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

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 with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to 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 after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability. Measurements and Main Results: 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. Conclusions: 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.

Tissue Plasminogen Activator Prevents Mortality from Sulfur Mustard Analog–Induced Airway Obstruction

“…We previously described a rat model of acute life-threatening plastic bronchitis (22), where bronchial fibrinous cast formation was induced by inhalation of the toxic SM analog, 2-chloroethyl ethyl sulfide (CEES). In the present study, we used this CEES inhalation model producing airway casts and obstruction to evaluate the effects of escalating doses of intratracheally administered tPA on quantifiable measures of outcome, including airway morphometry, and compared those findings to both placebo-treated and untreated groups.…”

“…Animals were terminated by pentobarbital overdose (Sleepaway; Fort Dodge Animal Health, Fort Dodge, IA) (22).…”

“…Although occasionally seen in adults (4,5), plastic bronchitis not due to chemical inhalation is a disorder affecting mostly children. It can develop after Fontan surgery for congenital cyanotic heart diseases (6-12), or after various bronchopulmonary diseases, such as asthma (13,14), cystic fibrosis (15,16), acute chest syndrome, or sickle cell disease (17), viral lower respiratory tract infections, including H1N1 (18), neoplasms, such as lymphoma (19), chemical or thermal inhalation injuries (5,(20)(21)(22), or idiopathic causes (23). Presenting symptoms include wheezing, coughing, expectoration of rubbery casts, chest pain, hypoxemia, and/or frank respiratory distress (11,24).…”

Successful Management of Plastic Bronchitis in a Child Post Fontan: Case Report and Literature Review

“…Cardiac patients described by them include eight Fontan patients, three Blalock-Taussig shunt patients, and one Glenn shunt patient. Bronchial casts are noted in other disease states, such as sickle cell disease [12][13][14], metastatic lung tumors [4,15,16], viral infections [17,18], smoke inhalation [19][20][21], bronchopulmonary aspergillosis [22][23][24][25][26][27], thalassemia alpha [28], sulfur mustard inhalation [29], solvent aspiration [30], and the use of pegylated interferon [31].…”

Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation

“…Vascular Leakage Assessment-After hyperoxic exposure, mice were injected with Evans blue dye (EBD) (20 mg/kg) via the tail vein (15). After 30 min, the mice were then anesthetized using pentobarbital and euthanized by using thoracotomy.…”