Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis

2021 ◽  
pp. 194589242110210
Author(s):  
Jacqueline Ho ◽  
Raquel Alvarado ◽  
Janet Rimmer ◽  
William A. Sewell ◽  
Sophie Walter ◽  
...  

Background Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = −8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = −2.37, p = 0.02). Conclusion Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.

2019 ◽  
Vol 10 (1) ◽  
pp. 89-94
Author(s):  
Masahiro Ikeda ◽  
Chiharu Iwahashi ◽  
Takashi Hirai ◽  
Kenji Hattori ◽  
Keiichi Mitarai

We report a case of eosinophilic chronic rhinosinusitis (ECRS) associated with choroidal folds and ocular motility disorder. A 50-year-old male with rhinosinusitis and bronchial asthma presented with anorthopia of the lower visual field and ocular motility disorder of the left eye. Dilated fundus examination and optical coherence tomography (OCT) revealed wavy choroidal folds in the upper retina. An emergent computed tomography (CT) showed sinusitis, a partial defect of the superior wall of the orbit on the left side, and deformation of the left eye. Based on the clinical findings, the patient was diagnosed with sinusitis complicated by ocular motility disorder. Endoscopic sinus surgery (ESS) was performed. A histopathological examination of the excised polyps showed extensive eosinophil invasion. According to the clinical findings of the nasal polyps, CT images, and peripheral blood tests, he was diagnosed as ECRS. One month after ESS, both ocular movement and anorthopia were improved. The choroidal folds observed using OCT disappeared 2 months after ESS. Although ECRS is rarely associated with ocular complications, bone involvement in sinusitis may result in deformation of the eyeball leading to choroidal folds and ocular motility disorder.


2021 ◽  
pp. 194589242098743
Author(s):  
Nyssa F. Farrell ◽  
Jess C. Mace ◽  
David A. Sauer ◽  
Andrew J. Thomas ◽  
Mathew Geltzeiler ◽  
...  

Background Chronic rhinosinusitis (CRS) is often differentiated by histopathologic phenotypes (eosinophilic versus neutrophilic), which may impact disease severity measures and outcomes. As such, it has been suggested that counts of cellular elements be included as part of a standard pathological report following endoscopic sinus surgery (ESS). Objectives This cross-sectional study evaluated associations of mucosal eosinophilia and neutrophilia with measures of quality-of-life (QoL) and olfactory function. Methods Patients with medically refractory CRS completed the SNOT-22 survey and Brief Smell Identification Test (BSIT) at enrollment. In addition, baseline Lund-Mackay computed tomography (CT) and Lund-Kennedy endoscopy scores were collected. Ethmoid mucosa was biopsied during ESS and reviewed using microscopy to quantify densest infiltrate of eosinophils or neutrophils per high-powered-field (HPF). Eosinophilic CRS (eCRS) and neutrophilic CRS (nCRS), both with and without nasal polyposis (NP), were compared across SNOT-22 and BSIT scores. Results 77/168 patients demonstrated mucosal eosinophilia (eCRS) while a total of 42/168 patients demonstrated mucosal neutrophilia (nCRS). After adjusting for polyp status, 35/168 had eCRSsNP, 42/168 eCRSwNP, 75/168 non-eCRSsNP, 16/168 non-eCRSwNP. Additionally, 22/161 were noted to have nCRSsNP, 20/161 nCRSwNP, 84/161 non-nCRSwNP, and 35/161 non-nCRSsNP. A small subset of patients demonstrated both eosinophilia and neutrophilia: 14 CRSwNP and 7 CRSsNP. When evaluating average Lund-Mackay Scores (LMS), significant differences existed between non-eCRSsNP and eCRSsNP (p = 0.006). However, after controlling for nasal polyps, eosinophilia did not significantly associate with differences in the Lund-Kennedy Score. Neutrophilia did not significantly associate with any changes in LMS or LKS after controlling for NP. Eosinophilic and neutrophilic histopathologic subtypes did not significantly associate with differences in baseline SNOT-22 or BSIT measures after controlling for NP. Conclusion Neither the presence of mucosal eosinophilia nor mucosal neutrophilia demonstrated significant associations with SNOT-22 quality-of-life or BSIT olfactory function scores when controlling for comorbid nasal polyposis.


Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1059
Author(s):  
Yu-Tsai Lin ◽  
Wei-Chih Chen ◽  
Ming-Hsien Tsai ◽  
Jing-Ying Chen ◽  
Chih-Yen Chien ◽  
...  

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.


2021 ◽  
Vol 59 (4) ◽  
pp. 380-386
Author(s):  
D.A.E. Dietz de Loos ◽  
S. Ronsmans ◽  
M.E. Cornet ◽  
P.W. Hellings ◽  
V. Hox ◽  
...  

Background: Chronic rhinosinusitis (CRS) is a frequent condition that is treated by endoscopic sinus surgery (ESS) when medical treatment fails. Irritating or sensitizing airborne agents can contribute to uncontrolled CRS. A prior study showed a linear correlation between occupational exposure and the number of ESS. Methods: In this cross-sectional study we tested the hypothesis that occupational exposure is a risk for undergoing ESS. We sent questionnaires enquiring occupational exposure in patients with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). An expert assessed blindly the reported work exposures to inhaled agents. The relationship between occupational exposure on undergoing ESS was analysed. Results: Among all patients who underwent ESS (n=343), 30% reported a relevant occupational exposure, which is significantly higher than the 4.8% found among CRS patients that underwent no prior sinus surgery (n=21). Besides occupational exposure, self-reported doctor-diagnosed asthma were independent variables contributing to the chance of undergoing ESS. Conclusion: In our study we confirm occupational exposure as a risk factor for uncontrolled CRS, if defined by undergoing ESS. In CRS patients with uncontrolled symptoms, despite maximal conservative therapy, the clinician should explore the possible contribution of occupational exposure.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takanori Numata ◽  
Katsutoshi Nakayama ◽  
Hirofumi Utsumi ◽  
Kenji Kobayashi ◽  
Haruhiko Yanagisawa ◽  
...  

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.


2020 ◽  
Vol 7 (2) ◽  
pp. 427-431
Author(s):  
Anna Mailasari Kusuma Dewi ◽  
Rano Aditomo ◽  
Riece Hariyati ◽  
Meira Dewi Kusuma Astuti

Latar belakang : Hidung tersumbat dapat disebabkan karena kelainan struktur hidung seperti deviasi septum, atresia koana, konka hipertrofi, celah palatum, hipertrofi adenoid, dan neoplasma. Dua puluh persen populasi dengan hidung tersumbat disebabkan konka hipertrofi. Konka hipertrofi merupakan pembesaran konka akibat bertambahnya ukuran sel konka, yang disebabkan hiperplasia dan hipertrofi lapisan mukosa dan tulang konka. Gambaran hipertrofi dan hiperplasi dapat dilihat melalui pemeriksaan histopatologi. Tujuan penelitian ini untuk mengetahui hubungan gambaran histopatologi dan derajat konka hipertrofi dengan sumbatan hidung pada pasien rinosinusitis kronik (RSK). Metode : Desain penelitian korelasi dengan metode belah lintang pada pasien RSK dengan konka hipertrofi yang menjalani operasi Bedah Sinus Endoskopik Fungsional (BSEF) dan konkotomi. Derajat konka hipertrofi dinilai berdasarkan nasoendoskopi, sedangkan sumbatan hidung menggunakan kuesioner Nasal Obstruction Symptom Evaluation (NOSE). Uji hipotesis yang digunakan adalah uji korelasi Spearman. Hasil : Karakteristik subyek penelitian sebanyak 33 orang, perempuan 60% lebih banyak daripada laki-laki 40%. Derajat sumbatan hidung ringan (30%), sedang (27%), berat (30%) dan sangat berat (13%). Konka hipertrofi terbanyak yaitu derajat 3 (54,5%). Hasil analisis dengan uji korelasi Spearman menunjukkan terdapat korelasi positif dengan nilai korelasi sedang antara derajat konka hipertrofi dengan derajat sumbatan hidung (p=0.02 dan rho = 0.404. Tidak terdapat hubungan yang bermakna antara derajat sumbatan hidung dengan gambaran histopatologi konka inferior (hiperplasia sel goblet, pembentukan kelenjar submukosa, eosinofil, limfosit, neutrofil). Simpulan : Derajat konka hipertrofi berpengaruh terhadap sumbatan hidung. Gambaran histopatologi konka hipertrofi tidak berpengaruh terhadap derajat sumbatan hidung pada pasien RSK. Kata kunci : Rinosinusitis kronik, sumbatan hidung, konka hipertrofi   Background: Nasal congestion can be caused by abnormalities of nasal structures such as deviation of the septum, choanal atresia, turbinate hypertrophy, cleft palate, adenoid hypertrophy, and neoplasms. Twenty percent of the population with nasal congestion is due to turbinate hypertrophy. Turbinate hypertrophy is an enlargement of turbinate due to an increase in the size of turbinate cells, which is caused by hyperplasia and hypertrophy of the mucosal layers and turbinate bones. Description of hypertrophy and hyperplasia can be seen through histopathological examination. The purpose of this study was to determine the relationship between histopathological features and the degree of turbinate hypertrophy with nasal obstruction in patients with chronic rhinosinusitis (CRS). Methode: The correlative study design with a cross-sectional method in CSR patients with turbinate hypertrophy who underwent Functional Endoscopic Sinus Surgery (FESS) and turbinectomy. The degree of turbinate hypertrophy was assessed based on nasoendoscopy, whereas nasal obstruction used the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire. The hypothesis test used is the Spearman correlation test. Result: The characteristics of the study subjects were 33 people, more women (60%) than men (40%). The degree of nasal obstruction is mild (30%), moderate (27%), severe (30%) and very severe (13%). Turbinate hypertrophy grade 3 was the most (54,5%). The analyzed using Spearman correlative test showed a positive correlation with a moderate correlation between the degree of turbinate hypertrophy with the degree of nasal obstruction (p=0.02 dan rho = 0.404). There was no significant relationship between the degree of nasal obstruction with histopathological features of the inferior turbinate (goblet cell hyperplasia, the formation of submucosal glands, eosinophils, lymphocytes, and neutrophils). Conclusion: The degree of turbinate hypertrophy affects nasal obstruction. Histopathological features of turbinate hypertrophy do not affect the degree of nasal obstruction in CSR patients. Keyword: Chronic rhinosinusitis, nasal obstruction, turbinate hypertrophy


2020 ◽  
Vol 69 (1) ◽  
pp. 144-145 ◽  
Author(s):  
Nobuo Ohta ◽  
Yusuke Suzuki ◽  
Hiroki Ikeda ◽  
Naoya Noguchi ◽  
Risako Kakuta ◽  
...  

Author(s):  
T Saito ◽  
K Okazaki ◽  
Y Hamada ◽  
K Hashimoto ◽  
K Tsuzuki

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.


2018 ◽  
Vol 128 (3) ◽  
pp. 233-240
Author(s):  
Daniela Parrino ◽  
Giuseppe Brescia ◽  
Claudia Zanotti ◽  
Giulia Tealdo ◽  
Luciano Giacomelli ◽  
...  

Objectives: Research selectively investigating non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is lacking. The inflammatory patterns seen in non-eosinophilic CRSwNP are still poorly understood. The present study is the first to compare blood eosinophil, basophil, and neutrophil counts before/after surgery in patients with non-eosinophilic CRSwNP stratified by their clinical features. Methods: The study concerned 107 consecutive patients with histologically confirmed non-eosinophilic CRSwNP who underwent endoscopic sinus surgery (ESS). Results: Statistical analysis ruled out any significant change in mean blood eosinophil, basophil, and neutrophil counts after ESS. A significant positive correlation emerged between blood eosinophil and basophil counts in both pre- and post-ESS laboratory tests. In the subcohort of allergic patients, a significant negative correlation was found after ESS between eosinophil and neutrophil levels and between basophil and neutrophil levels. Conclusions: In eosinophilic CRSwNP, ESS can clear polyps, remove inflammatory tissue, and reduce the inflammatory cytokines it generates, with a consequent reduction in blood eosinophil levels. The different results in non-eosinophilic CRSwNP support the conviction that the 2 types of CRSwNP are entities with distinct inflammatory response patterns.


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