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.

Public Health Relevance

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. 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 exposure. This proposal seeks to advance the development of therapeutics that can be used to treat victims of acrolein, carbon monoxide, and acrolein plus carbon monoxide exposure and thereby reduce mortality.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21ES027390-02
Application #
9357593
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Nadadur, Srikanth
Project Start
2016-09-30
Project End
2018-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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