Trajectories of Lung Function in Extremely Premature Infants

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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.