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

描述(申请人提供)：毛细支气管炎是美国婴儿住院的头号原因。小规模队列研究(n&lt；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，这一知识差距阻碍了初级预防工作。第35次多中心呼吸道研究合作(MARC-35)研究(U01 AI-87881；卡马戈，PI)是一项17中心前瞻性队列研究，将于2014年4月完成约940名毛细支气管炎住院婴儿(80%病房，20%重症监护病房)的登记。在这个多样化的美国队列中(约52%是非洲裔美国人或西班牙裔美国人)，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；以及初级保健、急诊科和住院患者的医疗记录。随访数据包括两年一次的家长访谈和每年一次的医疗记录回顾(约91%的随访到目前为止)。由于时机的原因，为期5年的U01补助金的主要结果是3岁前反复喘息。然而，所有参与者都同意接受6岁的随访，以允许确定哮喘(根据医生的诊断，加上过去一年中哮喘药物的使用或症状)；5岁时的哮喘事件是这项R01辅助应用的主要结果。具体目标是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婴儿患有这种疾病；2)C型鼻病毒，在约21%患有鼻病毒毛细支气管炎的婴儿中，C型鼻病毒是一个仍未确定的亚群(可能有一半)。目的3研究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)之间存在很强的相互作用，并有两个可用的结果：12个月前有反复喘息的风险，18个月前使用吸入性皮质类固醇(两者均为P交互作用和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，通过对指数住院期间的鼻病毒样本进行部分测序进行鼻病毒分型，以及在5岁之前继续跟踪两年一次的电话和年度图表审查，来纵向检查IgE致敏；这些活动不是由U01赠款资助的。由于新的为期42个月的考试和3年后的随访，这项申请对时间很敏感。这项研究对所有目标都有80%的力量。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。这项研究推进了哮喘一级预防的研究，并与NIH 2009年儿科呼吸系统研究战略计划很好地匹配。

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.