Prospective Cohort Study of Severe Bronchiolitis and Risk of Recurrent Wheezing

描述(申请人提供)：毛细支气管炎是美国婴儿住院的最常见原因。小规模队列研究(n=51至206)表明，20-60%患有严重毛细支气管炎(根据住院需求定义)的儿童会出现儿童时期反复喘息。尽管有这种强烈的联系，但仍不清楚哪些患有严重毛细支气管炎的儿童会出现反复喘息。拟议的前瞻性多中心队列研究有3个具体目标来解决这一知识差距：1)检查感染病原学、疾病严重性和CCL5水平与3岁前反复喘息的发展之间的联系。2)探讨儿童血清25-羟基维生素D[25(OH)D]水平与反复喘息的关系。3)结合这些临床和实验室数据，创建最先进的儿童喘息指数(WIND)，以识别患有严重毛细支气管炎的儿童，他们发生反复喘息的风险更高。这一指数将确定谁可能受益于2007年NIH哮喘指南所建议的吸入皮质类固醇或其他哮喘控制措施。研究团队由美国国立卫生研究院资助的研究人员组成，他们领导了这一领域的许多多中心研究。在为期两年的时间里，10家医院的研究人员将招募1000名患有严重毛细支气管炎的1岁儿童。这个队列的数据收集将包括日记、一年两次的访谈和对相关医疗记录的年度审查。这项研究将使用急诊医学网络，这是一个临床研究合作机构，已经完成了60项专注于呼吸系统紧急情况和公共卫生的多中心研究。现场调查人员将收集鼻咽和血液样本；人口统计、出生、营养、家庭和环境信息；以及来自父母和初级保健、急诊科和住院环境的临床数据。这项研究将有80%的能力来检测鼻病毒性毛细支气管炎(与呼吸道合胞病毒或其他病原体)、住进重症监护病房(与普通病房)的儿童以及鼻咽抽吸物中可检测到(或未检测到)CCL5的儿童在反复喘息的发展方面存在1.3至1.8倍的差异。将25(OH)D作为一个连续变量，这项研究将有80%的能力检测25(OH)D增加1SD(19nmol/L)导致复发喘息的几率增加1.3倍。研究调查人员估计，风对诊断患有严重毛细支气管炎的儿童将出现反复喘息的阳性预测值为e85%。这项研究与NIH 2009年儿科呼吸系统研究战略计划很好地匹配，并具有重大的公共卫生影响。

DESCRIPTION (provided by applicant): Bronchiolitis is the most common cause of infant hospitalization in the US. Small cohort studies (n=51 to 206) suggest that 20-60% of children with severe bronchiolitis (as defined by the need for hospitalization) will develop recurrent wheezing of childhood. Despite this strong association, it remains unclear which children with severe bronchiolitis will develop recurrent wheezing. The proposed prospective multicenter cohort study has 3 specific aims to address this knowledge gap: 1) To examine the association between infectious etiology, illness severity, and CCL5 level and the development of recurrent wheezing by age 3 years. 2) To examine the association between the child's level of serum 25-hydroxyvitamin D [25(OH)D] and recurrent wheezing. 3) To combine these clinical and laboratory data to create a state-of-the-art childhood wheezing index (WIND) to identify children with severe bronchiolitis who are at higher risk of developing recurrent wheezing. This index would identify who might benefit from initiation of inhaled corticosteroids or other asthma control measures, as recommended by the 2007 NIH asthma guidelines. The research team is comprised of NIH-funded researchers who have led many multicenter studies in this area. Over a 2-year period, researchers at 10 hospitals will enroll 1,000 children age <1 year with severe bronchiolitis. Data collection for this cohort will include diaries, biannual interviews, and an annual review of relevant medical records. The study will use the Emergency Medicine Network, a clinical research collaboration that has completed >60 multicenter studies focusing on respiratory emergencies and public health. Site investigators will collect nasopharyngeal and blood samples; demographic, birth, nutritional, family, and environmental information; and clinical data from the parents and from primary care, emergency department, and inpatient settings. The study will have 80% power to detect a 1.3- to 1.8-fold difference in the development of recurrent wheezing for comparisons of children with rhinovirus bronchiolitis (vs. RSV or other pathogens), admitted to the intensive care unit (vs. regular ward), and with detectable (vs. not detectable) CCL5 in nasopharyngeal aspirate. Treating 25(OH)D as a continuous variable, the study will have 80% power to detect a 1.3-fold increase in the odds of recurrent wheezing for a 1 SD (19 nmol/L) increase in 25(OH)D. Study investigators estimate that WIND will have a positive predictive value of e85% to identify children with severe bronchiolitis who will develop recurrent wheezing. The study matches well with the 2009 NIH strategic plan for pediatric respiratory research, and has major public health implications.