EPIDEMIOLOGY AND INFLAMMATORY RESPONSES IN ACUTE LUNG INJURY

有问题。急性肺损伤(ALI)和急性呼吸窘迫综合征 (ARDS)仍然是#年发病率和死亡率的主要原因。 危重病人。尽管最近取得了进展，但主要问题仍然存在。 关于确定ALI/ARDS风险最高的患者的方法，真实的 ALI/ARDS的发病率和流行率是 ALI/ARDS的发病机制及影响个体宿主因素 患者是否发展为ALI/ARDS。 明确的目标。具体目标是：1)开发临床预测 为发病和结果提供个人风险评估的工具 肺损伤；2)确定ALI/ARDS的发生率和转归。 超越单一机构的人口；3)确定关系 炎症反应与肺内皮细胞损伤之间的关系 上皮屏障；以及4)调查宿主的决定因素 影响ALI/ARDS发生的易感性 风险。 实验方法。我们将根据我们的经验研究 在Harborview医学中心开展ARDS的流行病学研究，并将我们的范围扩大到 对华盛顿州金县的人群队列进行研究。我们将链接来自 将7家公立医院的ICU记录计算机化，以构建详细的 ALI/ARDS患者数据库。这些数据，以及13个国家的资源 年西雅图SCOR ARDS注册表，将用于派生和验证 肺损伤、发病和死亡的临床预测工具；以及 描述肺损伤的人群发病率和结局。我们会 继续调查患者肺部的炎症反应 并确定ARDS发病前后的关系 炎症反应与内皮细胞和上皮细胞的损伤 肺的屏障。最后，我们将调查基因决定的 可能导致ALI/ARDS易感性的宿主因素。 数据的重要性。这些研究将提高我们对1)的理解 ALI和ARDS的流行病学；2)问题的严重性 (包括年发病率、死亡率、经济负担和发病率 幸存者)，我们相信这一群体将可推广到 3)炎症反应与肺损伤的关系； (4)可能改变肺损伤易感性的宿主因素。

Problem. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) continue to be a major cause of morbidity and mortality in critically ill patients. Despite recent advances, major questions remain about ways to identify patients at the highest risk for ALI/ARDS, the true incidence and prevalence of ALI/ARDS, the critical factors involved in the pathogenesis of ALI/ARDS, and individual host factors that influence whether patients develop ALI/ARDS. Specific Aims. The specific aims are: 1) to develop clinical prediction tools that provide individual risk assessment for the onset and outcome of lung injury; 2) to determine the incidence and outcome of ALI/ARDS in populations beyond a single institutions; 3) to determine the relationship between inflammatory responses and injury to the lung endothelial and epithelial barriers; and 4) to investigate determinants of host susceptibility that modulate the occurrence of ALI/ARDS in patients at risk. Experimental Approach. We will build on our experience studying the epidemiology of ARDS at Harborview Medical Center and expand our scope to study a population based cohort in King County WA. We will link data from computerized ICU records at 7 national hospitals to construct a detailed database on ALI/ARDS patients. These data, and the resources of the 13 year Seattle SCOR ARDS Registry, will be used to derive and validate clinical prediction tools for lung injury and onset and mortality; and to describe the population incidence and outcomes of lung injury. We will continue to investigate inflammatory responses in the lungs of patients before and after the onset of ARDS, and determine the relationship between inflammatory responses and injury to the endothelial and epithelial barriers of the lungs. Finally, we will investigate genetically determined host factors that might contribute to susceptibility to ALI/ARDS. Importance of the data. These studies will improve our understanding of 1) the epidemiology of ALI and ARDS; 2) the magnitude of the problem (including incidence, mortality, economic burden, and morbidity in survivors) in a population which we believe will be generalizable to the U.S.; 3) the relationship between inflammatory responses and lung injury; and 4) host factors that may modify susceptibility to lung injury.