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

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 787
Author(s):  
Yoshiki Kobayashi ◽  
Akira Kanda ◽  
Dan Van Bui ◽  
Yasutaka Yun ◽  
Linh Manh Nguyen ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Chronic Rhinosinusitis ◽  
Severe Asthma ◽  
Treatment Effectiveness ◽  
Therapeutic Option ◽  
Real Life ◽  
Sinus Surgery ◽  
Global Evaluation ◽  
Corticosteroid Resistance ◽  
Eosinophilic Chronic Rhinosinusitis

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.

scholarly journals Relationships between IL-17A and Macrophages or MUC5AC in Eosinophilic Chronic Rhinosinusitis and Proposed Pathological Significance

2012 ◽  
Vol 3 (2) ◽  
pp. ar.2012.3.0030 ◽  
Author(s):  
Noritsugu Ono ◽  
Takeshi Kusunoki ◽  
Katsuhisa Ikeda
Keyword(s):  
Airway Inflammation ◽  
Chronic Rhinosinusitis ◽  
Neutrophil Elastase ◽  
Nasal Polyps ◽  
Mucus Hypersecretion ◽  
Promotive Factors ◽  
Chemotactic Protein ◽  
Eosinophilic Chronic Rhinosinusitis ◽  
Semithin Sections ◽  
The Mean

Recently, some researchers have reported that macrophages and neutrophils were related to severe asthma. Mucus hypersecretion and persistent airway inflammation result from increased expression of mucin gene (MUC5AC). Eosinophilic chronic rhinosinusitis (ECRS) is considered as intractable rhinosinusitis. From the viewpoint of “one way one disease,” we examined whether ECRS is associated with infiltrating macrophages, neutrophils, their promotive factors, and MUC5AC. We examined 21 nasal polyps with CRS. Each specimen was fixed in 10% phosphate-buffered formalin, embedded in paraffin, processed routinely, and then prepared as semithin sections (3.5 μm). We immunohistochemically observed the macrophages by using CD68, neutrophils by using neutrophil elastase and the promotive factors, monocyte chemotactic protein (MCP) 1, IL-17A, and IL-8, in both ECRS and non-ECRS. The number of macrophages (CD68+ cells), IL-17A, and MUC5AC+ cells in ECRS were significantly greater than in non-ECRS. The mean number of MCP-1+ cells in ECRS was greater than that in non-ECRS, but not significantly. There was a significant correlation in all cases between IL-17A and macrophages or MUC5AC+ cells. Neither the numbers of neutrophils (positive cells for neutrophil elastase) nor the IL-8+ cells showed any significant differences between ECRS and non-ECRS. Our study suggested that infiltrating macrophages, IL-17A and MUC5AC, as well as eosinophils could have roles in the development of ECRS.

scholarly journals Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takanori Numata ◽  
Katsutoshi Nakayama ◽  
Hirofumi Utsumi ◽  
Kenji Kobayashi ◽  
Haruhiko Yanagisawa ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Severe Asthma ◽  
Predictive Factors ◽  
Systemic Corticosteroid ◽  
Multivariate Logistic Regression Analysis ◽  
Patient Characteristics ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Eosinophilic Chronic Rhinosinusitis

Abstract Background Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. Objective To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. Methods From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. Results The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Conclusion Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

scholarly journals Real-Life Experience of Monoclonal Antibody Treatments in Chronic Rhinosinusitis with Nasal Polyposis

2021 ◽  
Vol 182 (8) ◽  
pp. 736-743
Author(s):  
Eva C. Meier ◽  
Peter Schmid-Grendelmeier ◽  
Urs C. Steiner ◽  
Michael B. Soyka
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Rhinosinusitis ◽  
Successful Treatment ◽  
Nasal Polyposis ◽  
Real Life ◽  
Predictive Biomarkers ◽  
Sinus Surgery ◽  
Nasal Discharge ◽  
Eosinophilic Cationic Protein ◽  
Cationic Protein

<b><i>Introduction:</i></b> Few studies assess biologicals such as, omalizumab, mepolizumab, benralizumab, and dupilumab in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The reported success rate in these studies differ, and it remains uncertain if there are any biomarkers to predict successful therapy. Our aim was to analyze the therapeutic outcome in a real life setting and to identify predictive biomarkers for successful treatment. <b><i>Methods:</i></b> Data from patients with CRSwNP treated with a monoclonal antibody between November 2014 and January 2020 were analyzed retrospectively. Improvement in the polyp score and clinical symptoms like nasal obstruction, sense of smell, nasal discharge, and facial pain were evaluated. Other characteristics, including use of nasal or systemic steroids, comorbidities, previous history of sinus surgery, eosinophilia tissue, blood values (eosinophils, total immunoglobulin E, eosinophilic cationic protein, and interleukin 5), and allergic sensitization in serum were also investigated to identify possible predictive biomarkers. <b><i>Results:</i></b> Forty-eight treatments in 29 patients (m/f = 15/14) aged 27–70 years were reviewed. Treatments with mepolizumab showed the best success rates (78.9%), followed by omalizumab (50%) and benralizumab treatments (50%). However, a correlation between biomarkers and treatment success could not be found. <b><i>Discussion/Conclusion:</i></b> Treatment of CRSwNP with biologicals is a promising option for severe cases not responding to conventional therapy, including difficult-to-treat patients. Predictive biomarkers for a successful treatment could not be identified, but the reduction of eosinophilic cationic protein was linked with the response.

scholarly journals Real-life effects of benralizumab on allergic chronic rhinosinusitis and nasal polyposis associated with severe asthma

2020 ◽  
Vol 34 ◽  
pp. 205873842095085 ◽  
Author(s):  
Nicola Lombardo ◽  
Corrado Pelaia ◽  
Marco Ciriolo ◽  
Marcello Della Corte ◽  
Giovanna Piazzetta ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Chronic Rhinosinusitis ◽  
Severe Asthma ◽  
Eosinophil Count ◽  
Nasal Polyposis ◽  
Rating Scale ◽  
Real Life ◽  
Blood Eosinophil ◽  
Blood Eosinophil Count ◽  
Snot 22

The aim of this study has been to evaluate the efficacy of the IL-5 receptor blocker benralizumab on chronic rhinosinusitis with nasal polyposis (CRSwNP), associated with severe eosinophilic allergic asthma. Ten patients with severe eosinophilic allergic asthma and CRSwNP were enrolled. Sino-nasal outcome test (SNOT-22), numerical rating scale (NRS), endoscopic nasal polyp score, Lund Mackey CT (computed tomography) score, and blood eosinophil count were measured at baseline and after 24 weeks of treatment with benralizumab. All the above clinical, endoscopic, imaging, and hematological parameters significantly improved after 24 weeks of treatment with benralizumab. In particular, SNOT-22 decreased from 61.10 ± 17.20 to 26.30 ± 19.74 ( P < 0.001), NRS decreased from 7.20 ± 1.55 to 3.40 ± 2.22 ( P < 0.001), the endoscopic polyp nasal score decreased from 4.20 ± 1.32 to 2.50 ± 1.78 ( P < 0.001), the Lund-Mackay CT score decreased from 16.60 ± 5.50 to 6.90 ± 5.99 ( P < 0.001), and blood eosinophil count decreased from 807.3 ± 271.1 cells/μL to 0 cells/μL ( P < 0.0001). These results strongly suggest that benralizumab exerted a very effective therapeutic action on CRSwNP associated with severe asthma, thus improving nasal symptoms and decreasing polyp size.

scholarly journals Efficacy of endoscopic sinus surgery for eosinophilic chronic rhinosinusitis with asthma

2020 ◽  
Vol 69 (1) ◽  
pp. 144-145 ◽  
Author(s):  
Nobuo Ohta ◽  
Yusuke Suzuki ◽  
Hiroki Ikeda ◽  
Naoya Noguchi ◽  
Risako Kakuta ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Endoscopic Sinus Surgery ◽  
Sinus Surgery ◽  
Eosinophilic Chronic Rhinosinusitis

Therapeutic indications for sinonasal topical steroid treatment and its effects on eosinophilic chronic rhinosinusitis after endoscopic sinus surgery

2021 ◽  
pp. 1-6
Author(s):  
T Saito ◽  
K Okazaki ◽  
Y Hamada ◽  
K Hashimoto ◽  
K Tsuzuki
Keyword(s):  
Chronic Rhinosinusitis ◽  
Endoscopic Sinus Surgery ◽  
Topical Steroid ◽  
Steroid Treatment ◽  
Sinus Surgery ◽  
Olfactory Loss ◽  
Eosinophilic Chronic Rhinosinusitis ◽  
Group A ◽  
Operative Indications ◽  
Group B

Abstract Objective This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. Method Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. Results Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). Conclusion These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.

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