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.

众所周知，胎儿接触该物质会影响儿童期和以后生活中的肺功能。虽然大约有7% 所有出生均被归类为晚期早产（妊娠 32 至 366 周的出生），这些婴儿的出生率增加由于儿童时期出现肺部相关问题的风险，该人群的肺部结果研究很少。胎儿接触绒毛膜羊膜炎（炎症/感染）会对肺部发育产生不利影响调节胎儿免疫功能。与胎儿炎症/慢性相关的最常见的微生物人类绒毛膜羊膜炎是解脲支原体属。我们假设胎儿接触解脲支原体调节免疫反应并增加早产儿早期患肺部疾病的风险婴儿。我们将通过临床研究和小 U. parvum 的平行实验研究来检验这一假设胎羊绒毛膜羊膜炎。该临床研究将根据培养物选择晚期早产儿队列解脲支原体属，以及绒毛膜羊膜炎的组织病理学。将评估胎儿炎症反应通过脐带血中的细胞因子/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的免疫状态。解脲支原体暴露和未暴露晚期早产儿将在 9 个月和 2 岁时进行肺部健康评估，并在 9 岁时进行肺功能检查 mos 评估肺部结果。在平行实验中，我们将表征炎症和免疫胎羊对羊膜内注射小 U. parvum 引起的绒毛膜羊膜炎的调节反应。我们将探讨多带抗原 (MBA) 变异性的体内炎症/免疫反应，因为 MBA 已在体外被鉴定为 U. parvum 的毒力因子。我们将描述妊娠如何年龄和从接触到分娩的时间间隔调节胎儿对U.的免疫和炎症反应。微小的。我们将允许暴露于微小 U. parvum 的胎儿输送和测量免疫状态、肺功能和 2周和2个月龄时的结构。这些实验具有创新性，因为我们将重点关注晚期早产儿婴儿是一个未被研究的大群体，以确定出生时的免疫状态。我们将胎儿解脲支原体关联起来暴露和绒毛膜羊膜炎与肺部结果和免疫学测量。我们将使用一个绵羊绒毛膜羊膜炎的临床相关模型，用于评估免疫调节方面未涉及的方面在人类中是可能的。研究结果将首次将特定和常见的胎儿炎症暴露联系起来与肺部结果。该研究将由经验丰富的研究人员团队进行，他们具有以下方面的专业知识：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儿和胎羊、绒毛膜羊膜炎动物模型以及儿童肺部评估。

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.

胎盘解脲支原体感染与组织学绒毛膜羊膜炎和中度早产儿和晚期早产儿的不良后果相关。

DOI：
发表时间：
2016-04-15
期刊：
影响因子：
0
作者：
Sweeney, Emma L;Kallapur, Suhas G;Gisslen, Tate;Lambers, Donna S;Chougnet, Claire A;Stephenson, Sally;Jobe, Alan H;Knox, Christine L
通讯作者：
Knox, Christine L

Controversy: antenatal steroids.

争议：产前类固醇。