Prospective Cohort Study of Severe Bronchiolitis and Risk of Recurrent Wheezing

严重细支气管炎和反复喘息风险的前瞻性队列研究

基本信息

批准号：
8206080
负责人：
CARLOS A. CAMARGO
金额：
$ 131.61万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8206080
关键词：
1 year old 25-hydroxyvitamin D 3 year old 6 year old Accident and Emergency department Address Adrenal Cortex Hormones Allergic rhinitis Area Aspirate substance Asthma Atopic Dermatitis Biological Birth Blood specimen Breathing Bronchiolitis Child Childhood Childhood Asthma Clinical Clinical Data Clinical Research Cohort Studies Collaborations Data Data Collection Development Diagnosis Emergency Medicine Enrollment Eosinophilia Etiology Family Family history of Funding Future Guidelines Hospitalization Hospitalized Child Hospitals Hypersensitivity Immunity Immunology Infant Infectious Disease Epidemiology Inpatients Intensive Care Units Interview Knowledge Laboratories Long-Term Care Lung diseases Massachusetts Measures Medical Records Medicine Multicenter Studies New Zealand Nutritional Outcome Parents Pharmaceutical Preparations Positioning Attribute Predictive Value Primary Health Care Public Health Pulmonology RANTES Recurrence Research Research Design Research Personnel Rhinovirus Risk Role Sampling Serum Severities Severity of illness Site Strategic Planning Stratification Sum Testing United States National Institutes of Health Virus Vitamin D Wheezing Wisconsin base biobank cohort diaries early childhood experience high risk improved indexing novel pathogen prospective public health emergency respiratory ward

项目摘要

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.

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。小队列研究（n = 51 至 206）表明，20-60% 患有严重细支气管炎（根据需要住院治疗）的儿童会出现儿童期反复喘息。尽管存在这种密切的关联，但仍不清楚哪些患有严重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联。 2) 检查儿童血清 25-羟基维生素 D [25(OH)D] 水平与反复喘息之间的关联。 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 NIH 哮喘指南的建议，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。该研究团队由美国国立卫生研究院资助的研究人员组成，他们在该领域领导了许多多中心研究。在两年的时间内，10 家医院的研究人员将招募 1,000 名患有严重细支气管炎的 1 岁以下儿童。该队列的数据收集将包括日记、每两年一次的访谈以及相关医疗记录的年度审查。该研究将使用紧急医学网络，这是一个临床研究合作组织，已完成超过 60 项多中心研究，重点关注呼吸系统紧急情况和公共卫生。现场调查人员将采集鼻咽和血液样本；人口统计、出生、营养、家庭和环境信息；来自父母以及来自初级保健、急诊室和住院机构的临床数据。该研究将有 80% 的功效检测出 1.3 至 1.8 倍的复发性喘息发展差异，以比较入住重症监护病房（与普通病房）的鼻病毒性细支气管炎（与 RSV 或其他病原体）儿童），并且鼻咽抽吸物中可检测到（与不可检测）CCL5。将 25(OH)D 视为连续变量，该研究将有 80% 的功效检测到 25(OH)D 增加 1 SD (19 nmol/L) 时，复发性喘息的几率增加 1.3 倍。研究人员估计，WIND 的阳性预测值将达到 e85%，可识别患有严重细支气管炎且会出现反复喘息的儿童。该研究与 2009 年 NIH 儿科呼吸研究战略计划非常吻合，并且具有重大的公共卫生意义。公共卫生相关性：在一项针对 1,000 名儿童的多中心前瞻性队列研究中，研究小组将检查两种常见儿科疾病之间的关联：细支气管炎和幼儿期反复喘息。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非常吻合。具体来说，拟议的队列将改善患有严重细支气管炎的儿童的短期和长期护理，这种疾病通常会导致儿童哮喘。