PULMONARY EDEMA FROM SYNTHETIC SMOKE INHALATION

肺部并发症是火灾死亡的主要原因 受伤 肺损伤可能是由于吸入烟雾，循环 烧伤皮肤或器官释放的因子，或这些因素的组合。 有害物质是烟雾中的化学毒素，而不是热量。 那里 通常是火灾和肺损伤发作之间的滞后期， 肺水肿或ARDS，在此期间，炎症介质可能具有 造成肺部损伤 在这个提议中，假设是 吸烟引起的肺损伤不是通过产生 皮肤烧伤中的肺损伤，即补体激活、白细胞停滞 和聚集、O2自由基释放和花生四烯酸活化。 当然，这些机制中的一些涉及，但我们认为， 细胞如巨噬细胞或上皮细胞可能是 随着时间的推移，炎症介质会放大炎症的程度， 最初的烟雾可能是通过吸引粒细胞而造成的。 这项建议 然后将解决病理生理学，细胞生物学和分子 烟雾与皮肤烧伤引起的肺损伤的生物学比较。 为了解决我们的假设，我们已经开发了管理技术， 实验动物真实的烟雾与其多种毒素（不同的 含量取决于基质），合成烟雾含有大（4亩）或 小的（0.12 μ）烟尘加上单一的烟雾毒素，如丙烯醛或其他 烟雾中已知的毒素 我们可以监测 这些烟雾伴或不伴1）肺泡上的相关皮肤烧伤 通过监测雾化99 mTcDTPA的清除率测定渗透性，或2） 通过热稀释或通过监测淋巴液流量和含量造成的血管损伤 蛋白质和炎症介质（P物质、IL-1、TNF α或TNF α）的表达 白三烯），或3）气道功能， 监测气道压力和评估气道组织学。 我们文化 肺泡巨噬细胞、鳞状上皮细胞、血管平滑肌和 内皮细胞在一个特殊的房间里，我们可以将它们暴露在真实的环境中， 烟雾或各种合成烟雾毒素，并确定哪些细胞释放 炎症介质（IL-1和TNF α）以及吸烟如何诱导 mRNA的变化，使其发生。 我们做内皮细胞结合试验 白细胞对烟雾和烟雾毒素的反应。 我们已经开发出一种 低剂量的棉花和丙烯醛-碳烟雾， 肺淋巴液流动，但在18小时内未检测到肺水肿。 我们因此 我觉得我们有潜力充分探索烟雾是如何造成的，以及烟雾是如何造成的。 肺损伤以及与皮肤烧伤相比， 目的是开发有效的治疗方法来预防肺部并发症 在火灾受害者。

Pulmonary complications are the major cause of death in fire related injuries. The pulmonary injury may be due to smoke inhalation, circulating factors released by burned skin or organs, or the combination of these. The chemical toxins in smoke and not heat are the injurious agents. There is often a lag phase between the fire and the onset of lung injury such as pulmonary edema or ARDS during which time inflammatory mediators may have to build up to cause the lung damage. In this proposal the hypothesis is that smoke induced lung injury is not by the same pathways that produce lung injury in skin burn injury, i.e. complement activation, leukostasis and aggregation, 02 free radical release and arachidonic acid activation. Certainly some of these mechanisms are involved but we feel that airway cells such as the macrophage or the epithelial cells may be the sources of the mediators of inflammation that overtime magnify the extent of the original smoke insult perhaps by attracting granulocytes. This proposal then will address the pathophysiology, cellular biology and molecular biology of smoke in comparison to cutaneous burn induced pulmonary injury. To address our hypothesis we have developed the techniques of administering to experimental animals real smoke with its multiple toxins (varying in content depending on substrate), synthetic smoke containing large (4mu) or small (0.12mu) soot plus a single smoke toxin such as acrolein or other toxins known to be in smoke. We can monitor the physiologic impact of these smokes with or without associated cutaneous burn on 1) alveolar permeability by monitoring clearance of aerosolized 99mTcDTPA or 2) vascular injury by thermal dilution or by monitoring lymph flow and content of protein and mediators of inflammation (Substance P, IL-1, TNFa or leukotrienes) in the sheep lung lymphatics, or 3) airway function by monitoring airway pressures and assessing airway histology. We culture alveolar macrophages, squamous epithelial cells, vascular smooth muscle and endothelial cells in special chambers in which we can expose them to real smoke or various synthetic smoke toxins and determine which cells release the mediators of inflammation (IL-1 and TNFa) and how the smokes induce changes in mRNA to allow this to happen. We do endothelial binding assays for leukocytes in response to smoke and smoke toxins. We have developed a low dose of cotton and of acrolein-carbon smoke that produce an increase in lung lymph flow but no detectable pulmonary edema over 18 hrs. We thus feel we have the potential to fully explore how and what in smoke causes lung injury and how this compares to and is amplified by cutaneous burns, with a goal of developing effective therapy to prevent lung complications in fire victims.