Effects of montelukast and budesonide on airway responses and airway inflammation in asthma.
Inhaled corticosteroids are effective antiinflammatory therapy for asthma; however, they do not completely abolish allergen-induced airway inflammation. Leukotriene modifiers attenuate both early and late allergen responses and have antiinflammatory properties. We reasoned that treatment with budesonide and montelukast in combination might provide greater antiinflammatory effects than either drug alone, and the purpose of this study was to compare the effects of treatment with budesonide and montelukast, alone or in combination, on outcome variables after allergen inhalation. Ten subjects with asthma with dual responses after allergen inhalation were included in this randomized, double-blind, crossover study. Outcomes included early and late asthmatic responses, and changes in airway responsiveness and sputum eosinophilia, measured before and after challenge. Treatment with montelukast attenuated the maximal early asthmatic response compared with placebo (p < 0.001) and budesonide (p = 0.002). Both budesonide and montelukast, alone and in combination, attenuated the maximal late asthmatic response compared with placebo (p < 0.01). Budesonide and montelukast, alone and in combination, afforded protection against allergen-induced airway hyperresponsiveness (p < 0.05), although the treatment effect of budesonide was greater than that of montelukast (p < 0.05). Treatment with budesonide and montelukast, alone and in combination, also attenuated allergen-induced sputum eosinophilia. Thus, montelukast and budesonide attenuated allergen-induced asthmatic responses, airway hyperresponsiveness, and sputum eosinophilia, although combination treatment did not provide greater antiinflammatory effects than either drug alone.
Leigh
Richard
R
Asthma Research Group, Firestone Institute for Respiratory Health and Department of Medicine, St. Joseph's Healthcare-McMaster University, Hamilton, Ontario, Canada.
Vethanayagam
Dilini
D
Yoshida
Makoto
M
Watson
Richard M
RM
Rerecich
Tracy
T
Inman
Mark D
MD
O'Byrne
Paul M
PM
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001249:Asthma / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology; D013440:Sulfides
D000085:Acetates; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D019819:Budesonide; C093875:montelukast