Preemptive use of high-dose fluticasone for virus-induced wheezing in young children

N Engl J Med. 2009 Jan 22;360(4):339-53. doi: 10.1056/NEJMoa0808907.


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 microg 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 beta(2)-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. ( number, NCT00238927.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Androstadienes / administration & dosage*
  • Androstadienes / adverse effects
  • Asthma / prevention & control*
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Fluticasone
  • Glucocorticoids / administration & dosage*
  • Growth / drug effects
  • Humans
  • Infant
  • Male
  • Respiratory Sounds / drug effects*
  • Respiratory Sounds / etiology
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / virology
  • Virus Diseases / complications*


  • Androstadienes
  • Bronchodilator Agents
  • Glucocorticoids
  • Fluticasone

Associated data