Comparative effects of long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma.
BACKGROUND
Exercise-induced asthma (EIA) is a common problem that can be controlled with long-acting beta-agonists and leukotriene-modifying compounds. There is, however, limited information on the comparative effectiveness of the two classes of drugs, as well as the relative potencies of the antileukotriene agents.


OBJECTIVE
The purpose of the present study was to provide data on the above issues.


METHODS
We performed a random-order, blinded, double-dummy, placebo-controlled trial in 10 patients with EIA. Each subject received standard single doses of salmeterol, montelukast, zafirlukast, zileuton, and placebo on separate days. The participants performed 4 minutes of cycle ergometry while breathing frigid air 1, 4, 8, and 12 hours after administration of the test agents. The primary endpoint was the extent of the decrement in the FEV(1) 10 minutes after exertion.


RESULTS
With placebo, symptomatic airway narrowing developed at all times (mean +/- SE decrease in FEV(1) ranged between 21% +/- 5% and 26% +/- 5%). Salmeterol acted quickly and significantly blunted the obstructive response for 12 hours (DeltaFEV(1) first hour: 8% +/- 3%; DeltaFEV(1) twelfth hour: 8% +/- 3%; P <.0001 vs placebo and P =.72 vs time). The leukotriene-modifying agents produced effects within 1 hour of ingestion. Like salmeterol, montelukast and zafirlukast also offered long-lasting protection, and there were no significant differences between them (montelukast DeltaFEV(1) twelfth hour: 9% +/- 4%; zafirlukast DeltaFEV(1) twelfth hour: 11% +/- 2%; P =.75) or the beta(2)-agonist (montelukast vs salmeterol: P =.72; zafirlukast vs salmeterol: P =.48). Zileuton provided equivalent prophylaxis for the first 4 hours (DeltaFEV(1) fourth hour: 11% +/- 2%); however, by 8 hours, it was less efficacious than all of the other active compounds, and by 12 hours it did not differ from placebo (DeltaFEV(1) twelfth hour: 19% +/- 4%; P =.33).


CONCLUSIONS
Single doses of the currently available leukotriene receptor antagonists provide prompt effective and persistent defense against EIA that equals that seen with a long-acting beta(2)-agonist. The synthesis inhibitor zileuton affords a comparable magnitude of prophylaxis but has a considerably shorter duration of action.
Coreno
A
A
Division of Pulmonary and Critical Care Medicine and the Airway Disease Center of University Hospitals of Cleveland, 44106-5067, USA.
Skowronski
M
M
Kotaru
C
C
McFadden
E R
ER
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D001250:Asthma, Exercise-Induced / Q000188:drug therapy*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors; D008297:Male
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors