SCCOR in Translational Research in Acute Lung Injury

描述(由申请人提供)：申请成立一个专门的临床研究中心的总体目标是研究人类急性肺损伤的发病机制和治疗的新方面。急性肺损伤是危重患者的一个重要临床问题，在美国每年影响超过10万名患者。我们的主要假设是，在理解发病机制和治疗方面的新进展将来自考虑到人类生物反应的复杂性的研究方法。过去对这种疾病的治疗方法强调单一途径在发病机制和治疗中的作用，但最近生物技术的发展使从系统的角度处理肺损伤成为可能，认识到多途径在损伤和修复过程中的重要性。我们的应用程序汇集了一个由六个项目(三个临床项目和三个基础项目)和三个核心项目(行政、生物技术和教育)组成的紧密联系的小组。 项目1将调查正常和危重患者炎症反应的宿主决定因素的复杂性； 项目2将对急性肺损伤幸存者进行一项新治疗方案的随机试验，认识到这些患者的复杂临床需求； 项目3将实施新疗法的试点项目，目的是将积极成果推广到更大规模的临床试验中； 项目4调查影响细菌发病的细菌和肺泡环境之间复杂的早期相互作用； 项目5研究了一种新的保护小鼠免受全身败血症的新途径；以及 项目6研究控制肺泡上皮损伤的复杂机制。 拟议的研究从当前西雅图ARDS研究计划中正在进行的研究中逻辑演变而来。建议的SCCOR计划将加强对肺损伤发病机制的了解，并可能导致新的治疗方法和改善急性肺损伤患者的长期结果。

DESCRIPTION (provided by applicant): The overall objective of this application for a Specialized Center of Clinical Research is to investigate novel aspects of the pathogenesis and treatment of acute lung injury in humans. Acute lung injury is an important clinical problem in critically ill patients that affects more than 100,000 patients annually in the United States. Our major hypothesis is that new advances in understanding pathogenesis and treatment will come from research approaches that take into account the complexity of biological responses in humans. Past approaches to this disease have emphasized single pathways in pathogenesis and treatment, but recent developments in biotechnology have made it possible to approach lung injury from a systems point of view that recognizes the importance of multiple pathways in the injury and repair process. Our application brings together a cohesive group of six projects (three clinical and three basic) and three cores, Administrative, Biotechnology, and Educational. Project 1 will investigate the complexity of host determinants of inflammatory responses in normal and critically ill patients; Project 2 will perform a randomized trial of a new treatment program in survivors of acute lung injury, recognizing the complex clinical needs of these patients; Project 3 will perform pilot projects of new treatments with the aim of taking forward positive results to larger clinical trials; Project 4 investigates the complex early interactions between bacteria and the alveolar environment that influence bacterial pathogenesis; Project 5 investigates a novel new pathway that protects mice from systemic sepsis; and Project 6 investigates the complex mechanisms that control alveolar epithelial injury. The proposed studies evolve logically from ongoing studies in the current Seattle ARDS Research Program. The proposed SCCOR Program will enhance understanding of the pathogenesis of lung injury and could lead to new treatments and improved long-term outcome for patients with acute lung injury.