Ducharme FM, Lemire C, Noya FJD, et al. N Engl J Med. 2009;360(4):339–353
PURPOSE OF THE STUDY. To examine the efficacy and safety of preemptive, high-dose fluticasone treatment in reducing the severity of recurrent virus-induced wheezing in children.
STUDY POPULATION. Children between 1 and 6 years of age (N = 129) with moderate-to-severe, virus-induced wheezing were included. The investigators tried to exclude subjects with sensitization to aeroallergens, but 7% of the randomly assigned children developed symptoms of persistent or atopic asthma during the study period.
METHODS. The subjects received 750 μg of fluticasone propionate or placebo twice daily, beginning at the onset of an upper respiratory infection and continuing for a maximum of 10 days, over a period of 6 to 12 months. The primary outcome measured was the use of rescue oral steroid treatment. Secondary outcomes included symptoms, use of β2-adrenergic receptor agonists, acute care visits, hospitalizations, discontinuation of study drug administration, changes in growth and bone mineral density, basal cortisol level, and adverse events.
RESULTS. Over a median period of 40 weeks, 8% of upper respiratory infections in the fluticasone group led to systemic steroid treatment, compared with 18% in the placebo group (odds ratio: 0.49). However, children treated with fluticasone, compared with the placebo group, had smaller gains in height (6.23 ± 2.62 vs 6.56 ± 2.90 cm) and weight (1.53 ± 1.17 vs 2.17 ± 1.79 kg). There were no significant differences between the groups in basal cortisol levels, bone mineral density, or adverse events.
CONCLUSIONS. In preschool-aged children with moderate-to-severe, virus-induced wheezing, preemptive treatment with high-dose fluticasone, compared with placebo, reduced the use of rescue oral steroid treatment. High-dose fluticasone treatment, however, was associated with smaller gains in height and weight. Therefore, the authors concluded that this approach should not be adopted in clinical practice until long-term adverse effects are clarified.
REVIEWER COMMENTS. The investigators showed, on one hand, improvement in the need for oral steroid treatment for children treated with high-dose fluticasone but, on the other hand, smaller gains in height and weight for these patients. The question for the rest of us is how to incorporate these new data into clinical practice. For example, the dose of fluticasone that was used was quite substantial for small children. Was this dose on the flat part of the dose-response curve for corticosteroids? Would a smaller dose give the same benefit without the detriment? Also, how do these data apply to children with clinical allergy or risk factors for allergy?
- Copyright © 2009 by the American Academy of Pediatrics