In Utero Alcohol and Adverse Outcomes for Premature Newborn

埃默里酒精和肺生物学中心的基本和统一假设 更新是慢性酒精滥用导致氧化应激和破坏正常的调节途径， 从而产生“酒精性肺表型”，其对呼吸道感染、急性 肺损伤和其他严重的肺部疾病。尽管现代新生儿重症监护， 称为支气管肺发育不良（BPD）的早产新生儿引起显著的发病率， mortality.早产儿迟发性脓毒症（LOS）与BPD的发生有关。的 过度的转化生长因子β 1（TGF β 1） 和减少粒细胞巨噬细胞集落刺激因子（GM-CSF）在“酒精性肺”的风险， 成人呼吸窘迫综合征和感染是埃默里大学研究的中心主题 酒精和肺部生物学中心新生儿肺损伤的风险，特别是早产儿， 在子宫内接触酒精很少受到关注。我们有令人信服的证据， 动物模型和临床人类研究表明，在子宫内酒精暴露增加了氧化应激， 在新生儿肺中，在发育中的气道中增加TGF β 1和减少GM-CSF。我们已经证明 胎儿酒精暴露的动物肺泡巨噬细胞功能障碍，而人类临床数据表明， 增加酒精暴露早产儿BPD和败血症的风险。我们假设 早产儿在子宫内暴露于酒精中增加的肺氧化应激改变了信号传导， 向过度的TGF β 1和减少的GM-CSF的平衡，导致AM功能障碍和增加的 BPD和LOS的风险。我们将这个假设扩展到新生儿重症监护病房的临床竞技场 埃默里酒精和肺部生物学中心的一个新项目。在我们独特的网络， 研究人员，我们有新的机会来解决这些至关重要的，但尚未回答 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 识别酒精暴露的早产儿，并评估脂肪酸乙酯作为潜在的生物标志物 产前酒精暴露与中心研究者的互动将促进转化研究 确定这种暴露在早产儿肺中的生化生物标志物，确定酒精对 早产的人肺泡巨噬细胞，并最终确定支气管肺发育不良的风险， 酒精暴露的早产儿迟发性败血症这些研究将提供一个公司 未来研究的基础，旨在为我们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.