Reduction of Substance-P Mediated Neuronal Hyper-Reactivity By Dymista™ (Azelastine & Fluticasone) Correlates with Decreased Cough-Frequency in Non-Allergic Rhinitis

Rationale: Nonallergic triggers have been demonstrated to activate Ca2+ channels on sensory nerve endings resulting in release of neuropeptides, e.g. Substance P (SP) resulting in marked vasodilation and vascular permeability leading to nasal congestion and rhinorrhea. Clinical evidence supports the benefits of fluticasone and Azelastine in NAR.  The purpose of this study was to compare the effect of Dymista™ (Azelastine+Fluticasone) to placebo on reducing NP levels in nasal lavage fluid (NLF) and improving clinical symptoms before and after exposure to cold dry air (CDA) in an environmental exposure chamber.

Methods: In a double-blinded, placebo-controlled study, 30 NAR patients randomized to Dymista (n=20) or Placebo (n=10) treatment groups were initially (Pre-Rx visit) exposed to CDA (~14°C, ×1hr.) and again two-weeks post treatment (Post-Rx visit); NLFs were collected pre- and post-CDA exposure at each visit. Enzyme immunoassays were used to measure SP levels in NLF. Association of CDA-induced cough-counts with log-normalized SP ratio (post/pre-exposure) was determined by correlational and linear regression analysis. 

Results: Log(SP)-ratio differed significantly between Dymista-Post-Rx vs. Dymista-Pre-Rx samples (est.= -0.739, p=0.00004) and Dymista-Post-Rx vs. Placebo-Post-Rx (est.=-0.748, p=0.00051). Within the Dymista-group CDA-induced cough-counts post-Rx visit were significantly decreased (p=0.0003) and correlated with a reduction in the Log(SP)-ratio (Spearman rho=0.33, p=0.03).

Conclusions: Dymista may have a significant clinical effect in NAR by reduction in SP secretion. Larger clinical studies are warranted to demonstrate the clinical effect of Dymista in the NAR treatment.