Emory Alcohol and Lung Biology Center

埃默里酒精和肺部生物学中心于2003年1月1日正式成立，并继续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。中心的研究人员从一个新的观察开始，即酒精滥用增加了败血症、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，根据中心研究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- 75，000例急性肺损伤病例的致病因素。此外，即使采用最先进的护理，死亡率也为约50%，酒精介导的对急性肺损伤的易感性每年夺去数万人的生命。中心的研究人员是第一个在实验模型和人类受试者中确定慢性酒精摄入，即使在没有任何临床可检测到的肺损伤的情况下，也会导致气道中严重的氧化应激，使肺容易受到损伤。在这一竞争性更新中，该中心的研究人员假设，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β-（TGF β-）之间的信号平衡向有利于TGF α的促损伤影响超过GM-CSF的正常引发刺激的信号平衡的转变。研究人员进一步假设，这种不平衡与慢性氧化应激并行，改变了肺的表型，使其更容易受到急性肺损伤以及其他肺部疾病，包括哮喘，肺炎和气道纤维化。此外，妊娠期间酒精引起的氧化应激可能使新生儿易患严重疾病，特别是在肺部未完全发育的早产情况下。在这次竞争性更新中，该中心将扩展其先前的研究结果，并研究酒精滥用破坏成人和新生儿肺部正常细胞功能的离散分子机制，并确定可以降低与酒精性肺相关的发病率和死亡率的新型治疗干预措施。自四年前成立以来，该中心的规模已经扩大了一倍多，通过其合作互动，可以推进酒精相关肺部疾病的研究，并继续培训下一代致力于改善肺部健康的酒精研究人员。

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.