Differential effects of fluticasone and montelukast on allergen-induced asthma.
Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.
Palmqvist
M
M
Section of Allergy, The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.
Bruce
C
C
Sjöstrand
M
M
Arvidsson
P
P
Lötvall
J
J
D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000730:Androstadienes / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004804:Eosinophils / Q000473:pathology; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D016210:Methacholine Chloride; D011804:Quinolines / Q000627:therapeutic use*; D013183:Sputum; D013440:Sulfides; D013997:Time Factors
D000085:Acetates; D000485:Allergens; D000730:Androstadienes; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D016210:Methacholine Chloride; D000068298:Fluticasone; C093875:montelukast