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

• 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
• 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

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.

支气管炎是美国婴儿住院的第一号原因，约有13万 独一无二的研究（N <210）表明40-50％的婴儿住院 细支气管炎随后会出现哮喘。发展初选的最大挑战 这大批儿童的预防策略是对 可修改的危险因素和哮喘的异质性。第35次多中心气道研究 协作（MARC-35）研究（U01AI-87881; Camargo，pi）是17中心的前瞻性队列 2014年完成了921名住院婴儿纤维炎婴儿的研究。 各种队列（53％的非裔美国人或西班牙裔），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）。后续数据 包括双年度父母访谈和医疗记录至5岁，> 90％的随访 日期。这种竞争性更新将扩大这种最大，最全面的严重性 通过在6岁时进行面对面检查的世界内支气管炎队列 诊断和表型哮喘以及通过检查鼻气道microRNA和NFκB信号传导 指数住院和6岁时的调解人/结果。在AIM 1中，我们将 识别6岁时可能与哮喘相关的鼻气道microRNA。 在AIM 2中，我们将确定气道microRNA和炎症之间的相互关系 反应（例如NFκB信号传导）及其对入口哮喘风险的综合贡献。 试点数据为我们的假设提供了令人信服的支持。最后，使用系统生物学 方法，AIM 3将通过整合临床表型和分子来定义哮喘内型 6岁时的数据（例如气道microRNA和NFκB信号传导）。在这些婴儿中 严重的细支气管炎 - 自然实验 - 我们将有一个独特的机会来识别气道 在重要的肺发育时期，与哮喘的事件哮喘相关的microRNA 这将为主要干预提供关键窗口。此外，使用创新 方法，我们不仅会调查将细支气管炎与事件联系起来的基本机制 哮喘（例如，增强的NFκB信号传导），但也鉴定出哮喘的表型/内型 对不同的干预措施的反应可能有所不同。该研究将提供强大的 通过未来开发有针对性干预措施的初级预防证据基础 （例如，靶向microRNA的疗法）。研究人员是NIH资助的研究人员 该领域的国际专业知识。该研究推进了有关主要预防的研究 童年哮喘，与2013年的NIAID战略计划非常匹配。

项目成果

Allergic sensitization during early life: Concordance between ImmunoCAP and ISAC results.

• DOI: 10.1016/j.jaip.2020.12.028
• 发表时间: 2021-05
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Arroyo AC;Robinson LB;Geller RJ;Rudders SA;Sullivan AF;Hasegawa K;Camargo CA Jr
• 通讯作者: Camargo CA Jr

Characterizing Avoidable Transfer Admissions in Infants Hospitalized for Bronchiolitis.

• DOI: 10.1542/hpeds.2019-0226
• 发表时间: 2020-05-01
• 期刊: Hospital pediatrics
• 作者: Boyle, Tehnaz P;Macias, Charles G;Camargo, Carlos A Jr
• 通讯作者: Camargo, Carlos A Jr

The relationship between nasopharyngeal CCL5 and microbiota on disease severity among infants with bronchiolitis.

• DOI: 10.1111/all.13160
• 发表时间: 2017-11
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Hasegawa K;Mansbach JM;Ajami NJ;Petrosino JF;Freishtat RJ;Teach SJ;Piedra PA;Camargo CA Jr
• 通讯作者: Camargo CA Jr

Prenatal exposure to acid suppressant medications and risk of allergen sensitization.

• DOI: 10.1111/pai.13760
• 发表时间: 2022-03
• 期刊: PEDIATRIC ALLERGY AND IMMUNOLOGY
• 影响因子: 4.4
• 作者: Robinson, Lacey B.;Arroyo, Anna Chen;Geller, Ruth J.;Sullivan, Ashley F.;Camargo, Carlos A., Jr.
• 通讯作者: Camargo, Carlos A., Jr.

COVID-19 severity in hospitalized patients with asthma: A matched cohort study.

• DOI: 10.1016/j.jaip.2020.10.021
• 发表时间: 2021-01
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Robinson LB;Fu X;Bassett IV;Triant VA;Foulkes AS;Zhang Y;Camargo CA Jr;Blumenthal KG
• 通讯作者: Blumenthal KG