Countermeasure Therapeutics for Acute Lung Injury

急性肺损伤的对策治疗

基本信息

批准号：
9207983
负责人：
George Douglas Leikauf
金额：
$ 23.14万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
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/9207983
关键词：
Acrolein Acute Lung Injury Advanced Development Affinity Alveolar 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 Genus Hippocampus Healthcare Systems Heme Heme Iron Hemeproteins Hemoglobin Histidine Histologic Histology Hour Human Engineering Hydralazine Hypertension In Vitro Individual Inflammation Injury Irritants Lead Ligands Lung Measures Mediator of activation protein Mitochondria Mus Mutagenesis Myoglobin Necrosis Oxygen Patients Pharmaceutical Preparations Plants Poisoning Prevention Proteins Pulmonary Edema Railroads Respiration Respiratory Failure Signs and Symptoms Site Structure Symptoms TNFRSF5 gene Therapeutic Toxic effect Transportation Triage Work adduct base complex IV effective therapy extracellular improved in vivo lung injury macromolecule mortality mutant neuroglobin novel therapeutics preclinical study prevent programs surfactant

项目摘要

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.

恐怖分子袭击（包括恐怖袭击）释放的刺激性化学物质可能导致急性肺损伤故意爆炸化工厂、火车脱轨或化学品卡车劫持通常是致命的。急性肺损伤的初期诊断可能很困难，因为体征和症状的出现可能会延迟从组织学角度来看，急性肺损伤的特点是上皮和内皮损伤。导致迟发性肺水肿，表面活性物质破坏、肺泡塌陷、呼吸衰竭和根据其毒性和工业用途，丙烯醛是备受关注的化学品之一。 counterACT 计划期间意外释放导致致命的丙烯醛暴露。恐怖分子的袭击经常引发大规模火灾，从而导致丙烯醛暴露，目前的急性肺损伤治疗仅限于支持性治疗。重要的是，许多人可能会接触到。对于这些人来说，浓度不会立即致死，肺水肿可能会延迟发生。小时并且没有任何初始症状，因此，大多数受害者将难以诊断和健康。由于术后无法对患者进行充分的分类，护理系统可能会不堪重负。但在症状出现之前接触提供了预防或延迟的机会之窗该提案旨在制定有效且安全的治疗对策。用于预防和治疗丙烯醛、CO和丙烯醛加引起的迟发性肺水肿 CO，从而降低死亡率。