Acute changes in lung histopathology and bronchoalveolar lavage parameters in mice exposed to the choking agent gas phosgene

Phosgene (CG) is a highly irritant gas widely used industrially as a chemical intermediate for the production of dyes, pesticides, and plastics, and can cause life-threatening pulmonary edema within 24 hours of exposure. This study was designed to investigate acute changes in lung tissue histopathology and selected bronchoalveolar lavage fluid (BALF) factors over time to determine early diagnostic indicators of exposure. Three groups of 40 male mice each were exposed to 32 mg/m(3) (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were exposed to filtered room air for 20 minutes, both exposures were followed by room air washout for 5 minutes. At 1, 4, 8, 12, 24, 48, and 72 hours after exposure each group of mice was euthanized and processed for histopathology, bronchoalveolar lavage or gravimetric measurements, respectively. Over time, the histopathological lesions were characterized by acute changes consisting of alveolar and interstitial edema, fibrin and hemorrhage, followed by significant alveolar and interstitial flooding with inflammatory cell infiltrates and scattered bronchiolar and terminal airway epithelial degeneration and necrosis. From 48 to 72 hours, there was partial resolution of the edema and degenerative changes, followed by epithelial and fibroblastic regeneration centered on the terminal bronchiolar areas. Bronchoalveolar lavage was processed for cell differential counts, LDH, and protein determination. Comparative analysis revealed significant increases in both postexposure lung wet/dry weight ratios, and early elevations of BALF LDH and protein, and later elevations in leukocytes. This article describes the use of histopathology to chronicle the temporal pulmonary changes subsequent to whole body exposure to phosgene, and correlate these changes with BALF ingredients and postexposure lung wet weights in an effort to characterize toxic gas-induced acute lung injury and identify early markers of phosgene exposure.