5 years ago

MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite allergic rhinitis

Ahmad Kasran, Sven F Seys, Per Stahl Skov, Yeranddy A. Alpizar, Brecht Steelant, Ina Callebaut, Peter W Hellings, Karel Talavera, Mira M Wouters, Inge Kortekaas Krohn, Jan L Ceuppens, Laura Van Gerven
Background Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate (FP)) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. Methods A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction of nasal flow upon cold dry air exposure. The effects of AZE+/-FP on barrier integrity and airway inflammation were studied in a murine model of HDM induced NHR and on reduced activation of murine sensory neurons and human mast cells. Results MP29-02 but not placebo reduced NHR (p<0.0001 vs. p=0.21), levels of substance P (p=0.026 vs. p=0.941) and β-hexosaminidase (p=0.036 vs. p=0.632) in human nasal secretions. In wild type C57BL6 mice, the reduction of β-hexosaminidase levels (p<0.0001) by AZE+FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (p=0.0012) and completely reversed eosinophilic inflammation (p=0.0013). In vitro, repeated applications of AZE+FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE+FP reduced MC degranulation to the same extent as AZE alone. Conclusion MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE+FP on MC degranulation, nasal epithelial barrier integrity and TRP channels provide novel insights into the pathophysiology of allergic rhinitis. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/all.13349

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