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Bronchoprotective Effects of Single Doses of Salmeterol Combined With Montelukast in Thermally Induced Bronchospasm*

From the Center for Academic Clinical Research, Case Western Reserve University School of Medicine, and the Division of Pulmonary Critical Care and Sleep Medicine and Department of Medicine of MetroHealth Medical Center, Cleveland, OH.

Correspondence to: E.R. McFadden, Jr., MD, Division of Pulmonary, Critical Care, and Sleep Medicine, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109; e-mail: erm2{at}cwru.edu

Study objectives: 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.

Design: Randomized trial.

Setting: University teaching hospital.

Participants: Atopic asthmatic patients with sensitivity to thermal provocations.

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

Measurements and results: Minute ventilation (E) was increased in 20-L increments until FEV₁ fell 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) FEV₁ decreased 24.6 ± 1.7% from baseline. S and M both increased the mean prechallenge FEV₁ 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).

Conclusion: 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.

Key Words: airway hyperresponsiveness • bronchospasm • montelukast • prophylaxis • salmeterol • thermally induced asthma

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				G. Philip, D. S. Pearlman, C. Villaran, C. Legrand, T. Loeys, R. B. Langdon, and T. F. Reiss Single-Dose Montelukast or Salmeterol as Protection Against Exercise-Induced Bronchoconstriction Chest, September 1, 2007; 132(3): 875 - 883. [Abstract] [Full Text] [PDF]