ARDS--CLINICAL EPIDEMIOLOGY AND ROLE OF THE INFLAMMATORY RESPONSE

ARDS--临床流行病学和炎症反应的作用

• 批准号: 6241804
• 负责人: LEONARD D HUDSON
• 金额: $ 20.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241804
• 关键词: adult respiratory distress syndrome; blood toxicology; cytokine; disease /disorder proneness /risk; human subject; interleukin 8; leukocyte adhesion molecules; lung injury; lung lavage; neutrophil; pathology; prognosis; protease inhibitor; respiratory disorder diagnosis; respiratory disorder epidemiology; respiratory infections; von Willebrand factor

This project will investigate the epidemiology of ARDS and the evolution of the inflammatory process in patients with acute lung injury. The epidemiological aspects will focus on refining our clinical criteria that predict patients at high risk for the onset of ARDS, and identifying these patients as early as possible before the onset of lung injury. Our major hypothesis is that uncontrolled and sustained alveolar inflammation increases the severity of ARDS and prolongs its course, and that sustained inflammation is more likely to occur when ARDS follows sepsis syndrome than multiple trauma. We also will investigate the hypothesis that the pattern of the inflammatory response in blood and lungs is an important determinant of whether lung inflammation persists of resolves. Important components of the inflammatory response that we intend to study include; 1) a coordinated sequence of cytokines in blood and lung lavage fluid; 2) the expression of adhesion molecules on blood leukocytes; 3) circulating markers of diffuse endothelial injury (VWF and ELAM1); 4) products of the arachidonic acid cascade; 5) the induction of endogenous proteins that modify the host response to bacterial products such as endotoxin; and 6) inflammatory cell populations and proteins in the lung. We will correlate patterns of inflammation with clinical risks,critical clinical events, and outcome measures. We expect that our results will provide: a) a better understanding of the evolution of inflammation in clinical conditions leading to lung injury; b) a better understanding of the mechanisms of the initial injury and its propagation; and c) information that will help predict the course and outcome in individual patients. We also expect that these data will be useful in guiding the choice and timing of specific therapeutic interventions.

本研究将探讨急性呼吸窘迫综合征的流行病学及其演变， 急性肺损伤患者的炎症过程。的 流行病学方面将侧重于完善我们的临床标准， 预测ARDS发病的高危患者， 这些患者尽可能早在肺损伤发作之前。 我们 一个主要的假设是不受控制的持续性肺泡炎症 增加了ARDS的严重程度和病程， 脓毒症后发生ARDS时更容易发生持续性炎症 综合征而不是多发性创伤 我们还将研究假设 血液和肺部的炎症反应模式是 决定肺部炎症是否持续或消退的重要因素。 我们打算研究的炎症反应的重要组成部分 包括：1）血液和肺灌洗液中细胞因子协调序列 2）血液白细胞表面粘附分子的表达; 3） 弥漫性内皮损伤的循环标志物（VWF和ELAM 1）; 4） 花生四烯酸级联的产物; 5）内源性的诱导 改变宿主对细菌产物的反应的蛋白质， 内毒素;和6）肺中的炎性细胞群和蛋白质。 我们将把炎症模式与临床风险联系起来， 临床事件和结果测量。 我们希望我们的结果 提供：a）更好地了解炎症的演变， 导致肺损伤的临床状况; B）更好地了解 初始损伤及其传播的机制;以及c） 这些信息将有助于预测个体的过程和结果， 患者我们还希望这些数据将有助于指导 具体治疗干预的选择和时机。