ArticlesUse of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial
Introduction
In children with mild persistent asthma, guidelines recommend the daily use of inhaled corticosteroids in low doses as the preferred treatment for the control of symptoms and asthma exacerbations.1, 2 Often, parents or children have great difficulty adhering to twice daily treatment during long asymptomatic periods, and either use inhaled corticosteroids sparingly or interrupt treatment altogether.3 Moreover, for children whose illness is well controlled with such treatment, no studies have established the optimum period for which treatment should be maintained, or at which point an individual should be weaned from treatment. Guidelines1 suggest weaning or withdrawal (step-down) of treatment after asthma control is achieved and maintained, without any clear evidence to support these recommendations.
Even when good day-to-day control is achieved with inhaled corticosteroids, children with mild persistent asthma can have a high frequency of exacerbations.4, 5 Thus, two essential and related challenges exist in the treatment of childhood asthma. First, what is the best strategy for discontinuing treatment in children with well controlled, mild asthma, but who are still at risk for exacerbations. Second, is there a treatment regimen that will decrease the risk of exacerbations in children with mild disease to a greater extent than is achieved with daily inhaled corticosteroids? Does this regimen need to be added to continued treatment with daily inhaled corticosteroids or can it be given on an as-needed basis?
Use of inhaled corticosteroids as rescue medication in combination with a bronchodilator can substantially decrease the frequency of asthma exacerbations that require prednisone.6, 7, 8, 9 Use of budesonide plus formoterol as rescue, when added to daily treatment with either budesonide or budesonide plus formoterol, substantially reduces the frequency of asthma exacerbations in both children and adults.6, 7, 8 In adults with mild asthma who took placebo twice daily, the use of beclomethasone plus albuterol as rescue was associated with substantially fewer exacerbations than was treatment with rescue albuterol alone, and with a similar frequency of exacerbations as with beclomethasone twice daily.9 These results suggest that inhaled corticosteroids used together with a bronchodilator as rescue could provide additional protection against exacerbations in children who are taking daily inhaled corticosteroids, and might also decrease the frequency of exacerbations in those who are not.
The goals of this TREXA study were to establish whether discontinuation of daily inhaled corticosteroids in children with well controlled, mild persistent asthma is associated with an increased risk of exacerbations, and whether or not the use of beclomethasone plus albuterol for relief, with or without concomitant use of daily beclomethasone, provides better protection against exacerbations than does a rescue strategy that uses albuterol alone.
Section snippets
Participants
Between January, 2007, and May, 2009, we recruited children and adolescents aged between 6 and 18 years from five clinical centres in the USA: Denver, CO; Madison, WI; Saint Louis, MO; San Diego, CA; and Tucson, AZ (satellite centres in Milwaukee, WI, and Albuquerque, NM, also recruited participants). All individuals recruited had a history of mild persistent asthma during the previous 2 years, and qualified for interruption or discontinuation of controller treatment because their illness was
Results
843 children were enrolled into the trial, of whom 288 (34%) were assigned to one of the four treatment groups (figure 1). Sociodemographic and clinical characteristics were much the same between participants who were randomised and those who were enrolled but were not eligible for the treatment phase (n=555; webappendix p 4). Baseline characteristics were much the same between individuals in the four treatment groups (table 1).
Figure 2 shows the Kaplan-Meier plots for time to first
Discussion
In this trial, we noted that, compared with treatment with only albuterol as rescue, daily beclomethasone reduced the risk for a first exacerbation by half, whereas rescue beclomethasone decreased the risk by more than a third, but this effect was not significant. Treatment failures were also substantially decreased in both groups that used daily beclomethasone and in the rescue beclomethasone group. Our results therefore suggest that rescue beclomethasone can lower the risk of exacerbations
References (26)
- et al.
Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial
J Allergy Clin Immunol
(2007) - et al.
Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial
Chest
(2006) - et al.
Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma
Chest
(2006) Guidelines for the diagnosis and management of asthma
Global strategy for asthma management and prevention
- et al.
Assessing adherence and factors associated with adherence in young children with asthma
Respirology
(2008) Long-term effects of budesonide or nedocromil in children with asthma
N Engl J Med
(2000)- et al.
Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma
Am J Respir Crit Care Med
(2005) - et al.
Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma
N Engl J Med
(2007) - National Asthma Education Prevention Program Coordinating Committee. Expert Panel II. Guidelines for the diagnosis and...
Analysis and reporting of factorial trials: a systematic review
JAMA
Factorial trials in cardiology: pros and cons
Eur Heart J
Epinephrine and dexamethasone in children with bronchiolitis
N Engl J Med
Cited by (274)
The Role of ICS-Containing Rescue Therapy Versus SABA Alone in Asthma Management Today
2024, Journal of Allergy and Clinical Immunology: In PracticeBeginning to Address an Implementation Gap in Asthma: Clinicians’ Views of Prescribing Reliever Budesonide-Formoterol Inhalers and SMART in the United States
2023, Journal of Allergy and Clinical Immunology: In PracticeMild asthma: Lessons learned and remaining questions
2023, Respiratory Medicine“As-Needed” Inhaled Corticosteroids for Patients With Asthma
2023, Journal of Allergy and Clinical Immunology: In PracticeThe ICS/Formoterol Reliever Therapy Regimen in Asthma: A Review
2023, Journal of Allergy and Clinical Immunology: In Practice