Prospective Cohort Study of Severe Bronchiolitis and Risk of Recurrent Wheezing

描述（由申请人提供）：毛细支气管炎是美国婴儿住院的最常见原因。小队列研究（n=51 ~ 206）表明，20-60%的严重毛细支气管炎患儿（根据需要住院治疗的定义）会出现儿童期复发性喘息。尽管存在这种强烈的联系，但仍不清楚哪些患有严重毛细支气管炎的儿童会出现复发性喘息。提出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差距：1)检查感染性病因、疾病严重程度和CCL5水平与3岁时复发性喘息的发展之间的关系。2)探讨儿童血清25-羟基维生素D [25(OH)D]水平与复发性喘息的关系。3)将这些临床和实验室数据结合起来，创建最先进的儿童喘息指数（WIND），以识别患有严重细支气管炎的儿童，这些儿童发生复发性喘息的风险较高。根据2007年美国国立卫生研究院哮喘指南的建议，该指数将确定谁可能从吸入皮质类固醇或其他哮喘控制措施中受益。该研究小组由美国国立卫生研究院资助的研究人员组成，他们在该领域领导了许多多中心研究。在2年的时间里，10家医院的研究人员将招募1000名年龄<1岁的严重毛细支气管炎儿童。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回顾。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项多中心研究，重点是呼吸紧急情况和公共卫生。现场调查人员将收集鼻咽和血液样本；人口、出生、营养、家庭和环境信息；以及来自父母、初级保健、急诊科和住院病人的临床数据。该研究将有80%的能力检测出复发性喘息发生的1.3- 1.8倍差异，以比较鼻病毒细支气管炎（与RSV或其他病原体相比），入住重症监护病房（与普通病房相比），以及在鼻咽吸入物中检测到（与未检测到）CCL5的儿童。将25(OH)D作为一个连续变量，该研究将有80%的能力检测到25(OH)D每增加1 SD (19 nmol/L)，复发性喘息的几率增加1.3倍。研究人员估计，在鉴别患有严重毛细支气管炎的儿童是否会出现复发性喘息时，WIND的阳性预测值为85%。这项研究与2009年美国国立卫生研究院儿科呼吸系统研究战略计划非常吻合，并具有重大的公共卫生意义。

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.