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
• 负责人: CARLOS A. CAMARGO
• 金额: $ 85.15万
• 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/9188529
• 关键词: 3 year old; 5 year old; 6 year old; Accident and Emergency department; Address; Adrenal Cortex Hormones; African American; Age; Ancillary Study; Asthma; Base Sequence; Blood specimen; Breathing; Bronchiolitis; Child; Childhood; Childhood Asthma; Cohort Studies; Collaborations; Consent; DNA; Data; Development; Diagnosis; Enrollment; Evaluation; Food; Funding; Grant; Guidelines; Hispanics; Hospitalization; IgE; Immunity; Infant; Inpatients; Intensive Care Units; International; Interview; Investigation; Knowledge; Lung diseases; Measures; Medical Records; National Institute of Allergy and Infectious Disease; Outcome; Parents; Participant; Pattern; Persons; Pharmaceutical Preparations; Positioning Attribute; Primary Health Care; Primary Prevention; Prospective cohort study; 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; asthma prevention; base; biobank; cohort; follow-up; high risk; high risk population; improved; indexing; novel; pathogen; personalized medicine; prevent; primary outcome; public health relevance; 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）：支气管炎是美国婴儿住院的第一名。小型队列研究（N <210）表明，40-50％的住院儿童将患有细支气管炎，会发展儿童哮喘。不幸的是，目前尚不清楚哪些婴儿会发展哮喘，而这种知识差距阻碍了主要的预防工作。第35届多中心气道研究合作（MARC-35）研究（U01 AI-87881; Camargo，PI）是一项17中心的前瞻性队列研究，将在2014年4月在2014年4月或在此不同的地点（80％WARD，20％强化）（80％Ward）（80％WARD）入学（在这一多元化的美国）。研究人员已收集鼻咽和血液样本（包括DNA）。广泛的访谈和调查数据；以及初级保健，急诊科和住院设置的病历。随访数据包括双年度父母访谈和医疗记录的年度审查（迄今为止约91％的随访）。出于时间原因，5年U01赠款的主要结果是在3岁时反复喘息。但是，所有参与者均同意进行6岁以下的随访，以确定哮喘（如医生诊断所定义，以及过去一年的哮喘药物使用或症状）； 5岁时的哮喘发生是此R01辅助应用的主要结果。该特定目的涉及儿童哮喘的两个危险因素：1）特定的IgE，初步数据显示的MARC-35婴儿中约有20％； 2）C型Rhinovirus，是隆突病毒细支气管炎的约21％的仍未定义的子群（可能一半）。 AIM 3检查了这两个因素与入口哮喘之间的潜在相互作用。初步数据（n = 745）已经显示出婴儿特异性和鼻病毒（尚未键入）之间存在很强的相互作用和两个可用的结果：到12个月大时出现喘息的风险，并在18个月中使用吸入的皮质类固醇（PinterAction <0.01）。 R01将通过在42个月（3.5岁）测试血清特异性IGE，通过部分测序进行指数住院的鼻病毒样本，并继续对双年度电话和年度图表评论进行持续随访，从而提供资金来检查IgE敏感性。这些活动不是由U01赠款资助的。由于新的42个月的考试和3岁以后的随访，该应用程序对时间敏感。该研究的所有目标具有> 80％的功率。研究人员是NIH资助的研究人员，在该领域拥有国际专业知识。该研究对哮喘的主要预防进行了研究，并与2009年NIH儿童呼吸研究战略计划非常匹配。