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Rationale for leukotriene antagonism in childhood asthma |
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The use of LTRAs as preventer therapy in children with asthma has been investigated following the emergence of 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 contributing to bronchial hyperresponsiveness.4
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.5
The prevention of viral-induced wheeze or infrequent intermittent asthma in young children has proven to be very difficult. Parents are commonly advised to begin giving their child a short course of oral prednisolone at the onset of an exacerbation, but recent evidence suggests this is not an effective strategy for recurrent viral-induced wheeze,6and does not reduce the risk of hospital admission in preschoolers.7 Although short courses of high-dose ICS in response to viral-induced wheeze may be partially effective, regular low-dose ICS does not reduce episode frequency or severity in children with episodic viral-induced wheeze.8 Standard current treatment for acute episodes is inhaled short-acting beta2 agonist (SABA) bronchodilators and oral corticosteroids. Based on the observation that cysteinyl leukotrienes are released in the airway during respiratory syncytial virus infection and are thought to contribute to inflammation, the use of LTRAs has been suggested as a strategy to reduce airway reactivity in these children.
Montelukast is administered once daily as a 4 mg (ages 2–5) or 5 mg (ages 6–14) chewable tablet, with or without food. The onset of therapeutic effects occurs within 1 day of commencing treatment.9 Studies in children with exercise-induced bronchoconstriction have demonstrated that equal protection against exercise-induced asthma is achieved when montelukast is taken at night or in the morning.10 One study that examined the effect of montelukast at 2 and 12 hours in children with mild exercise-induced asthma found that maximal effect occurs 12 hours after dosing.11
Montelukast is well tolerated and associated with high levels of adherence. No attenuation of the bronchoprotective effect was seen after 4 weeks’ treatment in children with asthma and exercise-induced bronchoconstriction in a small (n=32) double-blind randomised clinical trial.12
Clinical trials in children have reported montelukast adverse event rates comparable with those in placebo-treated children.9,13,14 It does not appear to affect linear growth in pre-pubescent children.
Content Updated June 2007
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Last Updated ( Saturday, 26 July 2008 )
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