Effect of levocetirizine on nasal provocation testing with adenosine monophosphate compared with allergen challenge in allergic rhinitis

Abstract

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). 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). 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)). 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. 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.