UCSF Clinical Research Center for Prematurity and Respiratory Outcomes Program

描述(由申请人提供)：在早产儿和呼吸结局计划中设立临床研究中心的建议侧重于特定的生物学过程，这些过程有助于婴儿慢性肺部疾病和不良呼吸结局的发病机制。我们推测，在早产儿肺对空气呼吸的早期适应过程中，肺液中低含量的表面活性蛋白B和升高的炎性细胞因子水平反映了肺不成熟和损伤的程度，因此可作为预测长期结果的生物标志物。我们进一步假设，肺一氧化氮的产生水平和弹性蛋白的周转可作为肺修复和生长的生物标志物。目标1的目标是登记一组28周的早产儿，收集气管吸气和尿液样本，用于生物标志物的分析，以及与他们的临床病程和呼吸结局相关的数据。我们将在三个有成功合作历史的NICU地点招募和招募160名早产儿。新生儿肺部疾病的严重程度将通过早期和晚期临床指标进行评估，包括在1wk时需要机械通气，在40wk PMA时需要氧气。我们提出了一个临床评分来量化第一年的肺功能，该评分由评估肺部症状、住院和药物治疗的问卷产生，并通过低氧(海拔)挑战测试和肺功能测试进行验证。目标2的目的是确定预测一年后呼吸结果的选定候选生物标志物的水平。作为早期肺损伤的标志物，我们将收集出生后3-14天内插管早产儿的气管吸液样本，以评估表面活性物质和炎症生物标志物。作为肺生长和修复的标志，我们将利用肺部疾病演变过程中的非侵入性尿液收集来评估一氧化氮/环GMP的产生和肺弹性蛋白的周转。我们期望生物标记物的发现，当结合临床参数时，将高度预测一年后的结果，并将提供与婴儿肺部疾病发病机制相关的新信息。联合PIs在临床研究以及基础和翻译研究中具有丰富的经验。(摘要结束) 相关性：这项研究将提供有关早产儿肺部疾病的原因和临床病程的新信息，这是一个重要的公共卫生问题。这些发现将提出新的预测因素和潜在的治疗方法，以改善肺部疾病高危婴儿的长期结果。

DESCRIPTION (provided by applicant): This proposal for a Clinical Research Center in the Prematurity and Respiratory Outcome Program focuses on selected biological processes that contribute to the pathogenesis of infant chronic lung disease and adverse respiratory outcome. We hypothesize that during early adaptation of the premature lung to air breathing, low content of surfactant protein B and increased levels of inflammatory cytokines in lung fluid reflect the extent of lung immaturity and injury and as such serve as biomarkers for long-term outcome. We further hypothesize that levels of lung nitric oxide production and turnover of elastin serve as biomarkers of lung repair and growth. The objective of Aim 1 is to enroll a cohort of premature infants ^28 wk and collect tracheal aspirate and urine samples for assay of biomarkers as well as data related to their clinical course and respiratory outcome. We will recruit and enroll 160 premature infants at three NICU sites with a history of successful collaboration. Severity of newborn lung disease will be assessed by early and late clinical markers, including requirement for mechanical ventilation at 1 wk and oxygen requirement at 40 wk PMA. We propose a clinical score to quantify lung function during the first year, generated from questionnaires assessing pulmonary symptoms, hospitalizations and medications, and validated by a hypoxic (altitude) challenge test and pulmonary function testing. The objective of Aim 2 is to determine levels of selected candidate biomarkers that are predictive of respiratory outcome at 1 yr. As markers of early lung injury, we will collect tracheal aspirate samples from the subset of intubated premature infants between postnatal d 3- 14 for assessment of surfactant and inflammatory biomarkers. As markers of lung growth and repair, we will utilize noninvasive collections of urine during the evolution of lung disease to evaluate production of nitric oxide/cyclic GMP and turnover of pulmonary elastin. We expect that the biomarker findings, when combined with clinical parameters, will be highly predictive of outcome at 1 y and will provide new information related to the pathogenesis of infant lung disease. The co-PIs are experienced in clinical studies as well as basic and translational research. (End of Abstract) RELEVANCE: This study will provide new information on causes and clinical course of lung disease in premature infants, which is an important public health concern. The findings will suggest new predictors and potential therapies to improve long-term outcome for infants at high risk of lung disease.