Li Wenli, Pauluhn Juergen
4th Department of Toxicology, Fourth Military Medical University, No. 169 Changle West Road, Xi'an, 710032, Shaanxi Province, China.
Covestro Deutschland AG, Global Phosgene Steering Group, K9, 565, 51365, Leverkusen, Germany.
Clin Transl Med. 2017 Dec;6(1):19. doi: 10.1186/s40169-017-0149-2. Epub 2017 Jun 2.
Phosgene (carbonyl dichloride) gas is an indispensable chemical inter-mediate used in numerous industrial processes. There is no clear consensus as to its time- and inhaled-dose-dependent etiopathologies and associated preventive or therapeutic treatment strategies.
Cardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight. Noninvasive diagnostic and prognostic endpoints in exhaled breath (carbon dioxide and nitric oxide) were used to detect the clinically occult stage of pulmonary edema.
The first event observed in rats following high but sublethal acute exposure to phosgene was the stimulation of alveolar nociceptive vagal receptors. This afferent stimulation resulted in dramatic changes in cardiopulmonary functions, ventilation: perfusion imbalances, and progressive pulmonary edema and phospholipoproteinosis. Hematology revealed hemoconcentration to be an early marker of pulmonary edema and fibrin as a discriminating endpoint that was positive for the airway irritant chlorine and negative for the alveolar irritant phosgene.
The application of each gas produced typical ALI/ARDS (acute lung injury/acute respiratory distress syndrome) characteristics. Phosgene-induced ALI showed evidence of persistent apnea periods, bradycardia, and shifts of vascular fluid from the peripheral to the pulmonary circulation. Carbon dioxide in expired gas was suggestive of increased ventilation dead space and appeared to be a harbinger of progressively developing lung edema. Treatment with the iNOS inhibitor aminoguanidine aerosol by inhalation reduced the severity of phosgene-induced ALI when applied at low dose-rates. Symptomatic treatment regimens were considered inferior to causal modes of treatment.
光气（碳酰氯）气体是众多工业生产过程中不可或缺的化学中间体。关于其时间和吸入剂量依赖性病因及相关预防或治疗策略，目前尚无明确共识。
在大鼠吸入肺泡刺激物光气或气道刺激物氯气期间及之后，对其心肺功能进行检查。终末测量重点关注血液学指标、支气管肺泡灌洗（BAL）中的蛋白渗出以及肺重量增加情况。利用呼出气中的非侵入性诊断和预后指标（二氧化碳和一氧化氮）来检测肺水肿的临床隐匿阶段。
大鼠在高剂量但亚致死性急性暴露于光气后观察到的首个事件是肺泡伤害性迷走神经受体受到刺激。这种传入刺激导致心肺功能发生显著变化、通气/灌注失衡以及进行性肺水肿和磷脂蛋白沉积症。血液学检查显示血液浓缩是肺水肿的早期标志物，而纤维蛋白是一个鉴别指标，对气道刺激物氯气呈阳性，对肺泡刺激物光气呈阴性。
每种气体的应用都产生了典型的急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）特征。光气诱导的ALI表现出持续性呼吸暂停、心动过缓以及血管内液体从外周循环向肺循环转移的迹象。呼出气中的二氧化碳提示通气死腔增加，似乎是进行性肺水肿发展的先兆。吸入诱导型一氧化氮合酶（iNOS）抑制剂氨基胍气雾剂在低剂量率应用时可减轻光气诱导的ALI的严重程度。对症治疗方案被认为不如病因性治疗模式。
