Bronchoprotective effects of single doses of salmeterol combined with montelukast in thermally induced bronchospasm.
OBJECTIVE
Salmeterol (S) and montelukast (M) individually inhibit the obstructive consequences of thermal stimuli such as exercise and hyperventilation (HV), but there is no information on whether these drugs can interact positively.


METHODS
Randomized trial.


METHODS
University teaching hospital.


METHODS
Atopic asthmatic patients with sensitivity to thermal provocations.


METHODS
Eleven asthmatic patients generated stimulus-response curves to isocapnic HV while breathing frigid air without any interventions and then after pretreatment with 42 mug of S, 10 mg of M, and the combination. The order of testing was randomly determined.


RESULTS
Minute ventilation (Ve) was increased in 20-L increments until FEV(1) fell >or= 15%. Measurements were obtained before and 1 h after drug administration, and then again 5 min after each bout of HV. In the nonintervention trial, the provocation commenced after the patients presented to the laboratory. In the control challenge, the mean (+/- SEM) FEV(1) decreased 24.6 +/- 1.7% from baseline. S and M both increased the mean prechallenge FEV(1) significantly (S, 10.4 +/- 1.7% [p < 0.01]; M, 4.1 +/- 1.3% [p = 0.02]; S + M, p = 0.01). The combination of S + M produced greater bronchodilatation (mean improvement, 12.4 +/- 2.3%) than M alone (p = 0.004), but not greater than S alone (p = 0.80). Both drugs blunted the obstructive response similarly (protection: M, 34.6 +/- 15.1%; S, 60 +/- 8.7%; p = 0.13). The benefits added arithmetically with the combined regimen (protection with S + M, 84.9 +/- 5.5%; p = 0.01 vs S alone; p = 0.003 vs M alone).


CONCLUSIONS
These data indicate that the concurrent administration of single standard doses of S and M appears to provide greater protection against thermal stimuli than does either drug alone. Further experimentation will be required to ascertain whether the combination will provide additional clinical benefits to patients over those of the single agents.
Coreno
Albert
A
Center for Academic Clinical Research, Case Western Reserve University School of Medicine, Department of Medicine of MetroHealth Medical Center, Cleveland, OH 44109, USA.
Skowronski
Mary
M
West
Erin
E
El-Ekiaby
Amr
A
McFadden
E R
ER
D000085:Acetates / Q000008:administration & dosage*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D003521:Cyclopropanes; D003680:Deglutition Disorders; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage*; D000068299:Salmeterol Xinafoate; D013440:Sulfides; D013696:Temperature
D000085:Acetates; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast; D000420:Albuterol