Phosgene‐induced acute lung injury (ALI): differences from chlorine‐induced ALI and attempts to translate toxicology to clinical medicine

Abstract

BackgroundPhosgene (carbonyl dichloride) gas is an indispensable chemical inter‐mediate used in numerous industrial processes. There is no clear consensus as to its time‐ and inhaled‐dose‐dependent etiopathologies and associated preventive or therapeutic treatment strategies. MethodsCardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight. Noninvasive diagnostic and prognostic endpoints in exhaled breath (carbon dioxide and nitric oxide) were used to detect the clinically occult stage of pulmonary edema. ResultsThe first event observed in rats following high but sublethal acute exposure to phosgene was the stimulation of alveolar nociceptive vagal receptors. This afferent stimulation resulted in dramatic changes in cardiopulmonary functions, ventilation: perfusion imbalances, and progressive pulmonary edema and phospholipoproteinosis. Hematology revealed hemoconcentration to be an early marker of pulmonary edema and fibrin as a discriminating endpoint that was positive for the airway irritant chlorine and negative for the alveolar irritant phosgene. ConclusionsThe application of each gas produced typical ALI/ARDS (acute lung injury/acute respiratory distress syndrome) characteristics. Phosgene‐induced ALI showed evidence of persistent apnea periods, bradycardia, and shifts of vascular fluid from the peripheral to the pulmonary circulation. Carbon dioxide in expired gas was suggestive of increased ventilation dead space and appeared to be a harbinger of progressively developing lung edema. Treatment with the iNOS inhibitor aminoguanidine aerosol by inhalation reduced the severity of phosgene‐induced ALI when applied at low dose‐rates. Symptomatic treatment regimens were considered inferior to causal modes of treatment.

Phosgene Inhalation Causes Hemolysis and Acute Lung Injury

“…To this extent, the results of these studies mimic what has been found in humans. COCl 2 -induced ALI show evidence of persistent apnea periods, bradycardia, and higher pulmonary edema compared to Cl 2 toxicity (35). At higher concentrations (>150 ppm·min) COCl 2 exposure can cause life-threatening and latent non-cardiogenic pulmonary edema that is seen 6 to 24 hours post-exposure (11; 47).…”

What are the mechanisms underlying vaping-induced lung injury?

“…This results in diffuse lung damage and ARDS, similar to what is observed in EVALI. Phosgene gas (carbonyl dichloride), used as a bioweapon during World War I, similarly causes ARDS by direct cellular toxicity and increased free radical generation (18). The decreased water solubility of phosgene (compared nary toxicity, chloride gas (Cl 2 ) combines with water in the airway mucosa to form hydrochloric acid (HCl) and hypochlorous acid (HOCl), both of which directly damage the airway epithelial surface.…”

Blue-Emitting BODIPY Dyes

“…It reacts with the amine species and generates cross-linking by urea formation. This reaction can occur with proteins in the pulmonary alveoli, the site of gas exchange, and destroy the barrier of bloodair, causing suffocation [35]. Thus, a rapid and facile method for detecting phosgene is required.…”