Airway dual-transcriptomics in bronchiolitis and risk of asthma: MARC-35 cohort

细支气管炎和哮喘风险的气道双转录组学：MARC-35 队列

• 批准号: 10331773
• 负责人: Kohei Hasegawa
• 金额: $ 80.79万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-14 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331773
• 关键词: 16S ribosomal RNA sequencing; 6 year old; Acute; Admission activity; African American; Age; American; Apoptosis; Asthma; BIRC5 gene; Bronchiolitis; Child; Childhood; Childhood Asthma; Chronic; Clinical; Cohort Studies; Collaborations; Data; Diagnosis; Enrollment; Funding; Gene Expression; Geography; Hispanic; Hospitalization; IgE; Immune response; Immunity; Immunology; Infant; Intensive Care; International; Intervention; Interview; Knowledge; Lead; Link; MAPKAPK2 gene; Medical Records; Messenger RNA; Methods; Microbe; Moraxella; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Natural experiment; Outcome; Parents; Participant; Pathway interactions; Persons; Phenotype; Pilot Projects; Positioning Attribute; Primary Prevention; Prospective cohort study; Public Health; RNA; Recording of previous events; Recurrence; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Serum; Severities; Signal Pathway; Strategic Planning; Streptococcus; Systems Biology; Technology; Testing; Tissue-Specific Gene Expression; United States National Institutes of Health; Virus; Wheezing; Work; acute bronchiolitis; base; cohort; critical period; evidence base; follow-up; high risk; high risk population; indexing; innovation; lung development; metatranscriptome; metatranscriptomics; microbiome; microbiome composition; nano-string; novel strategies; premature; pressure; prevent; racial and ethnic; respiratory; respiratory microbiome; transcriptome; transcriptome sequencing; transcriptomics; treatment strategy; ventilation

Bronchiolitis is the leading cause of infant hospitalization in the US. Yet, its acute severity is not explained by traditional risk factors. Additionally, while infants hospitalized for bronchiolitis are at very high risk for incident asthma, little is known about the mechanisms linking these two conditions. 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 (U01AI087881; Camargo, PI) is an ongoing 17-center cohort study that enrolled 1,016 hospitalized infants with bronchiolitis during 2011- 2014. In this racially-, ethnically-, and geographically-diverse cohort, investigators have collected high-quality biospecimens, including nasopharyngeal airway samples at the index hospitalization. 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 present R01 project would extend this large well-characterized bronchiolitis cohort by profiling the gene expression of both nasopharyngeal airway microbiome (metatranscriptome) and host response (transcriptome) in the setting of bronchiolitis, and by examining their relations to both acute (bronchiolitis severity) and chronic (incident asthma) outcomes. In Aim 1, we will examine the relations among the airway microbiome profiles, host transcriptomic profiles, and acute severity of bronchiolitis. In Aim 2, we will determine the relations among the airway microbiome and host transcriptomic profiles in infants with bronchiolitis, and the risk of developing childhood asthma. Finally, using a systems biology approach, Aim 3 will define bronchiolitis endotypes by integrating clinical, virus, immunology (e.g., IgE), microbiome (composition and function) and host transcriptome data, and determine their associations with both the acute and chronic outcomes. Our pilot data lend compelling support to our hypotheses. The present R01 project will provide a unique opportunity to define the pathobiology of bronchiolitis through examining the functional activity of microbiome and host response in the airway. Furthermore, we will also determine the mechanisms linking bronchiolitis to asthma, by investigating young infants with bronchiolitis (median age, 3 months) – a natural experiment during a critical period of lung development. The project will provide a strong evidence base for developing targeted interventions for acute bronchiolitis treatment and asthma primary prevention (e.g., through modulation of microbiome and immune responses). The investigators are NIH-funded researchers with international expertise in all relevant fields. The study matches well with the 2013 NIAID Strategic Plan.

细支气管炎是美国婴儿住院的主要原因，但其严重程度却并非如此。 此外，因细支气管炎住院的婴儿处于 发生哮喘的风险非常高，但人们对这两者之间的联系机制知之甚少 这些主要的知识差距阻碍了开发细支气管炎的努力。 治疗策略并预防这一高危人群的哮喘。第 35 届多中心会议。 气道研究合作 (MARC-35) 研究 (U01AI087881；Camargo, PI) 是一项正在进行的研究 2011 年期间纳入 1,016 名患有细支气管炎住院婴儿的 17 中心队列研究 2014 年。在这个种族、族裔和地理上多样化的队列中，研究人员 收集高质量的生物样本，包括索引处的鼻咽气道样本 住院随访数据包括每年两次的家长访谈、病历审查和 6 岁时进行现场检查，目前的 R01 项目的随访率超过 90%。 通过分析这两种疾病的基因表达来扩展这一大型的、已明确表征的细支气管炎队列 鼻咽气道微生物组（元转录组）和宿主反应（转录组） 细支气管炎的情况，并检查它们与急性（细支气管炎严重程度）的关系 在目标 1 中，我们将研究以下因素之间的关系。 气道微生物组特征、宿主转录组特征和细支气管炎的急性严重程度。 目标2，我们将确定气道微生物组与宿主转录组之间的关系 患有细支气管炎的婴儿的概况以及患儿童哮喘的风险。 系统生物学方法，目标 3 将通过整合临床、病毒、 免疫学（例如 IgE）、微生物组（组成和功能）和宿主转录组数据， 并确定它们与急性和慢性结果的关联。 目前的 R01 项目将提供一个独特的机会。 通过检查毛细支气管炎的功能活动来定义细支气管炎的病理学 此外，我们还将确定呼吸道中的微生物组和宿主反应。 通过调查患有细支气管炎的小婴儿，了解细支气管炎与哮喘之间的联系机制 （中位年龄，3 个月）——肺部发育关键时期的自然实验。 该项目将为制定针对急性发作的有针对性的干预措施提供强有力的证据基础 细支气管炎治疗和哮喘一级预防（例如通过调节微生物组） 和免疫反应）。研究人员是 NIH 资助的国际研究人员。 该研究与 2013 年 NIAID 战略计划非常吻合。