Dose-dependent effects of inhaled mometasone furoate on airway function and inflammation after allergen inhalation challenge.
Comparisons of the potency of different inhaled corticosteroids, delivery devices, and treatment regimens in the management of asthma can only be made when outcome measurements display a dose-dependent effect. These outcomes have been difficult to identify. In this study, we compared in a randomized, double-blind, crossover design, the effects of 6 d treatment with placebo and three doses (50, 100, and 400 microg, twice daily) of mometasone furoate delivered by dry powder inhaler (MF-DPI) on responses after allergen inhalation challenge. Twelve mild asthmatic subjects with dual responses after allergen inhalation were studied. Outcome measurements included early and late asthmatic responses, the change in methacholine airway responsiveness 24 h after challenge, and sputum eosinophilia measured 7 and 24 h after challenge. All three doses of MF-DPI demonstrated similar attenuation of early responses and allergen-induced airway hyperresponsiveness relative to placebo (p < 0.05). The late maximal %fall in FEV(1) after placebo treatment was 23.5% and was significantly reduced in a dose-dependent manner to 12.3%, 11.0%, and 5.9% for the 50-, 100-, and 400-microg twice-daily treatments (p = 0.007). The allergen-induced increase in sputum eosinophilia (x10(4) cells/ml) 24 h after challenge during placebo treatment was 60.2 and was significantly reduced to 24.0, 15.3, and 6.2 for the 50-, 100-, and 400-microg twice-daily treatments. MF-DPI is effective at attenuating allergen-induced early and late responses, airway hyperresponsiveness, and sputum eosinophilia, and dose-response effects exist for the attenuation of the late response.
Inman
M D
MD
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Watson
R M
RM
Rerecich
T
T
Gauvreau
G M
GM
Lutsky
B N
BN
Stryszak
P
P
O'Byrne
P M
PM
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D000485:Allergens / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D016085:Bronchoconstrictor Agents / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D008297:Male; D016210:Methacholine Chloride / Q000009:adverse effects; D008875:Middle Aged; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology; D013997:Time Factors; D016896:Treatment Outcome
D000485:Allergens; D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D016210:Methacholine Chloride