Prospective Cohort Study of Severe Bronchiolitis and Risk of Recurrent Wheezing

描述（由申请人提供）：细支气管炎是美国婴儿住院的最常见原因。小型队列研究（n=51 - 206）表明，20-60%的严重毛细支气管炎（定义为需要住院治疗）儿童会出现儿童期反复喘息。尽管有这种强烈的相关性，但仍不清楚哪些严重毛细支气管炎儿童会发生反复喘息。拟定的前瞻性多中心队列研究有3个具体目的来解决这一知识缺口：1）检查感染病因、疾病严重程度和CCL 5水平与3岁时复发性喘息发生之间的相关性。2)探讨儿童血清25-羟维生素D [25（OH）D]水平与反复喘息的关系。3)结合联合收割机这些临床和实验室数据，建立一个最先进的儿童喘息指数（WIND），以确定患有严重毛细支气管炎的儿童谁是复发性喘息的风险较高。该指数将确定谁可能受益于开始吸入皮质类固醇或其他哮喘控制措施，如2007年NIH哮喘指南所建议的。该研究小组由NIH资助的研究人员组成，他们在该领域进行了许多多中心研究。在2年的时间里，10家医院的研究人员将招募1,000名年龄<1岁的严重细支气管炎儿童。该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组织，已经完成了60多项多中心研究，重点是呼吸系统急诊和公共卫生。研究中心研究者将收集鼻咽和血液样本;人口统计学、出生、营养、家庭和环境信息;以及来自父母和初级保健、急诊科和住院机构的临床数据。该研究将有80%的把握度检测到复发性喘息发生的1.3- 1.8倍差异，以比较患有鼻病毒细支气管炎（与RSV或其他病原体）、入住重症监护室（与普通病房）和鼻咽抽吸物中可检测到（与不可检测到）CCL 5的儿童。将25（OH）D作为连续变量处理，研究将有80%的把握度检测到25（OH）D增加1 SD（19 nmol/L），喘息复发的几率增加1.3倍。研究人员估计，WIND将有85%的阳性预测值，以确定儿童严重毛细支气管炎谁将发展为复发性喘息。这项研究与2009年NIH儿科呼吸研究战略计划非常吻合，并具有重大的公共卫生意义。 公共卫生相关性：在一项1,000名儿童的多中心前瞻性队列研究中，一组研究人员将研究两种常见儿科疾病之间的关系：细支气管炎和儿童早期反复喘息。该项目与NIH利用临床网络和关注早期风险分层的路线图倡议相匹配。具体来说，拟议的队列将改善严重细支气管炎儿童的短期和长期护理，这种疾病通常会导致儿童哮喘。

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. PUBLIC HEALTH RELEVANCE: In a multicenter prospective cohort study of 1,000 children, a team of investigators will examine the association between two common pediatric conditions: bronchiolitis and recurrent wheezing of early childhood. The project matches well with NIH roadmap initiatives of utilizing clinical networks and focusing on early risk stratification. Specifically, the proposed cohort would improve the short- and long-term care of children with severe bronchiolitis, a condition that often leads to childhood asthma.