SCCOR in Translational Research in Acute Lung Injury

描述（由申请人提供）：本申请的临床研究专业中心的总体目标是研究人类急性肺损伤发病机制和治疗的新方面。急性肺损伤是危重患者的重要临床问题，在美国每年影响超过100，000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复杂性的研究方法。 过去对这种疾病的治疗方法强调发病机制和治疗的单一途径，但生物技术的最新发展使人们有可能从系统的角度来看待肺损伤，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六个项目（三个临床和三个基本）和三个核心，行政，生物技术和教育的凝聚力组。 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将在急性肺损伤幸存者中进行一项新治疗方案的随机试验，认识到这些患者复杂的临床需求; 项目3将开展新疗法的试点项目，目的是将积极成果推广到更大规模的临床试验; 项目4研究了影响细菌发病机制的细菌和肺泡环境之间复杂的早期相互作用; 项目5研究了一种保护小鼠免受全身性脓毒症的新途径; 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研究计划正在进行的研究中逻辑地发展而来。 拟议的SCCOR计划将提高对肺损伤发病机制的理解，并可能导致新的治疗方法和改善急性肺损伤患者的长期预后。

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.