Late Preterm Birth, Ureaplasma Species and Childhood Lung Disease

晚期早产、解脲支原体和儿童肺病

基本信息

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
项目类别：
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

项目摘要

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.

已知胎儿暴露会影响童年和以后生活的肺功能。虽然大约有7％所有出生均被归类为晚期（32o-366 wks妊娠的出生），这些婴儿正在增加童年时期与肺部相关问题的风险，该人群的肺部结局最少。胎儿暴露于绒毛膜炎（炎症/感染）可能会对肺发育产生不利影响和调节胎儿免疫功能。与胎儿炎症/慢性相关的最常见生物人类的绒毛膜炎是尿素质量属。我们假设胎儿暴露于尿素倍率spp 调节免疫反应并增加幼儿期肺病的风险婴儿。我们将通过临床研究和与U. Parvum进行平行的实验研究检验这一假设胎儿绵羊的绒毛膜炎。临床研究将根据培养选择晚期早产儿的人群用于尿素质量SPP和用于绒毛膜炎的组织病理学。将评估胎儿炎症反应通过脐带血的细胞因子/趋化因子谱，分子表型和脐带血的免疫调节单核细胞和树突状细胞将表征胎儿免疫状态。暴露和未暴露的尿素成倍率晚期婴儿将在9个MO和2年进行肺部健康评估，而肺功能检查为9 MOS评估肺癌的结果。在并行实验中，我们将表征炎症和免疫胎羊对肌膜炎的调节反应是由U. parvum注射肿瘤内引起的。我们将探索对多带抗原（MBA）变异性的体内炎症/免疫反应，因为 MBA在体外已被鉴定为U. Parvum的毒力因子。我们将表征妊娠的方式接触到分娩的年龄和间隔可调节胎儿免疫和对美国的炎症反应 parvum。我们将允许U. Parvum暴露的胎儿传递和衡量免疫状态肺功能和在2周和2 mos年龄的结构。实验是创新的，因为我们将重点放在晚期上婴儿，一个大量的人群，以定义出生时的免疫状态。我们将相关暴露和绒毛膜炎，肺部结局和免疫学测量。我们将使用一个绵羊中绒毛膜膜炎的临床相关模型，以评估不是免疫调节的各个方面在人类中可能。结果将首次链接与肺部结局。这项研究将由一支经验丰富的调查员团队进行专业知识项目的每个组成部分：尿素质量属，免疫和炎症反应的生物学新生的人类和胎儿绵羊，绒毛膜炎的动物模型以及儿童的肺部评估。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
作者：
E. Sweeney;S. Kallapur;Tate Gisslen;D. Lambers;C. Chougnet;Sally A Stephenson;A. Jobe;C. Knox
通讯作者：
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。