Physiological Phenotyping of Respiratory Outcomes in Infants Born Premature

随着极低胎龄新生儿存活率的提高， 发育不良（BPD）和呼吸道疾病在整个儿童期持续存在。早产会导致 肺泡和血管生长以及气道疾病。BPD的标准NIH定义，基于 需要氧气和呼吸支持，在36周胎龄，是不准确的，并提供了一个穷人替代 在整个童年时期都有持续的呼吸系统问题。重要的是，早产儿即使没有BPD 诊断为持续性呼吸道疾病。此外，BPD不是单一的呼吸道疾病， 代表一系列气道和实质异常，可能导致不同的临床 表型和NICU出院后的晚期呼吸道发病率。然而，小气道的相对作用 功能障碍和远端肺和血管疾病对早产后晚期呼吸结局的影响仍然存在 未知这个问题的重要性在最近的NIH早产研讨会上得到了进一步的强调 和肺部疾病，该研究得出结论，早产后呼吸表型特征的改善 需要更好地了解疾病异质性和结果的变异性;准确识别风险 婴儿晚期疾病;改善特定的治疗目标;并加强早期临床试验设计 干预措施。我们以前已经证明了减少用力呼气流量（FEF）和肺扩散 与足月对照组相比，BPD婴儿的DLCO; FEF和DLCO的下降并不好 彼此相关;并且每种测量可能反映了对BPD病理生理学的不同贡献 和晚期呼吸道疾病因此，我们假设早产后的婴儿呼吸道疾病 由于气道、实质和血管发育的不同损害， 特征为不同的生理表型;这些特定损伤的性质和严重程度， 肺功能与婴儿期呼吸道疾病发病率的增加密切相关， 生物标志物可以增强表型的生理表征和晚期呼吸道疾病的预测， 成果。

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.