[A comparative study of the effectiveness of azoximer bromide and surgery on the quality of the life of patients with chronic rhinosinusitis without nasal polyps]. / Sravnitel'naya otsenka vliyaniya azoksimera bromida i khirurgicheskogo lecheniya na kachestvo zhizni patsientov s khronicheskim rinosinusitom bez polipov.

OBJECTIVE: The aim of this study was to compare the effects of azoximer bromide and surgery on the quality of life of patients with chronic rhinosinusitis (CRS) without polyps. We also wanted to examine changes in the patient's emotional state and the nature of their complaints. MATERIAL AND METHODS: The results of using the Visual Analogue Scale (VAS) and the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire in patients with CRS without severe or moderate-severe polyps, before treatment and 3 months after treatment, are presented. Patients, depending on their choice, were treated with functional endoscopic intervention or a course of 6 mg/ml azoximer bromide (1 ml per day, a course of at least 10 days). RESULTS: The median [interquartile range] score for VAS in patients before azoximer bromide treatment was 6.7 [6.3; 7.05] points, after treatment 4.2 [3.50; 4.70] points. The median [interquartile range] of VAS scores in patients before surgical treatment was 6.4 [6.1; 6.9] points, and after 4.8 [4.50; 5.30] points. The median [interquartile range] of the SNOT-22 score before azoximer bromide treatment was 33 [32; 36] points, after treatment - 24 [22; 25] points. The median [interquartile range] of the SNOT-22 score before surgery was 34 [32; 36] points, after treatment - 19 [18; 21.25] points. CONCLUSION: Azoximer bromide treatment and surgery improve the quality of life of patients with CRS (according to the visual analog scale and all SNOT-22 domains) during a control survey after 3 months (p<0.001). Surgical treatment has a stronger impact on the quality of life, which is more noticeable in the influence on the domains "Rhinological symptoms", "Extranasal symptoms", "Ear/facial symptoms" (p<0.05). According to the domains "Psychological dysfunction", "Sleep dysfunction", surgical intervention had no advantages in affecting the quality of life, compared with taking azoximer bromide (p<0.05).

[Problems of polypragmasia and drug interaction in the treatment of uncomplicated acute rhinosinusitis]. / Problemy polipragmazii i lekarstvennogo vzaimodeistviya v terapii neoslozhnennogo ostrogo rinosinusita.

This publication discusses polypragmasia and drug interactions in the treatment of uncomplicated acute rhinosinusitis in children and adults. Treatment of rhinosinusitis on an outpatient basis in multimorbid patients may be accompanied by multiple prescriptions, which increases the risk of drug interactions. The article reflects the most significant inappropriate combinations of both medicines and biologically active additives, herbal preparations. The advantages of using drugs with proven effectiveness, in particular intranasal glucocorticosteroids, are considered.

The interleukin-4/interleukin-13 pathway in type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.

A multi-view fusion lightweight network for CRSwNPs prediction on CT images.

Accurate preoperative differentiation of the chronic rhinosinusitis (CRS) endotype between eosinophilic CRS (eCRS) and non-eosinophilic CRS (non-eCRS) is an important topic in predicting postoperative outcomes and administering personalized treatment. To this end, we have constructed a sinus CT dataset, which comprises CT scan data and pathological biopsy results from 192 patients of chronic rhinosinusitis with nasal polyps (CRSwNP), treated at the Second Affiliated Hospital of Shantou University Medical College between 2020 and 2022. To differentiate CRSwNP endotype on preoperative CT and improve efficiency at the same time, we developed a multi-view fusion model that contains a mini-architecture with each network of 10 layers by modifying the deep residual neural network. The proposed model is trained on a training set and evaluated on a test set. The multi-view deep learning fusion model achieved the area under the receiver-operating characteristics curve (AUC) of 0.991, accuracy of 0.965 and F1-Score of 0.970 in test set. We compared the performance of the mini-architecture with other lightweight networks on the same Sinus CT dataset. The experimental results demonstrate that the developed ResMini architecture contribute to competitive CRSwNP endotype identification modeling in terms of accuracy and parameter number.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics. METHODS AND ANALYSIS: The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample. TRIAL REGISTRATION: NCT05228041/DRI_2021/0030.

Endotypes of Chronic Rhinosinusitis with Primary and Recurring Nasal Polyps in the Latvian Population.

Chronic rhinosinusitis (CRS) is a complex syndrome with various inflammatory mechanisms resulting in different patterns of inflammation that correlate with the clinical phenotypes of CRS. Our aim was to use detected IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, Ki 67, HBD-2, HBD-3, and LL-37 to classify specific inflammatory endotypes in chronic rhinosinusitis with the tissue of nasal polyps (CRSwNP). Samples from 35 individuals with primary and recurrent CRSwNP were taken during surgery. The tissues were stained for the previously mentioned biomarkers immunohistochemically. A hierarchical cluster analysis was performed. The clinical parameters were compared between clusters. Five clusters had significantly different biomarkers between groups. There were no significant differences in the clinical parameters, except for the Lund-Mackay score, which was significantly higher in cluster 4 compared to that of cluster 1 (p = 0.024). Five endotypes of (CRSwNP) are characterized by different combinations of type 1, type 2, and type 3 tissue inflammation patterns. In the Latvian population, endotypes associated with neutrophilic inflammation or a combination of neutrophilic inflammation and type 2 inflammation are predominant. Increased proliferation marker Ki 67 values are not associated with more severe inflammation in the tissue samples of chronic rhinosinusitis with nasal polyps.

[Blood eosinophilia in patients with severe bronchial asthma and chronic polypous rhinosinusitis treated with dupilumab: A review].

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation. Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity. Results: The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants. Conclusion: Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP.

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including "positive regulation of intracellular signal transduction", "arachidonic acid metabolic process", "spermatogenesis" and "negative regulation of cellular protein metabolic process". Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies.

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.

[Baseline characterization of a cohort of colombian patients with chronic rhinosinusitis with nasal polyps]. / Caracterización clínica y demográfica de pacientes colombianos con rinosinusitis crónica con poliposis nasal.

OBJECTIVE: To present the baseline clinical and demographic characteristics of CRSwNP patients over the age of 18 enrolled in a Patient Support Program (PSP) prior to biologic treatment. METHODS: Descriptive, cross-sectional study performed in a Colombian CRSwNP asthma PSP sponsored by Sanofi from Aug-2021 to Jul-2022. Data was collected from CRSwNP patients, prior to the start of Dupilumab treatment, who consented to the use of their data. The following information was reported: Age, reporting city, treating medical specialty, comorbidities, and persistence of treatment. RESULTS: 339 patients were included, 171 (50,4%) were women and 168 (49,6%) were men. The mean age at Dupilumab treatment initiation was 52,4 years. 62,8% began treatment during adulthood (26-59y), while 34.1% started at elderly (+60y) and 3.1% were young adults (18-25y). Most cases (29,7%) were included in Bogotá, followed by Antioquia (19%), Valle del Cauca (7,3%) and the remaining 44% nationwide. Comorbidities were present in 67,1% of the patients, with diagnosis of allergic rhinitis, atopic dermatitis, asthma, and other non-type 2 inflammatory diseases. Nasal surgical history was present in 89,6% of the patients, most of them with one to three previous surgeries. Continuous treatment was observed in 70,3% of patients for 6 to 12 months, in 21,3% for more than 12 months and in 8,4% for less than six months. The most frequently treating medical specialty was otorhinolaryngology (79,6%), followed by allergology (16%) and other medical professionals (4,4%). CONCLUSIONS: There is concordance with the literature on a higher presentation of the disease in women than in men. There is a large proportion of patients with nasal surgical history and type 2 inflammatory comorbidities by the moment of biologic treatment initiation. The care and identification of CRSwNP colombian patients is mainly provided by otorhinolaryngologists, followed by allergologists.

OBJETIVO: Presentar las características clínicas y demográficas iniciales de los pacientes con RSCcPN, mayores de 18 años, inscritos en un Programa de Soporte al Paciente (PSP), antes del inicio de tratamiento biológico. MÉTODOS: Estudio descriptivo y transversal realizado en un PSP para RSCcPN en Colombia, entre agosto de 2021 y julio de 2022, patrocinado por Sanofi. Los datos se recopilaron de pacientes con RSCcPN, antes de comenzar el tratamiento con Dupilumab, quienes dieron su consentimiento para el uso de sus datos. Se reportó la siguiente información: edad, ciudad de origen, especialidad médica tratante, comorbilidades y persistencia del tratamiento. RESULTADOS: Se incluyeron 339 pacientes, 171 mujeres (50,4%), y 168 hombres (49,6%). La edad promedio al inicio del tratamiento con Dupilumab, fue de 52,4 años. El 62,8% inició tratamiento durante la edad adulta (entre 26 y 59 años), mientras que el 34,1% comenzó en la vejez (+60 años), y el 3,1% entre los 18 y 25 años. La mayoría de los casos (29,7%) se incluyeron en Bogotá, seguidos por Antioquia (19%), Valle del Cauca (7,3%) y el 44% restante en todo el país. Las comorbilidades estuvieron presentes en el 67,1% de los pacientes, con diagnóstico de rinitis alérgica, dermatitis atópica, asma y otras enfermedades no inflamatorias tipo 2. El 89,6% de los pacientes tenía antecedentes de cirugía nasal, la mayoría de ellos con entre una y tres cirugías previas. Se observó tratamiento continuo en el 70,3% de los pacientes durante 6 y 12 meses, en el 21,3%, durante más de 12 meses, y en el 8,4% durante menos de 6 meses. La especialidad médica que trató a los pacientes con más frecuencia fue la otorrinolaringología (79,6%), seguida por la alergología (16%) y otros profesionales médicos (4,4%). CONCLUSIONES: Existe concordancia con la literatura con una mayor presentación de la enfermedad en mujeres que en hombres. Hay una gran proporción de pacientes con antecedentes de cirugía nasal y comorbilidades inflamatorias tipo 2, al inicio del tratamiento biológico. La atención e identificación de los pacientes colombianos con RSCcPN es proporcionada principalmente por otorrinolaringólogos, seguidos por alergólogos.

Diagnostic accuracy of clinical visual assessment using endoscopic images for nasal cavity mass lesions.

Objectives: Discrimination of nasal cavity lesions using nasal endoscopy is challenging because of the differences in clinical manifestations and treatment strategies. We aimed to investigate the diagnostic accuracy of clinical visual assessment (CVA) of nasal cavity masses using endoscopic images and determine whether there is a difference according to pathologic class and the examiners' experience. Methods: We collected pathologically confirmed endoscopic images of normal findings, nasal polyp (NP), benign tumor, and malignant tumor (each class contained 100 images) randomly selected. Eighteen otolaryngologists, including six junior residents, six senior residents, and six board-certified rhinologists classified the test set images into four classes of lesions by CVA. Diagnostic performance according to the pathologic class and the examiner's experience level was evaluated based on overall accuracy, F1-score, confusion matrix, and area under the receiver operating characteristic curve (AUC). Results: Diagnostic performance was significantly different according to the pathological class of nasal cavity mass lesions with the overall accuracy reported high in the order of normal, NP, benign tumor, and malignant tumor (0.926 ± 0.100; 0.819 ± 0.135; 0.580 ± 0.112; 0.478 ± 0.187, respectively), F1 score (0.937 ± 0.076; 0.730 ± 0.093; 0.549 ± 0.080; 0.554 ± 0.146, respectively) and AUC value (0.96 ± 0.06; 0.84 ± 0.07; 0.70 ± 0.05; 0.71 ± 0.08, respectively). The expert rhinologist group achieved higher overall accuracy than the resident group (0.756 ± 0.157 vs. 0.680 ± 0.239, p < .05). Conclusion: CVA for nasal cavity mass was highly dependent on the pathologic class and examiner's experience. The overall accuracy was reliably high for normal findings, but low in classifying benign and malignant tumors. Differential diagnosis of lesions solely based on nasal endoscopic evaluation is challenging. Therefore, clinicians should consider further clinical evaluation for suspicious cases.

S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis.

Staphylococcus aureus mucosal biofilms are associated with recalcitrant chronic rhinosinusitis (CRS). However, S. aureus colonisation of sinus mucosa is frequent in the absence of mucosal inflammation. This questions the relevance of S. aureus biofilms in CRS etiopathogenesis. This study aimed to investigate whether strain-level variation in in vitro-grown S. aureus biofilm properties relates to CRS disease severity, in vitro toxicity, and immune B cell responses in sinonasal tissue from CRS patients and non-CRS controls. S. aureus clinical isolates, tissue samples, and matched clinical datasets were collected from CRS patients with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. B cell responses in tissue samples were characterised by FACS. S. aureus biofilms were established in vitro, followed by measuring their properties of metabolic activity, biomass, colony-forming units, and exoprotein production. S. aureus virulence was evaluated using whole-genome sequencing, mass spectrometry and application of S. aureus biofilm exoproteins to air-liquid interface cultures of primary human nasal epithelial cells (HNEC-ALI). In vitro S. aureus biofilm properties were correlated with increased CRS severity scores, infiltration of antibody-secreting cells and loss of regulatory B cells in tissue samples. Biofilm exoproteins from S. aureus with high biofilm metabolic activity had enriched virulence genes and proteins, and negatively affected the barrier function of HNEC-ALI cultures. These findings support the notion of strain-level variation in S. aureus biofilms to be critical in the pathophysiology of CRS.

Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

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.

[Correlation study of NCF2 in chronic rhinosinusitis with nasal polyps].

Objective:After selecting NCF2 based on bioinformatics, clinical experiments were conducted to verify the expression of NCF2 in chronic rhinosinusitis with nasal polyps to study its correlation. Methods:The differentially expressed genes（DEGs） between CRSwNP and non-CRS patients were explored using the CRS-related dataset from the gene expression omnibus GEO database. The weighted gene co-expression network（WGCNA） was used for cluster analysis. The expression and cell distribution of NCF2 in the tissues were determined by single gene enrichment analysis（GSEA）, immune inflammatory infiltration analysis, and principal component（PCA） analysis. The expression degree of NCF2 in the tissues of the subjects was determined by immunohistochemistry, and the percentage of EOS in the peripheral blood of the subjects was detected and the correlation was analyzed. EOS in the tissues of the subjects were counted under a microscope and compared. Results:①The Venn diagram was obtained by crossing the module with the highest correlation between DEGs and WGCNA to determine the core gene NCF2. ②GSEA analysis showed that NCF2 was significantly related to the immunological processes such as allogeneic rejection and asthma. ③The area under the ROC curve was 1, indicating that NCF2 had diagnostic value for CRSwNP. ④NCF2 was highly expressed in nasal polyps, mainly distributed in monocytes and eosinophils. ⑤HE staining showed that the number of EOS in ECRSwNP tissues and the percentage of eosinophils in peripheral blood were higher than those in nonECRSwNP and control groups. ⑥The immunohistochemistry results showed that NCF2 was significantly expressed in the nasal polyps of ECRSwNP patients, which was higher than that in the nasal mucosa of nonECRSwNP group and control group. ⑦The expression of NCF2 in tissues was positively correlated with EOS count in ECRSwNP group and EOS expression in peripheral blood. Conclusion:The expression of NCF2 is increased in eosinophilic chronic rhinosinusitis with nasal polyps, and it is significantly correlated with the expression of eosinophils in peripheral blood and tissues, suggesting that NCF2 may be used as a basis for the intrinsic classification of ECRSwNP and a reference index for clinical diagnosis and treatment.

Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

Ganglioside GD3 Regulates Inflammation and Epithelial-to-Mesenchymal Transition in Human Nasal Epithelial Cells.

Chronic sinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and involves tissue remodeling. One of the key mechanisms of tissue remodeling is the epithelial-mesenchymal transition (EMT), which also represents one of the pathophysiological processes of CRS observed in CRSwNP tissues. To date, many transcription factors and forms of extracellular stimulation have been found to regulate the EMT process. However, it is not known whether gangliosides, which are the central molecules of plasma membranes, involved in regulating signal transmission pathways, are involved in the EMT process. Therefore, we aimed to determine the role of gangliosides in the EMT process. First, we confirmed that N-cadherin, which is a known mesenchymal marker, and ganglioside GD3 were specifically expressed in CRSwNP_NP tissues. Subsequently, we investigated whether the administration of TNF-α to human nasal epithelial cells (hNECs) resulted in the upregulation of ganglioside GD3 and its synthesizing enzyme, ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialytransferase 1 (ST8Sia1), and the consequently promoted inflammatory processes. Additionally, the expression of N-cadherin, Zinc finger protein SNAI2 (SLUG), and matrix metallopeptidase 9 (MMP-9) were elevated, but that of E-cadherin, which is known to be epithelial, was reduced. Moreover, the inhibition of ganglioside GD3 expression by the siRNA or exogenous treatment of neuraminidase 3 (NEU 3) led to the suppression of inflammation and EMT. These results suggest that gangliosides may play an important role in prevention and therapy for inflammation and EMT.