Countermeasure Therapeutics for Acute Lung Injury

急性肺损伤的对策治疗

• 批准号: 9357593
• 负责人: George Douglas Leikauf
• 金额: $ 19.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9357593
• 关键词: Acrolein; Acute Lung Injury; Advanced Development; Affinity; Alveolar; Antidotes; Apoptosis; Binding; Bronchoalveolar Lavage; Carbon Monoxide; Carbon Monoxide Poisoning; Cell Survival; Cells; Cessation of life; Chemical Exposure; Chemicals; Data; Diagnosis; Distal; Environmental air flow; Epithelial; Exhibits; Fire - disasters; Genetic Transcription; Genus Hippocampus; Healthcare Systems; Heme; Heme Iron; Hemeproteins; Hemoglobin; Histidine; Histologic; Histology; Hour; Human Engineering; Hydralazine; Hypertension; In Vitro; Individual; Industrialization; Inflammation; Injury; Irritants; Lead; Ligands; Lung; Measures; Mediator of activation protein; Mitochondria; Molecular; Mus; Mutagenesis; Myoglobin; Necrosis; Oxygen; Patients; Pharmaceutical Preparations; Plants; Poisoning; Prevention; Proteins; Pulmonary Edema; Railroads; Respiration; Respiratory Failure; Signs and Symptoms; Site; Structure; Symptoms; Therapeutic; Toxic effect; Transportation; Triage; adduct; base; complex IV; effective therapy; extracellular; improved; in vivo; lung injury; macromolecule; mortality; mutant; neuroglobin; novel therapeutics; preclinical study; prevent; programs; surfactant; therapeutic development

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.

急性肺损伤可由恐怖分子袭击释放的刺激性化学品引起， 故意引爆化工厂、火车出轨或化学品卡车劫持。通常是致命的， 急性肺损伤的初步诊断可能很困难，因为体征和症状的发作可能延迟 暴露后数小时或数天。在组织学上，急性肺损伤以上皮和内皮损伤为标志， 导致迟发性肺水肿伴表面活性剂破坏、肺泡萎陷、呼吸衰竭， 最终，死亡。基于其毒性和工业用途，丙烯醛是高度关注的化学品之一， 反ACT计划致命的丙烯醛暴露导致意外释放， 运输和使用。恐怖分子的袭击通常会引起大火，这也会导致丙烯醛暴露， 以及一氧化碳（CO）暴露。目前的急性肺损伤治疗仅限于支持性治疗， 策略（管理通气和供氧）。重要的是，许多人可能会接触到 不会立即致命的浓度。在这些人中，肺水肿可以延迟许多 几个小时，并没有出现最初的症状。因此，大多数受害者将难以诊断和健康 护理系统可能不堪重负，因为不能对病人进行适当的分类。治疗后的个人 在症状出现之前的暴露提供了一个机会窗口，可以预防或减少延迟的 肺水肿该建议旨在制定有效和安全的治疗对策， 用于预防和治疗丙烯醛、CO和丙烯醛加 CO，从而降低死亡率。