EPIDEMIOLOGY AND INFLAMMATORY RESPONSES IN ACUTE LUNG INJURY

问题.急性肺损伤与急性呼吸窘迫综合征 （ARDS）仍然是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， 关于如何识别ALI/ARDS风险最高的患者， ALI/ARDS的发病率和患病率， ALI/ARDS的发病机制，以及影响其的个体宿主因素 患者是否发生ALI/ARDS。 具体目标。具体目标是：1）开展临床预测 提供个人风险评估的工具， 肺损伤; 2）确定ALI/ARDS的发生率和结局， （3）超越一个单一的机构;（4）确定 炎症反应和肺内皮损伤之间的关系， 上皮屏障;和4）调查宿主的决定因素 调节患者ALI/ARDS发生的易感性 风险 实验方法。我们将根据我们的经验， 在Harborview医疗中心的ARDS流行病学，并扩大我们的范围， 研究了华盛顿州国王县的一个基于人口的队列。我们将数据从 在7家国家医院建立了一个详细的ICU记录， ALI/ARDS患者数据库。这些数据和13个国家的资源 西雅图SCOR ARDS登记研究，将用于推导和验证 肺损伤、发病率和死亡率的临床预测工具; 描述肺损伤的人群发病率和结局。我们将 继续研究患者肺部的炎症反应， 急性呼吸窘迫综合征（ARDS）发病前后， 炎症反应和损伤的内皮和上皮 肺的屏障。最后，我们将研究基因决定的 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） ALI和ARDS的流行病学; 2）问题的严重性 （包括发病率、死亡率、经济负担和发病率） 幸存者）在一个人口，我们相信这将是普遍适用于 美国; 3)炎症反应与肺损伤的关系; 和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.