Lung Injury with Resuscitation of the Preterm

描述(由申请人提供)：本建议书描述了诺亚·希尔曼的五年学术生涯发展计划，他已经完成了新生儿-围产期医学研究员学位，目前是CCHMC新生儿/肺生物学部门的全职教员。本研究将利用早产羊模型研究早产复苏引起肺损伤的机制。该计划将为早产儿复苏指南提供新的证据。从胎儿到新生儿的转变需要开始呼吸，清除呼吸道中的液体，并对远端空间进行通风。在这一过渡期间，早产羊的换气会导致肺部炎症、细胞因子诱导、急性期炎症变化和呼吸道损伤。复苏引起的肺损伤可能会引发极早产儿的支气管肺发育不良。我们以前曾使用胎羊模型来评估复苏动作对肺的影响。在这项提案中，我们将检验这样一种假设，即肺表面活性物质缺乏的早产儿肺的通风会导致小气道损伤，并引发IL-1依赖的炎症反应。具体目标包括：L)呼吸机所致肺损伤的区域和时间差异，2)IL-1在复苏所致肺损伤中的作用，以及3)PEEP和潮气量在复苏所致肺损伤中的作用。这项研究将在Jobe和Kallapur博士的监督下进行，他们都是肺部炎症和早产羊模型使用方面的专家。儿童研究基金会和肺生物学分部为实施拟议的研究计划提供了理想的环境，因为有一批有才华的研究人员拥有丰富的资源和广泛的专业知识。该提案包含了可实现的目标，这些目标将提供有关早产儿复苏的重要知识。相关性(见说明)：尽管大多数早产儿在出生时需要进行一些复苏，但人们对如何在最大限度地减少肺损伤风险的同时启动呼吸机知之甚少。早产儿出生时的呼吸机可能有助于早产儿的BPD。利用胎羊复苏模型，我们可以测试早产儿的常规操作，并提出减少肺损伤的建议。(摘要结束)

DESCRIPTION (provided by applicant): This proposal describes a 5 year program for academic career development for Noah Hillman who has completed a fellowship in Neontal-Perinatal medicine and is currently a fulltime faculty member of the division of Neonatology/Pulmonary Biology at CCHMC. The research will focus on the mechanisms of lung Injury caused by the resuscitation of preterms using preterm sheep models. This program will provide new evidence for resuscitation guidelines for preterm infants. The transition from a fetus to a newborn requires the initiation of breathing, clearance of fluid from airways, and ventilation of the distal airspaces. Ventilation of the preterm sheep during this transition leads to lung inflammation, cytokine induction, acute phase inflammatory changes, and airway injury. Lung injury from resuscitation may initiate bronchopulmonary dysplasia in extremely premature infants. We have previously used a fetal sheep model to evaluate the effects of resuscitation maneuvers on the lung. In this proposal we will test the hypothesis that ventilation of the surfactant-deficient, preterm lung causes small airway injury and initiates an IL-1 dependant inflammatory response. The specific aims include l) Regional and temporal differences in ventilator induced lung injury, 2)Role of IL-1 in resuscitation induced lung injury, and 3)Role of PEEP and tidal volume on resuscitation induced lung injury. The research will be conducted under the supervision of Drs. Jobe and Kallapur, who are both experts in lung inflammation and the use of preterm sheep models. The Children's Research Foundation and the Division of Pulmonary Biology provides an ideal setting in which to conduct the proposed research program because of the abundant resources and wide ranging expertise of a talented group of investigators. This proposal incorporates achievable goals that will provide important knowledge on the resuscitation of preterm infants. RELEVANCE (See instructions): Although the majority of preterm infants require some resuscitation at birth, little is known about how best to initiate ventilation while minimizing the risk of lung injury. Ventilation of the preterm infant at birth may contribute to BPD in premature infants. Using fetal sheep models of resuscitation, we can test the maneuvers performed routinely on preterm infants and make recommendations to decrease lung injury. (End of Abstract)