Physiological Phenotyping of Respiratory Outcomes in Infants Born Premature

早产儿呼吸结果的生理表型

基本信息

批准号：
10383746
负责人：
Steven Herbert Abman
金额：
$ 74.85万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2025-03-01
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10383746
关键词：
Adult Adult asthma Age Air Airway Disease Alveolar Area Asthma COPD Overlap Syndrome Biological Markers Blood Vessels Blood Volume Blood capillaries Bronchopulmonary Dysplasia Child Childhood Clinical Trials Design Data Development Diagnosis Diffusion Disease Disease Outcome Distal Early Intervention Echocardiography Educational workshop Environment Extremely low gestational age newborn Functional disorder Gases Gestational Age Growth Growth and Development function Impairment Incidence Infant Lung Lung diseases Measures Nature Outcome Oxygen Pattern Phenotype Physiological Premature Birth Premature Infant Proteomics Pulmonary Diffusing Capacity Pulmonary function tests Recovery Research Respiratory Disease Risk Role Secondary to Severities Signal Pathway Spirometry Structure of parenchyma of lung Surface Testing United States National Institutes of Health Vascular Diseases base clinical phenotype disease heterogeneity disorder subtype early childhood high risk improved improved functioning infancy injured airway innovation novel premature lungs pulmonary function pulmonary vascular disorder resilience respiratory respiratory morbidity specific biomarkers therapeutic target

项目摘要

With improved survival of extremely low gestational age newborns, a high incidence of bronchopulmonary dysplasia (BPD) and respiratory morbidities persist throughout childhood. Premature birth results in impaired lung alveolar and vascular growth and airways disease. The standard NIH definition of BPD, as based on the need for oxygen and respiratory support at 36 weeks gestational age, is imprecise and provides a poor surrogate for persistent respiratory problems throughout childhood. Importantly, premature infants even without the BPD diagnosis have persistent respiratory disease. Furthermore, BPD is not a homogenous respiratory disease, but represents a spectrum of airway and parenchymal abnormalities that likely contribute to different clinical phenotypes and to late respiratory morbidities after NICU discharge. However, the relative roles of small airways dysfunction and distal lung and vascular disease to late respiratory outcomes after preterm birth remain unknown. The importance of this problem has been further highlighted at recent NIH Workshops on prematurity and lung disease, which concluded that improved characterization of respiratory phenotypes after preterm birth is necessary to better understand disease heterogeneity and variability in outcomes; to accurately identify at risk infants for late disease; to improve specific therapeutic targets; and to enhance clinical trial design for early interventions. We have previously demonstrated reduced forced expiratory flows (FEF) and pulmonary diffusion capacity (DLCO) in BPD infants compared to full term controls; that decrements in FEF and DLCO are not well correlated with each other; and that each measure likely reflects different contributions to BPD pathophysiology and late respiratory morbidities. Therefore, we hypothesize that infant respiratory morbidities after preterm birth are highly variable due to differential impairment of airway, parenchymal and vascular development that can be characterized as distinct physiologic phenotypes; that the nature and severity of these specific impairments of lung function are strongly associated with increased respiratory morbidities during infancy; and that proteomic biomarkers can enhance the physiologic characterization of phenotype and prediction of late respiratory outcomes.

随着极低胎龄新生儿的生存率提高，支气管肺的发病率很高整个童年时期，发育不良（BPD）和呼吸病变持续存在。早产结果受损肺肺泡和血管生长和气道疾病。 BPD的标准NIH定义，基于 36周胎龄的氧气和呼吸支持的需求是不精确的，并且提供了较差的替代品对于整个儿童期持续的呼吸问题。重要的是，即使没有BPD，早产儿诊断患有持续的呼吸道疾病。此外，BPD不是同质呼吸道疾病，而是代表一系列气道和实质异常，可能导致不同的临床 NICU出院后的表型和晚期呼吸道病。但是，小气道的相对角色早产后，功能障碍，肺远端肺和血管疾病至晚期呼吸系统疾病未知。在最近的NIH早产研讨会上，该问题的重要性进一步强调了和肺部疾病，得出的结论是早产后改善了呼吸表型的表征对于更好地了解疾病异质性和结果的可变性是必要的；准确识别有风险晚期疾病的婴儿；改善特定的治疗靶标；并增强早期的临床试验设计干预措施。我们以前已经证明了强迫呼气流（FEF）和肺扩散减少与完整期限对照相比，BPD婴儿的容量（DLCO）； FEF和DLCO的下降不好彼此相关；并且每种措施可能反映了对BPD病理生理学的不同贡献和晚期呼吸道病。因此，我们假设早产后婴儿呼吸道病由于气道的差异，实质和血管发育的差异，可能是高度可变的被描述为不同的生理表型；这些特定损害的性质和严重性肺功能与婴儿期间呼吸道病的增加密切相关。和那个蛋白质组学生物标志物可以增强表型的生理表征和晚期呼吸道的预测结果。