STOP BPD

 描述(由申请人提供)：支气管肺发育不良(BPD)是极低出生体重(ELBW)婴儿的常见发病率。我们的研究小组在BPD的翻译研究方面拥有相当多的专业知识。我们已经：(A)开发了仅使用有限的临床信息来预测出生后BPD或ELBW婴儿死亡的模型，(B)前瞻性地评估了BPD的肺动脉高压，以及(C)使用多个临床变量和血液中的25种细胞因子在1067名ELBW婴儿队列中确定了与BPD/死亡相关的生物标记物。最近，我们通过对751名ELBW婴儿进行全基因组分析，对BPD的遗传基础进行了新的观察。在其他正在进行的研究中，我们已经确定了BPD的新的蛋白质组生物标记物，并确定了BPD患者呼吸道微生物组的变化。“停止BPD”(BPD中顶级基因组特征的签名)的总体目标是前瞻性地定义和验证与BPD的复原力或发展风险相关的临床和“OMIC”签名。为了达到这一目标，我们将在基因组学、蛋白质组学、呼吸道微生物组和BPD模型发展的最新研究基础上再接再厉。我们将通过以下具体目标评估一个预期队列(NICHD新生儿研究网络的通用数据库或GDB队列)，该队列包括2015-2017年出生的300名早产儿和29周妊娠(仅2013年就有213名，登记人数超过80%)：特定目标1-使用全基因组表达分析和出生后72小时内采集的血液中有针对性的SNP图谱，开发和验证BPD和严重BPD的个性化基因组风险/复原力评分。 出生后第一周测量的BPD和重度BPD的个性化尿蛋白质组风险/弹性评分(B)在出生后72小时内测量的BPD和重度BPD的个性化血浆蛋白质组和细胞因子风险/弹性评分的开发和验证特定目标3-使用出生后第一周收集的气管抽吸物为BPD和重度BPD开发和验证个性化的呼吸道微生物组风险/弹性评分特定目标4-开发结合基因组、蛋白质组和微生物体评分与临床模型的组合“基因组”评分系统我们将开发和确定发育队列(n=150)中各种模型的准确性，并在验证队列(n=150)中验证它们。这些新模型可用于确定未来干预措施的目标人群，评估特定干预措施的效果，开发“芯片实验室”，并支持未来对BPD生物学的研究。

 DESCRIPTION (provided by applicant): Bronchopulmonary dysplasia (BPD) is a common morbidity in extremely low birth weight (ELBW) infants. Our research group has considerable expertise in translational research on BPD. We have: (a) developed models using only limited clinical information to predict BPD or death by postnatal age or respiratory illness severity in ELBW infants, (b) prospectively evaluated pulmonary hypertension in BPD and (c) identified biomarkers associated with BPD/death in a cohort of 1067 ELBW infants using multiple clinical variables and 25 cytokines in blood. More recently, we have made novel observations on the genetic basis of BPD by genome-wide analysis in 751 ELBW infants. In additional ongoing studies, we have identified novel proteomic biomarkers of BPD, and have determined alterations in the airway microbiome in BPD. The overall objective of "STOP BPD" (Signature of Top Omic Profiles in BPD) is to prospectively define and validate clinical and "omic" signatures associated with resilience against, or risk for development of BPD. To address this objective, we will build upon our recent studies on genomics, proteomics, respiratory microbiome, and model development in BPD. We will evaluate a prospective cohort (Generic Database or GDB cohort of the NICHD Neonatal Research Network) of 300 preterm infants <29 weeks gestation born in 2015-2017 (n=213 in 2013 alone, with 80%+ enrollment) by the following Specific Aims: Specific Aim 1- Development and validation of a personalized genomic risk/resilience score for BPD and severe BPD using a combination of genome-wide expression analysis and targeted SNP profiling in blood collected within 72h of birth Specific Aim 2 - (a) Development and validation of a personalized urinary proteomic risk/resilience score for BPD and severe BPD measured in the first postnatal week (b) Development and validation of a personalized plasma proteomic and cytokine risk/resilience score for BPD and severe BPD measured within 72h of birth Specific Aim 3 - Development and validation of a personalized airway microbiome risk/resilience score for BPD and severe BPD using tracheal aspirates collected in the first postnatal week Specific Aim 4 - Development of a combined "Omic" scoring system combining the genomic, proteomic, and microbiomic scores with the clinical model We will develop and determine the accuracy of the various models in the Development cohort (n=150), and validate them in the Validation cohort (n=150). These novel models can be used to define the target population for future interventions, assess efficacy of specific interventions, develop a "lab on chip", and support future studies on the biology of BPD.