Emory Alcohol and Lung Biology Center

埃默里酒精和肺生物学中心于2003年1月1日正式成立，此后一直在不断扩大其动态研究和培训环境，以研究酒精滥用影响肺部健康的机制。中心研究人员从一项新的观察开始，即酗酒会增加脓毒症、创伤和其他严重炎症性疾病后发生急性肺损伤和呼吸衰竭的风险。事实上，根据中心调查人员发表的两项大型流行病学研究，人们可以估计，酒精滥用是美国每年多达50-7.5万例急性肺损伤的致病因素。此外，即使在最先进的护理下，死亡率也只有-50%，酒精介导的急性肺损伤易感性每年夺走数万人的生命。中心研究人员首先在两个实验模型和人类受试者中发现，长期饮酒，即使在没有任何临床可检测到的肺损伤的情况下，也会在呼吸道中引起严重的氧化应激，使肺容易受到损伤。在这一竞争性更新中，中心研究人员假设，酒精诱导的氧化应激促进粒细胞/巨噬细胞集落刺激因子(GM-CSF)和转化生长因子p-1(TGFp-1)之间的信号平衡转变为有利于TGFfa的前损伤影响，而不是GM-CSF的正常启动刺激。研究人员进一步假设，在慢性氧化应激的同时，这种失衡会改变肺的表型，使其更容易受到急性肺损伤以及其他肺部疾病的影响，包括哮喘、肺炎和呼吸道纤维化。此外，妊娠期间酒精引起的氧化应激可能会使新生儿容易患上危重疾病，特别是在肺部发育不完全的早产情况下。在这次竞争性更新中，该中心将扩展其先前的发现，研究酒精滥用扰乱成人和新生儿肺的正常细胞功能的离散分子机制，并确定可以降低与酒精肺相关的发病率和死亡率的新的治疗干预措施。自四年前成立以来，该中心的规模已经翻了一番多，通过其协作互动，可以推进与酒精相关的肺部疾病的研究，并继续培训致力于改善肺部健康的下一代酒精研究人员。

The Emory Alcohol and Lung Biology Center formally began on January 1, 2003, and has since continued to expand its dynamic research and training environment to study the mechanisms by which alcohol abuse impacts lung health. Center investigators began with the novel observation that alcohol abuse increases the risk of developing acute lung injury and respiratory failure following sepsis, trauma, and other severe inflammatory illnesses. In fact, based on two large epidemiologic studies published by Center investigators, one can estimate that alcohol abuse is a causative factor in as many as 50-75,000 cases of acute lung injury in the U.S. each year. Further, with a mortality of -50% even with state-of-the-art care, alcohol-mediated susceptibility to acute lung injury claims tens of thousands of lives annually. Center investigators were the first to identify in both experimental models and in human subjects that chronic alcohol ingestion, even in the absence of any clinically detectable pulmonary impairment, causes severe oxidant stress in the airway that renders the lung susceptible to injury. In this competitive renewal the Center investigators hypothesize that alcohol-induced oxidant stress promotes a shift in the signaling balance between granulocyte//macrophage colony-stimulating factor (GM-CSF) and transforming growth factor p-, (TGFp-,) to one that favors the proinjurious influences of TGFfa over the normal priming stimulation by GM-CSF. The investigators further hypothesize that this imbalance, in parallel with the chronic oxidant stress, changes the phenotype of the lung such that it is more susceptible to acute lung injury as well as to other lung diseases including asthma, pneumonia, and airway fibrosis. In addition, alcohol-induced oxidant stress during gestation may render neonates vulnerable to critical illnesses, particularly in the setting of premature delivery when the lungs are not fully developed. In this competitive renewal, the Center will extend its previous findings and examine the discrete molecular mechanisms by which alcohol abuse disrupts normal cellular function in the adult and neonatal lung, and identify novel therapeutic interventions that can decrease the morbidity and mortality associated with the alcoholic lung. The Center has more than doubled in size since it began four years ago, and through its collaborative interactions can advance the study of alcohol-related lung diseases and continue to train the next generation of alcohol researchers dedicated to improving lung health.