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Physiological Phenotyping of Respiratory Outcomes in Infants Born Premature

Physiological Phenotyping of Respiratory Outcomes in Infants Born Premature
早产儿呼吸结果的生理表型
批准号:
10383746
负责人:
Steven Herbert Abman
金额:
$74.85万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
未结题
起止时间:
2019-03-01 至 2025-03-01

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中文摘要
翻译
随着极低胎龄新生儿存活率的提高,支气管肺病的发生率较高 发育不良(BPD)和呼吸道疾病贯穿整个童年。早产导致身体受损 肺泡和血管生长与呼吸道疾病。NIH对BPD的标准定义,基于 在36周时需要氧气和呼吸支持,这是不准确的,提供了一个很差的替代品 治疗儿童时期持续的呼吸道问题。重要的是,早产儿即使没有BPD也是如此 确诊有持续性呼吸道疾病。此外,BPD不是一种同质性呼吸道疾病,但 代表一系列可能导致不同临床症状的呼吸道和实质异常。 NICU出院后的表型和晚期呼吸道疾病。然而,小气道的相对作用 功能障碍和远端肺血管疾病对早产后晚期呼吸结局的影响 未知。这个问题的重要性在最近的美国国立卫生研究院早产问题研讨会上得到了进一步的强调。 和肺部疾病,其结论是早产后呼吸道表型特征的改善 有必要更好地了解疾病的异质性和结果的可变性;准确地识别风险 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。我们已经证实了用力呼气流量(FEF)和肺弥散的减少。 BPD婴儿的容量(DLCO)与足月对照组比较;FEF和DLCO的下降不是很好 每个指标可能反映出对BPD病理生理学的不同贡献 以及晚期呼吸道疾病。因此,我们假设早产后婴儿的呼吸道疾病 由于呼吸道、实质和血管发育的不同损害而高度可变 以明显的生理表型为特征;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的增加密切相关;蛋白质组 生物标志物可以增强表型的生理特征和对晚期呼吸的预测 结果。
英文摘要
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.
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DOI: 10.1113/jp281848
发表时间: 2022-03
期刊: JOURNAL OF PHYSIOLOGY-LONDON
影响因子: 5.5
作者: [Duke, Joseph W., Lewandowski, Adam J., Abman, Steven H., Lovering, Andrew T.]
通讯作者: Lovering, Andrew T.
Multidisciplinary Research Training in Pediatric Pulmonary Vascular Disease
1/2 Kids MoD PAH Trial: Mono- vs. Duo-Therapy In Pediatric Pulmonary Arterial Hypertension
  • 批准号:
    10214935
  • 项目类别:
  • 资助金额:
    $95.26万
  • 财政年份:
    2021
  • 负责人:
    Steven Herbert Abman
  • 依托单位:
1/2 Kids MoD PAH Trial: Mono- vs. Duo-Therapy In Pediatric Pulmonary Arterial Hypertension
  • 批准号:
    10505262
  • 项目类别:
  • 资助金额:
    $129.89万
  • 财政年份:
    2021
  • 负责人:
    Steven Herbert Abman
  • 依托单位:
Colorado StARR Program in Medicine and Pediatrics (CSPMP)
  • 批准号:
    10671451
  • 项目类别:
  • 资助金额:
    $34.31万
  • 财政年份:
    2020
  • 负责人:
    Steven Herbert Abman
  • 依托单位:
海外基金