Effects of single or combined mediator antagonism on nasal adenosine monophosphate challenge in perennial allergic rhinitis

Abstract

Rationale We evaluated the effects of usual clinically recommended doses of fexofenadine (FEX), montelukast (ML), and FEX+ML combination, compared to placebo (PL), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). Methods 12 PAR patients were randomized in a double-blind, crossover fashion to receive for 1 week, either FEX 180 mg, ML 10 mg, FEX 180 mg + ML 10 mg combination, or PL, with nasal AMP challenge performed 12 hours after dosing. The primary outcome was measurement of peak nasal inspiratory flow (PNIF) made over a 60-minute period after nasal challenge with a single 400 mg/ml dose of AMP. Domiciliary total nasal symptoms were measured as a secondary outcome. Results There was significant attenuation ( p<0.05) of the mean maximum % PNIF fall from baseline after nasal AMP challenge vs. PL: 48, with FEX: 37; 95%CI for difference (2–20), ML: 35 (4–22), and FEX+ML: 32 (7–24). The area under the 60-minute time-response curve (AUC %.min) was also significantly attenuated ( p<0.05) vs. PL: 1893, with FEX: 1306 (30–1143), ML: 1246 (214–1078), and FEX+ML: 1153 (251–1227). There were no significant differences for FEX vs. ML vs. FEX+ML comparing either the maximum or AUC responses. The total nasal symptom score (out of 12) was also significantly improved ( p<0.05) vs. PL: 3.3, with FEX: 2.1 (0.3–2.0), ML: 2.0 (0.5–1.9), and FEX+ML: 2.5 (0.1–1.4). Conclusion FEX and ML as monotherapy significantly attenuated the response to nasal AMP challenge and improved nasal symptoms compared to PL, while combination therapy conferred no additional benefit.