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. 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. MP29-02 but not placebo reduced NHR (p