Nasal microRNA during bronchiolitis and age 6y asthma phenotypes: MARC-35 cohort

细支气管炎和 6 岁哮喘表型期间的鼻 microRNA：MARC-35 队列

基本信息

批准号：
10267407
负责人：
CARLOS A. CAMARGO
金额：
$ 8.6万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-16 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10267407
关键词：
5 year old 6 year old Adult Affect African American Age Asthma Blood specimen Bronchiolitis Cells Cellular Structures ChIP-seq Child Childhood Asthma Clinical Cohort Studies Collaborations Complex DNA Binding Data Development Diagnosis Disease Early identification Enrollment Environment Environmental Exposure Epigenetic Process Funding Future Gene Expression Genetic Predisposition to Disease Heterogeneity Hispanics Hospitalization Immune Immune response Immunologics Infant Infection Inflammatory Response Influenza International Intervention Interview Knowledge Link Literature Measures Mediator of activation protein Medical Records Messenger RNA Methods MicroRNAs Molecular National Institute of Allergy and Infectious Disease Natural experiment Nose Outcome Parents Participant Pathogenesis Pathologic Persons Phenotype Positioning Attribute Prevention strategy Primary Prevention Prospective cohort study Proteins Recurrence Research Research Personnel Rhinovirus Risk Risk Factors Sampling Signal Transduction Strategic Planning Structural Protein Sum Swab System Systems Biology Technology Testing Time United States National Institutes of Health Viral Viral Respiratory Tract Infection Virus Wheezing airway epithelium asthma prevention asthmatic base biobank chemokine clinical phenotype cohort critical period cytokine differential expression evidence base follow-up high risk high risk population indexing infancy inhibitor/antagonist innovation lung development modifiable risk nano-string nasal swab novel phenotypic data prevent preventive intervention prospective sex targeted treatment therapeutic target

项目摘要

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 subsequently develop asthma. The greatest challenges for developing primary prevention strategies for this large group of 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-87881; 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). Follow-up data include biannual parent interviews and medical records to age 5 years, with >90% follow-up to date. This competitive renewal would extend this largest, most comprehensive severe bronchiolitis cohort in the world by conducting an in-person examination at age 6 years to diagnose and phenotype asthma and by examining nasal airway microRNA and NFκB signaling mediators/outcomes, at both the index hospitalization and at age 6 years. In Aim 1, we will identify nasal airway microRNAs that are prospectively associated with asthma at age 6 years. In Aim 2, we will determine the inter-relations among airway microRNAs and inflammatory response (e.g., NFκB signaling) and their integrated contributions to risk of incident asthma. Pilot data provide compelling support for our hypotheses. Lastly, using a systems biology approach, Aim 3 will define asthma endotypes by integrating clinical phenotype and molecular data (e.g., airway microRNAs and NFκB signaling) at age 6 years. Among these infants with severe bronchiolitis – a natural experiment – we will have a unique opportunity to identify airway microRNAs associated with incident asthma during an important period of lung development that would provide a critical window for primary intervention. Furthermore, using innovative approaches, we will not only investigate underlying mechanisms linking bronchiolitis to incident asthma (e.g., enhanced NFκB signaling) but also identify phenotypes/endotypes of asthma that are likely to respond differently to different interventions. The study will provide a strong evidence base for primary prevention through the future development of targeted interventions (e.g., microRNA-targeting therapy). The investigators are NIH-funded researchers with international expertise in the field. The study advances research on the primary prevention of childhood asthma, and matches well with the 2013 NIAID Strategic Plan.

细支气管炎是美国婴儿住院的第一大原因，约有 130,000 名婴儿住院每年进行的小规模队列研究 (n<210) 表明 40-50% 的婴儿因患有此类疾病而住院。细支气管炎随后会发展为哮喘。针对这一大群儿童的预防策略是及早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-87881；Camargo, PI）是一项 17 个中心的前瞻性队列 2014 年完成了 921 名患有细支气管炎住院婴儿的研究。多样化的队列（53％非裔美国人或西班牙裔），研究人员收集了生物样本，包括首次住院时的鼻拭子（中位年龄 3 个月）。包括每年两次的家长访谈和 5 岁之前的医疗记录，并且超过 90% 的随访此次竞争性续签将延长这一规模最大、最全面的严厉措施。通过在 6 岁时进行现场检查，在世界范围内开展细支气管炎队列研究通过检查鼻气道 microRNA 和 NFκB 信号来诊断哮喘并确定其表型在目标 1 中，我们将在住院指数和 6 岁时进行调解/结果。识别出与 6 岁时哮喘潜在相关的鼻气道 microRNA。在目标 2 中，我们将确定气道 microRNA 与炎症之间的相互关系反应（例如 NFκB 信号传导）及其对哮喘事件风险的综合贡献。最后，利用系统生物学，试验数据为我们的假设提供了令人信服的支持。方法，目标 3 将通过整合临床表型和分子水平来定义哮喘内型这些婴儿 6 岁时的数据（例如气道 microRNA 和 NFκB 信号）。严重细支气管炎 – 一个自然实验 – 我们将有一个独特的机会来识别气道 microRNA与肺部发育重要时期的哮喘事件相关这将为初级干预提供一个关键窗口。方法，我们不仅会研究细支气管炎与事件之间的联系的潜在机制哮喘（例如，增强的 NFκB 信号传导），还可以识别哮喘的表型/内型可能会对不同的干预措施产生不同的反应，这项研究将提供强有力的证据。通过未来制定有针对性的干预措施来建立初级预防的证据基础（例如，microRNA 靶向治疗）。研究人员是 NIH 资助的研究人员。该研究推进了该领域一级预防的研究。儿童哮喘，与 2013 年 NIAID 战略计划非常吻合。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Late Pre-term Infants with Severe Bronchiolitis and Risk of Asthma by Age 5 Years.

晚期早产儿患有严重细支气管炎和 5 岁哮喘风险。

DOI：
发表时间：
2022-02
期刊：
影响因子：
0
作者：
Mansbach, Jonathan M;Qi, Ying Shelly;Espinola, Janice A;Hasegawa, Kohei;Puls, Henry T;Sullivan, Ashley F;Camargo Jr, Carlos A
通讯作者：
Camargo Jr, Carlos A

Recurrent wheezing phenotypes after severe bronchiolitis and progression to asthma.

严重细支气管炎和进展为哮喘后反复出现喘息表型。

DOI：
发表时间：
2023-02
期刊：
影响因子：
0
作者：
Mansbach, Jonathan M;Ying, Qi Shelly;Espinola, Janice A;Hasegawa, Kohei;Sullivan, Ashley F;Camargo, Carlos A
通讯作者：
Camargo, Carlos A

Rhinovirus Species in Children With Severe Bronchiolitis: Multicenter Cohort Studies in the United States and Finland.

严重细支气管炎儿童中的鼻病毒种类：美国和芬兰的多中心队列研究。

DOI：
发表时间：
2019-03
期刊：
影响因子：
0
作者：
Hasegawa, Kohei;Jartti, Tuomas;Bochkov, Yury A;Gern, James E;Mansbach, Jonathan M;Piedra, Pedro A;Toivonen, Laura;Camargo Jr, Carlos A
通讯作者：
Camargo Jr, Carlos A

Association of nasopharyngeal microbiota profiles with bronchiolitis severity in infants hospitalised for bronchiolitis.

因细支气管炎住院婴儿的鼻咽微生物群特征与细支气管炎严重程度的关联。

DOI：
发表时间：
2016-11
期刊：
影响因子：
0
作者：
Hasegawa, Kohei;Mansbach, Jonathan M;Ajami, Nadim J;Espinola, Janice A;Henke, David M;Petrosino, Joseph F;Piedra, Pedro A;Shaw, Chad A;Sullivan, Ashley F;Camargo Jr, Carlos A;the MARC
通讯作者：
the MARC

Multicenter Study of Albuterol Use Among Infants Hospitalized with Bronchiolitis.

因毛细支气管炎住院婴儿使用沙丁胺醇的多中心研究。

DOI：
发表时间：
2018-05
期刊：
影响因子：
0
作者：
Condella, Anna;Mansbach, Jonathan M;Hasegawa, Kohei;Dayan, Peter S;Sullivan, Ashley F;Espinola, Janice A;Camargo Jr, Carlos A
通讯作者：
Camargo Jr, Carlos A