The full protocol and statistical analysis plan are available in Supplement 1. The institutional review board at each center approved and monitored the study. Parents or guardians provided written informed consent. Participants received compensation for time and travel expenses. Details about inclusion and exclusion criteria are provided in Supplement 2. Briefly, eligible participants were children aged 12 through 71 months with recurrent severe wheezing in the context of clinically significant LRTIs that required systemic corticosteroids, an unscheduled physician office visit, an urgent or emergency department visit, or hospitalization. Exclusion criteria included more than 4 courses of systemic corticosteroids or more than 1 hospitalization in the past 12 months, or use of long-term controllers for asthma for more than 8 months in the past 12 months. These criteria excluded children with more severe disease who require daily controller medication. Children receiving monotherapy with asthma controllers (either low-dose inhaled corticosteroids or montelukast) at enrollment were eligible but had their controller discontinued upon study entry, consistent with recommendations for step-down therapy. Children with significant symptomatic asthma and those with inadequate adherence to diary card completion (<80% of days) during the 2 to 4 week run-in period (defined in Supplement 2) were also excluded. Race was assessed by parent/guardian report, using National Institutes of Health race/ethnicity reporting standards and categories.
A participant was classified as having a positive modified asthma predictive index (API) if the participant had experienced at least 4 wheezing episodes in the past year and had 1 major criterion (physician-diagnosed atopic dermatitis, parental history of asthma, or allergic sensitization to ≥1 aeroallergen) or 2 minor criteria (wheezing unrelated to colds, blood eosinophils ≥4%, or allergic sensitization to milk, eggs, or peanuts).12 (link)