Lung Injury with Resuscitation of the Preterm

描述（由申请人提供）：本提案描述了一个为期5年的诺亚希尔曼学术职业发展计划，他已经完成了新生儿围产期医学奖学金，目前是CCHMC新生儿/肺生物学部门的全职教员。本研究将利用早产绵羊模型，探讨早产儿复苏后肺损伤的发生机制。该项目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，清除气道中的液体，并对远端空气空间进行通气。在此过渡期间早产绵羊的通气导致肺部炎症、细胞因子诱导、急性期炎症变化和气道损伤。复苏引起的肺损伤可能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操作对肺的影响。在本提案中，我们将检验表面活性剂缺乏的早产儿肺通气会导致小气道损伤并引发IL-1依赖性炎症反应的假设。具体目标包括：1）呼吸机诱导的肺损伤的区域和时间差异，2）IL-1在复苏诱导的肺损伤中的作用，和3）PEEP和潮气量在复苏诱导的肺损伤中的作用。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使用早产绵羊模型的专家。儿童研究基金会和肺生物学部提供了一个理想的环境，在其中进行拟议的研究计划，因为丰富的资源和广泛的专业知识的一组有才华的研究人员。该提案纳入了可实现的目标，将提供有关早产儿复苏的重要知识。相关性（参见说明）：尽管大多数早产儿在出生时需要一些复苏，但人们对如何最好地启动通气同时最大限度地降低肺损伤的风险知之甚少。早产儿出生时的通气可能有助于早产儿的BPD。使用胎羊复苏模型，我们可以测试早产儿常规操作，并提出减少肺损伤的建议。 (End摘要）

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)