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（由适用提供）：过早出生的婴儿有支气管肺发育不良的风险，该疾病定义为在36 WK后月经后的通风支持，以及以后的呼吸系统疾病，包括哮喘。慢性肺部疾病仍然是早产婴儿目的地目前的预防和重症监护支持的主要原因。该提案对RFA-HL-15-025的响应以及利用纵向人群的要求产生临床，生理，生物学和/或基因组数据，以定义慢性肺病。我们将使用2个最新的发现/验证人群，这些良好表型，非常过早的婴儿与气管抽吸物，尿液和DNA的生物循环库，以检查蛋白质组学发现的关联，并与肺部结果的纵向测量。表面活性剂（Tolsurf）研究的试验是在25家美国医院进行的介入试验，随访了511名婴儿，直到24个月。早产和呼吸结果项目（Prop）在13个中心招募了835名早产婴儿，以研究有助于持续呼吸系统疾病风险的分子机制。该项目的总体假设是，肺部内膜液中的特定蛋白质和/或尿液的过早婴儿的含量改变，反映出发育阶段和对肺损伤的反应都与肺部不良结局有关。第一个目的使用全球蛋白质组学方法加上免疫测定方法来识别和验证新生儿肺液中的蛋白质，这是肺部不良肺预后的生物标志物。第二个目标将识别和验证与第一年呼吸道发病率相关的尿蛋白。使用极端表型方法增加了统计的功率 - 第一年与没有肺部疾病的婴儿相比，每个季度患有疾病的婴儿。与36周（早产）肺状况相比，入院后评估提供了更有意义的临床意义。这项研究将在良好的婴儿中提供肺液和尿液的第一个蛋白质组学特征，并确定婴儿持续性肺部疾病的生物标志物，并有可能增强对机制的理解并制定预防策略。