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.

急性肺损伤可能是由于恐怖分子的袭击中释放出的刺激性化学暴露造成的有意爆炸化学厂，铁路脱轨或化学卡车劫持。经常致命，一个急性肺损伤的初始诊断可能很困难，因为体征和症状的发作可能会延迟接触后数小时或几天。在组织学上，急性肺损伤以上皮和内皮损伤为特征导致肺水肿延迟，表面活性剂破坏，肺泡塌陷，呼吸衰竭和最终，死亡。根据其毒性和工业用法，丙烯醛是高度关注的化学物质之一反对程序。致命的丙烯醛暴露是在意外释放后导致的运输和使用。恐怖分子的袭击通常会引起大火，这也可能导致丙烯醛暴露，以及一氧化碳（CO）暴露。当前的急性肺损伤治疗仅限于支持策略（托管通风和氧气）。重要的是，许多人可能会接触到没有立即致命的浓度。在这些人中，肺水肿可以延迟小时，没有初始症状。那，大多数受害者将难以诊断和健康护理系统可能不知所措，因为不能适当地将患者分类。在治疗个人之后暴露但在症状发展之前提供了预防或减少延迟的机会之窗肺水肿。该建议旨在开发有效且安全的理论对策用于预防和治疗由丙烯醛，CO和Acrolein Plus诱导的延迟肺水肿 CO，从而降低死亡率。