Airway microbiome and age 6y asthma phenotypes in 2 diverse multicenter cohorts

2 个不同多中心队列中的气道微生物组和 6 岁哮喘表型

基本信息

批准号：
10012789
负责人：
CARLOS A. CAMARGO
金额：
$ 136.85万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-21 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10012789
关键词：
16S ribosomal RNA sequencing 3 year old 5 year old 6 year old 9 year old Affect African American Age Area Asthma Boston Bronchiolitis CCL7 gene Child Childhood Asthma Cohort Studies Collaborations Complex Data Data Set Development Diagnosis Diet Disease Early identification Enrollment Environment Environmental Exposure Epigenetic Process European Extrinsic asthma Flavin Mononucleotide Funding Future Genetic Genetic Predisposition to Disease Heterogeneity Hispanics Hospitalization Human Microbiome Immune response Infant Intervention Interview Knowledge Literature Longterm Follow-up Mediating Medical Records Metabolic Metagenomics Methods Moraxella Nitric Oxide Pathway Nose Outcome Parents Pathogenesis Pattern Persons Phenotype Positioning Attribute Prevention strategy Primary Prevention Procedures Prospective cohort study Recurrence Reporting Research Research Personnel Riboflavin Ribosomal RNA Risk Risk Factors Role Sampling Shotguns Site Swab Techniques Testing United States National Institutes of Health Viral Respiratory Tract Infection Wheezing Whole-Genome Shotgun Sequencing asthma prevention cohort demographics early childhood ethnic diversity evidence base follow-up high risk high risk population hypopharynx indexing infancy innovation microbiome microbiome research modifiable risk prevent psychosocial rRNA Genes racial and ethnic respiratory microbiome whole genome

项目摘要

PROJECT SUMMARY / ABSTRACT Bronchiolitis is the #1 cause of hospitalization in US infants, with ~130,000 hospitalizations annually. Small cohort studies (n<210) suggest that 40-50% of infants hospitalized with bronchiolitis will later develop asthma. The greatest challenges for developing primary prevention strategies for this large group of children (indeed, all children) are the very early identification of modifiable risk factors and the heterogeneity of asthma. The 35th Multicenter Airway Research Collaboration (MARC-35) study (U01AI-087881; Camargo, PI) is a 17-center prospective cohort study that completed enrollment of 921 hospitalized infants with bronchiolitis in 2014. In this diverse cohort (53% African-American or Hispanic), investigators have collected biospecimens, including nasal swabs at the index hospitalization (median age 3 months) and at an age 3y exam (R01AI-114552; Camargo, PI). Follow-up data include biannual parent interviews and medical records to age 5 years, with ~90% follow-up to date. This UG3/UH3 application would: 1) extend the largest severe bronchiolitis cohort in the world (e.g., through an age 6y in-person exam to diagnose and phenotype asthma), and 2) build on our local MARC-43 cohort of 120 healthy infants by adding 600 healthy infants from four diverse sites (total n=720). Both cohorts undergo similar procedures (e.g., serial nasal swabs during early childhood). Our overarching hypothesis is that airway Moraxella abundance is associated with increased risk of childhood asthma, and our pilot data are supportive. In Aim 1, we will investigate the relation of the airway microbiome in early infancy to risk of age 6y asthma among infants with severe bronchiolitis (MARC-35). In Aim 2, we will do the same but among healthy infants (MARC-43). In Aim 3, we will investigate the relation of longitudinal patterns of the airway microbiome (e.g., infancy, age 3y, age 6y) to risk of childhood asthma in the two cohorts combined. In a subset of 200 children (100 from each cohort), we will use whole genome shotgun (WGS) sequencing to examine the relations of bacterial species and metabolic potential in early infancy to risk of asthma. For all 3 Aims, we will examine if associations differ by asthma phenotype (e.g., allergic asthma). The investigators are NIH-funded researchers working in an outstanding research environment. The proposed project is innovative and, by providing a strong evidence base for the future development of targeted microbiome interventions, advances research on the primary prevention of asthma. Moreover, the two racially/ethnically-diverse cohorts will provide the ECHO Consortium with comprehensive data on demographics, development, environmental exposures, genetics, and outcomes from two already-harmonized, multicenter U.S. studies.

项目摘要 /摘要支气管炎是美国婴儿住院的第一号原因，约有13万每年。小型队列研究（N <210）表明40-50％的婴儿住院细支气管炎后来会出现哮喘。发展初选的最大挑战这大批儿童（实际上，所有儿童）的预防策略是很早的鉴定可修改的危险因素和哮喘的异质性。第35个多中心气道研究合作（MARC-35）研究（U01AI-087881; Camargo，pi）是17个中心前瞻性队列研究完成了921例住院婴儿的入学率在2014年。在这种多样的队列（53％的非裔美国人或西班牙裔）中，调查人员收集了生物测量，包括指数住院的鼻拭子（中位年龄3个月）和年龄3岁的考试（R01AI-114552; Camargo，pi）。后续数据包括双年度父母访谈和医疗记录至5岁，迄今为止的随访约为90％。这个UG3/UH3 应用将：1）扩展世界上最大的严重细支气管炎队列（例如，通过 6岁的面对面考试以诊断和表型哮喘）和2）建立在我们的本地MARC-43上通过从四个不同部位的600名健康婴儿（总数n = 720）增加了120名健康婴儿的队列。这两个队列都接受了类似的程序（例如，在童年时期，串行鼻拭子）。我们的总体假设是，气道摩拉氏菌的丰度与增加的风险有关童年哮喘和我们的飞行员数据具有支持。在AIM 1中，我们将调查婴儿早期的气道微生物组，患有严重的婴儿的哮喘风险支气管炎（MARC-35）。在AIM 2中，我们将在健康的婴儿中做同样的事情（MARC-43）。在AIM 3中，我们将研究气道微生物组纵向模式的关系（例如，婴儿期，3岁，6岁），在两个人群中伴有儿童哮喘的风险。在一个子集中 200名儿童（每个队列100个），我们将使用整个基因组shot弹枪（WGS）测序检查婴儿早期的细菌物种和代谢潜力的关系哮喘。对于所有三个目标，我们将检查关联是否因哮喘表型而有所不同（例如，过敏反应哮喘）。研究人员是NIH资助的研究人员，从事杰出研究环境。拟议的项目具有创新性，并通过为有针对性的微生物组干预措施的未来发展，对主要的研究进行了进步预防哮喘。此外，两个种族/种族多样性人群将提供 Echo联盟拥有有关人口统计，发展，环境的全面数据来自两项已有折磨的，多中心的美国研究的暴露，遗传学和结果。