Biomarkers of Immunologic Function and Preterm Respiratory Outcomes

描述(由申请者提供)：这是辛辛那提儿童医院新生儿和肺部服务部门作为临床中心参与NHLBI早产和呼吸结局计划(PROP)的建议。临床新生儿服务中心每年接纳140名出生体重在1公斤以下的婴儿。这些婴儿中约有20%死亡，约40%将患有BPD。该中心每年可以为至少100名患者或400名患者提供超过4年的合作研究，以更好地描述BPD的表型，并确定预测幸存者LYR肺结局的生物标记物。新生儿和肺部服务机构拥有优越的研究基础设施，以及与肺发育、肺损伤和BPD相关的生产性基础研究和转化性研究的悠久历史。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。该研究项目包括3个目标，旨在检验免疫调节有助于BPD的发生、发展和缓解，以及这些免疫因素是预测BPD预后的生物标志物的假说。目的1将测试在BPD进展过程中持续的促炎Th17淋巴细胞激活情况。目的2将使用唾液样本评估蛋白多糖表型和/或分泌型是否预测严重的BPD或死亡。目标3将询问表面活性蛋白SP-A和SP-D是否可以预测出生时的BPD，以及血液水平是否表明肺损伤在生命早期进展为BPD。这些测量将与临床数据、校正胎龄36周时的BPD结果以及通过肺健康问卷和婴儿肺功能研究评估的一年内肺结果相关。该中心与其他中心之间的协作活动将由一个数据和样本核心来促进，以处理和整合所有信息和样本。该中心预计将我们对每个目标的样本评估扩展到其他中心，并期待参与合作的、多中心的bpd表型鉴定方法。(摘要结束) 相关性：该项目将评估最小和最高风险婴儿的免疫功能调节剂对早产儿BPD的主要不良肺部后果。这些评估针对的是预测疾病严重程度和1年的生物标志物。结果，目标是开发新的治疗策略。

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.