In Utero Alcohol and Adverse Outcomes for Premature Newborn

埃默里酒精与肺生物学中心竞争性研究的基本统一假说 更新换代的是，长期酗酒会导致氧化应激，并扰乱正常的调控途径， 从而产生一种“酒精性肺表型”，极易患呼吸道感染、急性 肺损伤，以及其他严重的肺部疾病。尽管现代新生儿重症监护，慢性肺损伤 早产儿，称为支气管肺发育不良(BPD)，会导致显著的发病率和 死亡率。早产儿迟发性败血症(LOS)与BPD的发生有关。这个 过度转化生长因子-β1(TGFp1)之间信号平衡的假说转变 和减少的粒细胞巨噬细胞集落刺激因子(GM-CSF)在“酒精肺”的风险 成人呼吸窘迫综合征和感染是埃默里大学内部调查的中心主题 酒精和肺部生物中心。新生儿，特别是早产儿的肺损伤风险， 在子宫中暴露在酒精中的人几乎没有受到关注。我们有来自临床前的令人信服的证据 动物模型和临床人类研究在宫内酒精暴露增加氧化应激 新生儿肺，发育中气道TGFpl升高，GM-CSF降低。我们已经证明了 胎儿酒精暴露动物肺泡巨噬细胞功能障碍而人类临床数据显示 增加酒精暴露的早产儿患BPD和败血症的风险。我们假设 宫内酒精暴露的早产儿肺氧化应激增加改变了信号转导 平衡过度的TGFj3i和减少的GM-CSF，导致AM功能障碍和增加 BPD和LOS的风险。我们将把这一假设扩展到新生儿重症监护病房的临床领域。 在埃默里酒精和肺部生物学中心的这个新项目中。在我们独特的网络中 研究人员，我们有一个新的机会来解决这些至关重要的问题，但到目前为止还没有得到回答 关于人类早产儿的问题。凭借临床核心的专业知识，我们将前瞻性地 鉴定酒精暴露的早产儿并评估脂肪酸乙酯作为潜在生物标志物的价值 孕期酒精暴露的可能性。与中心调查人员的互动将催化翻译研究 在早产儿肺中确定这种暴露的生化标志物，确定酒精对 早产的人肺泡巨噬细胞，并最终确定了支气管肺发育不良和 酒精暴露的早产儿迟发性败血症。这些研究将提供一个确定的 为未来的研究奠定基础，旨在开发潜在的治疗干预措施 最小的高危病人。

The fundamental and unifying hypothesis in the Emory Alcohol and Lung Biology Center competitive renewal is that chronic alcohol abuse causes oxidant stress and disrupts normal regulatory pathways, thereby producing an "alcoholic lung phenotype" that is highly susceptible to respiratory infections, acute lung injury, and other serious lung diseases. Despite modern neonatal intensive care, chronic lung injury in the premature newborn, known as bronchopulmonary dysplasia (BPD) causes significant morbidity and mortality. Late onset sepsis (LOS) in the premature newborn is linked to the development of BPD. The hypothesized shift in the signaling balance between excessive transforming growth factor-beta 1 (TGFpl) and diminished granulocyte macrophage-colony stimulating factor (GM-CSF) in the "alcoholic lung" at risk for adult respiratory distress syndrome and infection is a central theme to investigations within the Emory Alcohol and Lung Biology Center. The risk of lung injury for the newborn, particularly the premature newborn, exposed to alcohol in utero has received little attention. We have compelling evidence from pre-clinical animal models and clinical human studies that in utero alcohol exposure increased oxidant stress in the neonatal lung, increased TGFpl and decreased GM-CSF in the developing airway. We have demonstrated dysfunction of the fetal alcohol-exposed animal alveolar macrophage while human clinical data suggested an increased the risk of BPD and sepsis for the alcohol-exposed premature newborn. We hypothesize that increased pulmonary oxidant stress in the premature newborn exposed to alcohol in utero shifts the signaling balance towards excessive TGFj3i and diminished GM-CSF, resulting in AM dysfunction and an increased risk of BPD and LOS. We will extend this hypothesis to the clinical arena of the neonatal intensive care unit in this new Project within the Emory Alcohol and Lung Biology Center. Within our unique network of researchers, we have the novel opportunity to address these vitally important and as of yet unanswered questions for the human premature newborn. With the expertise of the Clinical Core, we will prospectively identify the alcohol-exposed premature newborn and evaluate fatty acid ethyl esters as a potential biomarker of prenatal alcohol exposure. Interactions with Center investigators will catalyze translational studies identifying biochemical biomarkers of this exposure in the premature lung, determining alcohol's effect on premature human alveolar macrophage, and ultimately defining the risks of bronchopulmonary dysplasia and late onset sepsis in the alcohol-exposed premature newborn infant. These studies will provide a firm foundation for future investigations aimed at the development of potential therapeutic interventions for our tiniest at-risk patients.