Eosinophilic Chronic Rhinosinusitis Research Articles

ЭФФЕКТИВНОСТЬ РЕСЛИЗУМАБА В ЛЕЧЕНИИ АСТМЫ И КОМОРБИДНОГО ХРОНИЧЕСКОГО РИНОСИНУСИТА С ПОЛИПАМИ

Introduction. Chronic rhinosinusitis with polyps and asthma are comorbid, mutually aggravating, and difficult to treat diseases. The correlation between the severity of chronic rhinosinusitis with polyps and eosinophilic asthma, the similarity of the endotypes of these diseases and the success of humanized monoclonal antibodies for the treatment of severe asthma explain the interest in studying the possibility of using this group of drugs in patients with chronic rhinosinusitis with polyps. Aim. The aim of the study was to assess changes in the severity of symptoms of chronic rhinosinusitis in patients with comorbid asthma against the background of reslizumab treatment. We evaluated clinical effect of treatment, dynamics of subjective and objective characteristics of symptoms of chronic rhinosinusitis and asthma, indices of total and local eosinophilia. Material and methods. The study involved 18 patients with severe eosinophilic asthma selected for treatment with reslizumab. Study protocol: The first examination, performed before starting reslizumab treatment, included assessment of clinical symptoms using the standardized Sino-nasal Outcome Test-22 (SNOT-22) and Asthma Control Test (ACT) questionnaires, endoscopic nasal cavity examination, spiral computed tomography of the paranasal sinuses, rhino cytogram, determination of eosinophils and eosinophilic cationic protein (ECP) in blood, allergological examination using ImmunoCAP method, and external respiratory function study. The results of treatment were evaluated after 6 injections of reslizumab at the dose of 3 mg/kg weight once every 4 weeks. The obtained data were processed using Statistica 12.0 program (StatSoft, USA). The differences were considered statistically significant at p<0,05. Results and discussion. When assessing the outcomes of treatment after 6 injections of reslizumab, both a marked improvement in asthma control (Asthma Control Test – increase from 7,0 [6–8] to 22,0 [16–22]) and a decrease in nasal symptoms (SNOT-22 was 78,0 [62–81] and 39,0 [29–49], respectively) were noted. There was a significant improvement in the Lund-Mackay spiral computed tomography data of the paranasal sinuses (16,0 [11–19] and 7,0 [5–12], respectively), spirometry values, and a decrease in eosinophils and eosinophilic cationic protein content in the blood. In the presence of polyposis rhinosinusitis in patients with severe eosinophilic asthma, a more pronounced effect of reslizumab on the attenuation of asthma symptoms was obtained comparing to patients without polyps. Conclusions. Treatment with reslizumab in patients with eosinophilic asthma and concomitant chronic rhinosinusitis with polyps and eosinophilic chronic rhinosinusitis leads not only to better control of asthma symptoms but also to a significant regression of nasal symptoms.

Effect of Dupilumab on Depression in Asthma with Eosinophilic Chronic Rhinosinusitis in the Japanese Population

Introduction: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). Methods: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. Results: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. Discussion/Conclusion: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

Different concentrations of specialized pro-resolving mediators in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps

Objective: To investigate the difference of concentrations of specialized pro-resolving mediators (SPMs) derived from fatty acids in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP). Methods: A total of 36 patients with bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent endoscopic nasal surgeries in Peking Union Medical College Hospital from May 2019 to September 2020 were enrolled, including 27 males and 9 females, with the age from 13 to 67 years. There were 23 cases of ECRSwNP and 13 cases of nECRSwNP. At the same time, 12 control subjects were enrolled. The concentrations of multiple SPMs, including lipoxins (LXA4 and LXB4), resolvins (RvD1, RvD2, RvD3, RvD5 and RvE1), protectins (PDX) and maresins (Mar-1) in nasal polyps with different histological subtypes and normal nasal mucosa were analyzed using liquid chromatography-tandem mass spectrometry. The concentrations of SPMs between groups were compared using Mann-Whitney U test. Spearman's rank correlation coefficient was used to measure the correlation between the concentrations of SPMs in nasal polyps and tissue eosinophil counts. Results: The concentrations of RvD2, RvD3, RvD5, LXA4, LXB4, Mar-1 and PDX in ECRSwNP group were significantly higher than that in controls (Z value was -2.276, -2.313, -3.371, -2.094, -2.051, -3.104 and -2.294, respectively, all P<0.05). The concentrations of RvD2, RvD5, Mar-1 and PDX in ECRSwNP group were significantly higher than those in nECRSwNP group (Z value was -2.175, -2.289, -2.243 and -2.124, respectively, all P<0.05). There was no significant difference in all these SPMs between nECRSwNP and controls (all P>0.05). The concentrations of RvD2, RvD3, RvD5, LXB4, Mar-1 and PDX in nasal polyps correlated positively with tissue eosinophil counts (r value was 0.443, 0.436, 0.371, 0.502, 0.340 and 0.386, respectively, all P<0.05). Conclusions: A varienty of SPMs are elevated in ECRSwNP. Dysregulation of fatty acid metabolism might play an important role in the chronic inflammation of ECRSwNP.

Predictive diagnostic value of serum 25-hydroxyvitamin D3 in eosinophilic chronic rhinosinusitis with nasal polyps

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.

Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis.

Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Predictive value of clinical characteristics in eosinophilic chronic rhinosinusitis with nasal polyps: A cross-sectional study in the Chinese population.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), with clinical characteristics differing from those of non-ECRSwNP. We aimed to explore the predictive value of clinical characteristics, including medical history, symptoms, and signs, prior to ECRSwNP diagnosis, and to develop a nomogram for use in clinical practice. A total of 502 patients with CRSwNP were enrolled. Based on the degree of eosinophilic infiltration in nasal polyps (NPs), patients were classified as ECRSwNP or non-ECRSwNP group. Participants' demographic characteristics, asthma history, severity of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia, and facial pain/headache) according to the visual analog scale, and nasal polyp scores based on polyp scoring system were recorded. Logistic regression analysis was performed to screen for independent risk factors, and a model nomogram was constructed. The percentage of asthmatic patients and the hyposmia, rhinorrhea, and total nasal symptom scores were significantly higher in ECRSwNP patients than that in non-ECRSwNP patients. The nasal polyp score was lower in the eosinophilic group than that in the non-eosinophilic group. Logistic regression analysis revealed that asthma history and hyposmia, rhinorrhea and nasal polyp scores were independent predictors of ECRSwNP. A nomogram consisting of these four independent risk factors was constructed, and its C-index was 0.808 (95% CI, 0.771 to 0.846). The nomogram based on asthma history and olfactory, rhinorrhea, and nasal polyp scores could help predict ECRSwNP, providing a simple, fast, and practical way to distinguish ECRSwNP from non-ECRSwNP cases in clinical practice.

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

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. 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. 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). 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.

Effects of HMGB1 on Tricellular Tight Junctions via TGF-β Signaling in Human Nasal Epithelial Cells.

The airway epithelium of the human nasal mucosa acts as a physical barrier that protects against inhaled substances and pathogens via bicellular and tricellular tight junctions (bTJs and tTJs) including claudins, angulin-1/LSR and tricellulin. High mobility group box-1 (HMGB1) increased by TGF-β1 is involved in the induction of nasal inflammation and injury in patients with allergic rhinitis, chronic rhinosinusitis, and eosinophilic chronic rhinosinusitis. However, the detailed mechanisms by which this occurs remain unknown. In the present study, to investigate how HMGB1 affects the barrier of normal human nasal epithelial cells, 2D and 2.5D Matrigel culture of primary cultured human nasal epithelial cells were pretreated with TGF-β type I receptor kinase inhibitor EW-7197 before treatment with HMGB1. Knockdown of angulin-1/LSR downregulated the epithelial barrier. Treatment with EW-7197 decreased angulin-1/LSR and concentrated the expression at tTJs from bTJs and increased the epithelial barrier. Treatment with a binder to angulin-1/LSR angubindin-1 decreased angulin-1/LSR and the epithelial barrier. Treatment with HMGB1 decreased angulin-1/LSR and the epithelial barrier. In 2.5D Matrigel culture, treatment with HMGB1 induced permeability of FITC-dextran (FD-4) into the lumen. Pretreatment with EW-7197 prevented the effects of HMGB1. HMGB1 disrupted the angulin-1/LSR-dependent epithelial permeability barriers of HNECs via TGF-β signaling in HNECs.

Achieving the best method to classify Eosinophilic Chronic Rhinosinusitis: a systematic review.

Chronic Rhinosinusitis is currently classified into eosinophilic and non-eosinophilic, according to the histologic quantification of the number of eosinophils in nasal mucosa biopsy. There is a lack of unanimous histopathologic criteria and methodology for this classification and no consensus regarding a cut-off point for Eosinophils per High power field. A systematic electronic search was performed on BVS, PUBMED, PUBMED PMC, SCOPUS, WEB OF SCIENCE, EMBASE, COCHRANE and PROQUEST databases looking for studies that reported a cut point for classification of Eosinophilic Chronic Rhinosinusitis (eCRS), and data concerning methodology of classification was extracted. We identified 142 studies that reported 29 different cut-off values for classification of eCRS, and different methods of histologic analysis. Out of these studies 13 reported their own methodology to establish the cut-off point, and used different reference standards as polyp recurrence, asthma and allergy, immunocytochemistry, quality of life index, standard deviation of the control population and cluster analysis. Further studies are needed to determine a precise cut-off point, especially international multicentered cluster analysis. Moreover, methodologic standardization of biopsy and analysis is needed to certify comparable results. Multiple biopsy sites, densest cellular infiltration area examination and oral steroids restriction at least four weeks before sampling are advisable.

Endotype-related recurrence pattern of chronic rhinosinusitis in revision functional endoscopic sinus surgery

ObjectiveThe recurrence of chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS) is influenced by various factors, potentially including the endotype based on the molecular pathophysiology of CRS. This study investigated differences in the recurrence pattern of CRS by endotype after primary FESS. MethodsThis retrospective study enrolled patients who had undergone revision FESS for recurrent CRS. Based on their clinical diagnosis, the patients were divided into two endotype groups: recurrent eosinophilic CRS (rECRS) and recurrent non-eosinophilic CRS (rNECRS). We compared and analyzed preoperative computed tomography (CT) findings, including typical anatomical findings of recurred CRS such as lateralized middle turbinate and retained uncinate process, the sinus where recurrence took place, and previous surgical completeness of the sinuses, between the rECRS and rNECRS groups. ResultsIn total, 142 patients were enrolled (48 rECRS, 94 rNECRS). No significant difference was found in the typical anatomic findings of recurrent CRS between the rECRS and rNECRS groups. The rates of the completeness of previous surgeries was significantly higher in rECRS than in rNECRS(P=.031). Despite the completeness of previous surgeries, the recurrence rate of frontal and ethmoidal sinuses was higher in the rECRS than rNECRS(P=.012, P<.001, respectively). In subgroup analysis according to the severity of ECRS, the number of involved sinuses and the rates of CRS recurrence and surgical completeness in frontal and anterior ethmoidal sinuses increased with ECRS severity. ConclusionsCT findings of revision FESS cases differed by CRS endotype. The rECRS group showed higher recurrence in the frontal and ethmoidal sinuses despite a higher surgical completeness rate. Incomplete surgery was more often found in the rNECRS group.

Sinus Microbiota in Patients With Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2-skewed inflammation and increased colonization by Staphylococcus aureus. CRSwNP can be distinguished as eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP) by the infiltration of eosinophils. The local microbiota plays an important role in the persistent inflammation of CRSwNP. To evaluate the bacterial community composition on the distinct types of CRSwNP patients, we collected nasal swabs from 16 ECRSwNP patients, 18 NECRSwNP patients, and 39 healthy control subjects. The microbiome structure for all the samples were analyzed by high-throughput 16S rRNA gene sequencing. Concentration of S. aureus was determined using TaqMan quantitative polymerase chain reaction (qPCR) targeting the nuclease (nuc) gene. The result showed significant differences in the sinus microbiome among healthy control subjects and CRSwNP patients. Microbiota community diversity was significantly lower in NECRSwNP samples compared to that of healthy control subjects. Interestingly, the abundance of several pathogenic bacteria was diverse between ECRSwNP and NECRSwNP patients. Although Staphylococcus prevailed in all groups, the abundance of Staphylococcus was significantly higher in the healthy control group than the ECRSwNP group. More importantly, the abundance of S. aureus was much higher in NECRSwNP patients. This study highlights that microbiota composition may contribute to the different clinical types of CRSwNP, inspiring new therapeutic strategies to resolve this chronic inflammation process.

Effects of Endoscopic Sinus Surgery for Eosinophilic Chronic Rhinosinusitis on Respiratory Functions and FeNO Production in the Lower Respiratory Tract.

To confirm the relevance of upper and lower airway inflammation in eosinophilic chronic rhinosinusitis (ECRS), the effects of endoscopic sinus surgery (ESS) on lower airway functions and inflammation need to be examined in ECRS patients. Chronic rhinosinusitis patients with nasal polyps (25 non-ECRS, 28 ECRS) were enrolled. The 12 patients in the ECRS group had comorbid asthma, in contrast to none in the non-ECRS group. We divided ECRS patients into 2 groups of ECRS with and without asthma. Clinical markers, including fraction of exhaled nitric oxide (FeNO), respiratory functions, and the Asthma Control Test (ACT) questionnaire, were investigated before and after ESS. The FeNO levels in the ECRS with asthma group decreased after ESS. The mean FeNO levels in this group were 56.3 ppb before ESS and 24.9, 25.1, 25.0, and 15.5 ppb 1, 2, 3, and 4 months, respectively, after ESS. The mean forced expiratory rates in 1 second before and after ESS were 67.6% and 73.0%, respectively. The mean maximal expiratory flow rates at 50% of the vital capacity before and after ESS were 45.8% and 58.0%, respectively. Significant differences were observed in respiratory functions before and after ESS. The mean ACT scores in the ECRS with asthma group before and after ESS were 17.5 and 23.5, respectively. The ACT scores were significantly higher after than before ESS. The present results indicate that ECRS and bronchial asthma are common eosinophilic airway inflammatory diseases, and ESS for eosinophilic sinusitis may improve lower airway function.

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 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.

Eosinophils Correlate with Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis with Nasal Polyps

Introduction: Chronic inflammation and tissue remodeling always occur together in chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) plays a critical role in airway remodeling. Objective: Changes of epithelial cells in sinus mucosa in different subtypes of CRS, especially in eosinophilic chronic rhinosinusitis with nasal polyps, and the role of EMT and eosinophils (EOS) in airway remodeling are still unknown. Methods: We included 85 patients in this study. They were divided into 4 groups: a normal control (NC) group, a chronic rhinosinusitis without nasal polyps (CRSsNP) group, an eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) group, and a noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group. Clinical data were all collected and analyzed. Standard hematoxylin and eosin staining, immunohistochemical staining, and 2-color immunofluorescence staining were performed. Biomarkers of EMT, epithelial cadherin, and vimentin were labeled. The immunohistochemistry results of each group were counted and statistically analyzed. Results and Conclusion: E-cadherin was downregulated, and vimentin was upregulated in epithelial tissue from the ECRSwNP group, compared with that from the control group and the other groups. The number of vimentin-expressing epithelial cells correlated with sinus CT imaging Lund-Mackay scores (r = 0.560, p < 0.001). Moreover, expression levels of vimentin in the epithelium were associated with numbers of infiltrating EOS in tissues (r = 0.710, p < 0.001) and the peripheral blood EOS ratio (r = 0.594, p < 0.001). EMT occurred in patients with CRSwNP, especially in those with ECRSwNP. Epithelial reprogramming correlates with eosinophil infiltration and disease severity. Eosinophils contributed to impairment of epithelial function and promoted EMT in CRSwNP.

Effect of Treatment with Dupilumab for Eosinophilic Chronic Rhinosinusitis

Effect of Treatment with Dupilumab for Eosinophilic Chronic Rhinosinusitis

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

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. 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. 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). 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.

Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status.

BackgroundThe human monoclonal antibody dupilumab blocks interleukin (IL)‐4 andIL‐13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS‐52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS‐52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy.MethodsPatients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund‐Mackay score assessed by CT (LMK‐CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm.ResultsDupilumab significantly improved NPS, NC, and LMK‐CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non‐/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK‐CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups.ConclusionDupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.

Anatomical Features Around Eustachian Tube in Eosinophilic Otitis Media With Eosinophilic Sinusitis.

This study investigated the relationships between anatomical findings around the eustachian tube (ET) and eosinophilic otitis media (EOM) accompanied by eosinophilic chronic rhinosinusitis (ECRS). This study employed axial, coronal, sagittal and oblique computed tomography. Patients who underwent endoscopic sinus surgery at the Department of Otolaryngology, Toho University Medical Center Omori Hospital and were diagnosed with ECRS (106 patients) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study were included. Subsequently, the presence of EOM accompanied by ECRS in 212 ear sides was assessed, and preoperative sinus computed tomography was used to evaluate various anatomical findings, such as the development of the sphenoid sinus and mastoid cells at the apex of petrous bone, the angle and length of the ET, and the size of the tympanic orifice of the ET. The relationships between these anatomical findings and the presence of EOM were analyzed statistically. EOM accompanied by ECRS was associated with a high peripheral blood eosinophil count and bronchial asthma. Among anatomical factors, the absence of peri-ET cells or petrous apex cells, and a low angle and short length of the ET, were risk factors for the onset of EOM. Anatomical factors such as the absence of peri-eustachian cells or petrous apex cells, and low angle or short length of the ET, are risk factors for the onset of EOM along with ECRS. Assessment of these factors may help in preventing the future onset or aggravation of EOM. 4 Laryngoscope, 131:E2689-E2695, 2021.

Effect of Functional Endoscopic Sinus Surgery on Gustatory Function in Patients With Chronic Rhinosinusitis.

In this study, we investigated the effect of functional endoscopic sinus surgery (FESS) on gustatory function in patients with chronic rhinosinusitis (CRS). Forty-three patients with CRS who underwent FESS were included in this study. Prior to FESS and 3 months after surgery, the severity of rhinosinusitis was assessed using the Taiwanese version of the 22-item SNOT (SNOT-22), endoscopic examination, and acoustic rhinometry. The olfactory function was evaluated using the phenylethyl alcohol odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test, and the gustatory function was evaluated using the whole mouth suprathreshold taste test (WMTT) and the taste quad test (TQT). Subgroup analyses were performed based on CRS phenotypes and endotypes. The SNOT-22 significantly improved 3 months after FESS for all patients with CRS. The endoscopic score and olfactory function significantly improved in patients with eosinophilic CRS and in patients with nasal polyps (CRSwNP). The WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in patients without nasal polyps. In addition, patients with noneosinophilic CRS had significantly decreased WMTT and salty scores 3 months after FESS. Our results showed that the effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the underlying inflammatory patterns.

Evaluation of nasal symptoms to distinguish eosinophilic from noneosinophilic nasal polyps based on peripheral blood.

Background: Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) have poorer outcomes after endoscopic sinus surgery and a higher recurrence rate. Objective: This study aimed to investigate the profile of clinical symptoms of eCRSwNP and the related risk factors. Methods: We prospectively enrolled 298 inpatients with CRSwNP from February 2019 to December 2019. The patients were divided into eCRSwNP and non-eCRSwNP groups based on the percentage of blood eosinophils; the cutoff value was set at 3.05%. Clinical data on questionnaires, visual analog scale (VAS) scores, and laboratory tests were collected. The differences in clinical symptoms, including nasal congestion, rhinorrhea, olfactory disorders, and head and/or facial pain, between the two groups were analyzed to identify the influential factors. Logistic analysis and receiver operating characteristic curves were used to determine the diagnostic benefit for the specific symptom in the patients in the eCRSwNP group. Results: Nasal congestion and olfactory disorders were significantly different between the eCRSwNP and non-eCRSwNP groups. The patients in the eCRSwNP group more frequently had concerns about olfactory disorders (p = 0.002), whereas patients in the non-eCRSwNP group mostly had nasal congestion (p = 0.001). The logistic analysis showed that the primary risk factors for olfactory disorders of eCRSwNP were disease duration (p = 0.014) and alcohol intake (p = 0.012). Olfactory disorders were not associated with the disease course of the eCRSwNP group but were correlated with the disease duration of non-eCRSwNP (p = 0.008). A VAS score for the olfactory disorders of >5.75 could be used to predict the diagnosis of eCRSwNP (area under the curve, 0.674 [95% confidence intervals, 0.559-0.689]; P < 0.001). Conclusion: Olfactory disorder might be the major nasal symptom that could be used to distinguish a peripheral eosinophilia-based definition of eCRSwNP and non-eCRSwNP. The disease duration was a limiting factor for using olfactory to distinguish two subgroups of nasal polyp. The investigation with regard to the accurate time boundary should be further addressed.