I Kortekaas Krohn1, I Callebaut2, Y A Alpizar3, B Steelant1, L Van Gerven2, P S Skov4, A Kasran1, K Talavera3, M M Wouters5, J L Ceuppens1, S F Seys1, P W Hellings1,2,6,7. 1. Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium. 2. Clinical Division of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium. 3. Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, VIB Center for Brain & Disease Research, KU Leuven, Leuven, Belgium. 4. RefLab, Copenhagen, Denmark. 5. Translational Research Center for Gastro Intestinal Disorders (TARGID), KU Leuven, Leuven, Belgium. 6. Clinical Division of Otorhinolaryngology, Head and Neck Surgery, Academic Medical Center, Amsterdam, the Netherlands. 7. Upper Airways Research Laboratory, University of Ghent, Ghent, Belgium.
Abstract
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 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:MP29-02 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 C57BL6 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 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.
RCT Entities:
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 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: MP29-02 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 C57BL6 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 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.
Authors: Jef Feijen; Sven F Seys; Brecht Steelant; Dominique M A Bullens; Lieven J Dupont; Maria García-Cruz; Alejandro Jimenez-Chobillón; Désirée Larenas-Linnemann; Laura Van Gerven; Wytske J Fokkens; Ioana Agache; Peter W Hellings Journal: World Allergy Organ J Date: 2020-07-01 Impact factor: 4.084
Authors: Wout Backaert; Brecht Steelant; Peter W Hellings; Karel Talavera; Laura Van Gerven Journal: Curr Allergy Asthma Rep Date: 2021-03-18 Impact factor: 4.806
Authors: Jean Bousquet; Wienczyslawa Czarlewski; Torsten Zuberbier; Joaquim Mullol; Hubert Blain; Jean-Paul Cristol; Rafael De La Torre; Nieves Pizarro Lozano; Vincent Le Moing; Anna Bedbrook; Ioana Agache; Cezmi A Akdis; G Walter Canonica; Alvaro A Cruz; Alessandro Fiocchi; Joao A Fonseca; Susana Fonseca; Bilun Gemicioğlu; Tari Haahtela; Guido Iaccarino; Juan Carlos Ivancevich; Marek Jutel; Ludger Klimek; Helga Kraxner; Piotr Kuna; Désirée E Larenas-Linnemann; Adrian Martineau; Erik Melén; Yoshitaka Okamoto; Nikolaos G Papadopoulos; Oliver Pfaar; Frederico S Regateiro; Jacques Reynes; Yves Rolland; Philip W Rouadi; Boleslaw Samolinski; Aziz Sheikh; Sanna Toppila-Salmi; Arunas Valiulis; Hak-Jong Choi; Hyun Ju Kim; Josep M Anto Journal: Int Arch Allergy Immunol Date: 2021-02-10 Impact factor: 2.749