Emory Alcohol and Lung Biology Center

修订后的摘要 埃默里大学的酒精研究小组已经确定 酗酒使患急性酒精性心脏病的风险增加3倍 呼吸窘迫综合征(ARDS)，一种严重的肺损伤形式， 每年杀死数以万计的美国人。事实上，该中心的 对近600名患者的研究表明，约50%的患者 患有急性呼吸窘迫综合征有明显的酗酒史。此外, 该中心的调查人员已经确定，乙醇介导的 关键抗氧化剂谷胱甘肽的耗尽会产生特定的 肺结构和功能缺陷，使肺易受影响 到急性损伤。ARDS是一系列组织损伤的一部分 被称为“多器官”的危重病人 “功能障碍综合征”。这种综合症会产生毁灭性的后果。 在幸存者的死亡率和长期发病率方面。然而， 它不是从头产生的，而是对各种急性 侮辱，如创伤和败血症。重要的问题是，如何 酗酒使肺和其他器官容易受到伤害， 危重病人的失败？该中心的调查人员 假设酗酒会在体内产生慢性氧化应激 肺，以及一系列由此导致的肺结构和 功能使患者容易发生呼吸衰竭和 相关的多器官功能障碍。此外，这种机制还会影响 有严重酗酒史的母亲早产婴儿 历史上除了成年人入院重症监护病房外 败血症、创伤或其他危重疾病的治疗。建议数 埃默里酒精和肺部生物学中心将扩展这项先前的工作，并 剖析其临床联系和基本机制 潜在的酗酒和多器官功能障碍。大写字母 关于已建立的合作以及最近的人才 招募教员后，该中心将在一个 包括体外和体内在内的一整套相关项目 动物模型，以及儿科和成人的临床研究 重症监护病房设置。该中心将开展六项合作 研究酒精对肺的影响的研究项目 上皮生物学、内皮生物学和基质生物学。与此同时，飞行员 组件将促进新的试点项目，这些项目将确定新的 酒精所致组织损伤的基础与临床研究进展 项目。最后，该中心将培育科学家的培训 在酒精研究方面的职业。该中心提出的工作有 对理解诊断和诊断的巨大影响 重症监护病房中数十万患者的预后 整个美国，并可能导致小说的发展 多器官功能障碍高危患者的治疗 长期酗酒导致的功能障碍。

REVISED ABSTRACT The alcohol research group at Emory University has determined that alcohol abuse increases the risk 3-fold of developing the Acute Respiratory Distress Syndrome (ARDS), a severe form of lung injury that kills tens of thousands of Americans each year. In fact, the Center's studies in nearly 600 patients indicate that ~50% of all patients who develop ARDS have a significant history of alcohol abuse. In addition, the Center's investigators have determined that ethanol-mediated depletion of the critical antioxidant glutathione produces specific defects in lung structure and function that render the lung susceptible to acute injury. ARDS is part of a spectrum of tissue injury in critically ill patients that has been termed the 'multiple organ dysfunction syndrome'. This syndrome produces devastating consequences in terms of mortality and prolonged morbidities in survivors. However, it does not arise de novo but rather in response to a variety of acute insults, such as trauma and sepsis. The important question is how does alcohol abuse render the lung and other organs susceptible to injury and failure in critically ill patients? The Center investigators hypothesize that alcohol abuse produces chronic oxidative stress within the lung, and that an array of consequent defects in lung structure and function render patients susceptible to respiratory failure and associated multiple organ dysfunction. Further, this mechanism affects infants born prematurely to mothers with a significant alcohol abuse history in addition to adults admitted to intensive care units for treatment of sepsis, trauma, or other critical illnesses. The proposed Emory Alcohol and Lung Biology Center will extend this previous work and dissect the clinical associations as well as the fundamental mechanisms underlying alcohol abuse and multiple organ dysfunction. Capitalizing on established collaborations as well as the talents of recently recruited faculty, the Center will test the central hypothesis in a comprehensive set of related projects that include in vitro and in vivo animal models, as well as clinical studies in pediatric and adult intensive care unit settings. The Center will conduct six collaborative research projects that examine the effects of ethanol on lung epithelial, endothelial, and matrix biology. In parallel, the Pilot Component will facilitate novel pilot projects that will identify new aspects of alcohol-mediated tissue injury in basic and clinical projects. Finally, the Center will nurture the training of scientists for careers in alcohol research. The work proposed by this Center has enormous implications for the understanding of the diagnosis and prognosis of hundreds of thousands of patients in intensive care units throughout the U.S., and could lead to the development of novel therapies for those patients at greatest risk for multiple organ dysfunction as a consequence of chronic alcohol abuse.