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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.