Sulfur Mustard Analog Inhalation

Department of Pediatrics, University of Colorado Health Sciences Center, Denver, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 12/2010; 182(11):1352-61. DOI: 10.1164/rccm.200910-1618OC
Source: PubMed


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.
To develop a rat inhalation model for airway obstruction with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to investigate the pathogenesis of bronchial cast formation.
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 after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability.
Bronchial casts, composed of abundant fibrin and lacking mucus, occluded dependent lobar bronchi within 18 hours of 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.
After 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.


Available from: Heidi O'Neill
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    • "Sulfur mustard (bis(2-chloroethyl) sulfide)/CEES (2-chloroethyl ethyl sulfide) Vesicant SM, HD Lung [5,7,13141516171820, 21,77,78,85,100], skin [9,10,19,85,90,98] [7,10,11,16,31,48,77] NAC [78,79], GSH [85], MEL [5,12,48], MP [18,90], TRO [5,85,100,101], QUE [5,85,96,101], SIL [5,98,99] Nitrogen mustard Vesicant NM, HN1, HN2, HN3 Lung [87,102], skin [22,24,97] [22,24,48,102] NAC [103], GSH [104], MEL [48,87], SIL [97] Chlorine Choking Cl Lung [25,27,28,91,105– 113] [27,28,48,108–115] NAC [25,105], GSH [106,107], MEL [48], MP [91] Chloropicrin Choking PS Lung [33], eye [30] [ [66,126,127], eye [66,67], skin [66] [66,67] NAC [84], GSH [68], MEL [126], QUE [127] a Antioxidant abbreviations: N-acetylcysteine (NAC), glutathione (GSH), melatonin (MEL), metalloporphyrin (MP), trolox (TRO), quercetin (QUE), silibinin (SIL). "
    [Show abstract] [Hide abstract] ABSTRACT: The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising.
    Full-text · Article · Oct 2015 · Biochemical pharmacology
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    • "To test this hypothesis, a TRPA1-expressing HEK293 cell line and the alkylating agent 2-chloroethyl- ethylsulfide (CEES) were used. The monoalkylating agent CEES was used as a well-established surrogate for SM (Veress et al. 2010), while proof-of-concept experiments using SM and lung epithelial cells were also conducted. "
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    Full-text · Article · Nov 2014 · Archive für Toxikologie
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    • "The most common late complication of SM inhalation is respiratory tract injury. There are about 100,000 surviving victims who were exposed to chemical warfare agents in Iran, many with permanent pulmonary disabilities such as bronchiolitis obliterans.[234567] "
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    Full-text · Article · Feb 2014 · Journal of research in medical sciences
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