Airway metagenome & metabolome in bronchiolitis and risk of asthma: MARC-35 cohort

气道宏基因组

• 批准号: 10305664
• 负责人: Kohei Hasegawa
• 金额: $ 70.95万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10305664
• 关键词: 6 year old; Accounting; Activities of Daily Living; Acute; African American; Age; Asthma; Bronchiolitis; Child; Childhood; Childhood Asthma; Chronic; Clinical; Cohort Studies; Collaborations; Complex; DNA Methylation; Data; Development; Diagnosis; Enrollment; Funding; Future; Hemophilus; Hispanic; Hospitalization; IgE; Immune; Immune response; Immunity; Immunology; Infant; Intensive Care; International; Intervention; Interview; Investigation; Knowledge; Lead; Link; Lipids; Mediator of activation protein; Medical Records; Metabolic Pathway; Metagenomics; Methionine; Microbe; Modification; Molecular; Moraxella; National Institute of Allergy and Infectious Disease; Natural experiment; Outcome; Parents; Participant; Pathway interactions; Persons; Phenotype; Pilot Projects; Positioning Attribute; Prevention strategy; Primary Prevention; Prospective cohort; Prospective cohort study; Public Health; Recurrence; Research; Research Personnel; Respiratory Disease; Risk; Risk Factors; Role; Sampling; Serum; Severities; Severity of illness; Sphingolipids; Strategic Planning; Streptococcus; Systems Biology; Testing; United States National Institutes of Health; Viral Bronchiolitis; Virus; Wheezing; Work; acute bronchiolitis; asthma prevention; cohort; evidence base; follow-up; high risk; high risk population; improved; indexing; innovation; lung development; metabolome; metabolomics; metagenome; metagenomic sequencing; microbiome; microbiome composition; personalized medicine; premature; prevent; respiratory; respiratory microbiome; respiratory microbiota; small molecule; treatment strategy; virology

Project Summary/Abstract Bronchiolitis is the leading cause of hospitalization in US infants. However, the differences in acute severity are not explained by traditional risk factors. In addition, although infants hospitalized with bronchiolitis are at very high risk for incident asthma, the mechanisms linking these two conditions remain unclear. These major knowledge gaps have hindered efforts to develop bronchiolitis treatment strategies and to prevent asthma in this high-risk population. The 35th Multicenter Airway Research Collaboration (MARC-35) study (U01AI-87881; Camargo, PI) is an ongoing 17-center cohort study that completed enrollment of 1016 hospitalized infants with bronchiolitis in 2014. In this diverse cohort (54% African-American or Hispanic), investigators have collected high-quality biospecimens, including nasopharyngeal samples at the index hospitalization (median age, 3 months). Follow-up data include biannual parent interviews, medical record reviews, and in-person exam at age 6 years, with >90% follow-up to date. The current R01 project would extend this large well-characterized bronchiolitis cohort by defining nasopharyngeal airway metagenomic and metabolomic profiles in the setting of bronchiolitis, and by examining their relations to both acute (bronchiolitis severity) and chronic (incident asthma) outcomes in childhood. In Aim 1, we will determine the relations among the airway microbiome (metagenome) profiles, metabolome profiles, and acute bronchiolitis severity. In Aim 2, we will examine the relations among the airway microbiome and metabolomic profiles in infants with bronchiolitis, and the risk of developing asthma. Lastly, using a systems biology approach, Aim 3 will define bronchiolitis endotypes by integrating clinical, virus, molecular data (e.g., airway microbiome and metabolome), and determine their associations with the acute and chronic outcomes. Our pilot data demonstrate compelling support for our hypotheses. The current R01 project will provide a unique opportunity to define the pathobiology of bronchiolitis through examining the functional capacity of microbiome (metagenome) as well as the small molecules representing functional activity of both microbiome and host (metabolome). In addition, by investigating young infants with bronchiolitis – a natural experiment during a crucial period of lung development – we will also define the mechanisms linking bronchiolitis to incident asthma. The study will provide a strong evidence base for bronchiolitis treatment and asthma prevention strategies through the future development of targeted interventions (e.g., modulation of microbiome and metabolic pathways). The investigators are NIH-funded researchers with international expertise in the field. The study matches well with the 2013 NIAID Strategic Plan.

项目概要/摘要 细支气管炎是美国婴儿住院的主要原因。 此外，虽然婴儿的急性严重程度无法用传统的危险因素来解释。 因细支气管炎住院的事件发生哮喘的风险非常高，其机制与 这两个条件仍不清楚。这些主要的知识差距阻碍了努力。 制定细支气管炎治疗策略并预防这一高危人群的哮喘。 第 35 次多中心气道研究合作 (MARC-35) 研究（U01AI-87881；Camargo，PI） 是一项正在进行的 17 中心队列研究，完成了 1016 名住院婴儿的入组 2014 年发生细支气管炎。在这个多元化的队列中（54% 为非洲裔美国人或西班牙裔），研究人员 收集了高质量的生物样本，包括索引处的鼻咽样本 住院治疗（中位年龄，3 个月）。 病历审查和 6 岁时的现场检查，迄今为止随访率超过 90%。 当前的 R01 项目将通过定义扩展这个大型的、特征明确的细支气管炎队列 细支气管炎背景下的鼻咽气道宏基因组和代谢组学特征， 并通过检查它们与急性（细支气管炎严重程度）和慢性（事件 在目标 1 中，我们将确定气道之间的关系。 微生物组（宏基因组）概况、代谢组概况和急性细支气管炎严重程度。 目标 2，我们将研究气道微生物组和代谢组谱之间的关系 最后，使用系统生物学。 方法，目标 3 将通过整合临床、病毒、分子数据来定义细支气管炎内型 （例如，气道微生物组和代谢组），并确定它们与急性和慢性疾病的关系 我们的试验数据有力地支持了我们的假设。 当前的 R01 项目将为定义细支气管炎的病理学提供独特的机会 通过检查微生物组（宏基因组）以及小微生物组的功能能力 代表微生物组和宿主（代谢组）功能活动的分子。 此外，通过调查患有细支气管炎的小婴儿——这是一个关键时期的自然实验 肺部发育时期 – 我们还将定义细支气管炎与事件之间的联系机制 该研究将为细支气管炎治疗和哮喘提供强有力的基础证据。 通过未来制定有针对性的干预措施（例如调节 微生物组和代谢途径）研究人员是 NIH 资助的研究人员。 该研究与 2013 年 NIAID 战略计划非常吻合。

项目成果

Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze.

婴儿期鼻病毒 C 细支气管炎和免疫球蛋白 E 致敏与复发性喘息的关系。

• 发表时间: 2019
• 影响因子: 26.1
• 作者: Hasegawa, Kohei;Mansbach, Jonathan M;Bochkov, Yury A;Gern, James E;Piedra, Pedro A;Bauer, Cindy S;Teach, Stephen J;Wu, Susan;Sullivan, Ashley F;Camargo Jr, Carlos A
• 通讯作者: Camargo Jr, Carlos A

Machine learning-based prediction of acute severity in infants hospitalized for bronchiolitis: a multicenter prospective study.

基于机器学习的对因细支气管炎住院婴儿急性严重程度的预测：一项多中心前瞻性研究。

• 发表时间: 2020-07-03
• 影响因子: 4.6
• 作者: Raita, Yoshihiko;Camargo Jr, Carlos A;Macias, Charles G;Mansbach, Jonathan M;Piedra, Pedro A;Porter, Stephen C;Teach, Stephen J;Hasegawa, Kohei
• 通讯作者: Hasegawa, Kohei

Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma.

患有呼吸道合胞病毒细支气管炎的婴儿的综合组学内型分析和儿童哮喘的风险。

• 发表时间: 2021-06-14
• 影响因子: 16.6
• 作者: Raita, Yoshihiko;Pérez;Freishtat, Robert J;Harmon, Brennan;Mansbach, Jonathan M;Piedra, Pedro A;Zhu, Zhaozhong;Camargo, Carlos A;Hasegawa, Kohei
• 通讯作者: Hasegawa, Kohei

Circulating 25-hydroxyvitamin D, nasopharyngeal microbiota, and bronchiolitis severity.

循环 25-羟基维生素 D、鼻咽微生物群和细支气管炎严重程度。

• 发表时间: 2018-12
• 作者: Toivonen, Laura;Hasegawa, Kohei;Ajami, Nadim J;Celedón, Juan C;Mansbach, Jonathan M;Petrosino, Joseph F;Camargo Jr, Carlos A
• 通讯作者: Camargo Jr, Carlos A

Haemophilus-Dominant Nasopharyngeal Microbiota Is Associated With Delayed Clearance of Respiratory Syncytial Virus in Infants Hospitalized for Bronchiolitis.

以嗜血杆菌为主的鼻咽微生物群与因细支气管炎住院的婴儿呼吸道合胞病毒清除延迟有关。

• 发表时间: 2019
• 作者: Mansbach, Jonathan M;Hasegawa, Kohei;Piedra, Pedro A;Avadhanula, Vasanthi;Petrosino, Joseph F;Sullivan, Ashley F;Espinola, Janice A;Camargo, Carlos A
• 通讯作者: Camargo, Carlos A