OBJECTIVES:To investigate the relationship between vitamin D (VD) levels and chronic rhinosinusitis (CRS), and to evaluate the therapeutic efficacy of VD supplementation for CRS. DATA SOURCES:Two independent reviewers systematically searched PubMed, Embase, and the Cochrane Library to identify studies that assessed the association between CRS and VD, as well as the therapeutic effects of VD supplementation on CRS outcomes. REVIEW METHODS:Meta-analyses were conducted to compare VD levels between CRS patients and controls and to evaluate the efficacy of VD supplementation. Random- or fixed-effects models were applied as appropriate. Sensitivity and subgroup analyses were performed to investigate potential sources of heterogeneity. RESULTS:A pooled analysis of 15 studies showed significantly lower serum VD levels in CRS patients compared to controls (SMD = -0.98; P < .001). Both 25(OH)D3 and 25(OH)D assays showed lower VD levels in CRS patients (SMD = -1.24, P < .001 vs SMD = -0.77, P < .001). Subgroup analyses also revealed consistent reductions in both CRS with nasal polyps (CRSwNP; SMD = -1.05; P < .001) and CRS without nasal polyps (CRSsNP; SMD = -1.02; P < .001). Moreover, four randomized controlled trials indicated that VD supplementation significantly improved Sino-Nasal Outcome Test-22 (SNOT-22) scores at <3 months (MD = -1.44; P = .001); however, this benefit was not maintained at ≥3 months (MD = -6.52; P = .12). CONCLUSIONS:CRS patients show significantly lower serum VD levels than healthy controls. VD supplementation may provide short-term symptomatic improvement, although its long-term efficacy remains unproven.

BACKGROUND:Sinonasal inverted papilloma(SNIP) is a benign tumor with a potential of malignant transformation but has a certain recurrence. OBJECTIVES:A retrospective analysis of risk factors for SNIP was conducted. MATERIALS AND METHODS:Univariate analysis and multivariate logistic regression were performed to identify the independent predictors of SNIP recurrence. Nomogram and ROC curve were constructed for the prediction of the final model. Machine-learning interpretation was further provided by SHAP analysis, and a decision-tree algorithm was built to validate the predictive performance. RESULTS:A total of 171 patients were enrolled, 30 patients in recurrent group, and 141 patients in non-recurrent group, yielding a recurrence rate of 17.54%. Multivariable logistic regression identified Krouse stage and peripheral monocyte count as independent predictors of recurrence, the same as SHAP analysis. Nomogram constructed from these variables and produced an area under the ROC curve of 0.75, with 93.3% sensitivity and 83.8% specificity. A decision-tree algorithm demonstrated absence of management of the tumor attachment site, 'osteitis', and 'convoluted cerebriform pattern' achieved an predictive accuracy for recurrence. CONCLUSION AND SIGNIFICANCE:Krouse stage and peripheral monocyte count are the independent risk factors for recurrence of SNIP. For recognition of 'osteitis' and 'convoluted cerebriform pattern', the management of the tumor attachment site can substantially reduce the recurrence.

[This corrects the article on p. 1922 in vol. 9, PMID: 31598395.].

NLRP3 (NLR family pyrin domain containing 3) is one of the crucial receptors in pathogen recognition receptor (PRR) families which can recognize the pathogen-associated molecular patterns (PAMPs) and the damage-associated molecular patterns (DAMPs), thus triggering innate immune response. After NLRP3 activation, it recruits the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) and the effector protein caspase-1 (CASP-1) to form a multiprotein complex, which is named NLRP3 inflammasome, enables the cleavage of caspase-1. Furthermore, the active c-caspase-1 proteolytically cleaves GSDMD into N-GSDMD, which forms pores on the membrane, thus inducing the leakage of pro-inflammatory cytokines, including IL-1β and IL-18, which leads to lytic cell death, defined as pyroptosis. Recent studies suggest that the abnormal activation of NLRP3 inflammasome in human nasal epithelial cells, mucosal T lymphocytes, and mucosal macrophages is associated with the pathogenesis of chronic rhinosinusitis (CRS). However, the underlying mechanism is still unclear. To provide further perspective on how the NLRP3 inflammasome is activated in CRS, this review focuses on the structure-derived assembly and activation of the NLRP3 inflammasome, and its roles and the potential activation mechanism in CRS. We also discuss major cellular stress signals that trigger the NLRP3 inflammasome.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is likely to relapse due to aberrant eosinophil infiltration. The deficiency of Vitamin D (VD) is associated with increased eosinophil infiltration in eosinophilic oesophagitis. However, the role of VD in eosinophilic CRSwNP (ECRSwNP) remains unclear. This study aims to explore the effects of VD on eosinophil chemotaxis in ECRSwNP and the underlying mechanisms. Human nasal mucosal tissues were collected from the control group, patients with non-ECRSwNP and those with ECRSwNP. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of VD and CCL26 in the nasal mucosa, plasma, or human primary nasal epithelial cells (hNECs). hNECs and eosinophils from patients were cultured to investigate the effect of VD on eosinophil chemotaxis and CCL26 expression via eosinophil migration assay, Western blot, and ELISA. Transcriptome sequencing, pathway enrichment analysis, Western blot and immunohistochemical staining were used to determine the key signaling pathway involved in eosinophil chemotaxis. A significant decrease in VD levels was observed in the nasal mucosa of patients with ECRSwNP, which correlated with increased local eosinophil infiltration. Furthermore, pathway enrichment analysis suggested that glycolysis signaling was promoted in the ECRSwNP group, verified by enhanced expression of glycolytic key enzymes that were positively correlated with eosinophil infiltration in nasal mucosa from patients with ECRSwNP. VD suppressed eosinophil chemotaxis in vitro by inhibiting CCL26 expression. Glycolysis regulated CCL26 expression via the ERK pathway and lactate, which promoted the expression and stability of CCL26 protein. VD attenuated glycolysis, leading to decreased production of lactate and inactivation of the ERK pathway. The decrease in lactate production suppressed eosinophil chemotaxis. Moreover, the ERK pathway activator reversed the inhibitory effect of VD on eosinophil chemotaxis. VD impedes eosinophil chemotaxis by inhibiting glycolysis - induced CCL26 expression via attenuating the activation of the ERK pathway and reducing lactate production. VD supplementation may be a novel strategy to treat ECRSwNP.

Chronic rhinosinusitis (CRS) has a high incidence rate and different endotypes. Serum 25-hydroxyvitamin D (25(OH)D) deficiency is common in patients with eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP and nECRSwNP, respectively). This study explored the relationship between serum 25(OH)D levels and CRS risk and determined the value of combining serum 25(OH)D with peripheral blood markers in distinguishing between ECRSwNP and nECRSwNP. This study enrolled 275 CRS patients and 298 healthy controls. The relationship between serum 25(OH)D levels and CRS risk was determined using logistic regression after propensity score matching (PSM). The efficiency of various peripheral blood markers in distinguishing between ECRSwNP and nECRSwNP was assessed using a decision-tree model. The final analysis included 189 CRS patients and 189 controls after 1:1 PSM. Serum 25(OH)D levels were significantly lower in CRS patients than in controls. Patients with mild CRS showed higher serum 25(OH)D levels than those with moderate or severe CRS, and ECRSwNP patients had lower serum 25(OH)D levels than nECRSwNP patients (all Ps < 0.05). Eosinophil percentages and IgE levels were independent risk factors for ECRSwNP, whereas serum 25(OH)D was an independent protective factor. 25(OH)D deficiency increased the ECRSwNP risk (OR = 3.074, P = 0.04). An eosinophil percentage ≥ 5

To compare the efficacy and safety of middle turbinate resection (MTR) and preservation (MTP) during endoscopic sinus surgery (ESS) in in patients with chronic rhinosinusitis (CRS). We evaluated postoperative outcomes, including quality of life, postoperative safety, and postoperative complications. Both fixed- and random-effects meta-analyses, as well as sensitivity and subgroup analyses, were conducted. Twenty-five studies including 4,314 cases were analyzed. For quality-of-life outcomes, no significant differences were found between MTR and MTP in Sino-Nasal Outcome Test-22 (SNOT-22: MD = –4.20; 95

OBJECTIVE:To evaluate the prognostic role of systemic inflammatory markers and vitamin D in chronic rhinosinusitis (CRS) and to establish predictive models for eosinophilic CRS (ECRS) based on the clinical characteristics. METHODS:Retrospective analysis of data from 1072 CRS patients and 229 controls identified CRS and ECRS risk factors using systemic inflammatory markers and serum 25-hydroxyvitamin D (25(OH)D), with all analyses performed on propensity score-matched (PSM) cohorts. Logistic regression constructed an ECRS prediction model, evaluated by the receiver operating characteristic (ROC) curve's area under the curve (AUC). Kaplan-Meier (K-M) curve assessed serum 25(OH)D's prognostic impact on CRS. Cox regression identified CRS prognostic factors and built a nomogram model, with accuracy assessed by the ROC curve and Harrell's concordance index (C-index). RESULTS:Logistic regression showed increased eosinophil-to-lymphocyte ratio (ELR), decreased serum 25(OH)D, and concomitant polyps were ECRS predictors (all p < 0.05), incorporated into the nomogram prediction model with AUC = 0.858. The K-M curve showed poor prognosis of CRS patients with VD deficiency (p = 0.024). Cox regression identified absolute eosinophil count (EOS#), lymphocyte percentage, platelet-to-lymphocyte ratio (PLR), platelet distribution width (PDW), osteitis score, and decreased serum 25(OH)D levels as independent prognosis predictors in CRS (all p < 0.05), included in a nomogram predictive model with a C-index of 0.724. AUC values were 0.962, 0.750, and 0.814 at 12, 18, and 24 months post-surgery. CONCLUSIONS:Elevated EOS#, lymphocyte percentage, PLR, PDW, osteitis score, and decreased serum 25(OH)D levels predict poor prognosis in CRS. Incorporating these factors enhances predictive accuracy. Combining ELR, serum 25(OH)D levels, and concomitant polyps may improve ECRS prediction. LEVEL OF EVIDENCE: 3:

Objective:To investigate the criteria for selecting surgical approaches for frontal and ethmoid sinus osteomas of different locations and sizes on CT imaging.Methods:Using sagittal and coronal CT images,the fol-lowing lines were delineated:the F-line(a horizontal line passing nasofrontal beak),the M-line(a vertical line passing paries medialis orbitae),and the P-line(a vertical line passing the center of the pupil).Classification of frontal and ethmoid sinus osteomas was based on their relationship with these lines.Appropriate surgical approa-ches were selected,including pure endoscopic approaches,endoscopic combined with eyebrow incision approach,and endoscopic combined with coronal incision approach.This method was applied to a single center at the Third Affiliated Hospital of Sun Yat-sen University for endoscopic resection of frontal and ethmoid sinus osteoma.Case Data:Sixteen cases of ethmoid sinus osteomas were treated from January 2020 to September 2023.Among these cases,there were 9 males and 7 females,with ages ranging from 18 to 69 years,and a median age of 48 years.Results:Thirteen cases underwent pure endoscopic resection of the osteoma,while in three cases,a combined ap-proach was utilized.Among the combined approach cases,two exceeded both the M-line and the F-line but did not cross the P-line;therefore,they underwent endoscopic combined with eyebrow incision approach.One case excee-ded all three lines and thus underwent endoscopic combined with coronal incision.In all cases,complete resection of the osteoma was achieved as per preoperative planning,and none of the patients experienced significant postop-erative complications.Conclusion:For frontal and ethmoid sinus osteomas,it is advisable to perform a thorough preoperative radiological assessment.Based on the size of the osteoma and its relationship to the three lines,an appropriate surgical approach should be chosen to optimize the diagnostic and treatment plan.

BACKGROUND:The mucosal epithelial barrier, the first line of immune defense, is vulnerable to allergens, pathogens, and inflammatory cytokines, contributing to CRS development. Our previous studies found high interleukin-17A(IL-17A) expression correlated with CRS severity and low glucocorticoid efficacy. The role of IL-17A in disrupting the nasal mucosal epithelial barrier leading to CRS remains unclear. We aimed to investigate how IL-17A promoting epithelial barrier damage and identify new treatment targets for CRS. METHODOLOGY:Nasal tissue samples from 36 CRSwNP, 34 CRSsNP, and 39 controls were examined for the expression of IL-17A and tight junction (TJ) proteins using qRT-PCR, immunohistochemistry and immunofluorescence. The integrity of TJs and signaling pathways activation were observed using western blot, immunofluorescence, TEER and FITCâ€"FD4, transmission electron microscopy before and after IL-17A stimulation in human primary nasal epithelial cells (hNECs). Concurrently, studies were also conducted in an CRS mouse model induced by anti-IL-17A neutralizing antibody administration. RESULTS:TJs expression in the nasal mucosa of CRS patients was lower than in controls. IL-17A stimulation reduced TJs expression and TEER while increasing hNECs permeability. Inhibition of the (ERK/STAT3) pathway reversed the downregulation of TJs and the disruption of the epithelial barrier induced by IL-17A stimulation. In the CRS mouse model, anti-IL-17A antibody treatment rescued the nasal mucosal epithelial barrier. CONCLUSIONS:IL-17A disrupts the nasal mucosal epithelial barrier by activating the ERK/STAT3 pathway in patients with CRS.

BACKGROUD:The recurrence rate of chronic rhinosinusitis with nasal polyps (CRSwNP) is positively correlated with eosinophil infiltration. Increased interleukin (IL)-19 and eosinophil chemokine RANTES levels have been reported in patients with CRSwNP. This study aimed to clarify the role of IL-19 in mediating RANTES expression and eosinophilic infiltration in eosinophilic CRSwNP (Eos CRSwNP).METHODS:Nasal tissue samples were obtained from patients with CRSwNP and controls. The expression of IL-19, its receptors, ECP, and RANTES in tissues was investigated. Primary human nasal epithelial cells (HNECs) and nasal polyp tissue blocks were cultured, then stimulated by IL-19; ERK phosphorylation, NF-κB pathway activation, RANTES level, eosinophils migration and infiltration were detected using RT-qPCR, ELISA, western blotting, HE, immunohistochemistry, immunofluorescence staining, confocal microscopy, and transwell migration assay.RESULTS:The expression of IL-19 and its receptors (IL-20R1/IL-20R2), eosinophil cationic protein, and RANTES in nasal tissues from patients with Eos CRSwNP was significantly increased compared to that in non-Eos CRSwNP and control subjects. IL-19 co-localized with RANTES in nasal tissues and significantly elevated RANTES expression in HNECs. IL-19-blocking antibody and siRNA knockdown of IL-20R1 ameliorated the effect of IL-19 on RANTES secretion in HNECs. Moreover, IL-19-induced RANTES upregulation was associated with the activation of the ERK and NF-κB pathways. NF-κB activation was mediated by the ERK pathway in IL-19-treated HNECs, and IL-19 enhanced eosinophil infiltration in nasal polyp tissue blocks.CONCLUSIONS:Our findings indicate that IL-19 promotes RANTES expression via the ERK/NF-κB pathway in HNECs and is implicated in eosinophil infiltration in patients with Eos CRSwNP.

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

随着人口老龄化加剧，以及鼻科手术技术发展与领域的延伸，围手术期的安全与风险管理备受关注，尤其是患者前期慢性疾病的用药管理问题。虽然某些慢病用药管理有相关的指南，但少数慢病用药因临床研究有限，尚未达成共识。本文就常见慢病围手术期的用药管理进行综述，以期为鼻科围手术期慢病用药管理提供参考。

BackgroundEosinophilic chronic rhinosinusitis (ECRS) is predominantly characterized by nasal type 2 inflammation. The pathogenesis of this condition is complex. High levels of IL-17A are associated with eosinophil infiltration in some inflammatory diseases and contribute to the severity and insensitivity of corticosteroid therapy for chronic rhinosinusitis. MethodsIn the first experiment, we constructed a modified ECRS mouse model using four groups of mice: phosphate-buffered saline (PBS)-sensitized and nasal instillation (control); PBS-sensitized and Staphylococcus aureus enterotoxin B (SEB) nasal instillation after nasal tamponade (SEB group); ovalbumin (OVA)-sensitized and nasal instillation (OVA group); and OVA-sensitized combined with OVA and SEB nasal instillation after nasal tamponade (OVA + SEB group). In the second experiment, we examined the role of IL-17A by dividing the mice into four groups: control group; ECRS group; ECRS + anti-IL-17A group; and ECRS + IL-17A group. The latter two groups received intraperitoneal injections of anti-IL-17A antibody or IL-17A, respectively. ResultsWe constructed a modified ECRS mouse model (OVA + SEB group), where the IL-17A levels were upregulated in the nasal sinus of ECRS mice and the IL-17A levels were significantly correlated with eosinophil infiltration. We further demonstrated that IL-17A induced type 2 inflammation and eosinophil infiltration in the ECRS group of mice. In contrast, IL-17A neutralization attenuated type 2 inflammatory cytokine secretion and eosinophil infiltration. ConclusionOVA sensitization and unilateral nasal tamponade, combined with SEB and OVA alternate nasal instillation (OVA + SEB group), could be used to construct a more typical ECRS mouse model in which IL-17A enhanced the expression of type 2 cytokines and eosinophil infiltration.

BACKGROUND:Regulatory T (Treg) cells, which prevent inflammation-induced eosinophil infiltration, are deficient in nasal polyps (NPs) in patients with eosinophilic chronic rhinosinusitis (ECRS). It is concomitant with loss of Foxp3 after certain inflammatory stimuli. OBJECTIVE:We sought to determine the inflammatory cytokines involved in inducing the loss of Treg cells in NPs. METHODS:The abundance of cytokines in ECRS patients or mice were tested using ELISA, immunochemistry, immunofluorescence, quantitative reverse transcription PCR (qPCR), and/or flow cytometry. Expression of eosinophil cationic protein (ECP), CD4+ T cells, IL-4, and IL-17A and eosinophils in nasal mucosa of mouse model was investigated by immunochemistry, immunofluorescence, and hematoxylin and eosin staining. The percentage and death of induced Treg (iTreg) cells, source of IL-21 in NPs from ECRS and non-ECRS patients, and abundance of different systemic phenotypes of CD4+ T cells in a mouse model were studied by flow cytometry. Western blot analysis, scanning, and transmission electronic microscopy were used to detect pyroptosis of iTreg cells. RESULTS:IL-21 was highly expressed in nasal mucosa of ECRS patients and mice, causing pyroptosis and preventing development of iTreg cells in vitro. The elevated IL-21 in NPs from ECRS patients was mainly produced by CD3+ T cells, including T follicular helper, T peripheral helper, TH2, and TH17 cells and CD3+CD4- T cells. T peripheral helper cells and CD3+CD4- T cells were the predominant source of IL-21 in NPs from non-ECRS patients. Blocking IL-21/IL-21R signaling significantly reduced the number of eosinophils and CD4+ T cells along with ECP, IL-4, and IL-17A expression in the nasal mucosa of ECRS mice. It also increased Treg cell percentage and systemically decreased TH2 and TH17 ratios. Akt-mTOR inhibition prevented IL-21-induced pyroptosis in human and mouse iTreg cells. CONCLUSION:Elevated IL-21 drives pyroptosis and prevents Treg cell development in ECRS patients. IL-21 induced pyroptosis via activating Akt-mTOR-NLRP3-caspase 1 signaling.

Purpose:Histopathologic characterizations of central compartment atopic disease (CCAD) by whole-slide imaging remains lacking. We aim to study clinical presentations and cellular endotyping diagnosis of Chinese CCAD using artificial intelligence (AI).Methods:A total of 72 patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled. CCAD was defined by positive result of serology specific IgE, endoscopic and radiological findings. The aeroallergen sensitization status, endoscopic results, radiological findings, and symptoms were evaluated and compared between patients with CCAD (n=14), eosinophilic CRSwNP (ENP, n=32) and non-eosinophilic CRSwNP (NENP, n=26). The cellular endotypes including eosinophils, neutrophils, lymphocytes, and plasma cells were analyzed by the AI chronic rhinosinusitis evaluation platform 2.0.Results:CCAD was most common in male (71.43%). The positive rate of aeroallergen in patients with CCAD is 100%, which is much higher than those in patients with ENP (40.63%) and NENP (23.08%). Allergic rhinitis incidence was found to be 57.14% in Chinese CCAD subjects, which is obviously higher when compared with those in patients with ENP (21.88%) or NENP (0.00%). The presence of asthma was not significantly different between groups. Chinese CCAD population demonstrated mild symptoms and lower endoscopic and radiological scores than those in patients with ENP and NENP. For cellular endotypes in CCAD subjects, the median of eosinophils, neutrophils, lymphocytes, and plasma cells was 26.55%, 0.49%, 60.85%, and 7.33%, respectively. The proportion of eosinophils in nasal tissue and peripheral blood mononuclear cells from the CCAD group is between the proportions in those patients with ENP and NENP.Conclusion:Chinese CCAD was associated with aeroallergen sensitivity, and displayed an eosinophil-dominant inflammatory pattern. Thus, proper management with allergy control and topical steroids could be recommended for CCAD treatment.

BACKGROUND:Pyroptosis is closely related to inflammation. However, the molecular mechanisms and pathologic contributions of pyroptotic epithelial cell are not yet fully understood. OBJECTIVE:This study aimed to explore the function and molecular mechanisms of IL-17A on human nasal epithelial cell (hNEC) pyroptosis. METHODS:The expression of pyroptosis-related biomarkers and IL-17A was assessed in sinonasal mucosa from control individuals, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by using quantitative RT-PCR. Their localization was analyzed via immunohistochemistry and immunofluorescence. The ultrastructural characteristics of IL-17A-induced pyroptosis in hNECs were visualized by using electron microscopy. IL-17A functional assays were performed on hNECs and airway epithelial cell lines. Cytokine levels were quantified via ELISA. The signaling pathways involved in IL-17A-induced pyroptosis were studied via unbiased RNA sequencing and Western blotting. RESULTS:The expression of IL-17A and the pyroptotic biomarkers NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D, and IL-1β was increased in nasal mucosa from patients with CRSwNP compared with in those with chronic rhinosinusitis without nasal polyps and the control subjects. IL-17A was positively correlated and colocalized with the pyroptotic biomarkers. IL-17A treatment induced pyroptosis in the hNECs and cell lines analyzed, primarily through the extracellular signal-regulated kinase (ERK)-NLRP3/caspase-1 signaling pathway, and increased IL-1β and IL-18 secretion in hNECs. Moreover, IL-17A-induced pyroptosis contributed to steroid resistance by affecting glucocorticoid receptor-α and glucocorticoid receptor-β expression, and the inhibition of pyroptotic proteins partially abolished IL-17A-induced steroid resistance in hNECs. CONCLUSION:Elevated IL-17A level promotes pyroptosis in hNECs through the ERK-NLRP3/caspase-1 signaling pathway and contributes to glucocorticoid resistance by affecting glucocorticoid receptor homeostasis in patients with CRSwNP.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.