Rationale for Leukotriene Antagonism in Childhood Asthma

The use of LTRAs as preventer therapy in children with asthma is supported by evidence suggesting that persistent elevation of cysteinyl leukotrienes in the serum and urine of children with asthma indicates the presence of an ongoing inflammatory process, which contributes to bronchial hyperresponsiveness.5

In children with asthma triggered by viral infections (see Box 2), the use of LTRAs as a strategy to reduce airway reactivity is based on the observation that cysteinyl leukotrienes are released in the airway during respiratory syncytial virus infection and are thought to contribute to inflammation.

In children with asthma symptoms in response to exercise, the use of LTRAs is based on evidence that the pathophysiology of exercise-induced bronchoconstriction involves the release of inflammatory mediators including cysteinyl leukotrienes in response to airway dehydration during exercise.6

Safety profile

Montelukast is well tolerated. Clinical trials in children have reported montelukast adverse event rates comparable with those in placebo-treated children.7-9 It does not appear to affect linear growth in pre-pubescent children.10, 11 Recently, concerns have been raised about behavioural adverse effects in children taking montelukast. These appear to be rare in clinical trials.12, 13 Since the introduction of montelukast in clinical practice, data from adverse event reports suggest that the use of montelukast in children is associated with a slight increase in the risk of psychiatric disorders,14 but a clear causal link has not been established due to potentially confounding effects including concomitant medication and the severity of underlying asthma. Cessation of therapy appears to be associated with resolution of symptoms.14 When prescribing montelukast to children, doctors should advise parents of the potential association of montelukast with behaviour-related adverse events and advise them to cease treatment if behavioural effects are suspected.

Convenience

An orally administered preventive treatment may be a useful alternative to other treatments, particularly for very young patients who have difficulty using inhalers reliably. Preference for a once-daily oral agent over a multiple-dose inhaled agent is likely to improve adherence.15

Box 2. Background: viral-induced wheeze

Preventing episodes of viral-induced wheeze or infrequent intermittent asthma has proven to be very difficult. Regular low-dose ICS does not reduce episode frequency or severity in children with episodic viral-induced wheeze.1

Parents of preschool-aged children with viral-induced wheeze are commonly advised to begin giving their child a short course of oral prednisolone at the onset of an exacerbation. However, current evidence suggests this is not an effective strategy for recurrent viral-induced wheeze,16 and does not reduce the risk of hospital admission in preschoolers.17

In school-aged children, a short course of oral prednisolone initiated by parents when their child experiences an episode of acute asthma (triggered by any cause) may reduce asthma symptoms and lost school days, but the benefits need to be balanced against potential adverse effects of repeated corticosteroid courses.18

Standard current treatment for acute episodes is inhaled short-acting beta2 agonist bronchodilators. Oral corticosteroids (in addition) remain the treatment of choice in severe acute asthma managed in hospital emergency departments, and are more effective than high-dose ICS in this context.19