The currently recommended options for children whose asthma is not adequately controlled on inhaled corticosteroids alone are:
- adding a long-acting beta2 agonist
- adding a leukotriene receptor antagonist
- increasing the dose of inhaled corticosteroids.
Before intensifying the treatment of poorly controlled asthma it is important to first exclude other factors contributing to poor control. These include incorrect diagnosis, poor adherence, inappropriate delivery device and poor inhaler technique.
When comparing the addition of long-acting beta2 agonists to an increased dose of inhaled corticosteroids, current evidence suggests that while regular use of long-acting beta2 agonists will predictably improve lung function, the risk of exacerbation appears, if anything, to increase.2,4
A randomised triple crossover study in 182 children aged 6–17 years of age who had uncontrolled asthma on 100 microgram of fluticasone propionate twice daily also provides relevant comparative information.1 These children received 16 weeks on each of the following therapies, in random order:
- 250 microgram of fluticasone twice daily (inhaled corticosteroid step-up)
- 100 microgram of fluticasone plus 50 microgram salmeterol twice daily (long-acting beta2 agonist step-up)
- 100 microgram of fluticasone twice daily plus 5 or 10 mg montelukast daily (leukotriene receptor antagonist step-up).
The response was assessed by a composite index comprising exacerbations requiring oral corticosteroids, asthma-control days and forced expiratory volume in one second. Overall the probability of the long-acting beta2 agonist step-up providing the best response was higher (45%), but the probability of having a best response to leukotriene receptor antagonist (28%) or inhaled corticosteroid (27%) step-up was also significant. This highlights the variability of children’s responses to these drugs, plus the need to regularly monitor and appropriately adjust each child’s therapy.9
What is clear is that leukotriene receptor antagonists are superior to long-acting beta2 agonists in protecting against exercise-induced bronchoconstriction as add-on therapy in children already receiving inhaled corticosteroids.7 Further, in contrast to regular use of long-acting beta2 agonists, leukotriene receptor antagonists are not associated with the development of tolerance to either protection against exercise-induced bronchoconstriction, nor responsiveness to short-acting beta2 agonists.7 Montelukast has now been listed in the Australian Pharmaceutical Benefits Scheme for add-on treatment (as an alternative to long-acting beta2 agonists) for children aged 6–14 years, who despite inhaled corticosteroids, have ongoing activity (exercise)-related asthma.
Recommendations on step-up options11
In situations where effective control of asthma cannot be achieved with doses of 400 microgram/ day budesonide, or 200 microgram/day fluticasone or hydrofluoroalkane-beclomethasone dipropionate or 160 microgram/day ciclesonide, the main step-up options include increasing the inhaled corticosteroids dose or adding a long-acting beta2 agonist or a leukotriene receptor antagonist. In the absence of evidence of safety and efficacy, the use of long-acting beta2 agonists is not recommended in children aged five years or younger. (Strong recommendation, moderate quality evidence)
In children with ongoing exercise-induced symptoms, despite inhaled corticosteroids, adding leukotriene receptor antagonists has been shown to be effective and superior to long-acting beta2 agonists, and does not have the problem of the development of tolerance. (Strong recommendation, moderate quality evidence)
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