Biomarkers of Immunologic Function and Preterm Respiratory Outcomes

描述（由申请人提供）：这是辛辛那提儿童医院新生儿科和肺科作为临床中心参与NHLBI早产和呼吸预后项目（PROP）的提案。临床新生儿科每年收治出生体重<1kg的婴儿约140例。这些婴儿中约有20%会死亡，约40%会患上BPD。该中心每年至少有100名患者或400名患者在4年内进行合作研究，以更好地表征BPD的表型，并确定生物标志物来预测幸存者的肺部预后。新生儿和肺部服务部门在肺发育、肺损伤和BPD方面拥有优越的研究基础设施和悠久的生产基础和转化研究历史。这项临床研究将与我们的NICHD -新生儿研究网络网站以及其他资助的临床研究和后续活动合作进行。本研究项目包括3个目的，旨在验证免疫调节参与BPD的发病、进展和消退的假设，这些免疫因子是预测BPD预后的生物标志物。目的1将测试BPD进展过程中持续的促炎Th17淋巴细胞激活。目的2将通过唾液样本评估蛋白聚糖表型和/或分泌基因型是否能预测严重BPD或死亡。目的3将询问表面活性蛋白SP-A和SP-D是否能预测出生时的BPD，以及血液水平是否能识别早期肺损伤进展为BPD。这些测量将与临床数据、36周校正胎龄时的BPD结果、以及通过肺部健康问卷和婴儿肺功能研究评估的1年肺部结果相关联。数据和样本核心将促进本中心与其他中心之间的协作活动，以处理和整合所有信息和样本。该中心期望将我们对每个目标的样本评估扩展到其他中心，并期待参与合作，多中心方法来分型BPD。（摘要结束）

DESCRIPTION (provided by applicant): 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.