STOP BPD
停止BPD
基本信息
- 批准号:9292368
- 负责人:
- 金额:$ 36.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-15 至 2020-06-30
- 项目状态:已结题
- 来源:
- 关键词:Actinobacteria classAddressAgeAlveolarAspirate substanceBiological MarkersBiologyBirthBloodBronchopulmonary DysplasiaCD44 geneCessation of lifeClinicalComplicationDNA MethylationDatabasesDevelopmentDiseaseEnrollmentExtremely Low Birth Weight InfantFibrosisFutureGene ExpressionGene Expression ProfilingGeneric DrugsGenesGeneticGenomicsGoalsHealthHumanImpairmentIncidenceInflammationInterferon-alphaInterleukin-1 betaInterleukin-17InterventionLab-On-A-ChipsLungLyaseMeasuresModelingMorbidity - disease rateMulticenter Neonatal Research NetworkMusNational Institute of Child Health and Human DevelopmentObservational StudyOutcomeOxygenPathway interactionsPhosphorusPlasmaPredispositionPregnancyPremature InfantPrevention strategyPrimary PreventionProspective cohortProteinsProteobacteriaProteomicsPulmonary HypertensionRANTESResearchResistanceRespiration DisordersRiskRisk FactorsSeverity of illnessStructure of parenchyma of lungSurvivorsSystemTNF geneTarget PopulationsTranslational ResearchUrineValidationVascular remodelingadenosine deaminaseclinical riskcohortcytokinegenome wide association studygenome-widegenome-wide analysishigh risklung developmentmicrobialmicrobiomemodel developmentmouse modelnovelpostnatalprospectivepublic health relevanceresiliencerespiratoryresponseurinary
项目摘要
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.
描述(由申请方提供):支气管肺发育不良(BPD)是极低出生体重(ELBW)婴儿的常见疾病。我们的研究小组在BPD的转化研究方面具有相当的专业知识。我们拥有:(a)仅使用有限的临床信息开发模型,通过出生后年龄或呼吸系统疾病严重程度预测ELBW婴儿的BPD或死亡,(B)前瞻性评估BPD中的肺动脉高压,(c)使用多种临床变量和血液中的25种细胞因子在1067名ELBW婴儿的队列中鉴定与BPD/死亡相关的生物标志物。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的新蛋白质组生物标志物,并确定了BPD气道微生物组的改变。“STOP BPD”(BPD中最重要的组学特征的特征)的总体目标是前瞻性地定义和验证与BPD的恢复力或发展风险相关的临床和“组学”特征。为了实现这一目标,我们将建立在我们最近对基因组学,蛋白质组学,呼吸道微生物组学和BPD模型开发的研究基础上。我们将评估一个前瞻性队列,(NICHD新生儿研究网络的通用数据库或GDB队列),2015-2017年出生的300例妊娠<29周的早产儿(仅2013年n=213,入组率为80%以上),具体目标如下:具体目标1-使用基因组-在出生后72小时内收集的血液中的广泛表达分析和靶向SNP谱分析
在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使用在出生后第一周收集的气管抽吸物对BPD和严重BPD的恢复力评分具体目标4 -开发一种组合的“Omic”评分系统,该系统将基因组学,蛋白质组学,我们将在开发组群(n=150)中开发和确定各种模型的准确性,并在验证组群(n=150)中验证它们。这些新模型可用于定义未来干预措施的目标人群,评估特定干预措施的有效性,开发“芯片实验室”,并支持未来对BPD生物学的研究。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Maternal antibiotics augment hyperoxia-induced lung injury in neonatal mice.
母体抗生素会加重新生小鼠高氧诱导的肺损伤。
- DOI:10.1152/ajplung.00442.2019
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Lal,CharitharthVivek;Ambalavanan,Namasivayam
- 通讯作者:Ambalavanan,Namasivayam
Biomarkers for Adverse Lung Injury Following Pediatric Cardiopulmonary Bypass.
- DOI:10.1097/cce.0000000000000528
- 发表时间:2021-09
- 期刊:
- 影响因子:0
- 作者:Asfari A;Hock KM;Byrnes JW;Borasino S;Halloran BA;Mobley JA;Ambalavanan N
- 通讯作者:Ambalavanan N
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Namasivayam Ambalavanan其他文献
Namasivayam Ambalavanan的其他文献
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10576754 - 财政年份:2023
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UAB Clinical Site HEAL Neonatal Opioid Withdrawal Pharmacological Treatments
UAB 临床站点 HEAL 新生儿阿片类药物戒断药物治疗
- 批准号:
10891299 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
Post-Vent, the Sequelae: Personalized Prognostic Modeling for Consequences of Neonatal Intermittent Hypoxemia in Preterm Infants at Pre-School Age
排气后的后遗症:学龄前早产儿新生儿间歇性低氧血症后果的个性化预后模型
- 批准号:
10363406 - 财政年份:2021
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- 批准号:
10372486 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
Post-Vent, the Sequelae: Personalized Prognostic Modeling for Consequences of Neonatal Intermittent Hypoxemia in Preterm Infants at Pre-School Age
排气后的后遗症:学龄前早产儿新生儿间歇性低氧血症后果的个性化预后模型
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9899244 - 财政年份:2019
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