Olfactory Loss in Rhinosinusitis: Mechanisms of Loss and Recovery.

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

Exploring the immunopathology of type 2 inflammatory airway diseases.

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

Butyrate inhibits type 2 inflammation in eosinophilic chronic rhinosinusitis.

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.

Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model.

Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests that Staphylococcus aureus, particularly in its biofilm form, is associated with the disease. This study aimed to investigate the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSFs), harvested from clinical isolates of non-CRS carrier and CRS patients, on the nasal mucosa in a rat model. Animals were randomised (n = 5/group) to receive daily intranasal instillations of 40 µL (200 µg/µL) SABSFs for 28 days or vehicle control. The sinonasal samples were analysed through histopathology and transcriptome profiling. The results showed that all three intervention groups displayed significant lymphocytic infiltration (p ≤ 0.05). However, only the SABSFs collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSFs significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSFs collected from CRS patients (p ≤ 0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE. This in vivo study indicates that long-term exposure to SABSFs leads to an inflammatory response in the nasal mucosa with increased severity for S. aureus isolated from a CRSwNP patient. Moreover, exposure to SABSFs does not induce local production of IgE.

Prelacrimal Recess Approach in Unilateral Maxillary Sinus Lesions: What Is the Impact and Efficacy?

Background and Objectives: Chronic sinusitis is a commonly encountered diagnosis for otorhinolaryngologists. The profound negative effect of rhinosinusitis on patients' quality of life is frequently overlooked, and surgical lines of treatment are numerous. The aim of the study was to assess the comparative efficacy of endoscopic middle meatal antrostomy with the endoscopic prelacrimal recess approach, combined with middle meatal antrostomy in the treatment of unilateral chronic maxillary sinus lesion. Materials and Methods: Thirty patients with unilateral chronic maxillary sinus lesions enrolled in the study at Alahsa hospital. Patients were divided into two groups: 15 treated through a middle meatal antrostomy and 15 treated via a combined middle meatal antrostomy and prelacrimal recess approach. Demographic and clinical information of the patients, including the medical history, CT scan findings, diagnosis, recurrence, and complications, were gathered and analyzed. Pre- and postoperative clinical findings were graded utilizing the Lund-Kennedy Endoscopic Scoring System. Results: The enrolled patients varied in age from 18 to 56, with 60% being male and 40% being female. Antrochoanal polyp, maxillary sinus mucocele, and unilateral allergic fungal sinusitis were among the pathological diagnoses. The follow-up period averaged 14.3 months. Following surgery, two patients in Group II encountered nasal discomfort, which included synechia and epiphora. The success rate for preserving a patient's disease-free condition was 86.7%. A statistically significant difference in disease-free incidence was observed among the patients in group II. In group I, recurrence was identified in 26.7% of the patients. The postoperative symptoms diminished considerably, and the VAS score was reduced substantially. In Group II patients, however, there was no significant difference in scarring. Clinically significant differences were observed in the mean total Lund-Kennedy Endoscopic scores when compared to their preoperative values. Conclusions: Achieving endoscopic access to the sinus's anterior, lateral, inferior, and inferomedial regions is facilitated by operating via the prelacrimal recess, which is the most advantageous approach. This approach facilitates rapid mucosal healing by maintaining the integrity of the nasolacrimal duct and mucosal covering. The specific pathology, surgical objectives, surgeon expertise, and equipment accessibility influence the choice of endoscopic surgical technique.

Mast Cells in Aspirin-Exacerbated Respiratory Disease.

PURPOSE OF REVIEW: Aspirin-exacerbated respiratory disease (AERD) is a syndrome of high type 2 inflammation and is known to critically involve mast cell activation. The mast cell is an important cell in the baseline inflammatory processes in the upper and lower airway by maintaining and amplifying type 2 inflammation. But it also is prominent in the hypersensitivity reaction to COX-1 inhibition which defines this condition. RECENT FINDINGS: Recent work highlights the mast cell as a focal point in AERD pathogenesis. Using AERD as a specific model of both high type 2 asthma and chronic sinusitis, the role of mast cell activity can be better understood in other aspects of airway inflammation. Further dissecting out the mechanism of COX-1-mediated mast cell activation in AERD will be an important next phase in our understanding of NSAID-induced hypersensitivity as well as AERD pathophysiology.

Matrix metalloproteinases in chronic rhinosinusitis.

INTRODUCTION: Matrix metalloproteinases (MMPs) are a group of enzymes that are essential in maintaining extracellular matrix (ECM) homeostasis, regulating inflammation and tissue remodeling. In chronic rhinosinusitis (CRS), the overexpression of certain MMPs can contribute to chronic nasal tissue inflammation, ECM remodeling, and tissue repair. AREAS COVERED: This review provides a comprehensive overview of the biological characteristics and functions of the MMP family, particularly focusing on the expression and activity of MMPs in patients with CRS, and delves into their role in the pathogenesis of CRS and their potential as therapeutic targets. EXPERT OPINION: MMPs are important in tissue remodeling and have been implicated in the pathophysiology of CRS. Previous studies have shown that the expression of MMPs is upregulated in the nasal mucosa of patients with CRS and positively correlates with the severity of CRS. However, there is still a large gap in the research content of MMP in CRS, and the specific expression and pathogenic mechanism of MMP still need to be clarified. The significance and value of the ratio of MMP to tissue inhibitors of metalloproteinase (TIMP) in diseases still need to be demonstrated. Moreover, further studies are needed to assess the efficacy and safety of biologics that target MMPs in patients with CRS.

Aggregated eosinophils and neutrophils characterize the properties of mucus in chronic rhinosinusitis.

BACKGROUND: Airway obstruction caused by viscous mucus is an important pathophysiologic characteristic of persistent inflammation, which can result in organ damage. OBJECTIVE: We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes affect the clinical properties of mucus. METHODS: Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, noneosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined. RESULTS: Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared to mucus from patients with noneosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathologic characteristics resembling those of mucus. Cotreatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. CONCLUSIONS: The present study elucidated the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases.

The mucosal concept in chronic rhinosinusitis: Focus on the epithelial barrier.

Chronic rhinosinusitis (CRS) is a common chronic nasal cavity and sinus disease affecting a growing number of individuals worldwide. Recent advances have shifted our understanding of CRS pathophysiology from a physical obstruction model of ventilation and drainage to a mucosal concept that recognizes the complexities of mucosal immunologic variations and cellular aberrations. A growing number of studies have demonstrated the alteration of the epithelial barrier during inflammatory states. Therefore, the current review has focused on the crucial role of epithelial cells within this mucosal framework in CRS, detailing the perturbed epithelial homeostasis, impaired epithelial cell barrier, dysregulated epithelial cell repair processes, and enhanced interactions between epithelial cells and immune cells. Notably, the utilization of novel technologies, such as single-cell transcriptomics, has revealed the novel functions of epithelial barriers, such as inflammatory memory and neuroendocrine functions. Therefore, this review also emphasizes the importance of epithelial inflammatory memory and the necessity of further investigations into neuroendocrine epithelial cells and neurogenic inflammation in CRS. We conclude by contemplating the prospective benefits of epithelial cell-oriented biological treatments, which are currently under investigation in rigorous randomized, double-blind clinical trials in patients with CRS with nasal polyps.

Levels of nasal nitric oxide and nitric oxide synthase expression in chronic rhinosinusitis with nasal polyposis.

KEY POINTS: CRSwNP patients had decreased nNO and increased SNOT-22, endoscopy, and CT scores. CRSwNP patients exhibited decreased nNO despite elevated iNOS and eNOS mRNA expression. The mechanism behind lowered nNO in CRSwNP may not be related to NOS expression.

Pathogenesis-based application of biologics for chronic rhinosinusitis: Current and future perspectives.

Chronic rhinosinusitis (CRS) is heterogeneous and contains diverse pathogenesis including type 1, type 2, and/or type 3 inflammation. For severe type 2 CRS especially CRS with nasal polyps (CRSwNP), biologics that target inflammatory molecules have recently been applied along with further changes in the treatment algorithm for CRS. Currently, a completed phase 3 clinical trial for biologics for severe CRSwNP with inadequate response to surgery and/or intranasal corticosteroids, including omalizumab (anti-IgE), mepolizumab (anti-IL-5), benralizumab (anti-IL-5Rα), and dupilumab (anti-IL-4Rα), have all shown efficacy. Similar phase 3 clinical trials for tezepelumab (anti-TSLP) and etokimab (anti-IL-33) are now underway and completed, respectively. Further studies need to evaluate how to optimally and cost-effectively use biologics for CRS and determine if any biomarkers are indicative of which biologics should be administered. A definition of complete and/or clinical remission of CRS is also needed to determine when to reduce or discontinue biologics. In addition, more precise basic research on CRS, such as endotyping and genotyping, will need to be undertaken in order to determine novel targets for biologics.

Neuroimmune interplay during type 2 inflammation: Symptoms, mechanisms, and therapeutic targets in atopic diseases.

Type 2 inflammation is characterized by overexpression and heightened activity of type 2 cytokines, mediators, and cells that drive neuroimmune activation and sensitization to previously subthreshold stimuli. The consequences of altered neuroimmune activity differ by tissue type and disease; they include skin inflammation, sensitization to pruritogens, and itch amplification in atopic dermatitis and prurigo nodularis; airway inflammation and/or hyperresponsiveness, loss of expiratory volume, airflow obstruction and increased mucus production in asthma; loss of sense of smell in chronic rhinosinusitis with nasal polyps; and dysphagia in eosinophilic esophagitis. We describe the neuroimmune interactions that underlie the various sensory and autonomic pathologies in type 2 inflammatory diseases and present recent advances in targeted treatment approaches to reduce type 2 inflammation and its associated symptoms in these diseases. Further research is needed to better understand the neuroimmune mechanisms that underlie chronic, sustained inflammation and its related sensory pathologies in diseases associated with type 2 inflammation.

Chronic rhinosinusitis with nasal polyps: eosinophils versus B lymphocytes in disease pathogenesis.

PURPOSE OF REVIEW: To highlight the current evidence that supports the view that eosinophils may not drive disease in chronic rhinosinusitis with nasal polyps (CRSwNP) and the emerging evidence for B cells as an important player in this disease. RECENT FINDINGS: Eosinophil depletion studies in CRSwNP do not fully support a critical role for eosinophils in CRSwNP. Almost complete eosinophil depletion with dexpramipexole had no impact on polyp size reduction or clinical improvement. Anti-interleukin (IL)-5 and IL-5Rα inhibition were more effective though with less clinical impact when compared to anti-immunoglobulin E (IgE) or IL-4Rα inhibition strategies. As IL-5Rα is also expressed on CRSwNP derived IgE+ and IgG4+ plasma cells to the same extent as eosinophils, improvements in CRSwNP with IL-5 inhibition may suggest a role for B cells over eosinophils in CRSwNP. We review both eosinophils and B cells in the context of CRSwNP and highlight the current evidence that supports an emerging role for B cells. SUMMARY: Despite many aspects of immunopathology in CRSwNP explainable by B cell dysfunction, B cells have so far been ignored in CRSwNP. Further work is needed, as targeting B cells may offer an exciting new therapeutic option in the future.

Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis.

BACKGROUND: Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear. OBJECTIVES: This study aimed to investigate the influence of NETs on the CRS epithelium. METHODS: Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63+ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model. RESULTS: NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63+ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67+p63+ cells. We found that ΔNp63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ΔNp63+ epithelial stem cells and reduced polyp formation. CONCLUSIONS: These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs.

Eosinophilic Chronic Rhinosinusitis and Pathogenic Role of Protease.

Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinus mucosa, and eosinophilic CRS (eCRS) is a subtype characterized by significant eosinophil infiltration and immune response by T-helper-2 cells. The pathogenesis of eCRS is heterogeneous and involves various environmental and host factors. Proteases from external sources, such as mites, fungi, and bacteria, have been implicated in inducing type 2 inflammatory reactions. The balance between these proteases and endogenous protease inhibitors (EPIs) is considered important, and their imbalance can potentially lead to type 2 inflammatory reactions, such as eCRS. In this review, we discuss various mechanisms by which exogenous proteases influence eCRS and highlight the emerging role of endogenous protease inhibitors in eCRS pathogenesis.

Change in Maxillary Sinus Mucosal Thickness in Patients with Preoperative Maxillary Sinus Mucosal Thickening as Assessed by Otolaryngologists: A Retrospective Study.

Background and Objectives: Maxillary sinus pathologic conditions may increase the risk of complications during posterior maxillary sinus augmentation surgery. The purpose of this study was to evaluate the changes in participants with preoperative maxillary sinus mucosal thickening and to assess this factor as a preoperative risk indicator for sinusitis after maxillary dental implantation. Materials and Methods: We compared the preoperative and postoperative maxillary sinus mucosal thickness (MSMT), the distance between the maxillary sinus ostium and sinus floor (MOD), and the MSMT/MOD ratio. The participants were divided into three groups (sinus augmentation, bone grafting, and no grafting). Results: The mean preoperative MSMT was 4.3 ± 2.0 mm, and the mean MSMT/MOD ratio was 0.13 ± 0.05. No postoperative sinusitis was observed in these patients, including cases caused by anatomical variations. The mean postoperative MSMT was 4.5 ± 2.3 mm, and the mean postoperative MSMT/MOD ratio was 0.15 ± 0.06. There was no statistically significant difference between the groups at each time point (p > 0.05). Conclusions: The study found no significant change in MSMT at post-treatment evaluation, even when considering different subgroups. It underscores the importance of preoperative maxillary sinus radiographic assessments and collaboration between dentists and otolaryngologists for better outcomes in patients with preoperative maxillary sinus mucosal thickening.

The destruction of mucosal barriers, epithelial remodeling, and impaired mucociliary clearance: possible pathogenic mechanisms of Pseudomonas aeruginosa and Staphylococcus aureus in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a pathological condition characterized by persistent inflammation in the upper respiratory tract and paranasal sinuses. The epithelium serves as the first line of defense against potential threats and protects the nasal mucosa. The fundamental mechanical barrier is formed by the cell-cell contact and mucociliary clearance (MCC) systems. The physical-mechanical barrier is comprised of many cellular structures, including adhesion junctions and tight junctions (TJs). To this end, different factors, such as the dysfunction of MCC, destruction of epithelial barriers, and tissue remodeling, are related to the onset and development of CRS. Recently published studies reported the critical role of different microorganisms, such as Staphylococcus aureus and Pseudomonas aeruginosa, in the induction of the mentioned factors. Bacteria could result in diminished ciliary stimulation capacity, and enhance the chance of CRS by reducing basal ciliary beat frequency. Additionally, bacterial exoproteins have been demonstrated to disrupt the epithelial barrier and induce downregulation of transmembrane proteins such as occludin, claudin, and tricellulin. Moreover, bacteria exert an influence on TJ proteins, leading to an increase in the permeability of polarized epithelial cells. Noteworthy, it is evident that the activation of TLR2 by staphylococcal enterotoxin can potentially undermine the structural integrity of TJs and the epithelial barrier through the induction of pro-inflammatory cytokines. The purpose of this article is an attempt to investigate the possible role of the most important microorganisms associated with CRS and their pathogenic mechanisms against mucosal surfaces and epithelial barriers in the paranasal sinuses. Video Abstract.

Middle meatus microbiome in patients with eosinophilic chronic rhinosinusitis in a Japanese population.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease and is subdivided into eosinophilic and noneosinophilic forms. There are few reports investigating the nasal microbiome and its pathological functions in patients with CRS. OBJECTIVE: We sought to analyze factors contributing to variations of the nasal microbiome in CRS, and on the basis of these factors, to elucidate whether the bacterial metabolites were related to the pathogenesis. METHODS: Nasal swabs were collected, and the V3 to V4 variable region of the 16S ribosomal RNA gene was amplified and sequenced. Factors contributing to variations of the nasal microbiome in patients with CRS were compared. The most influential factor was whether CRS was eosinophilic, and we compared α- and ß-diversity, bacterial species, and predictive bacterial functions between the 2 patient groups. In addition, the metabolites of the key bacteria were extracted, and we evaluated the predicted bacterial functions in airway epithelial cells. RESULTS: In total, 110 patients with CRS and 33 control subjects were enrolled. On the basis of the factors of variation, it was found that patients with eosinophilic CRS (n = 65) had different microbiomes with weighted UniFrac ß-diversity and lower α-diversity compared with those with noneosinophilic CRS (n = 45). A higher abundance of Fusobacterium nucleatum and an increased LPS pathway were observed in patients with noneosinophilic CRS compared with those with eosinophilic CRS. In airway epithelial cells, LPS derived from F nucleatum suppressed the expression levels of ALOX15 induced by TH2 cytokines. CONCLUSIONS: The differences in the nasal microbiome may play a key role in the pathophysiology of CRS.

Role of CD23 Activated ERK Signaling Pathway in the Pathogenesis of Eosinophilic Chronic Sinusitis with Nasal Polyps.

Objective: In the context of the rising prevalence of eosinophilic chronic sinusitis accompanied by nasal polyps, this study aims toinvestigate the role of CD23 in the pathogenesis of eosinophilic chronic sinusitis with nasal polyps. Methods: The cross-sectional study was conducted, 75 patients with chronic sinusitis and nasal polyps treated in our hospital from January 2019 to May 2021 were selected, including 40 cases of eosinophilic patients with the average age of 29.92 years and 35 cases of non-eosinophilic patients with the average age of 30.05 years and 30 patients with the average age of 30.14 years who underwent skull base benign tumor resection in our hospital were selected as the control group, the expression of CD23 in polyp tissue was detected by immunohistochemistry, and the expression of CD23, p-ERK and CCL20 in polyp tissue were detected by Western blot. Specifically, tissue samples were processed and subjected to staining using specific antibodies targeting CD23. The stained sections were then visualized under a microscope to determine the expression levels of CD23. CD23, p-ERK, and CCL20 expressions in polyp tissue were evaluated via Western blot. Total protein was extracted, separated on a gel, transferred to a membrane, and probed with specific antibodies. Chemiluminescence allowed visualization and quantification of protein expressions. Results: Immunohistochemistry showed that CD23 expression was high in the eosinophilic group but low in the non-eosinophilic and control groups. The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in polyp tissue s of the eosinophilic group were (0.892 ± 0.092), (0.733 ± 0.101) and (0.813 ± 0.106), respectively, which were significantly higher than those in non-eosinophilic group and control group (P < .05). The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in the non-eosinophilic group were (0.461 ± 0.087), 0.412 ± 0.096) and (0.424 ± 0.098), which were significantly higher than those in the control group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with the relative expression levels of p-ERK protein and CCL20 protein (P < .05). The Lund-Kennedy score in the eosinophilic group was (6.10 ± 1.01), which was significantly higher than that in the non-eosinophilic group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with Lund-Kennedy score (P < .05). Conclusion: Eosinophilic chronic sinusitis with nasal polyp mucosal tissue CD23 expression is up-regulated, which is positively correlated with the ERK signaling pathway and disease severity. This study provides valuable insights into potential therapeutic targets that could be explored to develop future treatment modalities. The potential clinical significance of the study is to reveal the important role of CD23 in the pathogenesis of chronic sinusitis with nasal polyps. The upward adjustment of CD23 is positively related to the severity of the disease, which provides valuable guidance for future treatment strategies. This discovery may provide new ways for the development of CD23 treatment methods, so as to better control the progress of the disease of eosinophilic chronic sinusitis with nasal polyps. Further research can explore the molecular mechanism of CD23 regulation, further verify the feasibility of CD23 as the treatment target, and evaluate the potential value of CD23 as a prognostic logo.

S. aureus biofilm metabolic activity correlates positively with patients' eosinophil frequencies and disease severity in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinus mucosa. Recalcitrant CRS patients are unresponsive to medical and surgical interventions and often present with nasal polyps, tissue eosinophilia, and Staphylococcus aureus dominant mucosal biofilms. However, S. aureus sinonasal mucosal colonisation occurs in the absence of inflammation, questioning the role of S. aureus in CRS pathogenesis. Here, we aimed to investigate the relationship between S. aureus biofilm metabolic activity and virulence genes, innate immune cells, and disease severity in CRS. Biospecimens, including sinonasal tissue and nasal swabs, and clinical datasets, including disease severity scores, were obtained from CRS patients and non-CRS controls. S. aureus isolates were grown into biofilms in vitro, characterised, and sequenced. The patients' innate immune response was evaluated using flow cytometry. S. aureus was isolated in 6/19 (31.58%) controls and 23/53 (43.40%) CRS patients of 72 recruited patients. We found increased S. aureus biofilm metabolic activity in relation to increased eosinophil cell frequencies and disease severity in recalcitrant CRS cases. Mast cell frequencies were higher in tissue samples of patients carrying S. aureus harbouring lukF.PV, sea, and fnbB genes. Patients with S. aureus harbouring lukF.PV and sdrE genes had more severe disease. This offers insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.