National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
J Pharmacol Exp Ther. 2024 Jan 17;388(2):560-567. doi: 10.1124/jpet.123.001822.
Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
吸入性毒物的用途多种多样，从农业、卫生和熏蒸等工业用途到人群控制和化学战，急性暴露可导致持久的呼吸道并发症。第一次世界大战期间蓄意释放化学战剂（CWA）对幸存者造成了终身伤害，国际条约禁止使用 CWA。然而，在过去二十年中，中东和东欧地区化学战的使用有所增加，并且转向肺部毒物。在流氓活动中使用工业和农业化学品的潜在可能性是一个主要关注点，因为它们通常存放在人口稠密地区附近，并且在这些地区，故意或意外释放可能会导致严重伤害和死亡。尽管有法律和监管机构来规范使用、储存、运输、排放和处置，但吸入性暴露仍会导致持久的肺部损伤。工业刺激物（例如，氨）会加重上呼吸道，导致肺炎、支气管收缩和呼吸困难。刺激气体（例如丙烯醛、氯化苦）会通过反应中间体或通过半胱氨酸丰富的蛋白质的直接加成破坏上皮屏障完整性并引起组织损伤。CWA（例如氯气、光气、芥子气）的症状从气道阻塞和肺水肿进展为急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS），这会导致几天后出现呼吸抑制。紧急治疗仅限于使用支气管扩张剂来控制气道收缩的支持性护理，并通过机械通气进行抢救以改善气体交换。急性暴露的并发症可促进阻塞性肺病和/或肺纤维化，这需要长期的临床护理。意义陈述：吸入性化学威胁在民用和军事环境中越来越受到关注，因此需要减少急性肺损伤和暴露后的延迟临床并发症。这篇小综述强调了我们对一些关注的化学物质的急性毒性和病理生理学的现有理解。它讨论了潜在的早期治疗发展以及在开发适用于大规模伤亡情况的对策方面的挑战。
