Trajectories of Lung Function in Extremely Premature Infants

项目摘要 早产影响了在美国出生的10%-12%的婴儿，扰乱了正常的肺部发育 并损害肺功能。发生这种情况是因为早产儿出生时正处于快速反应的关键时期。 通常发生在妊娠晚期的肺部发育。与健康术语形成对比 婴儿，其肺功能在整个童年期间按照可预测的轨迹增加，在早期达到顶峰 成年后才会衰败。对于早产儿来说，对他们的肺轨迹的了解明显较少 尽管早产是成人肺部疾病的一个主要风险因素，但这一点是显而易见的。到目前为止，无论是 早产儿肺功能的轨迹，以及可能改变它们的因素，都是客观存在的。 采用婴儿肺功能测试(PFTs)进行测量。这项建议将检查成人的围产期起源。 早产儿肺疾病的肺功能指标及其影响的研究 改变这些轨迹上的因素。这项提案的具体目标是：1)确定 早产儿出生后早期肺功能变化；2)比较早产儿肺功能 将患有支气管肺发育不良(BPD)的婴儿与没有BPD的婴儿进行比较；以及3)调查 影响因素，包括产前母亲吸烟和产后感染对改变这些轨迹的影响。 这些目的是为了验证这样的假设：1)像健康的足月儿一样，早产儿的肺功能 婴儿随着时间的推移而改善，沿着可预测的轨迹进行跟踪；2)早产儿的肺功能 在此期间，有BPD的人将与没有BPD的人背道而驰；以及3)影响因素包括 产前吸烟和产后感染会进一步改善肺功能。了解这些 早产儿肺功能的关键方面将允许识别其肺轨迹 功能异常，允许在肺快速发育的关键窗口期间进行干预以改善 长期的肺功能。本提案中的职业发展目标旨在实现三个目标 具体的目标，以确保我在完成后将具有独立资金的竞争力。这些目标是1) 在早产儿的婴儿PFT的表现和解释方面获得专业知识；2)获得 应用生物统计学方法研究肺纵向轨迹和发育的经验 成人肺部疾病的起源；以及3)通过培养所需的团队领导技能来实现独立 以获得资金并在团队科学方面取得成功。实现这些目标将提供工具 需要竞争独立的资金。本研究中早产儿的肺部轨迹 该提案将作为一个模型，全面探索早产儿如何与遗传易感性相互作用， 胎程规划、营养等因素对早产儿肺功能轨迹的影响 婴儿患成人肺部疾病的风险很高。这项研究计划的最终目标是 对有成人肺部疾病风险的早产儿实施早期干预，旨在优化其高峰期 肺功能与成人肺部疾病的预防。

Project Summary Prematurity, which affects 10-12% of all infants born in the United States, disrupts normal lung development and impairs lung function. This occurs because premature infants are born during a critical window of rapid lung development that typically occurs during the 3rd trimester of pregnancy. In contrast to healthy term infants, whose lung function increases throughout childhood following predictable trajectories, peaking in early adulthood before declining. For premature infants, significantly less is known about the trajectories of their lung function, though it is clear that prematurity is a major risk factor for adult lung disease. To date, neither the trajectories of lung function in premature infants, nor the factors that can alter them, have been objectively measured with infant pulmonary function tests (PFTs). This proposal will examine this perinatal origin of adult lung disease in premature infants by using PFTs to quantify these trajectories of lung function and the effects of modifying factors on those trajectories. The Specific Aims of this proposal are to 1) define the trajectory of changes in lung function in premature infants during the early postnatal period; 2) to compare the lung function of infants with bronchopulmonary dysplasia (BPD) to those without BPD; and 3) to investigate the impact of modifying factors, including prenatal maternal smoking and postnatal infections on altering these trajectories. These aims are designed to test the hypotheses that 1) like healthy term infants, the lung function of premature infants improves over time, tracking along predictable trajectories; 2) that the lung function of premature infants with BPD will diverge from those without BPD during this period; and 3) that modifying factors including prenatal maternal smoking and postnatal infections can further modify lung function. Understanding these critical aspects of premature lung function will allow for the identification of infants whose trajectory of lung function is abnormal, permitting intervention during this critical window of rapid lung development to improve long term lung function. The Career Developement Objectives in this proposal are designed to achieve three specific goals to ensure that I will be competitive for independent funding upon completion. These goals are 1) to gain expertise in the performance and interpretation of infant PFTs in premature infants; 2) to gain experience in the biostatistical methods needed to study longitudinal lung trajectories and the developmental origins of adult lung disease; and 3) to achieve independence by cultivating the team leadership skills needed to secure funding and achieve success in team science. Achievement of these goals will provide the tools needed to compete for independent funding. The lung trajectories for premature infants generated in this proposal will then serve as a model for fully exploring how prematurity interacts with genetic predisposition, fetal programming, nutrition and other modifying factors to impact the trajectory of lung function in premature infants, who are at high risk of developing adult lung disease. The ultimate goal of this research program is to implement early interventions for premature infants at risk for adult lung disease aimed at optimizing their peak lung function and preventing lung disease in adulthood.