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: 8974810
• 负责人: CARLOS A. CAMARGO
• 金额: $ 90.05万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8974810
• 关键词: 3 year old; 5 year old; 6 year old; Accident and Emergency department; Accounting; Address; Adrenal Cortex Hormones; African American; Age; Ancillary Study; Asthma; Base Sequence; Blood specimen; Breathing; Bronchiolitis; CCL7 gene; Child; Childhood; Childhood Asthma; Cohort Studies; Collaborations; Consent; DNA; Data; Development; Diagnosis; Enrollment; Environmental Wind; Evaluation; Food; Funding; Grant; Guidelines; Health; Hispanics; Hospitalization; IgE; Immunity; Infant; Inpatients; Intensive Care Units; International; Interview; Investigation; Knowledge; Left; Lung diseases; Measures; Medical Records; National Institute of Allergy and Infectious Disease; Outcome; Parents; Participant; Pattern; Persons; Pharmaceutical Preparations; Population; Positioning Attribute; Primary Health Care; Primary Prevention; Public Health; Recurrence; Research; Research Personnel; Respiratory syncytial virus; Rhinovirus; Risk; Risk Factors; Role; Sampling; Serum; Severity of illness; Site; Strategic Planning; Sum; Surveys; Symptoms; Telephone; Testing; Time; United States National Institutes of Health; Virus; Vitamin D; Wheezing; base; biobank; cohort; follow-up; high risk; improved; indexing; novel; pathogen; personalized medicine; prevent; primary outcome; prospective; respiratory; ward

DESCRIPTION (provided by applicant): Bronchiolitis is the #1 cause of infant hospitalization in the USA. Small cohort studies (n<210) suggest that 40-50% of hospitalized infants with bronchiolitis will develop childhood asthma. Unfortunately, it remains unclear which infants will develop asthma and this knowledge gap has hindered primary prevention efforts. The 35th Multicenter Airway Research Collaboration (MARC-35) study (U01 AI-87881; Camargo, PI) is a 17-center prospective cohort study that will complete enrollment of ~940 hospitalized infants with bronchiolitis (80% ward, 20% intensive care unit) in April 2014. In this diverse U.S. cohort (~52% African-American or Hispanic), site investigators have collected nasopharyngeal and blood samples (including DNA); extensive interview and survey data; and medical records from primary care, emergency department, and inpatient settings. Follow-up data include biannual parent interviews and annual review of medical records (~91% follow-up to date). For timing reasons, the primary outcome of the 5- year U01 grant is recurrent wheezing by age 3 years. However, all participants were consented for follow-up to age 6 years to permit ascertainment of asthma (as defined by doctor diagnosis, plus either asthma medication use or symptoms in past year); incident asthma at age 5 years is the primary outcome of this R01 ancillary application. The Specific Aims address two risk factors for childhood asthma: 1) specific IgE, which preliminary data show in ~20% of MARC-35 infants; and 2) rhinovirus type C, a still-undefined subset (likely half) of the ~21% of infants with rhinovirus bronchiolitis. Aim 3 examines the potential interaction between these two factors and incident asthma. Preliminary data (n=745) already show a strong interaction between infant specific-IgE and rhinovirus (not yet typed) and two available outcomes: risk of recurrent wheeze by age 12 months and use of inhaled corticosteroids by age 18 months (both Pinteraction<0.01). The R01 would provide funds to examine IgE sensitization longitudinally by testing serum specific IgE at age 42 months (3.5 years), rhinovirus typing by partial sequencing for rhinovirus samples from the index hospitalization, and continued follow-up with biannual telephone calls and annual chart reviews through age 5 years; these activities are not funded by the U01 grant. The application is time sensitive because of the new 42-month exam and follow-up after age 3 years. The study has >80% power for all aims. The investigators are NIH-funded researchers with international expertise in the field. The study advances research on the primary prevention of asthma, and matches well with the 2009 NIH strategic plan for pediatric respiratory research.

描述（由申请人提供）：细支气管炎是美国婴儿住院的第一大原因。小规模队列研究 (n<210) 表明，40-50% 的患有细支气管炎的住院婴儿会发展为儿童哮喘。不幸的是，目前尚不清楚哪些婴儿会患上哮喘，这种知识差距阻碍了一级预防工作。第 35 次多中心气道研究合作 (MARC-35) 研究（U01 AI-87881；卡马戈，PI）是一项 17 中心前瞻性队列研究，将完成约 940 名患有细支气管炎的住院婴儿的入组（80% 为病房，20% 为重症监护）单位）于 2014 年 4 月进行。在这个多元化的美国队列中（约 52% 为非裔美国人或西班牙裔），现场调查员采集了鼻咽和血液样本（包括DNA）；广泛的访谈和调查数据；以及来自初级保健、急诊室和住院机构的医疗记录。随访数据包括每年两次的家长访谈和每年一次的病历审查（迄今为止约 91% 的随访）。由于时间原因，5 年期 U01 补助金的主要结果是 3 岁时出现反复喘息。然而，所有参与者都同意随访至 6 岁，以确定是否患有哮喘（根据医生诊断，加上过去一年的哮喘药物使用情况或症状）； 5 岁时发生哮喘是 R01 辅助应用的主要结果。具体目标针对儿童哮喘的两个危险因素：1) 特异性 IgE，初步数据显示约 20% 的 MARC-35 婴儿存在这种情况； 2) C 型鼻病毒，约 21% 患有鼻病毒细支气管炎的婴儿中的一个尚未明确的亚群（可能是一半）。目标 3 检查这两个因素与哮喘事件之间的潜在相互作用。初步数据 (n=745) 已经显示婴儿特异性 IgE 和鼻病毒（尚未分型）之间存在很强的相互作用，并且有两种可用的结果：12 个月时反复喘息的风险和 18 个月时使用吸入皮质类固醇的风险（两者均< 0.01）。 R01 将提供资金，通过在 42 个月（3.5 岁）时测试血清特异性 IgE、通过对索引住院的鼻病毒样本进行部分测序来进行鼻病毒分型，以及通过每年两次的电话通话和年度图表审查进行持续随访，来纵向检查 IgE 致敏性5 岁以下；这些活动并非由 U01 赠款资助。由于新的 42 个月检查以及 3 岁后的随访，该申请对时间很敏感。该研究对所有目标的功效均大于 80%。研究人员是美国国立卫生研究院资助的研究人员，在该领域拥有国际专业知识。该研究推进了哮喘一级预防的研究，与 2009 年 NIH 儿科呼吸研究战略计划相吻合。