Infant specific-IgE, rhinovirus-C bronchiolitis, and incident asthma in MARC-35

描述（由申请人提供）：毛细支气管炎是美国婴儿住院的第一大原因。小队列研究（n<210）表明，40-50%的毛细支气管炎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哮喘，这种知识差距阻碍了初级预防工作。第35个多中心气道研究合作（MARC-35）研究（U01 AI-87881; Camargo， PI）是一项17个中心的前瞻性队列研究，将于2014年4月完成约940例毛细支气管炎住院婴儿（80%病房，20%重症监护病房）的入组。在这个多样化的美国队列中（约52%是非裔美国人或西班牙裔），现场调查人员收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、急诊科和住院的医疗记录。随访资料包括一年两次的父母访谈和每年一次的医疗记录回顾（迄今随访约91%）。由于时间原因，5年U01资助的主要结果是3岁前复发性喘息。然而，所有参与者都同意随访至6岁，以确定哮喘（根据医生诊断，加上哮喘药物使用或过去一年的症状）；5岁哮喘发生率是这项R01辅助应用的主要终点。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婴儿存在特异性IgE；2)鼻病毒C型，在约21%的鼻病毒细支气管炎婴儿中仍未确定的子集（可能是一半）。目的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）之间有很强的相互作用，以及两个可用的结果：12个月时复发性喘息的风险和18个月时吸入皮质类固醇的使用（p相互作用均<0.01）。R01将提供资金，通过在42个月（3.5岁）时检测血清特异性IgE，通过对指数住院的鼻病毒样本进行部分测序进行鼻病毒分型，并通过每年两次的电话随访和每年的图表回顾持续随访至5岁；这些活动不是由U01补助金资助的。申请是时间敏感的，因为新的42个月的检查和3岁后的随访。这项研究对所有目标都有80%的影响力。研究人员是美国国立卫生研究院资助的研究人员，在该领域具有国际专业知识。这项研究推进了哮喘初级预防的研究，并与2009年NIH儿科呼吸研究战略计划非常吻合。

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.