Countermeasure Therapeutics for Acute Lung Injury

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Acute lung injury can result from irritant chemical exposure released from terrorists' attacks including the intentional detonation of chemical plants, railroad car derailments, or chemical truck hijacking. Often fatal, an initial diagnosis of acute lung injury can be difficult because the onset of signs and symptoms can be delayed hours or days after exposure. Histologically, acute lung injury is marked by epithelial and endothelial injury that leads to delayed pulmonary edema with surfactant disruption, alveolar collapse, respiratory failure, and ultimately, death. Based on its toxicity and industrial usage, acrolein is one of the chemicals of high concern to the counterACT program. Lethal acrolein exposures have resulted following accidental release during transportation and use. Terrorists’ attacks often produce massive fires that also can result in acrolein exposure, as well as, carbon monoxide (CO) exposure. Current acute lung injury treatment is limited to supportive strategies (managed ventilation and supplied oxygen). Importantly, many people are likely to be exposed to concentrations that are not immediately lethal. In these individuals, pulmonary edema can be delayed for many hours and occur with no initial symptoms. Thus, the majority of victims will be difficult to diagnose and health care systems may be overwhelmed because patients cannot be triaged adequately. Treating individuals after exposure but before symptoms develop provides a window of opportunity to prevent or diminish delayed pulmonary edema. This proposal seeks to develop therapeutic countermeasures that are effective and safe for use in the prevention and treatment of delayed pulmonary edema induced by acrolein, CO, and acrolein plus CO and thereby reduce mortality.