S Vaidyanathan1, A Nair, M L Barnes, K Meldrum, B J Lipworth. 1. Asthma & Allergy Research Group, Department of Medicine and Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK. s.vaidyanathan@dundee.ac.uk
Abstract
BACKGROUND: End-organ hyperreactivity is an important feature of the allergic airway. There are no data directly comparing the responsiveness to treatment of different nasal provocation tests (NPT). OBJECTIVE: We compared the effect of levocetirizine on nasal adenosine 5'-monophosphate (AMP) with specific allergen challenge in patients with intermittent and persistent allergic rhinitis (AR). METHODS:Patients with AR were randomized in double-blind cross-over fashion to receive single doses of levocetirizine 5 mg or identical placebo, with nasal challenge performed 12 h after dosing. Sixteen participants completed per protocol. Nasal AMP or allergen challenge was conducted on separate days with 1- and 2-week washout periods in between, respectively. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after each challenge. The primary end-point was the provocative concentration of AMP or allergen causing a 20% drop in the PNIF (PC(20)). RESULTS: The time-profile for PNIF recovery [area under the 60 min time-response curve as % PNIF change (min)] were significantly attenuated for AMP challenge, as mean difference [95% confidence interval (CI)]: 11.57 (3.87, 19.25), P=0.005 and for allergen challenge: 17.82 (0.11, 35.53), P=0.04. A highly significant correlation was shown between methods for the area under the curve: (R=0.86, P<0.001). A statistically significant correlation was also seen for the PC(20): (R=0.94, P<0.001). PC(20) improvement amounted to a 1.26 (95% CI 0.16, 2.35) and 0.16 (95% CI -0.41, 0.73) doubling-dilution shifts for allergen and AMP challenges, respectively. Bland-Altman plots confirmed good agreement between methods. CONCLUSION: A high correlation and statistical agreement has been demonstrated between AMP and allergen challenge for all outcome measures. In particular, the recovery profile after NPT is a sensitive and discriminatory measure of anti-allergic treatment.
RCT Entities:
BACKGROUND: End-organ hyperreactivity is an important feature of the allergic airway. There are no data directly comparing the responsiveness to treatment of different nasal provocation tests (NPT). OBJECTIVE: We compared the effect of levocetirizine on nasal adenosine 5'-monophosphate (AMP) with specific allergen challenge in patients with intermittent and persistent allergic rhinitis (AR). METHODS:Patients with AR were randomized in double-blind cross-over fashion to receive single doses of levocetirizine 5 mg or identical placebo, with nasal challenge performed 12 h after dosing. Sixteen participants completed per protocol. Nasal AMP or allergen challenge was conducted on separate days with 1- and 2-week washout periods in between, respectively. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after each challenge. The primary end-point was the provocative concentration of AMP or allergen causing a 20% drop in the PNIF (PC(20)). RESULTS: The time-profile for PNIF recovery [area under the 60 min time-response curve as % PNIF change (min)] were significantly attenuated for AMP challenge, as mean difference [95% confidence interval (CI)]: 11.57 (3.87, 19.25), P=0.005 and for allergen challenge: 17.82 (0.11, 35.53), P=0.04. A highly significant correlation was shown between methods for the area under the curve: (R=0.86, P<0.001). A statistically significant correlation was also seen for the PC(20): (R=0.94, P<0.001). PC(20) improvement amounted to a 1.26 (95% CI 0.16, 2.35) and 0.16 (95% CI -0.41, 0.73) doubling-dilution shifts for allergen and AMP challenges, respectively. Bland-Altman plots confirmed good agreement between methods. CONCLUSION: A high correlation and statistical agreement has been demonstrated between AMP and allergen challenge for all outcome measures. In particular, the recovery profile after NPT is a sensitive and discriminatory measure of anti-allergic treatment.
Authors: H W Chu; C M Lloyd; W Karmaus; P Maestrelli; P Mason; G Salcedo; J Thaikoottathil; A J Wardlaw Journal: Clin Exp Allergy Date: 2010-11 Impact factor: 5.018