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:
- 金额:$ 8.6万
- 依托单位:
- 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:
- 关键词:5 year old6 year oldAdultAffectAfrican AmericanAgeAsthmaBlood specimenBronchiolitisCellsCellular StructuresChIP-seqChildChildhood AsthmaClinicalCohort StudiesCollaborationsComplexDNA BindingDataDevelopmentDiagnosisDiseaseEarly identificationEnrollmentEnvironmentEnvironmental ExposureEpigenetic ProcessFundingFutureGene ExpressionGenetic Predisposition to DiseaseHeterogeneityHispanicsHospitalizationImmuneImmune responseImmunologicsInfantInfectionInflammatory ResponseInfluenzaInternationalInterventionInterviewKnowledgeLinkLiteratureMeasuresMediator of activation proteinMedical RecordsMessenger RNAMethodsMicroRNAsMolecularNational Institute of Allergy and Infectious DiseaseNatural experimentNoseOutcomeParentsParticipantPathogenesisPathologicPersonsPhenotypePositioning AttributePrevention strategyPrimary PreventionProspective cohort studyProteinsRecurrenceResearchResearch PersonnelRhinovirusRiskRisk FactorsSamplingSignal TransductionStrategic PlanningStructural ProteinSumSwabSystemSystems BiologyTechnologyTestingTimeUnited States National Institutes of HealthViralViral Respiratory Tract InfectionVirusWheezingairway epitheliumasthma preventionasthmaticbasebiobankchemokineclinical phenotypecohortcritical periodcytokinedifferential expressionevidence basefollow-uphigh riskhigh risk populationindexinginfancyinhibitor/antagonistinnovationlung developmentmodifiable risknano-stringnasal swabnovelphenotypic datapreventpreventive interventionprospectivesextargeted treatmenttherapeutic 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.
毛细支气管炎是美国婴儿住院的头号原因,约有13万人住院
每年一次。小规模队列研究(n<;210)表明,40%-50%的婴儿住院时患有
毛细支气管炎随后会发展成哮喘。发展小学教育面临的最大挑战
针对这一大群儿童的预防策略是很早就确定
可改变的危险因素和哮喘的异质性。第35届多中心航道研究
协作(MARC-35)研究(U01AI-87881;卡马戈,PI)是一个17中心的前瞻性队列
这项研究在2014年完成了921名毛细支气管炎住院婴儿的登记。在这
不同的队列(53%的非裔美国人或西班牙裔),调查人员收集了生物标本,
包括鼻拭子在内的住院指标(中位年龄3个月)。跟踪数据
包括一年两次的家长访谈和5岁以下的医疗记录,并有90%的后续行动
约会。此次竞争性续签将延长这一最大、最全面的严重
毛细支气管炎在世界上的队列通过在6岁到10岁之间进行面对面检查
哮喘的诊断和表型以及通过检测鼻气道微RNA和核因子κB信号
调解人/结果,在指数住院和6岁时都是如此。在目标1中,我们将
确定鼻气道微RNA可能与6岁时的哮喘有关。
在目标2中,我们将确定呼吸道microRNA和炎症之间的相互关系
反应(例如,核因子κB信号)及其对偶发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,目标3将通过结合临床表型和分子来定义哮喘内型
6岁时的数据(例如,呼吸道microRNA和核因子κB信号)。在这些患有
严重的毛细支气管炎--一个自然的实验--我们将有一个独特的机会来识别呼吸道
肺发育重要时期与哮喘发病相关的microRNAs
这将为初级干预提供一个关键的窗口。此外,使用创新的
方法,我们将不仅调查毛细支气管炎与事件之间的潜在机制
哮喘(例如,增强的NFκB信号),但也识别哮喘的表型/内型
可能会对不同的干预做出不同的反应。这项研究将提供一个强有力的
通过未来制定有针对性的干预措施为初级预防提供证据基础
(例如,microRNA靶向治疗)。调查人员是由美国国立卫生研究院资助的研究人员
该领域的国际专业知识。这项研究促进了对甲型肝炎一级预防的研究
儿童哮喘,与2013年NIAID战略计划很好地匹配。
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)
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:
- 影响因子:0
- 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:
- 影响因子:0
- 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:
- 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
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:
- 影响因子:0
- 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
Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas.
- DOI:10.1186/s40168-018-0564-7
- 发表时间:2018-10-04
- 期刊:
- 影响因子:15.5
- 作者:Pérez-Losada M;Authelet KJ;Hoptay CE;Kwak C;Crandall KA;Freishtat RJ
- 通讯作者:Freishtat RJ
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CARLOS A. CAMARGO其他文献
CARLOS A. CAMARGO的其他文献
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{{ truncateString('CARLOS A. CAMARGO', 18)}}的其他基金
Host genetics, early-life microbiome, and childhood asthma: MARC-43 Boston
宿主遗传学、生命早期微生物组和儿童哮喘:MARC-43 波士顿
- 批准号:
10742124 - 财政年份:2016
- 资助金额:
$ 8.6万 - 项目类别:
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:
9215155 - 财政年份:2016
- 资助金额:
$ 8.6万 - 项目类别:
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:
10242707 - 财政年份:2016
- 资助金额:
$ 8.6万 - 项目类别:
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 - 财政年份:2016
- 资助金额:
$ 8.6万 - 项目类别:
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:
10062795 - 财政年份:2016
- 资助金额:
$ 8.6万 - 项目类别:
Comparative Effectiveness Research on Hospital Readmissions for COPD
慢性阻塞性肺病再入院的比较效果研究
- 批准号:
9768958 - 财政年份:2015
- 资助金额:
$ 8.6万 - 项目类别:
Comparative Effectiveness Research on Hospital Readmissions for COPD
慢性阻塞性肺病再入院的比较效果研究
- 批准号:
8885175 - 财政年份:2015
- 资助金额:
$ 8.6万 - 项目类别:
Comparative Effectiveness Research on Hospital Readmissions for COPD
慢性阻塞性肺病再入院的比较效果研究
- 批准号:
9147581 - 财政年份:2015
- 资助金额:
$ 8.6万 - 项目类别:
Comparative Effectiveness Research on Hospital Readmissions for COPD
慢性阻塞性肺病再入院的比较效果研究
- 批准号:
9349489 - 财政年份:2015
- 资助金额:
$ 8.6万 - 项目类别:
Infant specific-IgE, rhinovirus-C bronchiolitis, and incident asthma in MARC-35
MARC-35 中的婴儿特异性 IgE、鼻病毒 C 细支气管炎和哮喘事件
- 批准号:
9188529 - 财政年份:2014
- 资助金额:
$ 8.6万 - 项目类别:
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