Rationale
for leukotriene antagonism in childhood asthma
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.9,13,14It does not appear
to affect linear growth in pre-pubescent children.
