CLINICAL MODELS OF THE ADULT RESPIRATORY DISTRESS SYNDROME

(改编自申请人的摘要)：加州大学可持续发展分校/急性肺损伤SCOR的这个项目侧重于使用基于观察的有针对性的干预措施来预防或改善急性肺损伤，这些观察定义了导致急性肺损伤的具体机制。用于这些项目的人体模型包括接受肺血栓内膜切除术(PT-E)的患者。这些患者中高达60%的患者在PT-E后出现高通透性水肿/再灌注性肺损伤。本项目的目的是通过采集PT-E和其他ARDS高危患者的连续血液和BALF样本，并分析这些样本中ALI的标志物[中性粒细胞和蛋白内流、细胞因子(IL-8、肿瘤坏死因子-α)、氧化型α-蛋白酶抑制物、谷胱甘肽水平和可溶性黏附分子(E-P-、L-选择素、细胞间黏附分子-1、血管细胞黏附分子-1)]，来继续确定这种独特的、可预测的肺损伤模型。这三个介入试验提出了类似的方法，(2)使用抗氧化剂，(3)吸入一氧化氮预防再灌注性肺损伤。除了评估这三种干预措施的有效性和安全性外，还将在急性肺损伤缓解之前、急性期和缓解期间收集连续的血液和支气管肺泡灌洗样本。对这些标本的分析将提供对参与急性肺损伤的启动和持续的细胞成分和介质的洞察。这些标本将与加州大学圣迭戈分校其他SCOR项目的合作者共享，如果需要，还将与其他急性肺损伤评分共享。(摘要结束)

(Adapted from the Applicant's Abstract): This project of the UCSD/ACUTE Lung Injury SCOR focuses on the prevention or amelioration of acute lung injury using targeted interventions based on observations which define the specific mechanisms responsible for acute lung injury. The human model used for these projects consists of patients undergoing pulmonary thromboendarterectomy (PT-E). Up to 60 percent of these patients develop a high permeability edema/reperfusion lung injury following PT-E. The aims of this project are to continue to define this unique, predictable, model of lung injury in PT-E patients by collecting sequential blood and BALF samples from PT-E and other patients at risk for ARDS and analyzing these samples for markers of ALI [neutrophil and protein influx, cytokines (IL-8, TNF-alpha), oxidized alpha1-proteinase inhibitor, glutathione levels, and soluble adhesion molecules (E-P-, L-selectins, ICAM-1, VCAM-1)]. The three interventional trials proposed analog, (2) use of an anti-oxidant drug, and (3) inhaled nitric oxide in the prevention of reperfusion of reperfusion lung injury. In addition to assessing the efficacy and safety of these three interventions, serial blood and bronchoalveolar lavage specimens will be collected prior to, during the acute phase, and during resolution of acute lung injury. Analysis of these specimens will provide insights into the cellular components and mediators that are involved in the initiation and perpetuation of acute lung injury. These specimens will be shared with collaborators working on other SCOR projects at UCSD and, if desired, with other Acute Lung Injury SCORs. (End of Abstract)