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

Abstract Background Nasal hyperreactivity ( NHR ) is an important clinical feature of allergic rhinitis ( AR ). The efficacy of MP 29‐02 (azelastine hydrochloride ( AZE ) and fluticasone propionate [ FP ]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP 29‐02 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 MP 29‐02 treatment was conducted in 28 patients with house dust mite ( HDM ) AR . The presence of NHR was evaluated by measuring reduction in 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 MP 29‐02 but not placebo reduced NHR ( P < .0001 vs P = .21), levels of substance P ( P = .026 vs P = .941), and β‐hexosaminidase ( P = .036 vs P = .632) in human nasal secretions. In wild‐type C57 BL 6 mice, the reduction in β‐hexosaminidase levels ( P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage ( P = .0012) and completely reversed eosinophilic inflammation ( P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA 1 and TRPV 1. AZE + FP reduced MC degranulation to the same extent as AZE alone. Conclusion MP 29‐02 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.