Effect of Intranasal Azelastine on Substance P Release in Perennial Nonallergic Rhinitis Patients

Abstract

Rhinitis symptoms can be produced or augmented by neural mechanisms. Azelastine, a pharmacologic agent with potent H1-receptor blocking activity can inhibit the release of various mediators implicated in the pathogenesis of nasal hyperresponsiveness. The therapeutic benefits of topical intranasal azelastine on symptoms of perennial nonallergic rhinitis (NAR) are in part because of an impact on neural mechanisms. Assessment of changes in the concentration of substance P (SP) in nasal lavage fluid before and after saline hypertonic challenge may be a means of assessing the effect of intranasal azelastine on neuropeptide release and severity of rhinitis symptoms. Twenty-three patients with perennial NAR (negative skin-prick tests with inhalant allergens and concentration of total IgE in the normal range) were studied. Thirteen of 23 patients were treated with intranasal azelastine 0.15% spray at a dosage of 2 sprays (137 micrograms/spray) twice daily for 10 days. The control group consisted of 10 untreated patients with rhinitis. Nasal provocation using 4.5% saline solution was after 15 minutes by lavage before and after 10 days of treatment with intranasal azelastine. The concentration of SP in nasal lavage fluid was determined by enzyme immunoassay methods. Nasal lavage fluid baseline concentrations of SP were similar in both groups. After azelastine treatment, significantly greater concentrations of SP were seen in nasal lavage fluid 15 minutes after hypertonic saline challenge in the untreated patients (56.8 ± 13.8 pg/mL) in comparison with azelastine-treated patients (44.5 ± 16.5 pg/mL; p < 0.05). Total vasomotor rhinitis symptoms scores were substantially reduced in the azelastine-treated subjects compared with the control group. Azelastine intranasal spray reduces SP release into nasal lavage fluid of NAR patients immediately after hypertonic nasal saline challenge. Reduction of neuropeptide release may be an important aspect of the clinical efficacy of topical azelastine in perennial NAR patients.