Is montelukast effective and well tolerated in the management of asthma in young children?

Asthma in preschool children is a particularly troublesome problem for the clinician. This age group is susceptible to multiple virus infections, often in association with daycare, resulting in frequent exacerbations. In addition, inhaled medication, effective in older children, can be difficult to deliver to the toddler. Montelukast, therefore, is a welcome addition to the asthma treatment arsenal. It can be given by chewable tablet or sprinkled granules mixed with food.

Montelukast has a very narrow site of action in comparison to the broad anti-inflammatory action of the commonly used inhaled corticosteroids. As one of the leukotriene-receptor antagonists, it blocks the action of cysteinyl leukotrienes, which catalyze the inflammatory cascade from eosinophils, mast cells and alveolar macrophages (1). This reduces the main characteristics of asthma, such as airflow obstruction, mucus hypersecretion, mucosal edema and desquamation, bronchoconstriction, bronchial hyperresponsiveness and eosinophil accumulation.

The papers chosen (2–4) investigate whether montelukast is a useful and safe medication for the younger patient with asthma. It should be noted at the outset that the drug manufacturer sponsored all of these studies. Two studies looked at the preschool age group (two to five years of age), comparing montelukast with placebo (2,3). Both studies selected young patients with intermittent asthma triggered by colds. Some of the patients in the study were on inhaled steroids (29% for Knorr et al [3] to 45% for Bisgaard et al [2]). This is important because additive asthma control would be beneficial. Both studies were multinational, multicentre and well designed, although there were no details about allocation concealment. Patients had a run-in period and then were treated in a randomized, double-blind fashion. Knorr et al (3) followed patients for three months, and Bisgaard et al (2) followed patients for almost one year. In both studies, the conclusions were essentially the same: decreased asthma exacerbations and consequently, fewer requirements for ‘rescue’ treatment. The longer duration study quantified this as a reduction from 2.34 exacerbation episodes to 1.60 per year (2). This was a statistically significant result, but was it a clinically important improvement to justify a daily medication? The investigators commented that the benefit was greatest during the autumn and winter, suggesting, therefore, that patients may only require treatment for part of the year.

The other study (4) posed a different question in a different group of patients: does montelukast have serious adverse effects in infants and toddlers (six to 24 months of age)? This study again examined patients with physician-diagnosed asthma or at least three ‘asthma-like’ episodes. Approximately one-half of the patients were already on inhaled corticosteroids. Patients were randomly assigned into montelukast or placebo for a six-week period. The study was powered to detect an adverse effect rate of 19.4% in the montelukast group and 1% in the placebo arm. The patients were examined every two weeks, and all effects were recorded. There were no differences in adverse effects in each group. The conclusion was that the adverse effect frequency was similar in both the placebo and drug groups. The investigators also looked for a reduction in asthma symptoms, but there was no difference between montelukast and placebo groups. It is likely that the study was not of sufficient duration to fully assess these outcomes.

How do these studies help us in the care of patients? This medication has several advantages. It can be taken orally and this may improve compliance (5,6). It is not a steroid, which may appeal to some parents who are concerned about potential side effects. It appears to be safe and well-tolerated in our youngest patients. Its disadvantages are that it is generally weaker than 400 mg of inhaled beclomethasone (or equivalent), and that patients are more likely to suffer a flare up when on this medication alone (7). In very young patients (under two years of age), montelukast may be only modestly beneficial. In summary, montelukast would appear to be useful in reducing asthma exacerbations by approximately one-third. This drug is recommended as the next step after inhaled steroids in most guidelines (8,9). It appears to be useful for the preschool age group and when there is coexisting allergic rhinitis (10). Montelukast may also help reduce symptoms when used as a short course in intermittent asthma, but this remains to be confirmed in other studies (11).