The reproducibility of adenosine monophosphate bronchial challenges in mild, steroid-naive asthmatics.
OBJECTIVE
Repeated adenosine monophosphate (AMP) challenges are used to assess drug efficacy in clinical trials of mild, steroid-naive asthmatics. Refractoriness has been reported after repeated challenges over short intervals. This study evaluated possible tachyphylaxis after repeated AMP challenges at 12 and 24 h in mild, steroid-naive asthmatics.


METHODS
This was an open, three-way crossover study. Twenty-six steroid-naive asthmatic subjects were randomized to the following AMP challenge regimens separated by 7-14 days: (A) challenge at 08.00 h, repeated 24 h later; (B) challenge at 08.00 h, repeated 12 and 24 h later; (C) challenge at 20.00 h, repeated 12 h later. Comparisons within day were assessed using 90% confidence intervals (CIs). Non-inferiority approach taken with 1 doubling concentration (DC) as a clinically relevant difference.


RESULTS
Regimen A: Significant increase in AMP reactivity at 24 h. Mean DC difference was 0.6 (90% CI 0.24, 0.96). Regimen B: No evidence of difference between AMP reactivity at 08.00 h and a repeated challenge 12 h later. Repeated challenge at 24 h caused a significant increase in provocation concentration (PC)(20) compared with 12 h (mean DC difference 0.48, 90% CI 0.02, 0.95) and 0 h (mean DC difference 0.82, 90% CI 0.49, 1.14 - the upper CI exceeds the criteria of 1 DC). Challenge regimen C: No difference between challenges; mean DC difference of 0.28 (90% CI -0.2, 0.76).


CONCLUSIONS
The small decline in AMP reactivity during repeated challenges was not consistently observed, and was small compared with the known effects of inhaled drugs.
Singh
Dave
D
North West Lung Research Centre, University of Manchester, South Manchester University Hospitals Trust, Manchester, UK. dsingh@meu.org.uk
Fairwood
Jennifer
J
Murdoch
Robert
R
Weeks
Amanda
A
Russell
Paul
P
Roy
Kay
K
Langley
Steve
S
Woodcock
Ashley
A
D000249:Adenosine Monophosphate; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D001985:Bronchial Provocation Tests / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D013618:Tachyphylaxis / Q000502:physiology*; D013812:Therapeutics
D000249:Adenosine Monophosphate