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.

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.

Causal association of gastroesophageal reflux disease with chronic sinusitis and chronic disease of the tonsils and adenoids.

BACKGROUND: Exploring bidirectional causal associations between gastroesophageal reflux disease (GERD) and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively. METHODS: We first conducted a TSMR (two-sample mendelian randomization) study using the results of the inverse variance weighting method as the primary basis and bidirectional MR to rule out reverse causation. Subsequently, MVMR (multivariate MR) analysis was performed to identify phenotypes associated with SNPs and to explore the independent effect of GERD on two outcomes. Finally, we calculated MR-Egger intercepts to assess horizontal polytropy and Cochran's Q statistic to assess heterogeneity and ensure the robustness of the study. RESULTS: For each standard deviation increase in genetically predicted GERD rate, there was an increased risk of chronic disease of the tonsils and adenoids (OR 1.162, 95% CI 1.036-1.304, P: 1.06E-02) and of developing chronic sinusitis (OR 1.365, 95% CI 1.185-1.572, P: 1.52E-05), and there was no reverse causality. Causality for TSMR was obtained on the basis of IVW (inverse variance weighting) and appeared to be reliable in almost all sensitivity analyses, whereas body mass index may be a potential mediator of causality between GERD and chronic sinusitis. CONCLUSION: There is a causal association between GERD and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively, and the occurrence of GERD increases the risk of developing chronic disease of the tonsils and adenoids and chronic sinusitis.

Deep Learning-Based Multi-Class Segmentation of the Paranasal Sinuses of Sinusitis Patients Based on Computed Tomographic Images.

Accurate paranasal sinus segmentation is essential for reducing surgical complications through surgical guidance systems. This study introduces a multiclass Convolutional Neural Network (CNN) segmentation model by comparing four 3D U-Net variations-normal, residual, dense, and residual-dense. Data normalization and training were conducted on a 40-patient test set (20 normal, 20 abnormal) using 5-fold cross-validation. The normal 3D U-Net demonstrated superior performance with an F1 score of 84.29% on the normal test set and 79.32% on the abnormal set, exhibiting higher true positive rates for the sphenoid and maxillary sinus in both sets. Despite effective segmentation in clear sinuses, limitations were observed in mucosal inflammation. Nevertheless, the algorithm's enhanced segmentation of abnormal sinuses suggests potential clinical applications, with ongoing refinements expected for broader utility.

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.

Platelet-rich plasma following endoscopic sinus surgery in patients with chronic sinusitis: A systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: To comprehensively evaluate the reported clinical effectiveness of platelet-rich plasma (PRP) in patients with chronic sinusitis undergoing endoscopic sinus surgery (ESS). METHODS: We performed a systematic review and meta-analysis of randomised controlled trials (RCTs). Five digital online databases (PubMed, Scopus, Web of Science, Google Scholar and Cochrane CENTRAL) were searched from inception up to 1st May 2023. Our specific outcomes involved postoperative nasal endoscopy scores measured via Lund-Kennedy score or Meltzer score, olfactory sensation scores and pre-operative anosmia duration. All data were pooled as standardised mean difference (SMD) with a 95% confidence interval (CI), using the RevMan software. RESULTS: Six RCTs were included in this systematic review and meta-analysis, with a total of 169 patients. The risk of bias in the included RCTs was low in three RCTs, some concerns in one RCT and high risk in two RCTs. The overall analysis of the postoperative nasal endoscopy scores showed that the PRP group had lower scores compared to the control group (n = 3 RCTs, SMD = -1.19; 95% CI [-1.94, -0.44], p = .002). There was no significant difference between the PRP and control groups regarding anosmia duration (n = 2 RCTs, SMD = 0.21; 95% CI [-0.17, 0.59], p = 0.28) or olfactory sensation scores, despite the PRP group having higher scores (n = 2 RCTs, SMD = 0.53; 95% CI [-0.32, 1.39], p = 0.22). CONCLUSION: This study highlights the potential advantages of using PRP as an additional treatment for individuals with chronic sinusitis undergoing ESS. The improvements associated with PRP include facilitating wound healing, reducing inflammation and enhancing surgical outcomes. To optimise the use of PRP in clinical settings, future research should focus on conducting larger trials with standardised protocols.

Pheno-Endotyping Antrochoanal Nasal Polyposis.

PURPOSE OF REVIEW: Antrochoanal polyps (ACPs) are benign polypoid lesions arising from the inner wall of the maxillary sinus and extending into the choana. Although the diagnosis and treatment strategies of ACP have changed since this entity was first described, the underlying pathogenic mechanism of APC is poorly understood. This article reviews the current knowledge of the etiology, inflammatory parameters, and microscopic findings of ACP. RECENT FINDINGS: The inflammatory pattern of ACP appears to center around a neutrophilic inflammation T1-dominant endotype. Apart from the inflammatory component of ACP, at the microscopic level, the presence of tissue remodeling, mostly fibrin deposition and edema, and cysts in the epithelium and lamina propria has been described. Although the origin of this T1-dominant endotype immune response of ACPs is not entirely clear, it could be related to a lymphatic obstruction mechanism. This review serves to define a phenotype of ACP with potential endotypes based on the characteristics of the inflammatory parameters, microscopic findings, and hypotheses about the pathogenesis of ACP.

Sinus culture differences in patients with radiographic evidence of odontogenic disease.

PURPOSE: Odontogenic sinusitis is a well-known entity with a different pathogenesis than chronic rhinosinusitis. Nonspecific symptoms can make diagnosis difficult. This study aims to compare culture results between patients with and without computed tomography findings indicative of possible odontogenic disease. MATERIALS AND METHODS: This was a retrospective cohort study in which patients undergoing endoscopic sinus surgery for chronic sinusitis over a three-year period at a single institution were reviewed. CT imaging was reviewed for evidence of dental disease, specifically periapical lucency, dehiscence of the floor of the maxillary sinus, oroantral fistula, or foreign body. Culture results were then assessed and compared between groups with CT evidence of a possible odontogenic source to those without. RESULTS: Overall, 231 patients were evaluated. 92 patients (39.8 %) were found to have evidence of a likely odontogenic source on CT. Cultures were available for 118 of 231 patients (51.1 %). Patients with CT signs of odontogenic disease were significantly more likely to grow Proteus mirabilis (p = 0.018) and Klebsiella pneumoniae (p = 0.037) on culture. Patients without CT signs of odontogenic sources were significantly more likely to grow Pseudomonas aeruginosa (p = 0.009). Of note, patients with CT findings concerning for an odontogenic source were also more likely to grow fungi other than Aspergillus and Mucor species on culture (p = 0.004). CONCLUSION: Patients with CT findings concerning for an odontogenic source of sinus disease showed differences in culture results that could be important in differentiating pathogenesis of sinus disease.

Identification and validation of ferroptosis-related genes for chronic rhinosinusitis with nasal polyps.

PURPOSE: Even though the great progress in the field of chronic rhinosinusitis with nasal polyps (CRSwNP) has been achieved, ferroptosis and its molecular mechanism in CRSwNP remain blank. We are the first to study the relationship between CRSwNP and ferroptosis, aiming to identify ferroptosis-related genes in the process of CRSwNP. METHODS: Using the GEO database and the FerrDb database, significantly differentially expressed ferroptosis-related genes (DEFGs) were selected between CRSwNP-NP and CRSwNP-IT specimens. Then, the protein-protein interaction (PPI) network of ferroptosis-related genes was constructed. Functional enrichment analyses (GSVA, GO, KEGG, and GeneCodis analyses) were introduced in our study. Besides, based on the GSE136825 data set, DEFGs between CRSwNP-NP and CS-IT specimens were also analyzed. Finally, qRT-PCR was performed to validate the selected ferroptosis-related genes with clinical samples. RESULTS: 31 significantly DEFGs were identified between CRSwNP-NP and CRSwNP-IT specimens. Functional enrichment analyses and the analysis of GeneCodis 4 pointed out that DEFGs may potentially be involved in some related KEGG pathways. 8 DEFGs were selected between CRSwNP-NP and CS-IT specimens. The experimental verification indicated that 4 genes (GPX2, CDO1, CAV1, and TP53) were the important DEFGs of CRSwNP. The Venn diagrams proved that CDO1 and GPX2 were considered as the most important DEFGs genes of CRSwNP, especially GPX2. CONCLUSIONS: Though a comprehensive bioinformatics analysis and the experimental verification, CDO1 and GPX2 were considered as the important ferroptosis-related genes of CRSwNP, especially GPX2. However, further molecular biological experiments would be still required to uncover the underlying mechanism between ferroptosis and CRSwNP.

Clinical and imaging features of ethmomaxillary sinus compared to Haller's cell.

PURPOSE: Understanding the anatomy of the paranasal sinuses and their variations is essential to achieving safe and effective endoscopic sinus surgery. The ethmomaxillary sinus (EMS) is a relatively under-researched anatomical variation. This study investigated the prevalence, clinical features, and effect of EMS on the maxillary sinus in comparison with Haller's cells. METHODS: Patients who visited the Rhinology Clinic at our hospital for rhinologic symptoms between January 2020 and December 2020. Computed tomography (CT) scans of paranasal sinuses were obtained at 1 mm-section thickness. Using CT scans, we investigated the clinical features of EMS, measured maxillary sinus volume, and analyzed the presence of maxillary sinusitis. RESULTS: EMS was observed in 26 of the 250 patients (10.4%). The male-to-female ratio was equal. The age ranged from 18 to 83 years (mean age, 56.3). Of the patients with EMS, 65.4% were unilateral and 34.6% were bilateral. The prevalence of Haller's cells was similar to that in EMS (10.8%). In the analysis of patients with unilateral EMS, the EMS side was found to have a significantly reduced maxillary sinus volume compared to the opposite side, whereas the difference was not significant in Haller's cells. There was no significant relationship between EMS or Haller's cells and maxillary sinusitis. CONCLUSIONS: EMS can significantly affect maxillary sinus volume. Therefore, surgeons should thoroughly review PNS CT scans before paranasal sinus surgery to determine the presence and features of EMS.

Characterizing Adverse Events of Biologic Treatment of T2 Disease: A Disproportionality Analysis of the FDA Adverse Event Reporting System.

INTRODUCTION: Over the last 3 years, the FDA has approved dupilumab, omalizumab, and mepolizumab for the treatment of CRSwNP; however, adverse events of these biologics have not been described in post-marketing surveillance trials. By utilizing the FDA Adverse Event Reporting System (FAERS), this study describes and compares biologic-associated adverse events in T2 disease. METHODS: This case-non-case study assessed disproportionate reporting rates using reporting odds ratios (RORs). RORs and p values for biologic-associated AEs were categorized and compared among dupilumab, omalizumab, and mepolizumab. This analysis included AEs associated with all treatment indications. Relative AE rates and outcomes were calculated. RESULTS: There were a total of 112,560, 24,428, and 18,741 unique AE reports associated with dupilumab, omalizumab, and mepolizumab, respectively. Omalizumab had the strongest association with anaphylaxis (ROR = 20.80, 95% confidence interval [CI]: 18.58, 23.29). Dupilumab had large relative proportions and positive signals in the ophthalmologic category (7.76%, ROR = 6.20, 95% CI: 6.06, 6.35), such as with blurry vision (ROR = 3.80, CI: 3.52, 4.12) and visual impairment (ROR = 1.98, CI: 1.80, 2.19). Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). DISCUSSION/CONCLUSION: This is the first large-scale comparative analysis of the AE profiles of dupilumab, omalizumab, and mepolizumab. Our data suggest possible relations between dupilumab and ophthalmologic and injection-site AEs. Omalizumab was the only biologic with a positive anaphylaxis signal. This FAERS investigation suggests important AE differences among these biologics.

Periostin is an aggravating factor and predictive biomarker of eosinophilic chronic rhinosinusitis.

BACKGROUND: Patients with eosinophilic chronic rhinosinusitis (ECRS) respond poorly to many treatment modalities. Overproduction of periostin in the nasal mucosa is reported to contribute to polyp formation. This study examined periostin levels in patients with ECRS in comparison with levels in patients with non-ECRS. METHODS: Fifty-nine patients with chronic rhinosinusitis were grouped into those with ECRS and those with non-ECRS. We compared the relationships between peripheral blood eosinophil level, serum periostin level, histopathological findings, clinical and laboratory findings, nose findings, diagnostic score of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study, and postoperative recurrence of nasal polyps in each group. RESULTS: In the ECRS group, a positive correlation was found between peripheral blood eosinophil level and serum periostin level (rs = 0.49, P < 0.01: Spearman's rank correlation coefficient). ROC curve analysis was used to evaluate the serum periostin level that could predict postoperative recurrence of nasal polyps in the ECRS group: the area under the curve (AUC) was 0.95, sensitivity was 92%, and specificity was 100%; the serum periostin cutoff value for postoperative recurrence of nasal polyps was 130 ng/ml. In ROC curve analysis to evaluate peripheral blood eosinophil level, the AUC was 0.73, sensitivity was 69.2%, and specificity was 85.0%; the cutoff value was 8.8%. CONCLUSIONS: periostin was implicated in the pathophysiology of ECRS. Periostin shown to be a more useful biomarker than eosinophils in ECRS. Periostin was shown to likely be an important biomarker for pathological severity of ECRS and postoperative recurrence of nasal polyps.

[Chronic fungal sinusitis caused by Schizophyllum commune]. / Khronicheskii sfenoidit, vyzvannyi gribom Schizophyllum commune.

Treatment of patients with fungal sinusitis, in some cases, does not lead to complete sinus sanitation, which may be due to insufficient surgical intervention and/or incorrectly selected antimycotic therapy. Treatment of such patients must necessarily include the complete removal of fungal masses from the affected sinus and the further use of antimycotics that ensure complete elimination of the pathogen. A clinical case of chronic fungal operated isolated sphenoiditis caused by the fungus Schizophyllum commune is presented. For extensive drainage of the sphenoid sinus, the patient underwent translamellar sphenoidotomy on the right with further antifungal therapy.

Limited sinonasal Rosai-Dorfman disease presenting as chronic sinusitis.

AIMS: The sinonasal tract is a common extranodal site for Rosai-Dorfman disease (RDD). Recently, histiocytes with features of RDD were identified in the clinical setting of chronic sinusitis. This study evaluates whether this phenomenon should be considered part of the RDD spectrum or classified separately as RDD-like histiocytes. METHODS AND RESULTS: We prospectively collected 13 cases showing histological features of RDD in chronic sinusitis patients and identified 14 with similar findings (3.5%) via retrospective review of 403 sinus contents over 2 years. All 27 cases displayed nodular aggregates of eosinophilic histiocytes with intermixed lymphoplasmacytic inflammation, prominent eosinophils and emperipolesis. The histiocytes were positive for S100 protein and cyclin D1 and negative for CD1a and CD207. All patients presented with severe chronic sinusitis without tumour formation or systemic symptoms. Twelve patients with follow-up (55%) required repeat sinus surgery compared with just 43 other sinusitis patients evaluated (11%); features of RDD were present in their additional specimens. Two cases that underwent targeted next-generation sequencing (20%) had oncogenic mutations in NF1 and KEAP1. CONCLUSIONS: Overall, these findings confirm diagnostic histological and immunohistochemical features of RDD in a subset of chronic sinusitis specimens. While patients uniformly lack systemic involvement or tumefactive growth, they have a high risk of recurrent sinus disease. Although the relatively subtle nature of the findings raises consideration of separate classification, the presence of occasional oncogenic mutations and evidence of consistent MAPK/ERK pathway activation via cyclin D1 positivity suggests that this phenomenon represents a unique limited manifestation of RDD.

Real-life effectiveness of dupilumab in patients with mild to moderate bronchial asthma comorbid with CRSwNP.

BACKGROUND: Dupilumab, an anti-IL-4α receptor antibody, is a new treatment for severe or refractory asthma. However, real-world evidence on the efficacy of dupilumab in patients with mild to moderate bronchial asthma is lacking. METHODS: We retrospectively evaluated the effects of dupilumab in 62 patients who received dupilumab for eosinophilic sinusitis comorbid with asthma at a single centre in Japan. Type 2 inflammatory markers, ACT, respiratory function tests, and forced oscillation technique (FOT) were analysed before, three months after, and one year after dupilumab administration, mainly in patients with mild to moderate asthma. RESULTS: FEV1, %FEV1, %FVC, treatment steps for asthma and ACT improved significantly after three months of dupilumab treatment. FeNO was markedly decreased, whereas IgE and eosinophil counts showed no significant changes. Pre- and post-treatment respiratory resistance (Rrs) and respiratory reactance (Xrs) correlated significantly with FEV1. Improvement in %FEV1 was associated with higher FeNO and higher serum IgE before dupilumab treatment. CONCLUSION: Dupilumab treatment for sinusitis may improve respiratory functions, asthma symptoms, and asthma treatment reduction, even if the associated bronchial asthma is not severe.

Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear. OBJECTIVE: We sought to characterize the systemic and local basophil responses in patients with AERD compared with patients with CRSwNP. METHODS: Sinonasal tissues including inferior turbinate and/or nasal polyps (NPs) and peripheral blood were collected from controls, patients with AERD, and patients with CRSwNP. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63), and intracellular (2D7) markers associated with basophils was characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained. RESULTS: The mean number of basophils (CD45+CD203c+FcεRI+CD117-) detected in AERD NPs (147 ± 28 cells/mg tissue) was significantly elevated compared with that detected in CRSwNP NPs (69 ± 20 cells/mg tissue; P = .01). The number of circulating basophils was significantly elevated in patients with AERD (P = .04). Basophils in NPs had significantly higher CD203c and CD63 mean fluorescence intensity compared with blood in both conditions (P < .01). Basophils from AERD NPs had lower expression of the granule content marker 2D7 compared with those from matched blood (P < .01) or NPs of patients with CRSwNP (P = .06), suggesting ongoing degranulation. Basophil 2D7 mean fluorescence intensity significantly correlated with pulmonary function (r = 0.62; P = .02) and inversely correlated with sinonasal inflammation (r = -0.56; P = .004). CONCLUSIONS: Increased basophil numbers and extent of ongoing degranulation in NPs of patients with AERD compared with patients with CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD. OBJECTIVE: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD. METHODS: Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence. RESULTS: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO+ epithelium in NPs from patients with AERD. CONCLUSIONS: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.

[SUCCESSFUL TREATMENT FOR OTITIS MEDIA AND SINUSITIS ASSOCIATED WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS USING ANTI-IL-5 RECEPTOR MONOCLONAL ANTIBODY BENRALIZUMAB].

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of ANCA-related vasculitis. Asthma and sinusitis occur first in the course of EGPA, followed by vasculitis symptoms such as fever, weight loss, and peripheral neuropathy. Otitis media with effusion and sensorineural hearing loss occur occasionally in EGPA patients. Here we report a case of a 39-years-old female patient with asthma that developed at age 37 and sinusitis. The patient was diagnosed with EGPA and treatment was started with oral corticosteroids. During the course of treatment, otitis media with effusion and sensorineural hearing loss developed. Benralizumab was administered for severe asthma. After treatment with benralizumab, the symptoms of asthma, otitis media with effusion and sinusitis dramatically improved. This is the first reported case in which benralizumab was used for treating otitis media and sinusitis associated with EGPA. The findings suggest that benralizumab may be effective for otitis media and sinusitis associated with EGPA.

[Systematic review and Meta-analysis of efficacy and safety of Biyuan Tongqiao Granules in treatment of chronic sinusitis].

The present study conducted a systematic review and Meta-analysis on the efficacy and safety of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science were searched for randomized controlled trials(RCTs) of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. The quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment tool and the final included trials underwent Meta-analysis with RevMan 5.4.1. Fifty-four RCTs were included, with a total sample size of 7 278 cases. The results of Meta-analysis showed that the clinical efficacy of Biyuan Tongqiao Granules alone or in combination in the experimental group in the treatment of chronic sinusitis was superior to that in the control group with conventional western medicine, Chinese medicinal preparations, or surgery only(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01). The combined use of Biyuan Tongqiao Granules on the basis of the control group was superior to the control group in improving the main symptoms and signs of chronic sinusitis [RR_(nasal congestion)=1.33, 95%CI[1.21, 1.45], P<0.000 01, RR_(runny nose)=1.28, 95%CI[1.18, 1.40], P<0.000 01, RR_(turbinate congestion or swelling)=1.28, 95%CI[1.16, 1.41], P<0.000 01]. Biyuan Tongqiao Granules alone or in combination could effectively reduce the Snot-20 score, which was superior to the control group(MD=-2.94, 95%CI[-3.60,-2.28], P<0.000 01). Biyuan Tongqiao Granules alone and in combination could effectively reduce the VAS score, which was superior to the control group(MD_(total score)=-4.44, 95%CI[-6.05,-2.82], P<0.000 01; MD_(nasal congestion VAS score)=-0.99, 95%CI[-1.38,-0.60], P<0.000 01; MD_(runny nose VAS score)=-1.19, 95%CI[-1.62,-0.76], P<0.000 01; MD_(dysosmia VAS score)=-0.96, 95%CI[-1.26,-0.65], P<0.000 01; MD_(head and face pain VAS score)=-0.73, 95%CI[-0.98,-0.47], P<0.000 01). The combined use of Biyuan Tongqiao Granules could effectively reduce the sinus CT score and the Lund-Mackey score of the endoscopic mucosal morphology(MD_(sinus CT score)=-3.68, 95%CI[-5.47,-1.88], P<0.000 1, MD_(endoscopic mucosal morphology score)=-3.06, 95%CI[-5.53,-0.59], P=0.02). Compared with the control group with conventional western medicine, Chinese medicinal preparations, or surgery only, combined use of Biyuan Tongqiao Granules did not increase the occurrence of adverse reactions(RR=0.68, 95%CI[0.26, 1.77], P=0.43). As demonstrated by the existing evidence, Biyuan Tongqiao Granules can improve the clinical efficacy of chronic sinusitis, relieve the clinical symptoms and signs, and reduce the Snot-20 score, VAS score, and Lund-Mackey score, without inducing serious adverse reactions, indicating that Biyuan Tongqiao Granules alone or in combination are more effective and safe in the treatment of chronic sinusitis than conventional western medicine, Chinese medicinal preparations, or surgical treatment. Since the quality of the included trials was generally low, large-scale, high-quality, rigorous, multi-center, and blinded-designed RCTs that meet international standards should be adopted in the future to increase the strength and level of evidence.

Neurohormonal markers in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS), especially with nasal polyps, continues to elude precise pathogenesis and effective treatment. Prior work in our laboratory demonstrated interleukin-33 (IL-33) and Substance P (SP) activation of mast cells, and inhibitory effect of interleukin-37 (IL-37). Our objective is to study the expression of these neurohormonal mediators in mast cell stimulation of nasal polyposis. This was a prospective research study involving collection of nasal lavage fluid and nasal polyp tissue from adult patients with CRS. The study was divided into two arms. First, nasal lavage fluid was collected from normal controls, and patients with allergic rhinitis, CRS, or CRS with nasal polyposis. The second arm was collection of nasal tissue from normal controls undergoing inferior turbinoplasty, or patients with nasal polyposis. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction techniques were used to determine levels in the lavage fluid and relative gene expression in the tissue of SP, IL-33, and IL-37. In total, 70 lavage and 23 tissue specimens were obtained. The level of SP was highest in patients with polyps; however, gene expression was reduced compared to normal controls. The level of IL-33 was reduced in patients with polyps as compared to patients with allergy and sinusitis, and its gene expression was not significantly different from normal controls. IL-37 was elevated in the lavage fluid of patients with nasal polyps and its gene expression was increased in the polyp tissue. Levels of SP and IL-37 were elevated in the lavage fluid of patients with nasal polyps as compared to normal controls and other sinonasal pathologies, and gene expression of IL-37 was significantly increased in the polyp tissue itself. These findings implicate these neurohormonal molecules in the pathophysiology of nasal polyposis and provide possible novel therapeutic targets.