Proteomic Profile Associated with Chronic Lung Disease of Premature Infants

与早产儿慢性肺病相关的蛋白质组学特征

基本信息

批准号：
9144847
负责人：
PHILIP L. BALLARD
金额：
$ 23.78万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9144847
关键词：
Age Animal Model Applications Grants Aspirate substance Asthma Biochemical Biological Biological Assay Biological Markers Birth Bronchopulmonary Dysplasia Cell model Child Childhood Childhood Asthma Chronic lung disease Clinical Clinical Data Collection DNA Data Databases Development Diagnosis Disease Disease susceptibility Enrollment Genetic Predisposition to Disease Genomics Gestational Age Growth Health Hospitals Immunoassay Infant Infection Injury Intensive Care Intervention Trial Link Liquid substance Lung Lung diseases Measures Mechanical ventilation Molecular Morbidity - disease rate Neonatal Outcome Outcome Measure Oxygen Pathogenesis Pathway interactions Phase Phenotype Physiological Predisposition Premature Infant Prevention Prevention strategy Preventive Intervention Proteins Proteomics Resolution Respiration Disorders Risk Risk Factors Role Sampling Secondary to Severities Staging Technology Urine Validation Ventilator Wheezing candidate marker cohort follow-up genomic data high risk insight interest lung injury lung repair novel marker postnatal premature prevent primary outcome programs protein biomarkers protein profiling repository respiratory response surfactant urinary

项目摘要

DESCRIPTION (provided by applicant): Infants born prematurely are at risk for bronchopulmonary dysplasia, which is defined as a requirement for ventilatory support at 36 wk post-menstrual age, and for later respiratory disorders including asthma. Chronic lung disease remains the major cause of morbidity among premature infants despite current approaches to both prevention and intensive care support. This proposal responds to RFA-HL-15-025 and the request to leverage longitudinal cohorts to generate clinical, physiologic, biological, and/or genomic data that can define chronic lung disease(s). We will use 2 recent discovery/validation cohorts of well- phenotyped, extremely premature infants with biospecimen repositories of tracheal aspirate, urine and DNA to examine associations of proteomic findings with longitudinal measures of pulmonary outcome. The Trial Of Late SURFactant (TOLSURF) study was an interventional trial conducted in 25 US hospitals with follow- up of 511 infants through 24 months. The Prematurity and Respiratory Outcomes Project (PROP) enrolled 835 premature infants at 13 centers to investigate molecular mechanisms that contribute to risk for continuing respiratory disease. The overall hypothesis of this project is that altered amounts of specific proteins in lung lining fluid and/or urine of premature infants, reflecting both the developmental stage and response to lung injury, are associated with adverse pulmonary outcome. The first aim uses a global proteomic approach plus immunoassays to identify and validate proteins in neonatal lung fluid that are biomarkers for adverse pulmonary outcome. The second aim will Identify and validate urinary proteins associated with first-year respiratory morbidity. Statistica power is increased by the use of an extreme phenotype approach---infants with no lung disease in the first year versus those with disease in each quarter. The post-discharge assessment provides a more clinically meaningful outcome measure compared to 36 wk (preterm) pulmonary status. The studies will provide the first proteomic profile of lung fluid and urine in well-phenotyped infants and identify biomarkers for persistent lung disease of infants, with the potential to enhance understanding of mechanisms and to develop preventative strategies.

描述（由申请人提供）：早产婴儿有患支气管肺发育不良的风险，支气管肺发育不良的定义是在月经后 36 周需要通气支持，而后来出现的呼吸系统疾病（包括哮喘）仍然是其主要原因。尽管目前采取了预防和重症监护支持的方法，但早产儿的发病率仍然很高。该提案响应了 RFA-HL-15-025 和利用纵向队列来生成的要求。我们将使用 2 个最近发现/验证的良好、极早产儿队列以及气管抽吸物、尿液和 DNA 生物样本库来进行检查。蛋白质组学研究结果与肺部结果纵向测量的关联。晚期 SURFactant 试验 (TOLSURF) 研究是一项在美国 25 家医院进行的干预试验，对 511 名患者进行了随访。早产儿和呼吸系统结局项目 (PROP) 在 13 个中心招募了 835 名早产儿，以研究导致持续呼吸道疾病风险的分子机制。该项目的总体假设是肺内膜液中特定蛋白质的含量。早产儿和/或尿液反映了发育阶段和对肺损伤的反应，与不良肺部结果相关。第一个目标是使用整体蛋白质组学方法加上免疫测定来识别和验证中的蛋白质。第二个目标是识别和验证与第一年呼吸系统发病率相关的尿蛋白，通过使用极端表型方法（婴儿中没有肺部疾病）来提高统计能力。与每季度患病的患者相比，出院后的评估提供了更具临床意义的结果测量，这些研究将提供表型良好的肺液和尿液的第一个蛋白质组学特征。婴儿并确定婴儿持续性肺病的生物标志物，有可能增强对机制的理解并制定预防策略。