UCSF Clinical Research Center for Prematurity and Respiratory Outcomes Program

描述（由申请人提供）：早产和呼吸结局项目临床研究中心的这项提案重点关注导致婴儿慢性肺病发病机制和不良呼吸结局的选定生物过程。我们推测，在早产儿肺早期适应空气呼吸过程中，肺液中表面活性蛋白B含量低和炎性细胞因子水平升高反映了肺不成熟和损伤的程度，因此可作为长期预后的生物标志物。我们进一步假设，肺一氧化氮的产生和弹性蛋白的周转水平作为肺修复和生长的生物标志物。目标1的目的是招募一组早产儿，年龄≥ 28周，收集气管抽吸物和尿液样本，用于生物标志物测定以及与其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史的NICU地点招募并入组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标志物进行评估，包括1周时的机械通气需求和40周PMA时的氧气需求。我们提出了一个临床评分来量化肺功能在第一年，从问卷评估肺部症状，住院和药物治疗，并验证了低氧（海拔）挑战试验和肺功能测试。目标2的目的是确定预测1年时呼吸结局的选定候选生物标志物的水平。作为早期肺损伤的标志物，我们将从出生后3- 14天的插管早产儿亚组中收集气管吸出物样本，用于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物，我们将在肺部疾病的演变过程中利用无创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。我们希望生物标志物的发现，当结合临床参数，将高度预测的结果在1年，并将提供新的信息有关的婴儿肺部疾病的发病机制。co-PI在临床研究以及基础和转化研究方面经验丰富。(End摘要） 相关性：这项研究将为早产儿肺部疾病的病因和临床过程提供新的信息，这是一个重要的公共卫生问题。这些发现将为改善肺部疾病高危婴儿的长期预后提供新的预测因素和潜在的治疗方法。

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.