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Background: Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP)., Objective: This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved., Methods: Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence., Results: S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence., Conclusions: S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: In the past year, the endotype of chronic rhinosinusitis (CRS) has been studied from a new perspective. Eosinophilic and neutrophilic inflammation are not independent processes in the pathogenesis of CRS. In this review, we will focus on recent research on mixed eosinophilic-neutrophilic inflammation in CRS and discuss the mechanism and potential treatments., Recent Findings: Traditionally, patients with eosinophilic CRS (ECRS) present with severe clinical manifestations, comorbidities, and a higher recurrence rate. Recent studies have found that approximately 40% of patients with ECRS present with neutrophilic infiltration, while patients with predominantly eosinophilic infiltration along with neutrophilic inflammation present with more complex inflammation, clinical manifestations and exhibit refractory characteristics., Summary: The complex inflammatory profile and refractory clinical characteristics of mixed eosinophilic-neutrophilic inflammation in CRS are current challenges for clinicians. We summarize the features of eosinophilic and neutrophilic inflammation and current studies on the mechanisms of mixed eosinophilic-neutrophilic inflammation and suggest potentially effective therapeutic methods. We hope that this review will help with determining precise treatment options for patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic rhinosinusitis (CRS) is a highly heterogeneous disease characterized by inflammation in the nasal and sinus mucosa. The CRS phenotypes, based on the presence or absence of nasal polyps, are known as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). However, this classification has limitations in fully capturing the mechanisms and clinical manifestations of CRS. To address the heterogeneity of CRS, there has been a growing focus on classifying the condition into distinct endotypes. Endotype classification involves grouping patients based on specific molecular, immunological, and clinical characteristics, allowing for more personalized and targeted treatment approaches.This review delves into the current state of endotype classifications for CRS. It explores the role of geographic factors, microbiome, and subphenotype in shaping different endotypes. Additionally, the review examines how various clinical features are associated with specific endotypes, providing valuable insights into tailoring treatment options for better outcomes and transitions between different endotypes.Overall, this review offers a comprehensive and up-to-date perspective on the intricate realm of CRS endotype classifications. By unraveling the molecular and clinical intricacies, this review lays the foundation for more precise, effective, and individualized treatment strategies in the management of CRS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate whether changes in postoperative symptoms and signs in patients can predict the recurrence of ECRS after nasal endoscopic sinus surgery. Methods: A total of 70 adult patients with ECRS were enrolled for ESS surgery from June 2020 to March 2022 in a single center. There were 50 males and 20 females, with an average age of （46.9±14.5） years. Follow-up after ESS was at least 52 weeks. Patients undergo peripheral blood tests, CT of the sinuses, olfactory T&T test, visual analogue scale of symptoms（VAS）, and endoscopic scoring. Results: VAS scores and endoscopic scores were analyzed at preoperative and 6th week, 12th week, 24th week and 52th week postoperative. After 12th week postoperatively, there was a clear correlation between symptom scores and endoscopic scores. Moreover, olfactory disorder and nasal discharge were the two most obvious symptoms. There were differences in the expression of multiple preoperative clinical inflammatory indicators between the symptom-controled group and the symptom-uncontrolled group（previous surgical history, concomitant asthma, nasal smear eosinophil, serum EOS%, total IgE, CT score, olfactory score, and symptom score, all with P <0.05）, while there was no difference in baseline endoscopic score（ P >0.05）. At 12th week postoperative, the two groups of patients showed significant differences in both symptom scores and endoscopic scores. The symptoms and endoscopic score at the 12th week point of follow-up were used as predictive indicators for recurrence, with sensitivity and specificity of 62.5% and 83.3%, respectively. Conclusion: The changes in postoperative symptom score and endoscopic score in ECRSwNP patients indicated that the recurred ECRS. In the symptom-uncontrolled group, symptomatic and endoscopic scores showed consistent increased scores; In the symptom-controlled group, conflicting results between increased endoscopic scores and stable symptoms suggest that the presence of asymptomatic recurrence must be considered. The changes in symptoms and signs at the 12th week point of follow-up can serve as clinical indicators for preventing disease recurrence., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Chronic rhinosinusitis（CRS） is an inflammatory disease involving the mucosa of the nasal and paranasal sinuses for more than 12 weeks and can be classified as CRS with nasal polyp（CRSwNP） and CRS without nasal polyp（CRSsNP） depending on the phenotype. Clinical treatments reveal significant differences in disease prognosis and improvement in quality of life in patients with the same clinical phenotype. Inflammatory cells infiltration and inflammatory mediators are important factors driving CRS endotypes. In particular, CRS with predominantly eosinophilic infiltration and type 2 CRS present severe clinical symptoms, comorbidities, and high recurrence rates. CRS endotype-oriented treatment methods may better contribute to improving patient prognosis and quality of life. This article summarizes the current progress of CRS endotype research and reviews the endotype-oriented treatment options., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion samples were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted tooth extraction patients. DNA was extracted, and 16S rRNA sequencing was performed to explore the characteristics and structure of the microbiome in the sinuses and dental regions of OS patients., Results: The alpha diversity of the oral and nasal microbiomes in OS patients was higher than that in controls. Principal coordinate analysis (PCoA) showed that oral samples clustered separately from nasal samples, and the beta diversity of oral and nasal samples in OS patients was higher than that in controls. The dominant phylum was Bacteroidetes in OS patients and Firmicutes in controls in both the oral and nasal cavity. The dominant genera in the oral microbiome and nasal microbiome of OS patients were similar, including Fusobacterium, Porphyromonas and Prevotella. Co-occurrence network analysis showed decreased microbial connectivity in the oral mucosa and nasal secretion samples of OS patients., Conclusions: Odontogenic infection promotes structural and functional disorders of the nasal microbiome in OS. The interaction of dominant pathogens in the nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS., (© 2023. The Author(s).)

Introduction: Chronic rhinosinusitis (CRS) is a heterogeneous disease, and its complex pathophysiological characteristics pose a challenge to its clinical treatment. CRS is distinguished not only by clinical phenotype but also by endotype characteristics, which are divided into type 2 CRS and non-type 2 CRS., Areas Covered: In this review, we summarize and discuss current studies that depict the mechanisms and endotypes of CRS. In particular, inflammatory cells and the microbiome play a role in the pathophysiology of CRS. We also listed some of the biomarkers described in recent studies that may serve as a theoretical foundation for additional investigations. We have summarized the advantages and disadvantages of existing treatments and listed the available biological treatments for CRS in detail., Expert Opinion: Endotype-driven therapeutic options face many challenges because of the complexity of the disease. Glucocorticoids, nasal endoscopic surgery, and biological therapy are the main treatments used in clinical practice, but they have limitations. This review provides advice on the clinical management and treatment options for patients with different endotypes, which will be more conducive to improving the quality of life and reducing the financial burden on patients.

Background: Little evidence exists regarding an integrated multidimensional evaluation methodology to analyze the within-patient effects of medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to use an integrated evaluation model to analyze the effects of short-course oral corticosteroid (OCS) followed by intranasal corticosteroid spray (INCS) therapy in patients with severe CRSwNP., Methods: In all, 32 patients with severe CRSwNP received oral methylprednisolone for three weeks followed by intranasal budesonide spray for nine weeks in this prospective single-arm study. An evaluation model integrating the concepts of the core outcome set (COS), clinical control and minimum clinically important difference (MCID) was longitudinally evaluated., Results: All uncontrolled patients at baseline showed similar progressive improvements from baseline and more than 1 MCID response across core outcomes during the OCS period, with severe CRSwNP being partly controlled in 31 (96.9%) patients and uncontrolled in 1 (3.1%) patient at 3 weeks. During the subsequent INCS period, 14 (43.8%) patients gradually deteriorated to an uncontrolled status at 12 weeks, whereas 18 (56.2%) exhibited partly controlled CRSwNP until 12 weeks., Conclusions: In more than half of the patients, severe CRSwNP was partly controlled with the initial OCS followed by INCS therapy. An integrated evaluation model was used to facilitate the comprehensive evaluation of within-patient response, especially in patients with different responses to the same treatment., Trial Registration: ChiCTR1900024287.

Background: Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated., Objective: We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors., Methods: Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining., Results: Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5., Conclusion: Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Predicting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) may help for selection of appropriate surgical procedures or pharmacotherapies in advance. However, an accurate non-invasive method for diagnosis of type 2 CRSwNP is presently unavailable., Methods: To optimize the technique for collecting nasal secretion (NasSec), 89 CRSwNP patients were tested using nasal packs made with four types of materials. Further, Th2 low and Th2 high CRSwNP defined by clustering analysis in another 142 CRSwNP patients using tissue biomarkers, in the meanwhile, inflammatory biomarkers were detected in NasSec of the same patients collected by the selected nasal pack. A diagnostic model was established by machine learning algorithms to predict Th2 high CRSwNP using NasSecs biomarkers., Results: Considering the area under receiver operating characteristic curve (AUC) for IL-5 in NasSec, nasal pack in polyvinyl alcohol (PVA) was superior to other materials for NasSec collection. When Th2 low and Th2 high CRSwNP clusters were defined, logistic regression and decision tree model for prediction of Th2 high CRSwNP demonstrated high AUCs values of 0.92 and 0.90 respectively using biomarkers of NasSecs. Consequently, the pre-pruned decision tree model; based on the levels of IL-5 in NasSec (≤ 15.04 pg/mL), blood eosinophil count (≤ 0.475*10 9 /L) and absence of comorbid asthma; was chosen to define Th2 low CRSwNP from Th2 high CRSwNP for routine clinical use., Conclusions: Taken together, a decision tree model based on a combination of NasSec biomarkers and clinical features can accurately define type 2 CRSwNP patients and therefore may be of benefit to patients in receiving appropriate therapies in daily clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Duan, Zhang, Zhao, Zhang, Hao, Li, Wang, Wang, Zhang, Bachert, Zhang and Lan.)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is considered a nasal sinus inflammatory disease that can be dominated by immune cells and cytokines. IL-10 family cytokines exert essential functions in immune responses during infection and inflammation. Recently, the understanding of the roles of the IL-10 family in CRSwNP is being reconsidered. IL-10 family members are now considered complex cytokines that are capable of affecting epithelial function and involved in allergies and infections. Furthermore, the IL-10 family responds to glucocorticoid treatment, and there have been clinical trials of therapies manipulating these cytokines to remedy airway inflammatory diseases. Here, we summarize the recent progress in the understanding of IL-10 family cytokines in CRSwNP and suggest more specific strategies to exploit these cytokines for the effective treatment of CRSwNP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xuan, Zhang, Wang, Zhang and Bachert.)

Background: The conventional belief that glucocorticosteroid (GC) acts through a single brand glucocorticoid receptor (GR)α protein has changed dramatically with the discovery of multiple GR isoforms. We aimed to evaluate whether multiple GR protein isoforms are expressed in chronic rhinosinusitis with nasal polyps (CRSwNP) and whether GR protein isoform expression profiles differ between different endotypes of CRSwNP., Methods: Thirty-eight patients with CRSwNP and ten healthy volunteers were included. The protein expression of multiple GR isoforms in nasal polyps (NPs) tissue and control mucosae was examined by western blot analysis with different GR antibodies., Results: Five bands, including three bands for known proteins (GRα-A/B, GRα-C, and GRα-D) and two bands for unidentified proteins at 67 kilodaltons (kDa) and 60 kDa, were identified with both total GR antibody (PA1-511A) and GRα-specific antibody (PA1-516). GRα-D intensity, which was abundant in nasal mucosa, was significantly increased in the CRSwNP group and was especially elevated in the noneosinophilic CRSwNP (NE-CRSwNP) group (PA1-511A: P < 0.001 and P = 0.0018; PA1-516: P < 0.003 and P = 0.006, respectively). Additionally, the intensities of the newly recognized 67 kDa and 60 kDa bands were much greater in the NE-CRSwNP subgroup than in the eosinophilic CRSwNP (E-CRSwNP) subgroup; in the E-CRSwNP subgroup, the median intensities were even lower than those in the control group., Conclusions: This study provides evidence that nasal tissues express multiple GR protein isoforms. GR protein isoforms presented disease and tissue-specific expression profiles that differed between the CRSwNP and control groups and between the E-CRSwNP and NE-CRSwNP subgroups., (© 2022. The Author(s).)

Protein crystallization is a prevalent phenomenon existing in the formation of intricate protein-assembled structures in living cells. Whether the crystallization of a protein would exert a specific biological function, however, remains poorly understood. Here, we reconstructed a recombinant galectin-10 (gal-10) protein and artificially engineered a gal-10 protein assembly in two distinguishable states: i.e., an insoluble crystalline state and a soluble state. The potency of the gal-10 protein in either the crystalline state or the soluble state to induce chemokine or cytokine release in the primary human nasal epithelial cells and nasal polyps derived from chronic rhinosinusitis patients with nasal polyps was investigated. The crystalline gal-10 upregulated the gene expression of chemokines or cytokines, including IL-1β, IL-6, IL-8, TNF-α, and GM-CSF, in patient-derived primary cells and nasal polyps. In contrast, soluble gal-10 displayed a diminished potency to induce inflammation. Our results demonstrate that the gal-10 protein potency of activating inflammation is correlated with its crystalline state.

Background: Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence., Methods: Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression-based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post-admission., Results: By distinguishing recurrence-associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non-recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy., Conclusions: Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The preoperative prediction of the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) remains difficult in clinical practice., Objective: We aimed to develop a nomogram that combined peripheral risk factors to clinically predict the recurrence of CRSwNP., Methods: Data from 158 CRSwNP patients who underwent endoscopic sinus surgery (ESS) from January 2012 to December 2016 were collected, and the patients were followed up for 3 years. Of these, 96 patients who underwent ESS in an earlier period formed the training cohort for nomogram development, and 62 patients who underwent ESS thereafter formed the validation cohort to confirm the model's performance. Risk factors for recurrence identified by univariate and multivariate logistic regression were used to create a nomogram., Results: The recurrence rate was 29.2% (28/96) for the training cohort and 35.5% (22/62) for the validation cohort. Univariate analysis identified blood eosinophils (Eos), serum IgE level, asthma comorbidity, and the number of previous ESSs as risk factors for recurrence. Among those four parameters, serum IgE level and a previous ESS surgery were identified as two independent risk factors. A nomogram consisting of blood Eos, total serum IgE level, asthma comorbidity, and the number of previous ESSs was constructed, demonstrating a C index of 0.81 (95% CI, 0.79-0.83) and 0.80 (95% CI, 0.77-0.83) for predicting recurrence in the training and validation cohorts, respectively. The nomogram had well-fitted calibration curves., Conclusion: The nomogram might be able to preoperatively predict the recurrence of CRSwNP by using currently available and objective parameters. Further studies are required to validate its reliability and effectiveness.

Background: As a typical "united airway" disease, asthma-chronic rhinosinusitis (CRS) overlap has recently drawn more attention. Bronchiectasis is a heterogeneous disease related to a variety of diseases. Whether bronchiectasis exists and correlates with asthma-CRS patients has not been fully elucidated. The purpose of the study was to explore the presence and characteristics of bronchiectasis in patients with overlapping asthma and CRS., Methods: This report describes a prospective study with consecutive asthma-CRS patients. The diagnosis and severity of bronchiectasis were obtained by thorax high-resolution computed tomography (HRCT), the Smith radiology scale and the Bhalla scoring system. CRS severity was evaluated by paranasal sinus CT and the Lund-Mackay (LM) scoring system. The correlations between bronchiectasis and clinical data, fraction of exhaled nitric oxide, peripheral blood eosinophil counts and lung function were analyzed., Results: Seventy-two (40.91%) of 176 asthma-CRS patients were diagnosed with bronchiectasis. Asthma-CRS patients with overlapping bronchiectasis had a higher incidence rate of nasal polyps (NPs) (P = 0.004), higher LM scores (P = 0.044), higher proportion of ≥ 1 severe exacerbation of asthma in the last 12 months (P = 0.003), lower postbronchodilator forced expiratory volume in one second (FEV 1 ) % predicted (P = 0.006), and elevated peripheral blood eosinophil counts (P = 0.022). Smith and Bhalla scores were shown to correlate positively with NPs and negatively with FEV 1 % predicted and body mass index. Cutoff values of FEV 1 % predicted ≤ 71.40%, peripheral blood eosinophil counts > 0.60 × 10 9 /L, presence of NPs, and ≥ 1 severe exacerbation of asthma in the last 12 months were shown to differentiate bronchiectasis in asthma-CRS patients., Conclusions: Bronchiectasis commonly overlaps in asthma-CRS patients. The coexistence of bronchiectasis predicts a more severe disease subset in terms of asthma and CRS. We suggest that asthma-CRS patients with NPs, severe airflow obstruction, eosinophilic inflammation, and poor asthma control should receive HRCT for the early diagnosis of bronchiectasis.

Background: In this study we compared intraoperative bleeding and regional cerebral oxygenation in patients with different degrees of the reverse Trendelenburg position (RTP) during endoscopic sinus surgery (ESS)., Methods: In total, 120 patients with chronic rhinosinusitis treated by ESS were randomly assigned to the following 4 groups: a horizontal position (HP) group, and 5°, 10°, and 15° RTP (5-RTP, 10-RTP, and 15-RTP, respectively) groups. The primary outcome was the Boezaart grading scale (BS). The cerebral oxygen saturation (ScO 2 ), total blood loss, numerical rating scale (NRS) scores, and complications were also recorded., Results: The median BS values in the HP, 5-RTP, 10-RTP, and 15-RTP groups were 2.0, 2.0, 2.1, and 1.7, respectively. Multiple pairwise comparisons of the BS showed significant differences between the 15-RTP group and the other 3 groups (HP, 5-RTP, and 10-RTP). Regarding the NRS and bleeding rate, significant differences were found between the HP and 15-RTP groups. No difference was found in ScO 2 among the 4 groups, and no cerebral desaturation events occurred in any group. No complications, including vital organ (heart, brain, and kidney) dysfunction problems, were reported in this study during hospitalization., Conclusion: Compared with HP, 5-RTP, and 10-RTP, 15-RTP can improve visual clarity during ESS, and ScO 2 is not affected by the degree of RTP. No cerebral deoxygenation or vital organ dysfunction was observed in this study. Therefore, we recommend 15-RTP with moderate deliberate hypotension for ESS., (© 2020 ARS-AAOA, LLC.)

Objective: The purpose of the present study was to investigate the values of the serum (1,3)-β-D-glucan test (G test) alone, the galactomannan test (GM test) alone, and their combination in the diagnosis of invasive fungal rhinosinusitis (IFRS)., Methods: The present study retrospectively analysed the clinical data of 98 patients who were preliminarily diagnosed with "space-occupying lesions in nose". Of these 98 patients, 88 received the G test, 55 received the GM test, and 45 received both. A pathology analysis was used as the gold standard to diagnose IFRS. All data were analysed using SPSS 19.0., Results: The sensitivities (Se) of the G and GM tests alone were 60.0% and 28.6%, respectively, whereas the specificities (Sp) were 92.3% and 93.8%, respectively. Moreover, the positive predictive values (PPV) of the G and GM tests alone were 50.0% and 40.0%, respectively, and the negative predictive values (NPV) were 94.7% and 90.0%, respectively. In addition, the diagnostic odds ratios (DOR) were 18.0 and 6.0, respectively, and the Kappa values were 0.48 (P < 0.05) and 0.25 (P > 0.05), respectively. When the G and GM tests were parallel combined, the Se was 66.7%, the Sp was 92.3%, the PPV was 57.1%, the NPV was 94.7%, the DOR was 24.0, and the Kappa value was 0.55 (P < 0.05). The present study was unable to evaluate the serial diagnosis due to the lack of patients testing positive., Conclusions: The G/GM tests exhibited low Se and PPV when used to diagnose IFRS, while high Sp and NPV. Parallel diagnosis improved the diagnostic Se and DOR values., (Copyright © 2020. Published by Elsevier Inc.)

Background: There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non-asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non-asthmatic patients with CRSwNPs remains unclear., Objective: This study analysed the lung function of non-asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs., Methods: The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non-asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients., Results: Non-asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF 75 ) and FEF 50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non-asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF 50 was associated with the recurrence of non-asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type-2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non-asthmatic CRSwNP patients was related to serum IgE levels., Conclusions and Clinical Relevance: This study provides evidence that non-asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type-2 inflammation., (© 2020 John Wiley & Sons Ltd.)

Background: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces reactive oxygen species (ROS) involved in oxidative stress and signal transduction. Recent studies have suggested that NADPH oxidase is associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of this study was to detect the expression of NADPH oxidase subunits and 4-hydroxynonenal (4-HNE) in nasal polyp tissue and normal nasal mucosa, in order to explore the possible role played by NADPH oxidase in the pathogenesis of CRSwNP., Methods: Thirteen patients with CRSwNP and 9 normal control subjects were selected to participate in this study, in which we evaluated the expression of different NADPH oxidase subunits (gp91 phox , p67 phox , p47 phox , and p22 phox ) in nasal polyp (NP) tissue and control mucosa by Western blotting and real-time polymerase chain reaction (PCR). Immunohistochemistry and immunofluorescence staining were used to detect expression of the p67 phox subunit and 4-HNE in NP tissue and normal nasal mucosa., Results: Western blot and real-time PCR results showed that p67 phox expression was significantly increased in NP tissue when compared with its expression in control mucosa (p = 0.004). p67 phox was expressed in the eosinophils and neutrophils found in NP tissue, but not in the macrophages. Additionally, the levels of 4-HNE expression were also significantly increased in NP tissue when compared with control mucosa (p = 0.001)., Conclusion: The levels of p67 phox messenger RNA (mRNA) and protein as well as 4-HNE were both upregulated in NP tissue, suggesting that p67 phox and oxidative stress play roles in the pathogenesis of CRSwNP., (© 2020 ARS-AAOA, LLC.)

Background: Nasal nitric oxide (nNO) has been evaluated in patients with chronic rhinosinusitis with and without nasal polyps. However, nNO levels in patients with allergic rhinitis (AR) and nonallergic rhinitis (NAR) have shown conflicting results in previous studies., Objective: To evaluate the value of nNO in diagnosing AR and NAR and the impact of absence or presence of sinus inflammation (SI)., Methods: A total of 173 consecutive patients scanned with high-resolution computed tomography (CT) and 46 normal controls (NCs) were included in our study. Patients were evaluated according to their medical history, nasal symptoms, endoscopic examinations, and skin prick test results. On the basis of CT scans (Lund-Mackay score >2), all patients were subgrouped as AR with SI (ARwSI) and AR without SI (ARsSI), or NAR with SI (NARwSI) and NAR without SI (NARsSI). nNO levels were measured with the NIOX, and eosinophils in nasal smears were evaluated simultaneously. Receiver-operating characteristic analysis was performed for differential diagnosis of AR, NAR, and subgroups., Results: Ninety-four patients were diagnosed with AR and 79 patients with NAR. The levels of nNO were significantly higher in patients with AR and in NCs compared with patients with NAR (939 ± 335 in AR and 813 ± 272 in NCs vs 670 ± 188 in NAR; P < .001 for both), and significantly higher in patients with AR compared with NCs (P < .05). On the basis of sinus CT scans, 49% patients with AR (46 of 94) were defined as ARwSI and 51% patients with NAR (40 of 79) were defined as NARwSI. Patients with ARsSI showed the highest nNO levels (1180 ± 289) compared with other subgroups (P < .001), and patients with NARwSI showed the lowest nNO levels (522 ± 120) compared with other subgroups (P < .001). nNO could be used to discriminate AR, NAR, and subgroups with acceptable sensitivity and specificity. Moreover, patients with nasal smear eosinophilia had lower nNO levels than did patients with NAR (P < .05)., Conclusions: nNO levels are different between patients with ARwSI/ARsSI and NARwSI/NARsSI, and may be used to discriminate these phenotypes., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. T H 2- and T H 17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP., Objective: We sought to investigate the interregulation of T H 2 and T H 17 pathways in Chinese patients with CRSwNP., Methods: Levels of key T H 2- and T H 17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of T H 2 and T H 17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between T H 2- and T H 17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored., Results: Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive T H 2- and T H 17-related factors. The T H 2 cytokines IL-4 and IL-13 inhibited expression of T H 17-related factors, whereas the T H 17 cytokines IL-17 and TGF-β1 enhanced expression of T H 2-related factors. Dexamethasone treatment inhibited both the T H 2 and T H 17 pathways. A patient's atopic status was related to their T H 2 immune response. Edema scores were positively correlated with the T H 2 pathway and negatively correlated with the T H 17 pathway., Conclusion: The T H 2 and T H 17 pathways are mutually exclusive and regulate each other, favoring the development of a T H 2 immune response in Chinese patients with CRSwNP., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: IL-8 is an important chemokine implicated in the pathogenesis of chronic rhinosinusitis (CRS), but little is known about epigenetic regulation of IL8 in the pathogenesis of CRS., Objective: We sought to investigate the relationship between the DNA methylation level in the IL8 proximal promoter and CRS in Han Chinese subjects., Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP; n = 187), patients with chronic rhinosinusitis without nasal polyps (CRSsNP; n = 89), and control subjects (n = 57) were enrolled in 2 independent cohorts. Purified human nasal epithelial cells from each participant were assessed for percentage DNA methylation of CpG sites in the IL8 proximal promoter by using bisulfite pyrosequencing and for functional aspects of methylation status by using in vitro assays., Results: DNA methylation of CpG sites 1, 2, and 3, respectively, in the IL8 proximal promoter was significantly decreased in human nasal epithelial cells of patients with CRSwNP compared with that in patients with CRSsNP (P < .001) and control subjects (P < .001). Percentage of DNA methylation of the CpG3 site was correlated negatively with both tissue eosinophilic cationic protein (P < .01) and myeloperoxidase (P < .05) levels. IL-1β (P < .001) and TNF-α (P < .01) significantly increased IL8 expression accompanied by a reduction in methylation at the CpG3 site (P < .001). Electrophoretic mobility shift assays demonstrated that methylation status of CpG3 changed the binding of octamer-binding transcription factor 1 and nuclear factor κB., Conclusion: Decreased DNA methylation of particularly CpG sites in the IL8 proximal promoter might play a role in the pathogenesis of CRSwNP., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease. MicroRNAs (miRNAs) that are involved in the pathogenesis of CRSwNP in Northern China remain unknown., Methods: A miRCURY™ LNA Array was used to analyze miRNA profiles in nasal mucosa tissues of CRSwNP patients (n = 19) and healthy controls (n = 10). Subsequent pathways were predicted by DIANA-mirPath software., Results: Five upregulated miRNAs, including miR-210-5p, miR-3178, miR-585-3p, miR-3146, and miR-320e, and 19 downregulated miRNAs, including miR-32-3p, miR-1299, miR-3196, miR-3924, and miR-548e-3p, were differentially expressed (p < 0.05, fold change >2) in tissues of CRSwNP vs controls. Utilizing the Kyoto Encyclopedia of Genes and Genomes database (KEGG), which is an online database for pathway mapping, mucin type O-glycan biosynthesis pathway was significantly enriched in upregulated miRNAs. Transforming growth factor-beta (TGF-β), transient receptor potential (TRP) channels, and the mitogen-activated protein kinase (MAPK) signaling pathway were significantly linked to downregulated miRNAs., Conclusion: The mucin type O-glycan biosynthesis pathway and TGF-β signaling pathway are regulated by miRNAs, which could be our focus in the future studies., (© 2018 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) nasal polyps is a global health concern. Several clinical biomarkers, such as inhaled carbon monoxide and exhaled nitric oxide (NO), have been studied to assess the presence and degree of inflammation in the airway mucosa., Objective: To evaluate the clinical application of exhaled nasal NO (nNO) in distinguishing between CRSwNP and CRSsNP in consideration of the atopic status of patients., Methods: Eighty-eight patients with CRS and 20 healthy volunteers were recruited for this study. The exhaled nNO level was measured by using a hand-held device. Nasal endoscopy (with Lund-Mackay scoring of CRS) and sinus computed tomographies (CT) were used to evaluate the nasal cavity and sinuses of the subjects. Atopic status was confirmed by using skin prick tests (SPTs)., Results: The mean ± standard deviation (SD) levels of nNO in patients with CRSsNP were significantly higher than those in patients with CRSwNP (591 ± 153 ppb versus 360 ± 181 ppb, p < 0.001), whereas patients with CRS exhibited lower levels of nNO compared with the control subjects (449 ± 204 ppb versus 881 ± 161 ppb, p < 0.001). Patients with atopy and with and without nasal polyps exhibited significantly higher levels of nNO compared with patients without atopy (atopic CRSsNP versus nonatopic CRSsNP, 734 ± 120 ppb versus 503 ± 92 ppb [p < 0.001]; atopic CRSwNP versus nonatopic CRSwNP, 518 ± 161 ppb versus 299 ± 150 ppb [p < 0.001]). The levels of nNO were negatively correlated with the Lund-Mackay scores in both atopic (r = -0.45; p = 0.016) and nonatopic (r = -0.600; p < 0.001) patients with CRS. Receiver operating characteristic curves differentiated patients as CRSwNP, CRSsNP, and healthy controls, and in atopic and nonatopic subgroups, with acceptable sensitivity and specificity (>70 to 90%)., Conclusion: Exhaled nNO levels can be used to distinguish between patients with CRSwNP and patients with CRSsNP. However, the atopic status of the patient influenced the use of nNO as a diagnostic or monitoring biomarker in CRS.

Chronic rhinosinusitis (CRS), although possibly overdiagnosed, is associated with a high burden of disease and is often difficult to treat in those truly affected. Recent research has demonstrated that inflammatory signatures of CRS vary around the world, with less eosinophilic and more neutrophilic inflammation found in Asia compared with Europe and North America. Although in the Western world about 80% of nasal polyps carry a type 2 signature, this might be between 20% and 60% in China and Korea or Thailand, respectively. These differences are associated with a lower asthma comorbidity and risk of disease recurrence after surgery in the Asian population. As a hallmark of severe type 2 inflammation, eosinophils attacking Staphylococcus aureus at the epithelial barrier have been described recently; they also can be found in a subgroup of Asian patients with nasal polyps. Furthermore, the percentage of type 2 signature disease in patients with CRS is dramatically increasing ("eosinophilic shift") in several Asian countries over the last 20 years. Establishing an accurate diagnosis along with considering the current and shifting patterns of inflammation seen in Asia will enable more effective selection of appropriate pharmacotherapy, surgical therapy, and eventually biotherapy. Determining the causes and pathophysiology for this eosinophilic shift will require additional research., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Conclusions: There is clear correspondence between HU and histopathological evaluation of osteitis. It is feasible to evaluate bone remodeling in rabbit models with rhinosinusitis by measuring the HU., Objective: The objective of this study was to determine whether the HUs of rabbit CRS models can be used to objectively evaluate the degree of osteitis., Methods: Sixty rabbit models were inoculated with staphylococcus aureus. The rabbits were divided into three groups. Each group was divided into a medication administration team and a control team. The HU of the bone in each image was measured. All of the animals were executed after the CT exam. The samples for the mucous and bone changes using light microscope observation were scored. These scores and the HU measurements were compared to the actual bone remodeling over time to examine whether we could evaluate bone remodeling by measuring the HU., Results: The average HU scores in Groups A, B, and C were significantly higher than those of normal rabbits (p < .05). The mucous and bone scores increased as the experimental period lengthened (p = .042, 0.002). HU correlated with the mucous and bone scores in rabbit models with rhinosinusitis (coefficient r = .830, 0.641, 0.586, p = .000).

Background: To date, no study has evaluated the diversity of T H cell cytokine patterns of patients with chronic rhinosinusitis (CRS) among centers in different continents using identical methods., Objective: We sought to assess T H cytokine profiles in patients with CRS from Europe, Asia, and Australia., Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP; n = 435) and control subjects (n = 138) were recruited from centers in Adelaide, Benelux, Berlin, Beijing, Chengdu, and Tochigi. Nasal mucosal concentrations of T H 2, T H 17, and T H 1 cytokines; eosinophilic cationic protein (ECP); myeloperoxidase (MPO); IL-8; and tissue total and Staphylococcus aureus enterotoxin (SE)-specific IgE were measured by using identical tools., Results: Combinations of T H 1/T H 2/T H 17 cytokine profiles in patients with CRSwNP varied considerably between regions. CRSwNP tissues from patients from Benelux, Berlin, Adelaide, and Tochigi were T H 2 biased, whereas those from Beijing mainly demonstrated T H 2/T H 1/T H 17 mixed patterns, and patients from Chengdu showed an even lower T H 2 expression. Concentrations of IL-8 and tissue total IgE in patients with CRSwNP were significantly higher than those in control subjects in all regions. More than 50% of patients with CRSwNP in Benelux, Berlin, Adelaide, and Tochigi showed a predominantly eosinophilic endotype compared with less than 30% of patients in Beijing and Chengdu. SE-specific IgE was found in significantly greater numbers in patients with CRSwNP from Benelux, Adelaide, and Tochigi and significantly lower numbers in patients from Beijing and Chengdu. Moreover, the T H 1/T H 2/T H 17 cytokine profiles in patients with CRSsNP showed diversity among the 6 regions., Conclusion: T H cytokine levels, eosinophilic/neutrophilic patterns, and SE-specific IgE expressions show extreme diversity among patients with CRS from Europe, Asia, and Oceania., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS., Objective: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes., Methods: In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering., Results: Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE., Conclusion: Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: There is little evidence on the efficacy of glucocorticoid transnasal nebulization therapy in patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP)., Objective: We sought to evaluate the immunologic and remodeling effects of budesonide transnasal nebulization in patients with eosinophilic CRSwNP., Methods: Sixty patients with eosinophilic CRSwNP were randomized to receive budesonide or placebo treatment for 14 days by means of transnasal nebulization in a double-blind manner. Endoscopic polyp size scores (maximum = 6 points, Kennedy score) and visual analog scale scores for nasal symptoms were assessed before and after treatment. Similarly, polyp samples were evaluated for inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) by using an immunoassay; collagen by using histochemistry; eosinophils by using hematoxylin and eosin stain; and T-cell subsets by using flow cytometry., Results: Budesonide transnasal nebulization significantly reduced polyp size compared with placebo (mean difference between groups, -0.73 units; 95% CI, -1.15 to -0.32 units; P = .002) and improved symptoms. Polyp IL-5 and eotaxin expression decreased significantly, whereas TGF-β and IL-10 expression increased. Expression of IFN-γ and IL-17 was not altered. Budesonide transnasal nebulization consistently reduced eosinophil infiltration and TH2 cell frequency and increased natural regulatory T-cell and type 1 regulatory T-cell frequencies. Indices of remodeling, including albumin, MMP-2, MMP-7, MMP-8, and MMP-9, were significantly decreased, whereas collagen deposition and TIMP-1, TIMP-2, and TIMP-4 levels were significantly increased. Budesonide transnasal nebulization did not suppress the hypothalamic-pituitary-adrenal axis or cause any serious side effects., Conclusion: Short-term budesonide transnasal nebulization is an effective and safe treatment option in patients with eosinophilic CRSwNP, achieving clinical improvement by regulating remodeling, cytokine expression, and T-cell subset distribution., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Conclusion: Staphylococcus aureus, Streptococcus, Haemophilus, Enterobacter, and Corynebacterium appear to be more frequently associated with patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) than with patients with CRS without nasal polyps (CRSsNP) or control subjects. Furthermore, the isolation rate of Staphylococcus aureus appears to be much lower in Chinese CRSwNP patients compared with their caucasian counterparts., Objectives: To compare the predominant bacteriologic profiles in middle meatus of patients with CRSwNP, those with CRSsNP, and control subjects., Methods: A total of 165 CRSwNP patients, 76 CRSsNP patients, and 44 control subjects were recruited into the study. Swab samples were obtained from the middle meatus during endoscopic sinus surgery and processed for the presence of aerobic and non-aerobic bacteria and fungi., Results: Mostly aerobic and facultative anaerobic bacteria were detected in the samples from all three study groups, of which the most common aerobic bacteria were coagulase-negative staphylococci, Corynebacterium species, Staphylococcus aureus, and Haemophilus influenzae. In contrast, comparatively few anaerobic bacteria and fungi were isolated from the three study groups. In CRSwNP patients, significantly more Gram-negative aerobic and facultative anaerobic bacteria were isolated from the subgroup with normal eosinophil numbers than from the subgroup with increased blood eosinophils (p = 0.005). Correspondence analysis showed coagulase-negative staphylococci to be closely associated with all three patient groups, whereas Staphylococcus aureus, Streptococcus, Haemophilus, Enterobacter, and Corynebacterium species were associated with CRSwNP patients.

Objective: To evaluate the expression of five epithelial intercellular junctional proteins in the sinonasal tissue of subjects with chronic rhinosinusitis (CRS)., Methods: Forty-one samples of nasal polyp tissue of CRS patients with nasal polyps (wNP), 20 ethmoid sinus mucosa of CRS patients without nasal polyps (sNP) and 19 nasal mucosa of controls were collected and assessed for the expression of zonulae occludens (ZO-1), claudin-1, E-cadherin and desmoglein-1 and -2 (DSG1, DSG2) using immunohistochemical staining. Interleukin (IL)-5, IL-6 and IL-8 concentrations in the tissues were also measured using ELISA., Results: The expression of ZO-1, claudin-1, DSG1 and DSG2 in the CRSwNP patient group and the expression of claudin-1, DSG1 and DSG2 of the CRSsNP patient group was significantly lower compared to that of the control group. Furthermore, the expression of DSG1 in the CRSwNP patient group was also significantly lower than in the CRSsNP patient group. In contrast, the expression of E-cadherin in the CRSwNP and the CRSsNP patient groups was significantly greater compared to the controls. The assessment of associations between the expression of the intercellular junctional proteins and cytokines demonstrated negative correlations between IL-5 and claudin-1, IL-6 and claudin-1, IL-6 and DSG2, IL-8 and DSG1, and IL-8 and DSG2. In contrast, a positive correlation was found between IL-8 and E-cadherin., Conclusions: Differences in the expression of epithelial intercellular junctional proteins may play an important role in the pathogenesis of CRS., (© 2014 S. Karger AG, Basel.)

Background: Recent studies have suggested that thymic stromal lymphopoietin (TSLP), a key cytokine involved in the dendritic cell-mediated activation of Th2-mediated inflammatory responses, is significantly increased in nasal polyps from atopic individuals. Our objective was therefore to explore firstly any associations between single nucleotide polymorphisms (SNPs) in and around the TSLP gene and development of chronic rhinosinusitis (CRS; with (CRSwNP) or without (CRSsNP) nasal polyps and, and secondly the influence of nasal polyposis and gender., Methods: A population-based case-control association analysis was performed in a Han Chinese cohort. DNA extracted from peripheral blood leukocytes from 638 subjects with CRS (306 CRSwNP and 332 CRSsNP) and 325 healthy controls was assessed for 11 SNPs in and around TSLP gene, selected from the Chinese HapMap genotyping dataset. Genetic association tests were performed using the Haploview and STATA software package., Results: Single-locus analysis of CRS risk, showed no significant differences in allele or genotype frequencies between CRS subjects and controls. Stratified analyses of association between the selected SNPs and CRS adjusted for gender demonstrated that rs13156068 (CC genotype: P=0.010, OR=0.289) and rs764917 (CC genotype: P=0.040, OR=0.509) were significantly protective against CRS, whereas rs6886755 (GT genotype: P=0.040, OR=0.509) presented a risk among females. In contrast, rs764917 (CA genotype: P=0.033, OR=1.553) presented risk for CRS in males. Furthermore, SNPs rs252706 (AA genotype: P=0.012, OR=0.552) and rs764917 (CA genotype: P=0.001, OR=0.182) displayed protective roles among CRSwNP, but not CRSsNP, subjects., Conclusions: This study suggests that SNPs in TSLP gene may exert a gender and/or nasal polyposis-dependent risk for development of CRS in Chinese subjects., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the differences in clinical features and expression of cytokine thymic stromal lymphopoetin (TSLP) and its receptors in patients with eosinophilic and non-eosinophilic chronic rhinosinusitis (ECRS and NECRS)., Method: 36 ECRS patients and 50 NECRS patients were evaluated for symptoms, nasal sinus computed tomography scanning, nasal endoscopy, skin prick test (SPT) positivity, and total IgE. Expression of TSLP and receptors in ethmoid sinus mucosa from the ECRS and NECRS groups were investigated by using immunohistochemical staining., Results: ECRS patients demonstrated significantly higher scores of cough and hyposmia. 66.7% of ECRS patients also demonstrated nasal polyps, compared to 50% of NECRS patients, with significantly higher polyp endoscopy scores. 80.6% of ECRS patients demonstrated SPT positivity, compared to 14% of NECRS patients. The overall expression of TSLP, TSLP receptors and IL-7R was significantly greater in eosinophils in the mucosa of ECRS patients than in NECRS patients. The expression of TSLP and receptors in SPT-positive ECRS patients was significantly greater than in SPT-negative patients, with a significant correlation noted between the expression of TSLP and nasal polyp scores., Conclusion: The clinical manifestations of ECRS are likely to be influenced by atopic status of an individual and TSLP-mediated eosinophil infiltration of the rhinosinusoidal mucosa., (Copyright © 2013 S. Karger AG, Basel.)

Background: Subtypes of sinusitis have different symptoms and prognoses due to different pathogens. Odontogenic maxillary sinusitis (OMS) mainly occurs unilaterally and is different from chronic rhinosinusitis (CRS) usually occurring bilaterally in terms of clinical characteristics. However, comprehensive microbiological comparisons between OMS and CRS have never been systematically conducted and most comparisons are methodologically biased. This study aims to provide a comprehensive analysis of the microbiology associated with OMS and CRS through a meta-analysis approach in order to provide evidence for differential diagnosis of OMS and CRS from a microbiological perspective. Methods: The databases PubMed and CNKI were searched from their inception to July 2023. A random-effects model was employed to derive the pooled prevalence estimates of the identified bacterial species or genera. Results: The 17 represented studies included 6 concerning OMS, 12 concerning CRS, and 4 concerning normal sinus, yielding 191, 610, and 92 samples, respectively. Though not statistically significant, the prevalence of Peptostreptococcus and Prevotella was generally higher in OMS compared to CRS. Notably, Fusobacterium was identified as the only genus with a significantly higher prevalence in OMS compared to CRS. Conclusion: Fusobacterium was significantly more prevalent in OMS compared with CRS, while Staphylococcus aureus was more prevalent in CRS than in OMS. Such differences in bacterial profile may partly explain the distinct pathology observed and contribute to the development of novel strategies for diagnosis and therapeutic interventions in OMS. [ABSTRACT FROM AUTHOR]

This article explores the associations between the extracellular matrix proteins tenascin C (TNC), fibronectin (FN), and periostin (PN) with edema formation and Th2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The study found that TNC, FN, and PN levels were significantly higher in NP tissue compared to controls, and they were positively correlated with edema score and disease severity. Additionally, TNC was predominantly correlated with Th2-related factors. The findings suggest that TNC, FN, and PN play a role in edema formation and disease severity in NP, providing potential targets for treatment. [Extracted from the article]

The aim of this study was to analyze the oral etiology of patients with odontogenic sinusitis (ODS) and to compare the differences in demographic data, clinical symptoms, extent of sinus involvement, bone penetration of the maxillary sinus floor (MSF) between different etiologies. A retrospective investigation was conducted on 103 patients with ODS recruited from Beijing TongRen Hospital. All enrolled patients underwent sinus CT, nasal endoscopy, and oral examination. A comparison of the patients' clinical symptoms, the extent of involvement of the sinuses, and bone resorption of the MSF according to odontogenic etiologies was conducted. Follow-up was based on symptoms and clinical examination. The most common odontogenic etiologies were endo-periodontal lesions (EPLs, 49.5%), apical periodontitis (AP, 32.0%), and periodontitis (PE, 8.7%). There were statistically significant differences in age (p = 0.002), sex (p = 0.036), inflammation involving the ethmoid sinus (p = 0.037), and bone penetration of the MSF (p < 0.001) between the AP, EPL, and PE groups. There were no significant differences in sinusitis symptoms (p > 0.005) among patients with different odontogenic etiologies. In conclusion, EPL is a neglected oral etiology with a destructive effect on the bone of the MSF, which deserves more attention in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is considered a key factor in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific mechanism driving polypogenesis under hypoxic conditions is unclear. This study aimed to explore hypoxia‐induced alterations in the transcriptome of human nasal epithelial cells (HNECs) in vitro. Methods: HNECs derived from the tissue of patients with CRSwNP were established as air–liquid interface (ALI) cultures. Confluent cultures were kept submerged or treated with cobalt chloride (CoCl2) to induce hypoxia. Transcriptome analysis was used to identify key mRNAs involved in this process. Real‐time PCR (RT–PCR), Western blotting, and immunofluorescence were used to observe the effects of hypoxia on ciliogenesis. Results: Numerous genes, biological processes and pathways were altered under submerged culture conditions or after CoCl2 treatment. Analysis of the results under both hypoxic conditions revealed that the transcriptional program responsible for ciliogenesis was significantly impaired. Downregulation of cilia‐related genes and inhibition of ciliated cell differentiation under hypoxia were confirmed by RT–PCR, Western blot and immunofluorescence analyses. Conclusion: Hypoxia impairs ciliogenesis and ciliary function in HNECs, which might play a role in the pathogenesis of CRSwNP. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease with limited treatment options of corticosteroids, sinus surgery, or both. CRSwNP is frequently associated with allergic rhinitis and asthma, but the molecular mechanisms underlying CRSwNP inflammation are not completely understood. We obtained four gene expression profiles (GSE136825, GSE36830, GSE23552, and GSE72713) from four Gene Expression Omnibus (GEO), which collectively included 65 nasal polyp samples from CRSwNP patients and 54 nasal mucosal samples from healthy controls. Using an integrated analysis approach, we identified 76 co-differentially expressed genes (co-DEGs, including 45 upregulated and 31 downregulated) in CRSwNP patients compared with the healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified the terms including immune effector process, leukocyte migration, regulation of the inflammatory response, Staphylococcus aureus infection, and cytokine-cytokine receptor interaction. protein-protein interaction (PPI) network analysis and real-time quantitative PCR (RT-qPCR) showed that 7 genes might be crucial in CRSwNP pathogenesis. Repurposing drug candidates (Alfadolone, Hydralazine, SC-560, Iopamidol, Iloprost, etc) for CRSwNP treatment were identified from the Connectivity Map (CMap) database. Our results suggest multiple molecular mechanisms, diagnostic biomarkers, potential therapeutic targets, and new repurposing drug candidates for CRSwNP treatment. [ABSTRACT FROM AUTHOR]

Background: Mucus hypersecretion and goblet cell upregulation are common features of chronic rhinosinusitis with nasal polyps (CRSwNP). Although epidermal growth factor (EGF) has been reported to stimulate the expression of MUC5AC, the major macro-molecular constituent of airway mucus, the precise mechanisms underlying the regulation of MUC5AC expression are still not fully understood. The aim of this study therefore was to investigate the role of EGF in regulation of mucin MUC5AC expression and define the involvement of transmembrane protein 16A (TMEM16A) in mediating the EGF-induced mucus overexpression. Methods: Human nasal epithelial cells (HNECs) derived from tissue of patients with CRSwNP and control subjects were established as air–liquid interface (ALI) cultures. Differentiated cultures were treated with different concentrations of EGF for 4–24 h, and assessed for the expression of TMEM16A and MUC5AC by real-time RT-PCR, Western blotting, ELISA and immunofluorescence. Cultures pretreated for 30 min with T16Ainh-A01 (a specific TMEM16A inhibitor) or LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor) were also assessed similarly following EGF treatment. Results: EGF treatment (10–100 ng/ml for 4–24 h) significantly increased the expression of both TMEM16A and MUC5AC mRNA and protein, as well as the percentage of TMEM16A-positive cells, MUC5AC-positive cells and cells coexpressing TMEM16A and MUC5AC in HNECs compared to control non-EGF-treated HNECs. Pretreatment of the HNECs with T16Ainh-A01 and LY294002 attenuated these EGF-induced effects. Conclusions: This study demonstrated that EGF upregulates the expression of MUC5AC in HNECs from CRSwNP patients. Furthermore, the EGF-mediated regulation of MUC5AC expression is likely to involve a PI3K-TMEM16A signalling pathway in CRSwNP. [ABSTRACT FROM AUTHOR]

The article discusses a study which analyzed the clinical data of 16 patients with chronic invasive fungal rhinosinusitis (CIFRS) who were diagnosed in the Department of Rhinology of Beijing Tongren Hospital during the period from 2006 to 2014. Topics covered include the pathological features of CIFRS, its insidious onset and gradual progression, and the proposed feasible diagnosis and treatment strategies.

Background Precise localization and excision of the originating site of a sinonasal inverted papilloma (SNIP) is essential for decreasing tumor recurrence. In this study we evaluated the use of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) to pinpoint the attachment/originating sites of SNIPs in 143 patients. Methods Osteitis signs in CTs and convoluted cerebriform pattern (CCP)-based reverse tracings from MRIs of 143 SNIP patients were analyzed preoperatively to predict the originating site of SNIPs. The predicted sites were compared with actual SNIP attachment sites determined by surgery, and patients were followed-up for evaluation of SNIP recurrence rates over a mean period of about 4 years. Results Osteitis signs in CT accurately predicted the actual tumor attachment site in 49.7% of all patients. In comparison, convoluted cerebriform pattern (CCP)-based reverse tracings in MRI and combination CT plus MRI accurately predicted the SNIP originating sites in 84.1% and 86% of the patients, respectively. Sensitivity and specificity in predicting the SNIP originating site were: CT, 54.6% and 69.2%; MRI, 93.1% and 76.9%; and CT+MRI, 94.6% and 92.3%, respectively. A single postoperative recurrence occurred in 4.2% of the patients. Conclusions Preoperative combination of MRI and CT provides a better option to accurately predict the SNIP originating site, and thus may facilitate accurate and complete excision of the SNIP. [ABSTRACT FROM AUTHOR]

This study determined the microbial composition in maxillary sinusitis and determined the predominant fungal and bacterial species. Samples were obtained from 11 patients with fungal sinusitis and 2 healthy patients. The 13 samples were sequenced using an Illumina Hi-Seq 2000, and mapping to the human, bacterial, and the fungal genomes were based on several steps. Bioinformatics and statistical analyses were then performed for bacterial and fungal expressions in the samples. All samples were cultures for fungal growth. The sequencing data revealed that Aspergillus flavus and Aspergillus oryzae were the dominant fungal strains in the rhinosinusitis samples, and Bacillus cereus and Bacillus thuringiensis were the dominant bacterial strains. Indeed, the fungi and bacteria were associated with the development of fungal rhinosinusitis. Furthermore, B. cereus and B. thuringiensis may cooperate with Pseudomonas aeruginosa to inhibit the growth of fungal mycelia. Knowledge of the microbial composition can provide a diagnostic reference for patients with maxillary sinusitis. [ABSTRACT FROM AUTHOR]