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

描述（由申请人提供）：细支气管炎是美国婴儿住院的头号原因。小型队列研究（n<210）表明，40-50%的毛细支气管炎住院婴儿将发展为儿童哮喘。不幸的是，目前还不清楚哪些婴儿会患上哮喘，这种知识差距阻碍了初级预防工作。第35次多中心气道研究协作组（MARC-35）研究（U 01 AI-87881; Camargo，PI）是一项17中心前瞻性队列研究，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%重症监护室）的入组。在这个多样化的美国队列（约52%为非洲裔美国人或西班牙裔）中，研究中心研究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、急诊科和住院患者的医疗记录。随访数据包括一年两次的家长访谈和每年一次的医疗记录审查（迄今为止约91%的随访）。由于时间原因，5年U 01补助金的主要结果是3岁时的反复喘息。然而，所有受试者均同意随访至6岁，以确定哮喘（根据医生诊断，加上过去一年的哮喘药物使用或症状定义）; 5岁时的哮喘事件是该R 01辅助应用的主要结局。具体目标针对儿童哮喘的两个风险因素：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）C型鼻病毒，约21%的鼻病毒性细支气管炎婴儿中的一个尚未确定的亚组（可能是一半）。目的3探讨这两个因素与哮喘发病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）之间存在强相互作用，并有两个结果：12个月龄时喘息复发的风险和18个月龄时吸入皮质类固醇的使用（均P <0.01）。R 01将提供资金，通过在42个月（3.5岁）时检测血清特异性IgE来纵向检查IgE致敏性，通过对索引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一次的病历审查持续随访至5岁;这些活动不由U 01赠款资助。由于新的42个月检查和3岁后的随访，该应用程序具有时间敏感性。该研究对所有目标具有>80%的把握度。研究人员是NIH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一级预防的研究，并与2009年NIH儿科呼吸研究战略计划相吻合。

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.