Dose-response comparison of budesonide dry powder inhalers using adenosine monophosphate bronchial challenge.
BACKGROUND
Bronchial hyperresponsiveness to adenosine monophosphate, an indirect measure of airway inflammation, is a sensitive marker of inhaled corticosteroid efficacy.


OBJECTIVE
To evaluate the relative therapeutic efficacy of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in patients with mild-to-moderate persistent asthma.


METHODS
In a double-masked, dose-response crossover study, 27 patients received inhaled budesonide in cumulative sequential doubling dose increments, 2 weeks per dose, of 200, 400, and 800 microg/d. Each treatment block was preceded by 1- to 3-week placebo run-in and washout periods. End points were measured after each placebo (ie, baseline) and treatment period. Adenosine monophosphate bronchial challenge was the primary outcome, and exhaled nitric oxide, serum eosinophilic cationic protein, spirometry, domiciliary peak expiratory flow, symptoms, and rescue medication use were the secondary outcomes.


RESULTS
For the adenosine monophosphate provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20), a significant overall dose-response effect (P = .006) was found, and there was no significant difference between the devices (P = .8). The relative microgram dose potency ratio between Clickhaler and Turbuhaler was 1.11 (95% confidence interval [CI], 0.50-2.46). After administration of the highest dose of budesonide, the mean doubling dilution shift in adenosine monophosphate PC20 from placebo baseline was 3.46 (95% CI, 2.66-4.27) with the Clickhaler vs 3.41 (95% CI, 2.47-4.35) with the Turbuhaler. A significant overall dose-response effect was demonstrated for exhaled nitric oxide (P = .03) but not for any of the other secondary outcome measures. There were no significant differences between the devices for any of the outcome measures.


CONCLUSIONS
Inhaled budesonide exhibited overall dose-response effects on adenosine monophosphate PC20 delivered via Turbuhaler and Clickhaler, with no significant difference between the devices.
Lipworth
Brian J
BJ
Asthma and Allergy Research Group, Division of Medicine and Therapeutics, Ninewells University Hospital and Medical School, University of Dundee, Dundee, Scotland. b.j.lipworth@dundee.ac.uk
Sims
Erika J
EJ
Das
Sudip K
SK
Buck
Helen
H
Paterson
Michelle
M
D000249:Adenosine Monophosphate; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011208:Powders
D001993:Bronchodilator Agents; D011208:Powders; D000249:Adenosine Monophosphate; D019819:Budesonide