This is a proposal for the Cincinnati Children's Hospital Division of Neonatology and pulmonary services to participate as a Clinical Center in the NHLBI Prematurity and Respiratory Outcomes Program (PROP). The clinical neonatology services admit about 140 infants/year with birth weights <1kg. About 20% of these infants die and about 40% will have BPD. This Center can contribute at least 100 patients/year or 400 patients over 4yrs for collaborative studies to better characterize the phenotype of BPD and to identify biomarkers to predict lyr pulmonary outcomes of survivors. The neonatal and pulmonary services have a superior research infrastructure and long histories of productive basic and translational research related to lung development, lung injury, and BPD. This clinical research will be performed cooperatively with our NICHD - Neonatal Research Network site and with other funded clinical research and follow-up activities. The research project includes 3 Aims to test the hypothesis that immune regulation contributes to the onset, progression, and resolution of BPD and those immune factors are biomarkers for predicting BPD outcomes.
Aim 1 will test for sustained pro-inflammatory Th17 lymphocyte activation during the progression of BPD.
Aim 2 will evaluate if proteoglycan phenotype and/or secretor genotype predict severe BPD or death using saliva samples.
Aim 3 will ask if surfactant proteins SP-A and SP-D predict BPD at birth and if blood levels identify lung injury progressing to BPD during early life. These measurements will be correlated with clinical data, BPD outcomes at 36wks corrected gestational age, and 1yr pulmonary outcomes evaluated by a lung health questionnaire and infant pulmonary function studies. Collaborative activities between this Center and other Centers will be facilitated by a Data and Sample Core for processing and integrating all information and samples. The Center anticipates extending our sample assessments for each Aim to other Centers and looks forward to participating in collaborative, multi-center approaches to phenotyping BPD. (End of Abstract) Relevance: The project will assess modulators of immune function in the smallest and most high-risk infants for the major adverse pulmonary outcome of prematurity - BPD. These evaluations are directed toward biomarkers to predict disease severity and 1 yr. outcomes with a goal of developing new treatment strategies.
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