A proof-of-concept study to assess the putative dose response to topical corticosteroid in persistent allergic rhinitis using adenosine monophosphate challenge.
BACKGROUND
The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER).


METHODS
Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 microg or 400 microg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios.


RESULTS
Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 microg, and 12.9% (4.8-20.9, P=0.009) by FP 400 microg. The 400-100 microg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 microg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose.


CONCLUSIONS
FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER.
Barnes
M L
ML
Asthma and Allergy Research Group, Department of Medicine and Therapeutics, Ninewells Hospital and Perth Royal Infirmary, University of Dundee, Dundee DD1 9SY, Scotland, UK. mbarnes@rcsed.ac.uk
Menzies
D
D
Nair
A R
AR
Hopkinson
P J
PJ
Lipworth
B J
BJ
D000249:Adenosine Monophosphate; D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests / Q000379:methods; D011788:Quality of Life; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*; D016896:Treatment Outcome
D000730:Androstadienes; D005938:Glucocorticoids; D000249:Adenosine Monophosphate; D000068298:Fluticasone