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）：这项关于早产儿和呼吸结果计划临床研究中心的提案重点关注导致婴儿慢性肺病和不良呼吸结果发病机制的选定生物过程。我们假设，在早产肺对空气呼吸的早期适应过程中，肺液中表面活性蛋白 B 的低含量和炎症细胞因子水平的增加反映了肺不成熟和损伤的程度，因此可以作为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水平可作为肺修复和生长的生物标志物。目标 1 的目标是招募一组 ^28 周的早产儿，并收集气管抽吸物和尿液样本，用于分析生物标志物以及与其临床病程和呼吸结果相关的数据。我们将在三个有着成功合作历史的新生儿重症监护室 (NICU) 地点招募和登记 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 周机械通气的需求和 40 周 PMA 的氧气需求。我们提出了一个临床评分来量化第一年的肺功能，该评分是根据评估肺部症状、住院和药物的调查问卷生成的，并通过低氧（海拔）挑战测试和肺功能测试进行验证。目标 2 的目标是确定可预测 1 年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，我们将在出生后 3-14 天内从插管早产儿子集中收集气管抽吸物样本，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演变过程中的无创尿液收集来评估一氧化氮/环鸟苷酸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相结合，将高度预测 1 年的结果，并将提供与婴儿肺病发病机制相关的新信息。联合首席研究员在临床研究以及基础和转化研究方面拥有丰富的经验。 （摘要完） 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，以改善肺病高风险婴儿的长期结果。