UCSF Clinical Research Center for Prematurity and Respiratory Outcomes Program

描述（由申请人提供）：这是早产儿和呼吸系统预后项目临床研究中心的提案，重点研究导致婴儿慢性肺部疾病和不良呼吸系统预后的选定生物学过程。我们假设，在早产儿肺对空气呼吸的早期适应过程中，肺液中表面活性剂蛋白B含量低和炎症细胞因子水平升高反映了肺不成熟和损伤的程度，因此可以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。Aim 1的目的是招募一组早产儿^28周，收集气管抽吸和尿液样本，用于生物标志物的测定以及与临床过程和呼吸结果相关的数据。我们将在三个有成功合作历史的新生儿重症监护病房招募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1周机械通气需求和40周PMA氧气需求。我们提出了一个临床评分来量化第一年的肺功能，该评分来自评估肺部症状、住院和药物的问卷调查，并通过缺氧（高原）刺激试验和肺功能测试进行验证。Aim 2的目的是确定预测1年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天插管的早产儿亚群中收集气管吸入样本，以评估表面活性剂和炎症生物标志物。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。我们期望生物标志物的发现与临床参数相结合，将高度预测1岁时的预后，并将提供与婴儿肺部疾病发病机制相关的新信息。合作pi在临床研究以及基础和转化研究方面经验丰富。（摘要结束）

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.