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Corticosteroids for Virus-Induced Childhood Wheezing
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Professor of Pediatrics, Tufts University School of Medicine; Chief Academic Officer, Baystate Medical Center, Springfield, MA, is Associate Editor for Infectious Disease Alert.
Dr. Jenson is a speaker for Merck.
Synopsis: Two studies compared different approaches using corticosteroids for virus-associated wheezing in young children. The first study found no benefit of oral prednisolone in preschool children hospitalized with virus-induced wheezing. The second study showed modest benefit of preemptive use of intermittent, very high-dose inhaled fluticasone in preschool children with episodic wheezing. However, there were safety concerns, including a small reduction in linear growth that was observed in children receiving fluticasone. The current widespread practice of routine use of oral corticosteroids for virus-associated wheezing in preschool children is not warranted.
Source: Panickar J, et al: Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009;360:329-338.
A randomized, double-blind, placebo-controlled trial conducted in England among 687 children 10-60 months of age with acute virus-associated wheezing compared a five-day course of oral prednisolone (10 m once a day for children 10-24 months of age and 20 mg once a day for older children) with placebo. There were 343 children assigned to receive prednisolone and 344 assigned to receive placebo. There were no significant differences in the primary outcome of duration of hospitalization (11.0 hours for prednisolone vs 13.9 hours for placebo; ratio of geometric means, 0.90; 95% CI, 0.77-1.05), secondary outcomes, or adverse events between the two groups.
A randomized, placebo-controlled trial with triple blinding was conducted at five institutions in Quebec among 129 children 1-6 years of age with virus-induced wheezing and compared preemptive use of very high-dose inhaled fluticasone (1.5 mg per day) with placebo. Inclusion criteria included a history of ≥ 3 wheezing episodes seemingly triggered exclusively by upper respiratory tract infections, with at least one course of rescue systemic corticosteroids within six months or two courses within one year, and no intercurrent symptoms. Over a period of 6-12 months, children received fluticasone or placebo twice daily, beginning with the first signs of an upper respiratory tract infection and continuing until 48 hours had elapsed with no symptoms, for a maximum of 10 days.
Over a median period of 40 weeks, children with upper respiratory tract infections receiving fluticasone had to use rescue systemic corticosteroids only 8% compared to 18% for the placebo group (odds ratio, 0.49; 95% CI, 0.30-0.83). However, children treated with fluticasone had smaller gains from baseline in height (6.23 ± 2.62 cm vs 6.56 ± 2.90 cm; difference between groups in z score, -0.24; 95% CI -0.40 to -0.08) and in weight (1.53 ± 1.17 kg vs 2.17 ± 1.79 kg; difference between groups in z score, -0.26; 95% CI, -0.41 to -0.09). There were no significant differences between the groups in basal cortisol level or bone mineral density during the period of this study.
Wheezing is highly prevalent among young children, and is a common cause for clinic visits and hospitalization. Some children with underlying atopy develop wheezing that is associated with multiple triggers, including upper respiratory tract infections. Among non-atopic children, the most common trigger of episodic wheezing is a viral upper respiratory tract infection.
Young children in both groups presenting with wheezing are currently treated very similarly with β2-agonists, as well as the routine use of episodic oral corticosteroids, based upon the assumption that the wheezing represents a common outcome of different triggers. These two reports are disruptive and challenge this assumption.
The first paper shows no benefit of oral prednisolone in preschool children hospitalized with acute virus-induced wheezing. This indicates that the current routine use of oral corticosteroids for management of acute wheezing in preschoolers is overused. Preschoolers without atopy who present with episodic virus-induced wheezing do not need treatment with corticosteroids unless a severe clinical course is anticipated.
The second paper showed modest benefits of preemptive, intermittent use of inhaled fluticasone, but with a small reduction in linear growth. The clinical benefit of fluticasone was not durable and, because of this, safety concerns cannot be recommended; the safety concerns are much greater if fluticasone were to be used preemptively throughout childhood.