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

• 批准号: 8996845
• 负责人: PHILIP L. BALLARD
• 金额: $ 19.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8996845
• 关键词: Age; Animal Model; Applications Grants; Aspirate substance; Asthma; Biochemical; Biological; Biological Assay; Biological Markers; Birth; Breathing; 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; Hospitals; Immunoassay; Infant; Infection; Injury; Intensive Care; Intervention; 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; Proteins; Proteomics; Resolution; Respiration Disorders; Risk; Risk Factors; Role; Sampling; Secondary to; Severities; Staging; Technology; Urine; Validation; Ventilator; Wheezing; cohort; follow-up; high risk; insight; interest; lung injury; lung repair; novel marker; postnatal; premature; prevent; primary outcome; programs; protein profiling; public health relevance; repository; respiratory; response; surfactant; urinary

 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，以及后来出现包括哮喘在内的呼吸系统疾病的风险。尽管目前采取了预防和重症监护支持的方法，但慢性肺病仍然是早产儿发病的主要原因。该提案响应 RFA-HL-15-025 以及利用纵向队列生成可定义慢性肺病的临床、生理、生物和/或基因组数据的请求。我们将使用两个最近发现/验证的表型良好的极早产儿队列，以及气管抽吸物、尿液和 DNA 的生物样本库，来检查蛋白质组学结果与肺部结果纵向测量的关联。 Trial Of Late SURFactant (TOLSURF) 研究是一项在美国 25 家医院进行的干预性试验，对 511 名婴儿进行了为期 24 个月的随访。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，早产儿肺衬液和/或尿液中特定蛋白质含量的变化（反映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新生儿肺液中的蛋白质，这些蛋白质是不良肺部结果的生物标志物。第二个目标是识别和验证与第一年呼吸道疾病发病率相关的尿蛋白。通过使用极端表型方法（第一年没有肺部疾病的婴儿与每个季度患有肺部疾病的婴儿）来提高统计能力。与 36 周（早产）肺部状况相比，出院后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婴儿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。