The challenge of treating preschool wheezing

Abstract

In a post hoc analysis of data collected during 2 clinical trials evaluating interventions for wheezing episodes in preschool children, Beigelman et al attempt to answer the question of ‘‘whether OCS treatment, when given to preschool children with severe intermittent wheezing during acute episodes of severe LRTI, reduces illness burden as reflected by daily symptom scores during the LRTI. . . .’’ The authors report that the use of oral corticosteroids (OCSs) does not lessen the intensity of the symptoms or the duration of a wheezing episode. Given that OCSs have long been the recommended therapy for exacerbations of asthma, these results seem counterintuitive. Because this was not a planned analysis of either study, the analytic approach used must be scrutinized carefully to ensure the conclusions are not based on faulty methodology. For example, the use of OCSs during wheezing episodes was not assigned randomly in these trials, and therefore a simple comparison would potentially be biased because OCSs would be expected to be administered during the more severe wheezing episodes. The authors developed and used propensity score adjustment, a widely used approach that adjusts for predetermined factors to remove the influence of potential confounding variables between groups being compared. In these analyses propensity scores were used to ‘‘equalize’’ the level of severity between the wheezing episodes with and without treatment with OCSs to allow for an unbiased comparison. The results were replicated in 2 independent trials designed to study the same wheezing phenotype and which used identical criteria for the use of OCSs to reduce the probability of a chance finding. Finally, the primary comparisons were focused on the more severe wheezing episodes in which OCSs would be expected to have the greatest benefit. These steps and others taken by the authors make the methodology used in these post hoc analyses sound. To better understand the authors’ conclusions, one needs to look back at the 2 studies that contributed the data for these analyses: the Acute Intervention Management Strategies (AIMS) trial and the Maintenance and Intermittent Inhaled Corticosteroids in Wheezing Toddlers (MIST) trial. Both of these trials were directed at the phenotype of severe intermittent wheezing in preschool children, which is defined as children less than 6 years of age who have wheezing (high risk) with respiratory