Proteomic Profile Associated with Chronic Lung Disease of Premature Infants

 描述(申请人提供)：早产婴儿有患上支气管肺发育不良的风险，定义为在月经后36周需要呼吸机支持，以及后来的呼吸系统疾病，包括哮喘。慢性肺部疾病仍然是早产儿发病率的主要原因，尽管目前采取了预防和重症监护支持的方法。该建议响应了RFA-HL-15-025和利用纵向队列来生成可定义慢性肺部疾病的临床、生理、生物学和/或基因组数据的要求(S)。我们将使用2个最近发现/验证的表型良好的极早产儿的队列，以及气管抽吸物、尿液和DNA的生物样品库来检查蛋白质组发现与肺结果的纵向测量的相关性。晚期表面活性物质试验(TOLSURF)研究是在25家美国医院进行的干预性试验，对511名婴儿进行了长达24个月的随访。早产和呼吸结果项目(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，早产儿肺衬里液体和/或尿液中反映发育阶段和对肺损伤的反应的特定蛋白质的改变与不良的肺结局有关。第一个目标是使用全球蛋白质组学方法和免疫分析方法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结局的生物标志物。第二个目标是识别和验证与第一年呼吸道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有疾病的婴儿相比，STATISTICA的能力有所增加。与36wk(早产)肺状况相比，出院后评估提供了更有临床意义的结果衡量标准。这些研究将首次提供表型良好的婴儿肺液和尿液的蛋白质组图谱，并识别婴儿持续性肺部疾病的生物标记物，有可能加强对机制的理解和开发预防策略。

 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.