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MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis.
Allergy. 2018 05; 73(5):1084-1093.A

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.

Authors+Show Affiliations

Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium.Clinical Division of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, VIB Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium.Clinical Division of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.RefLab, Copenhagen, Denmark.Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium.Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, VIB Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.Translational Research Center for Gastro Intestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium.Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium.Laboratory of Clinical Immunology, Department Microbiology & Immunology, KU Leuven, Leuven, Belgium. Clinical Division of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium. Clinical Division of Otorhinolaryngology, Head and Neck Surgery, Academic Medical Center, Amsterdam, the Netherlands. Upper Airways Research Laboratory, University of Ghent, Ghent, Belgium.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29121401

Citation

Kortekaas Krohn, I, et al. "MP29-02 Reduces Nasal Hyperreactivity and Nasal Mediators in Patients With House Dust Mite-allergic Rhinitis." Allergy, vol. 73, no. 5, 2018, pp. 1084-1093.
Kortekaas Krohn I, Callebaut I, Alpizar YA, et al. MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis. Allergy. 2018;73(5):1084-1093.
Kortekaas Krohn, I., Callebaut, I., Alpizar, Y. A., Steelant, B., Van Gerven, L., Skov, P. S., Kasran, A., Talavera, K., Wouters, M. M., Ceuppens, J. L., Seys, S. F., & Hellings, P. W. (2018). MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis. Allergy, 73(5), 1084-1093. https://doi.org/10.1111/all.13349
Kortekaas Krohn I, et al. MP29-02 Reduces Nasal Hyperreactivity and Nasal Mediators in Patients With House Dust Mite-allergic Rhinitis. Allergy. 2018;73(5):1084-1093. PubMed PMID: 29121401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis. AU - Kortekaas Krohn,I, AU - Callebaut,I, AU - Alpizar,Y A, AU - Steelant,B, AU - Van Gerven,L, AU - Skov,P S, AU - Kasran,A, AU - Talavera,K, AU - Wouters,M M, AU - Ceuppens,J L, AU - Seys,S F, AU - Hellings,P W, Y1 - 2018/01/17/ PY - 2017/11/03/accepted PY - 2017/11/10/pubmed PY - 2019/5/11/medline PY - 2017/11/10/entrez KW - allergic rhinitis KW - azelastine hydrochloride KW - fluticasone propionate KW - nasal hyperreactivity KW - substance P SP - 1084 EP - 1093 JF - Allergy JO - Allergy VL - 73 IS - 5 N2 - 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. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/29121401/MP29_02_reduces_nasal_hyperreactivity_and_nasal_mediators_in_patients_with_house_dust_mite_allergic_rhinitis_ L2 - https://doi.org/10.1111/all.13349 DB - PRIME DP - Unbound Medicine ER -