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

Yoshiki Kobayashi,Mikiya Asako,Hiroshi Iwai,Akitoshi Mitani,Akira Kanda,Dan Van Bui,Hanh Hong Chu,Kensuke Suzuki,Linh Manh Nguyen,Yasutaka Yun

doi:10.3390/biomedicines9070787

Yoshiki Kobayashi, Mikiya Asako + Show 8 more

Open Access

https://doi.org/10.3390/biomedicines9070787

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Journal: Biomedicines	Publication Date: Jul 7, 2021
Citations: 11	License type: CC BY 4.0

Affiliation: Kansai Medical University

Abstract

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.

Highlights

Eosinophilic chronic rhinosinusitis (ECRS) is known as a subtype of chronic rhinosinusitis with nasal polyps characterized by type-2-predominant airway inflammation [1,2,3].Owing to the high incidence of bronchial asthma (80% or more in severe ECRS) [4,5], ECRS is recognized as an intractable eosinophilic airway disease.Intranasal corticosteroids have limited effectiveness against ECRS
We found no significant differences in baseline characteristics, except for complications of eosinophilic otitis media between the responders and the non-responders (Table 1)
To examine the mechanisms of omalizumab’s effects, we examined the association between the clinical markers of eosinophilic airway inflammation, such as CCL4, CD69, and IL-13, an inducer of iNOS [23] and PP2A, in BEAS-2B airway epithelial cells

Summary

Introduction

Eosinophilic chronic rhinosinusitis (ECRS) is known as a subtype of chronic rhinosinusitis with nasal polyps characterized by type-2-predominant airway inflammation [1,2,3].Owing to the high incidence of bronchial asthma (80% or more in severe ECRS) [4,5], ECRS is recognized as an intractable eosinophilic airway disease.Intranasal corticosteroids have limited effectiveness against ECRS. Eosinophilic chronic rhinosinusitis (ECRS) is known as a subtype of chronic rhinosinusitis with nasal polyps characterized by type-2-predominant airway inflammation [1,2,3]. Owing to the high incidence of bronchial asthma (80% or more in severe ECRS) [4,5], ECRS is recognized as an intractable eosinophilic airway disease. Intranasal corticosteroids have limited effectiveness against ECRS. Intermittent oral corticosteroids are effective, they are not suitable for long-term administration owing to their adverse effects. Under such conditions, we have shown the usefulness of inhaled corticosteroid (ICS) exhalation through the nose (ETN)

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