Inhaled corticosteroids are beneficial in treating asthma exacerbations in children with mild persistent asthma

Article Outline

• Question
• Design
• Setting
• Participants
• Intervention
• Outcomes
• Main Results
• Conclusions
• Commentary
• References
• Copyright

Martinez FD, Chinchilli VM, Morgan WJ, Boehmer SJ, Lemanske RF, Jr, Mauger DT, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet 2011; 377: 650-7.

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Question 

Among children with mild persistent asthma, how effective are inhaled corticosteroids as rescue treatment?

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Design 

Randomized, double-blind, placebo-controlled trial.

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Setting 

Five clinical centers in the United States.

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Participants 

843 children and adolescents (ages 5-18 years) with mild persistent asthma were enrolled.

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Intervention 

288 participants were assigned to one of four treatment groups (with the remainder excluded during the run-in period based on pre-defined criteria): (1) twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); (2) twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); (3) twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and (4) twice daily placebo with placebo plus albuterol as rescue (placebo group).

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Outcomes 

The primary outcome was time to first exacerbation that required oral corticosteroids. The secondary outcome measured linear growth.

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Main Results 

Compared with the placebo group (49%, 95% CI 37-61), the frequency of exacerbations was lower in the daily (28%, 18-40, P = .03, number needed to treat [NNT] = 5), combined (31%, 21-43, P = .07, NNT = 6), and rescue (35%, 24-47, P = .07, NNT = 8) groups. Frequency of treatment failure was 23% (95% CI 14-43) in the placebo group, compared with 5.6% (1.6-14) in the combined (P = .012), 2.8% (0-10) in the daily (P = .009), and 8.5% (2-15) in the rescue (P = .024) groups. Compared with the placebo group, linear growth was 1.1 cm (SD 0.3) less in the combined and daily arms (P < .0001), but not the rescue group (P = .26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.

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Conclusions 

Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects, such as growth impairment, can therefore be avoided.

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Commentary 

The TREXA study adds further support to the National Heart, Lung, and Blood Institute Guidelines that recommend daily inhaled corticosteroids for the treatment of mild persistent asthma. In addition, once children with mild persistent asthma are under control, there is less guidance in the National Heart, Lung, and Blood Institute Guidelines on how clinicians can step-down therapy. Although potential strategies have been described for adult patients,¹ the TREXA study adds to the evidence base regarding potential step-down approaches for children. While weaning from daily inhaled corticosteroid use, rescue inhaled corticosteroids with rescue albuterol might be an effective step-down strategy for children with well-controlled, mild asthma. Patients in this study were recruited from five large academic medical centers and were excluded from participation if they had any history of intubation for asthma, a hospitalization for asthma in the previous year or any asthma exacerbation in the last 3 months. In addition, this study population was a highly motivated group of participating families. According to the study criteria, subjects had to “demonstrate adherence with taking study medications (≥75% of scheduled doses), rescue medications (using both rescue inhalers for ≥75% of rescue doses) and completing patient diaries (≥75% of days).” This study highlights the importance of large clinical research network studies to develop a rigorous evidence base for clinical management strategies and fill in gaps in current clinical practice guidelines.² Evaluation of this approach in a primary care, practice-based research network setting can further assess if this strategy is appropriate for a more general pediatric population.³

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References 

1. Papi A, Canonica GW, Mesterelli P, Paggiaro P, Olivieri D, Pozzi E, et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med. 2007;356:2040–2052
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2. Denlinger LC, Sorkness CA, Chinchilli VM, Lemanske RF. Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network. J Allergy Clin Immunol. 2007;119:3–11
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3. Katz DL, Murimi M, Gonzalez A, Njike V, Green LW. From Controlled Trial to Community Adoption: the multisite translational community trial. Am J Public Health. 2011;June 16 (Epub ahead of print)
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