Late Preterm Birth, Ureaplasma Species and Childhood Lung Disease

晚期早产、解脲支原体和儿童肺病

• 批准号: 8304364
• 负责人: ALAN H JOBE
• 金额: $ 47.54万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-24 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304364
• 关键词: Affect; Age; Age-Months; Alveolar Macrophages; Amniocentesis; Amniotic Fluid; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Asthma; Bacteria; Biology; Birth; Bronchoalveolar Lavage; Bronchopulmonary Dysplasia; CD80 gene; Caring; Cells; Child; Childhood; Chronic; Clinical; Clinical Research; Dendritic Cells; Disease; Drug usage; Elderly; Exposure to; Fetal Membranes; Fetus; Freezing; Gestational Age; Grant; Growth; HLA-DR Antigens; Health; Health Surveys; Histologic; Histopathology; Human; Human Pathology; Hydrogen Peroxide; Hygiene; IL8 gene; Immune; Immune response; Immune system; Immunologics; In Vitro; Infant; Infection; Infection of amniotic sac and membranes; Inflammation; Inflammatory; Inflammatory Response; Injection of therapeutic agent; Interleukin-6; Length; Link; Lung; Lung Inflammation; Lung diseases; Measurement; Measures; Mediastinal lymph node group; Modeling; Mononuclear; Mothers; Mycoplasma; Neonatal; Newborn Infant; Organism; Outcome; Outcome Assessment; Perinatal Exposure; Plasma; Population; Population Study; Pregnancy; Premature Birth; Premature Infant; Production; Pulmonary function tests; Questionnaires; Regulatory T-Lymphocyte; Reporting; Research; Research Personnel; Respiratory physiology; Risk; Risk Factors; Role; Severities; Sheep; Signaling Molecule; Structure; TLR2 gene; TLR3 gene; TLR4 gene; TNF gene; Testing; Time; Umbilical Cord Blood; Umbilical cord structure; Ureaplasma; Variant; Virulence; Virulence Factors; Virulent; base; chemokine; cigarette smoking; clinically relevant; cohort; comparison group; cytokine; early childhood; experience; fetal; human disease; immune function; immunoregulation; in vivo; innovation; insight; lung development; mRNA Expression; macrophage; maternal diabetes; methacholine; molecular phenotype; monocyte; postnatal; prenatal; research study; response; surfactant; treatment strategy

Fetal exposures are known to influence lung function in childhood and later life. Although about 7% of all births are categorized as late-preterm (births at 32o-366 wks gestation) and these infants are at increased risk for lung related problems in childhood, this population has been minimally studied for lung outcomes. Fetal exposure to chorioamnionitis (inflammation/infection) can adversely affect lung development and modulate fetal immune function. The most frequent organism associated with fetal inflammation/chronic chorioamnionitis in the human is Ureaplasma spp. We hypothesize that fetal exposure to Ureaplasma spp modulates immune responses and increases the risk of lung disease in early childhood in late-preterm infants. We will test this hypothesis with a clinical study and a parallel experimental study with U. parvum chorioamnionitis in fetal sheep. The clinical study will select cohorts of late preterm infants based on cultures for Ureaplasma spp, and histopathology for chorioamnionitis. Fetal inflammatory responses will be evaluated by cytokine/chemokine profiles in cord blood, molecular phenotypes and immune modulation by cord blood monocytes, and dendritic cells will characterize fetal immune status. The ureaplasma exposed and unexposed late-preterm infants will have lung health assessments at 9 mos and 2 yrs, and pulmonary function tests at 9 mos to evaluate lung outcomes. In parallel experiments we will characterize the inflammatory and immune modulatory responses of fetal sheep to the chorioamnionitis caused by intra-amniotic injection of U. parvum. We will explore the in vivo inflammatory/immune responses to multi-banded antigen (MBA) variability because MBA has been identified in vitro as the virulence factor for U. parvum. We will characterize how gestational age and interval from exposure to delivery modulate the fetal immune and inflammatory responses to U. parvum. We will allow U. parvum exposed fetuses to deliver and measure immune status lung function and structure at 2 wks and 2 mos of age. The experiments are innovative be cause we will focus on late-preterm infants, a large understudied population, to define immune status at birth. We will correlate of fetal ureaplasma exposure and chorioamnionitis with pulmonary outcomes and with immunologic measurements. We will use a clinically relevant model of chorioamnionitis in sheep to evaluate aspects of immune modulation that are not possible in humans. The results will link for the first time a specific and common fetal inflammatory exposure with lung outcomes. The research will be performed by a team of experienced investigators with expertise for each component of the project: the biology of Ureaplasma spp, immune and inflammatory responses in the newborn human and fetal sheep, animal models of chorioamnionitis, and pulmonary assessments of children.

众所周知，胎儿暴露会影响儿童时期和以后的生活中的肺功能。尽管约有7%的 所有出生的婴儿都被归类为晚早产(孕32-366周出生)，这些婴儿的出生时间都在增加。 尽管儿童时期存在肺相关问题的风险，但对这一人群的肺部结局进行了最低限度的研究。 胎儿暴露于绒毛膜羊膜炎(炎症/感染)可对肺发育和 调节胎儿免疫功能。与胎儿炎症/慢性相关的最常见的生物体 人类绒毛膜羊膜炎是一种解脲支原体。我们假设胎儿接触解脲支原体 调节免疫反应，增加早产儿晚期肺部疾病的风险 婴儿。我们将通过一项临床研究和一项与微小U菌平行的实验研究来验证这一假说。 胎羊绒毛膜羊膜炎。这项临床研究将根据培养结果选择晚期早产儿的队列 解脲支原体和绒毛膜羊膜炎的组织病理学检查。将对胎儿炎症反应进行评估 脐血细胞因子/趋化因子谱、分子表型与脐血免疫调节 单核细胞和树突状细胞将表征胎儿的免疫状态。解脲支原体暴露与未暴露 晚期早产儿将在9个月和2岁时进行肺健康评估，并在9岁时进行肺功能测试。 MOS来评估肺结果。在平行实验中，我们将描述炎症和免疫的特征 胎羊对羊膜腔内注射解脲支原体所致绒毛膜羊膜炎的调节反应。 我们将探索体内对多带抗原(MBA)变异性的炎症/免疫反应，因为 MBA在体外已被确定为微小U形体的毒力因子。我们将描述如何孕育 年龄和从接触到分娩的间隔时间调节胎儿对U的免疫和炎症反应。 小儿麻痹症。我们将允许接触解脲支原体的胎儿分娩并测量免疫状态、肺功能和 结构在2周和2个月的年龄。这些实验是创新的，因为我们将专注于早产晚期 婴儿是一个研究不足的大群体，用来定义出生时的免疫状态。我们将与胎儿解脲支原体进行关联 暴露和绒毛膜羊膜炎与肺部结局和免疫学测量。我们将使用 临床相关的绵羊绒毛膜羊膜炎模型评估免疫调节方面的不同 在人类身上是可能的。这一结果将首次将特定和常见的胎儿炎症暴露联系在一起 与肺部结果有关。研究将由一组经验丰富的调查人员进行，他们具有以下专业知识 该项目的每个组成部分：解脲支原体的生物学，免疫和炎症反应 新生的人和胎羊，绒毛膜羊膜炎的动物模型，以及儿童的肺部评估。

项目成果

Placental Infection With Ureaplasma species Is Associated With Histologic Chorioamnionitis and Adverse Outcomes in Moderately Preterm and Late-Preterm Infants.

• DOI: 10.1093/infdis/jiv587
• 发表时间: 2016-04
• 期刊: The Journal of infectious diseases
• 作者: E. Sweeney;S. Kallapur;Tate Gisslen;D. Lambers;C. Chougnet;Sally A Stephenson;A. Jobe;C. Knox

Controversy: antenatal steroids.

争议：产前类固醇。

• DOI: 10.1016/j.clp.2011.06.013
• 发表时间: 2011
• 期刊: Clinics in perinatology
• 影响因子: 2.1
• 作者: Wapner,Ronald;Jobe,AlanH
• 通讯作者: Jobe,AlanH