Trajectories of Lung Function in Extremely Premature Infants

极早产儿肺功能的变化轨迹

• 批准号: 10457957
• 负责人: Brian K Jordan
• 金额: $ 16.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457957
• 关键词: Achievement; Address; Adult; Affect; Age; Ascorbic Acid; Biostatistical Methods; Bronchopulmonary Dysplasia; Childhood; Chronic lung disease; Clinical Trials Design; Continuous Positive Airway Pressure; Data; Development; Early Intervention; Early identification; Ensure; Exposure to; Funding; Future; Genetic Predisposition to Disease; Goals; Hospital Costs; Impairment; Infant; Infection; Inhalation Drug Administration; Intervention; Leadership; Longitudinal Studies; Lung; Lung diseases; Measurement; Measures; Modeling; Neonatal; Obstructive Lung Diseases; Performance; Perinatal; Pregnancy Trimesters; Premature Infant; Primary Prevention; Pulmonary function tests; Research; Risk; Risk Factors; Science; Secure; Smoke; Solid; Steroids; Strategic vision; Testing; Third Pregnancy Trimester; Time; United States; antenatal; career; clinical care; design; efficacy evaluation; emerging adult; experience; fetal programming; functional decline; high risk; improved; in utero; inflammatory lung disease; lung development; maternal cigarette smoking; neonatal period; normal aging; nutrition; peer; postnatal; postnatal period; premature; premature lungs; prenatal; prevent; programs; pulmonary function; skills; smoking during pregnancy; success; systemic inflammatory response; tool

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.

项目概要 早产影响了美国出生婴儿的 10-12%，它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在快速出生的关键窗口期。 肺部发育通常发生在妊娠第三期。与健康术语相反 婴儿的肺功能在整个童年时期按照可预测的轨迹增强，并在早期达到顶峰 衰退前的成年期。对于早产儿，人们对其肺部轨迹知之甚少 尽管早产显然是成人肺部疾病的主要危险因素。迄今为止，无论是 早产儿肺功能的轨迹以及可以改变它们的因素都已被客观地 通过婴儿肺功能测试（PFT）进行测量。该提案将审查成人的围产期起源 通过使用 PFT 量化肺功能的这些轨迹及其影响来评估早产儿的肺部疾病 改变这些轨迹的因素。该提案的具体目标是 1) 定义轨迹 早产儿产后早期肺功能的变化； 2）比较肺功能 患有支气管肺发育不良 (BPD) 的婴儿与无 BPD 的婴儿的比例； 3) 调查影响 改变这些轨迹的因素包括产前母亲吸烟和产后感染。 这些目标旨在检验以下假设：1) 与健康足月婴儿一样，早产儿的肺功能 随着时间的推移，婴儿会沿着可预测的轨迹进步； 2）表明早产儿的肺功能 在此期间，患有 BPD 的人将与没有 BPD 的人产生分歧； 3) 改变因素包括 产前母亲吸烟和产后感染可以进一步改变肺功能。了解这些 早产儿肺功能的关键方面将有助于识别婴儿的肺功能轨迹 功能异常，允许在肺部快速发育的关键窗口期间进行干预以改善 长期肺功能。本提案中的职业发展目标旨在实现三个目标 具体目标，以确保我在完成后能够获得独立资助的竞争力。这些目标是 1) 获得早产儿婴儿 PFT 的执行和解释方面的专业知识； 2）获得 研究纵向肺轨迹和发育所需的生物统计方法的经验 成人肺部疾病的起源； 3) 通过培养所需的团队领导技能来实现独立性 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 需要竞争独立资金。在此生成的早产儿的肺部轨迹 该提案将作为充分探索早产如何与遗传倾向相互作用的模型， 胎儿编程、营养和其他影响早产儿肺功能轨迹的调节因素 婴儿，他们是患成人肺部疾病的高风险人群。该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措施，以优化其高峰期 肺功能和预防成年肺部疾病。