UCSF Clinical Research Center for Prematurity and Respiratory Outcomes Program

加州大学旧金山分校早产和呼吸结果临床研究中心项目

• 批准号: 8464208
• 负责人: PHILIP L. BALLARD
• 金额: $ 45.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464208
• 关键词: Age; Air; Altitude; Aspirate substance; Basic Science; Biological Assay; Biological Markers; Biological Process; Breathing; Bronchopulmonary Dysplasia; Case Report Form; Clinical; Clinical Data; Clinical Markers; Clinical Research; Collaborations; Collection; Cyclic GMP; Data; Data Analyses; Elastin; Enrollment; Evolution; Growth; Hospitalization; Hypoxia; Infant; Inflammatory; Injury; Liquid substance; Lung; Lung Inflammation; Lung diseases; Measures; Mechanical ventilation; Monitor; Morbidity - disease rate; Neonatal; Newborn Infant; Nitric Oxide; Outcome; Oxygen; Pathogenesis; Pharmaceutical Preparations; Premature Infant; Principal Investigator; Production; Public Health; Pulmonary Surfactant-Associated Protein B; Pulmonary function tests; Questionnaires; Recording of previous events; Recruitment Activity; Respiratory physiology; Risk; Sampling; Severities; Site; Symptoms; Testing; Translational Research; Urine; abstracting; adverse outcome; cohort; cytokine; experience; high risk; improved; infant outcome; lung injury; lung repair; postnatal; premature; premature lungs; programs; repaired; respiratory; surfactant

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.

描述（由申请人提供）：对早产和呼吸结果计划中临床研究中心的这一建议着重于选择的生物学过程，这些过程有助于婴儿慢性肺部疾病和不良呼吸症状的发病机理。我们假设在早产肺对空气呼吸的早期适应期间，表面活性剂蛋白B的含量低以及肺液中炎性细胞因子的水平增加反映了肺部不成熟和损伤的程度，因此可以作为长期结局的生物标志物。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率是肺修复和生长的生物标志物。目标1的目的是注册一组早产婴儿 ^28周，并收集气管抽吸和尿液样品，以分析生物标志物，以及与其临床过程和呼吸系统结果有关的数据。我们将在三个具有成功合作历史的NICU网站上招募和注册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记来评估，包括在1 WK时进行机械通气的要求，以及在40周PMA的氧气需求。我们提出了一个临床评分，以量化第一年的肺功能，这是由评估肺症状，住院和药物的问卷产生的，并通过低氧（高度）挑战测试和肺功能测试进行了验证。 AIM 2的目的是确定可预测1年呼吸系统呼吸系统的选定候选生物标志物的水平。作为早期肺损伤的标志，我们将从插后插后d- 3-14之间的插管过早婴儿子集收集气管抽吸样品，以评估表面活性剂和炎症生物标志物。作为肺部生长和修复的标志物，我们将利用肺部疾病进化过程中尿液的无创收集来评估一氧化氮/环状GMP的产生和肺弹性蛋白的周转。我们预计，生物标志物的发现与临床参数结合使用，将在1 y时高度预测结果，并将提供与婴儿肺部疾病发病机理有关的新信息。 Co-Pis在临床研究以及基础和转化研究中都有经验。 （抽象的结尾） 相关性：这项研究将提供有关早产儿的肺部疾病原因和临床过程的新信息，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子和潜在疗法，以改善肺部疾病高风险的婴儿的长期预后。