Oral montelukast was better than inhaled salmeterol for reducing exercise induced bronchoconstriction in adults with asthma
Edelman JM, Turpin JA, Bronsky EA, et al, for the Exercise Study Group. Oral montelukast compared with inhaled
salmeterol to prevent exercise.induced bronchoconstriction. Ann Intern Med 2000 Jan 18;132:97-104
QUESTION: Is oral montelukast as effective as inhaled salmeterol for prevention of
exercise induced bronchoconstriction (EIB) in adults with asthma?
Design
Eight week, randomised {allocation concealed*}†, blinded {patients, clinicians, outcome assessors, statisticians},*† controlled trial.
Setting
17 asthma treatment centres in the US.
Patients
191 patients who were 15-45 years of age (mean age 26 y,
52% men), had a history of chronic asthma, had an FEV1
>65% of the predicted value at rest, and had a decrease in
FEV1 >20% after a standardised exercise challenge on
two occasions during baseline measurement. Exclusion
criteria were upper respiratory infection or exacerbation
of asthma that had required emergency care in the pre.
vious month or admission to hospital for asthma in the
previous three months. Follow up at eight weeks was 93%.
Intervention
After a two week period of placebo, 97 patients were
allocated to oral montelukast, 10 mg tablet once in the
evening for eight weeks, and 94 were allocated to inhaled
salmeterol, two puffs of 50 mg aerosol formulation twice
daily for eight weeks.
Main outcome measures
Main outcome was change from baseline in the maximal
percentage decrease in FEV1 after a standardised exercise
challenge at eight weeks. Other outcomes included maximal percentage decrease in FEV1 at one to three days and
four weeks, the need for rescue medication during or after
exercise, and adverse events and laboratory abnormalities.
Main results
Analysis was by intention to treat. Within three days of
initiation of treatment, both groups improved in the
maximal percentage decrease in FEV1 after exercise; this
improvement was maintained at four weeks and eight
weeks in patients who received montelukast but not in
patients who received salmeterol (p = 0.015 at four
weeks and p = 0.002 at eight weeks). At any time, fewer
patients who received montelukast required rescue
doses of β-agonist after exercise challenge than did
patients who received salmeterol (26% v 40%, p = 0.04).
The groups did not differ in frequency of clinical or
laboratory adverse events.
Conclusion
Oral montelukast reduced exercise induced bronchoconstriction in adults with asthma more than did inhaled
salmeterol at eight weeks of treatment.
COMMENTARY
Airway hyperresponsiveness to exercise and response to
treatment are important and quantifiable indexes of asthma
control. Currently, montelukast does not have an approved
indication in the US for the management of EIB. Previous
investigation has shown that at 12 weeks montelukast treatment offered greater protection against EIB than did
placebo.1 Edelman et al expand our understanding of the
role of montelukast by comparing it with an inhaled
bronchodilator rather than with placebo.
Several issues deserve mention. Firstly, this trial evaluated
and compared the protective effects of montelukast and
salmeterol at the end of their dosing intervals. Whether comparable protection against EIB exists earlier in the dosing
cycle was not studied. Secondly, the effect of montelukast in
patients with more severe chronic asthma was not investigated. These points aside, this study shows that montelukast
had a durable effect in reducing the magnitude of the broncho-constrictive response to provocative exercise challenge.
What should the practitioner take from these results? For
patients with mild asthma and near normal baseline lung
function, the prescriber must weigh the potential benefit and
burden (cost, convenience, and safety) of using a long term
drug, such as montelukast, against those of an as needed
inhaled β-agonist for the prophylaxis or management of
EIB. These findings also suggest that the protective effect of
salmeterol in EIB decreases after long term administration.
This finding is consistent with those of other studies of
salmeterol and other long acting inhaled β-agonists.2
Peter K Honig, Food and Drug Administration, Rockville, Maryland, USA
- Leff JA, Busse WW, Pearlman D, et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med 1998;339:147-52.
- Lipworth B, Tan S, Devlin M, et al. Effects of treatment with formoterol on bronchoprotection against methacholine. Am J Med 1998;104:431-8.
studentBMJ 2000;08:347-394 October ISSN 0966-6494
