Comparing Oral Montelukast with Inhaled Salmeterol for Exercise-Induced Bronchoconstriction?
abstract & commentary
Synopsis: This study concluded that montelukast provides a consistent inhibition of exercise-induced bronchoconstriction at the end of eight weeks without tolerance.
Source: Edelman JM, et al. Ann Intern Med 2000;132:97-104.
Exercise-induced bronchoconstriction occurs in a majority of adults with chronic asthma. It is defined as bronchial narrowing in association with vigorous exercise. The stimulus for exercise-induced bronchoconstriction is not the exercise itself but the cooling and drying of the airway mucosa hypothesized to stimulate the activation of mast cells and release of bronchoconstricting mediators. These mediators include histamine and the cysteinyl leukotrienes (LTC4, LTD4, and LTE4).
The selective b-2 adrenergic agonists, particularly the long-acting type such as inhaled salmeterol, have been used to prevent bronchoconstriction that occurs at night or after exercise. It has been recognized that a single dose of salmeterol attenuates exercise-induced bronchoconstriction for at least 12 hours. However, it has been shown that with extended administration of salmeterol, the duration of protection decreases.1
Montelukast is a potent, oral, leukotriene receptor antagonist for the treatment of asthma. It has been shown that once-daily treatment with montelukast provides significant protection against exercise-induced bronchoconstriction over a 12-week period and tolerance to the medication is not seen after this long-term administration.2
The present study was a comparative trial of the effect of inhaled salmeterol vs. oral montelukast for exercise-induced bronchoconstriction asthma. It involved 17 asthma treatment centers in which 191 adults with asthma and documented exercise-induced bronchoconstriction were randomly assigned to double-blind treatment with montelukast (10 mg once every evening) or inhaled salmeterol (50 mg [2 puffs] twice daily).
Changes in pre- and post-exercise values, mean change from baseline in maximal percentage decrease in FEV1, area under the FEV1 curve, and time to recovery of FEV1 were assessed at days 1, 2, 3, 28, and 56. Within three days of therapy, both treatments provided significant attenuation of exercise-induced bronchoconstriction for all study end points. At weeks 4 and 8, sustained improvement was demonstrated by montelukast and a loss of bronchoprotective effect in the salmeterol group was noted. The percentage inhibition of the maximal percentage decrease in FEV1 at week 8 was 57.2% in the montelukast group and 33.0% in the salmeterol group, representing greater bronchoprotective effect for montelukast.
Edelman and colleagues conclude that once-daily long-term therapy with montelukast may provide better bronchoprotection against exercise-induced asthma than long-term inhaled salmeterol.
COMMENT by David Ost, md
The prevalence of exercise-induced bronchoconstriction among asthmatics has been reported to range from 40-90%.3 It was evident that about half of the subjects in this study had mild intermittent asthma and about half had mild persistent asthma (based on FEV1 and symptoms). None of the patients was on inhaled steroids.
The article demonstrates that in this group of patients, montelukast rendered significantly greater inhibition of exercise-induced bronchoconstriction compared with salmeterol at four and eight weeks of therapy. Previous findings with salmeterol have suggested that partial tolerance develops at four and eight weeks. This is in contrast to montelukast, in which the bronchoprotective effect was maintained. They also noted that fewer patients on montelukast required b-agonist rescue after exercise compared with the salmeterol group.
Oral montelukast is more convenient to take than inhaled salmeterol and this study suggests that tolerance to montelukast does not develop as readily as it does to salmeterol. For mild asthmatics with primarily exercise-induced symptoms, montelukast may represent a good initial treatment.
References
1. Nelson JA, et al. N Engl J Med 1998;339:141-146.
2. Leff JA, et al. N Engl J Med 1998;339:147-152.
3. McFadden ER, Jr., Gilbert IA. N Engl J Med 1994;330: 1362-1367.
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