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Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma

Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of...

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Autores principales: Kobayashi, Yoshiki, Kanda, Akira, Bui, Dan Van, Yun, Yasutaka, Nguyen, Linh Manh, Chu, Hanh Hong, Mitani, Akitoshi, Suzuki, Kensuke, Asako, Mikiya, Iwai, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301363/
https://www.ncbi.nlm.nih.gov/pubmed/34356851
http://dx.doi.org/10.3390/biomedicines9070787
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author Kobayashi, Yoshiki
Kanda, Akira
Bui, Dan Van
Yun, Yasutaka
Nguyen, Linh Manh
Chu, Hanh Hong
Mitani, Akitoshi
Suzuki, Kensuke
Asako, Mikiya
Iwai, Hiroshi
author_facet Kobayashi, Yoshiki
Kanda, Akira
Bui, Dan Van
Yun, Yasutaka
Nguyen, Linh Manh
Chu, Hanh Hong
Mitani, Akitoshi
Suzuki, Kensuke
Asako, Mikiya
Iwai, Hiroshi
author_sort Kobayashi, Yoshiki
collection PubMed
description Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab’s effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.
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spelling pubmed-83013632021-07-24 Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma Kobayashi, Yoshiki Kanda, Akira Bui, Dan Van Yun, Yasutaka Nguyen, Linh Manh Chu, Hanh Hong Mitani, Akitoshi Suzuki, Kensuke Asako, Mikiya Iwai, Hiroshi Biomedicines Article Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab’s effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance. MDPI 2021-07-07 /pmc/articles/PMC8301363/ /pubmed/34356851 http://dx.doi.org/10.3390/biomedicines9070787 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kobayashi, Yoshiki
Kanda, Akira
Bui, Dan Van
Yun, Yasutaka
Nguyen, Linh Manh
Chu, Hanh Hong
Mitani, Akitoshi
Suzuki, Kensuke
Asako, Mikiya
Iwai, Hiroshi
Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
title Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
title_full Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
title_fullStr Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
title_full_unstemmed Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
title_short Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
title_sort omalizumab restores response to corticosteroids in patients with eosinophilic chronic rhinosinusitis and severe asthma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301363/
https://www.ncbi.nlm.nih.gov/pubmed/34356851
http://dx.doi.org/10.3390/biomedicines9070787
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