Preemptive Use of High-Dose Fluticasone for Virus-Induced Wheezing in Young Children

Francine M. Ducharme, M.D., Chantal Lemire, M.D., Francisco J.D. Noya, M.D., G. Michael Davis, M.D., Nathalie Alos, M.D., Hélène Leblond, M.D., Cheryl Savdie, M.Sc., Jean-Paul Collet, M.D., Ph.D., Lyudmyla Khomenko, Ph.D., Georges Rivard, M.D., and Robert W. Platt, Ph.D.

ABSTRACT

Background Although virus-induced wheezing is common in preschool-age children, optimal management remains elusive. We examined the efficacy and safety of preemptive treatment with high-dose fluticasone in reducing the severity of recurrent virus-induced wheezing in children.

Methods We randomly assigned 129 children who were 1 to 6 years of age to receive 750 µg of fluticasone propionate (ex-valve [manufacturer-measured] dose) or placebo twice daily, beginning at the onset of an upper respiratory tract infection and continuing for a maximum of 10 days, over a period of 6 to 12 months. The primary outcome was rescue oral corticosteroid use. Secondary outcomes included symptoms, use of β₂-agonists, acute care visits, hospitalizations, discontinuation of the study drug, change in growth and bone mineral density, basal cortisol level, and adverse events.

Results Over a median period of 40 weeks, 8% of upper respiratory tract infections in the fluticasone group led to treatment with rescue systemic corticosteroids, as compared with 18% in the placebo group (odds ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were treated with fluticasone, as compared with those who were given placebo, had smaller mean (±SD) gains from baseline in height (6.23±2.62 cm [unadjusted value]; z score, –0.19 ±0.42 vs. 6.56±2.90 cm [unadjusted value]; z score, 0.00±0.48; difference between groups in z score from baseline to end point, –0.24 [95% CI, –0.40 to –0.08]) and in weight (1.53±1.17 kg [unadjusted value]; z score, –0.15±0.48 vs. 2.17±1.79 kg [unadjusted value]; z score, 0.11±0.43; difference between groups in z score from baseline to end point, –0.26 [95% CI, –0.41 to –0.09]). There were no significant differences between the groups in basal cortisol level, bone mineral density, or adverse events.

Conclusions In preschool-age children with moderate-to-severe virus-induced wheezing, preemptive treatment with high-dose fluticasone as compared with placebo reduced the use of rescue oral corticosteroids. Treatment with fluticasone was associated with a smaller gain in height and weight. Given the potential for overuse, this preventive approach should not be adopted in clinical practice until long-term adverse effects are clarified. (ClinicalTrials.gov number, NCT00238927 [ClinicalTrials.gov] .)