Mometasone furoate antagonizes AMP-induced bronchoconstriction in patients with mild asthma.
BACKGROUND
Mometasone furoate (MF) is a new potent corticosteroid for use in treating asthma.


OBJECTIVE
To test the lower range of the dose-response curve, effects of MF delivered by dry powder inhaler (DPI) on AMP-induced bronchoconstriction were compared with those of placebo.


METHODS
In a placebo-controlled, 3-phase cross-over, single-center, double-blind study, 15 patients with mild asthma were randomized to three 2-week treatment phases (separated by 4-week washout phases) with MF DPI 50 microg twice daily, MF DPI 100 microg twice daily, or placebo. AMP challenge was performed before and at the end of each treatment phase.


RESULTS
Thirteen patients completed all 3 phases and were included in the primary efficacy analysis. Treatment with MF DPI 50 microg twice daily or with MF DPI 100 microg twice daily significantly reduced the bronchoconstrictor response to AMP, displacing the dose-response curve to the right by 2.81 and 3.11 doubling dilutions, respectively, compared with placebo (P <.001). The improvement in FEV(1) over the 2-week treatment phase was significantly (P < or =.033) greater during treatment with MF DPI 50 microg or 100 microg twice daily than with placebo. Peak expiratory flow rate, wheezing scores, difficulty breathing scores, nocturnal awakenings requiring salbutamol, and puffs of salbutamol per day also indicated a greater improvement in respiratory function and symptoms of asthma with MF DPI 50 or 100 microg twice daily than with placebo. Both doses of MF DPI were well tolerated.


CONCLUSIONS
Treatment with low doses of MF DPI decreased airway responsiveness to AMP challenge and improved secondary measures of pulmonary function and asthma symptoms.
Holgate
S T
ST
Southampton General Hospital, Southampton, United Kingdom.
Arshad
H
H
Stryszak
P
P
Harrison
J E
JE
D000249:Adenosine Monophosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D000068656:Mometasone Furoate; D010366:Peak Expiratory Flow Rate; D011244:Pregnadienediols / Q000008:administration & dosage / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D000249:Adenosine Monophosphate; D000420:Albuterol