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

• 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
• 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

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.

项目概要/摘要 细支气管炎是美国婴儿住院的第一大原因，约有 130,000 名婴儿住院 每年。小队列研究 (n<210) 表明 40-50% 的婴儿因以下原因住院 细支气管炎随后会发展为哮喘。发展初级教育面临的最大挑战 针对这一大群儿童（实际上是所有儿童）的预防策略是非常早期的 识别可改变的危险因素和哮喘的异质性。第35届多中心 气道研究合作 (MARC-35) 研究 (U01AI-087881；Camargo, PI) 是一项 17 个中心 前瞻性队列研究完成了 921 名患有细支气管炎的住院婴儿的入组 2014 年。在这个多元化的队列中（53% 是非裔美国人或西班牙裔），研究人员收集了 生物样本，包括首次住院时（中位年龄 3 个月）和 3 岁考试（R01AI-114552；Camargo，PI）。后续数据包括每两年一次的家长 访谈和医疗记录直至 5 岁，迄今为止约有 90% 的随访。这个UG3/UH3 应用程序将： 1）扩大世界上最大的严重细支气管炎队列（例如，通过 6 岁亲自检查以诊断哮喘并确定表型），以及 2）以我们当地的 MARC-43 为基础 120 名健康婴儿的队列添加了来自四个不同地点的 600 名健康婴儿（总数 n=720）。 两个队列都经历类似的程序（例如，在幼儿期进行连续鼻拭子检查）。我们的 总体假设是气道莫拉氏菌丰度与感染风险增加相关 儿童哮喘，我们的试点数据是支持性的。在目标 1 中，我们将研究以下关系： 婴儿早期气道微生物群与患有严重哮喘的婴儿 6 岁哮喘风险的关系 细支气管炎（MARC-35）。在目标 2 中，我们将在健康婴儿中做同样的事情 (MARC-43)。 在目标 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）与两组儿童哮喘风险的总和。在一个子集中 200 名儿童（每个队列 100 名），我们将使用全基因组鸟枪法 (WGS) 测序来 检查婴儿早期细菌种类和代谢潜力与风险的关系 哮喘。对于所有 3 个目标，我们将检查关联是否因哮喘表型而异（例如，过敏 哮喘）。研究人员是 NIH 资助的研究人员，从事一项杰出的研究 环境。拟议的项目具有创新性，并且通过提供强有力的证据基础 有针对性的微生物组干预措施的未来发展，推进了初级研究 预防哮喘。此外，这两个种族/民族多样化的群体将提供 ECHO 联盟拥有人口统计、发展、环境方面的综合数据 两项已经协调一致的美国多中心研究的暴露、遗传学和结果。