Prospective Cohort Study of Severe Bronchiolitis and Risk of Recurrent Wheezing

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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.