Chronic Rhinosinusitis Subtypes Research Articles

Variations in Ciliary Beat Frequency Based on Chronic Rhinosinusitis Endotype and Phenotype.

Chronic rhinosinusitis (CRS) is traditionally classified into CRS with or without nasal polyps and more recently into eosinophilic and non-eosinophilic endotypes. Limited research exists on the relationship between CRS subtype and mucociliary function. This study compares ciliary beat frequency (CBF) across CRS subtypes. To investigate CBF across different CRS subtypes and validate spectrally encoded interferometric microscopy (SEIM) against phase contrast microscopy (PCM) for measuring CBF. Sinonasal mucosa from endoscopic endonasal surgery cases were imaged ex vivo at physiologic temperature with PCM and SEIM. CBF measurements were compared between disease states (control vs chronic rhinosinusitis with nasal polyps (CRSwNP) vs chronic rhinosinusitis without nasal polyps (CRSsNP) and control vs eosinophilic chronic rhinosinusitis vs noneosinophilic chronic rhinosinusitis), as well as between PCM and SEIM. CRSwNP mucosa (5.77 ± 0.12 Hz) had significantly lower CBF compared to control (6.23 ± 0.11 Hz; p=0.001). Both eosinophilic rhinosinusitis (5.74 ± 0.16 Hz; p=0.005) and noneosinophilic CRS mucosa (6.00 ± 0.08 Hz; p=0.03) had significantly lower ciliary beat frequency compared to control (6.28 ± 0.11 Hz). There was no significant difference between PCM (7.65 ± 0.60 Hz) and SEIM (7.64 ± 0.51 Hz) as a means of evaluating CBF (p=0.36). Among CRS subtypes, eosinophilic, noneosinophilic, and CRSwNP are associated with lower ciliary beat frequency when compared to healthy controls. SEIM may have value in measuring ciliary beat frequency.

Prostaglandin E Receptor 2 (EP2) Dysregulation in Allergic Fungal Rhinosinusitis Nasal Polyp Epithelium.

Allergic fungal rhinosinusitis (AFRS) is an eosinophilic subtype of chronic rhinosinusitis with nasal polyposis (CRSwNP). This study aimed to investigate the transcriptome of AFRS nasal polyp epithelium. Sinonasal epithelial cells were harvested from healthy nasal mucosa and polyp tissue collected from participants undergoing elective sinonasal surgery. Primary epithelial cells were subsequently grown in air/liquid interface and subjected to RNA-seq analysis, RT-qPCR, immunoblotting, and immunostaining. A total of 19 genes were differentially expressed between healthy and AFRS sample epithelium. The second top candidate gene, ranked by adjusted p-value, was prostaglandin E receptor 2 (PTGER2). The upregulation of PTGER2 was confirmed by RT-qPCR and immunoblot. The presence of the EP2 receptor, encoded by the PTGER2 gene, was confirmed by immunocytochemistry. PTGER2 is a potential novel therapeutic target for AFRS. EP2 dysregulation is associated with aspirin-exacerbated respiratory disease, potentially giving insight into common mechanisms of disease in severe CRSwNP. NA Laryngoscope, 2024.

TFE3 and TP53 were novel diagnostic biomarkers related to mitochondrial autophagy in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) belongs to a subtype of Chronic rhinosinusitis which is a heterogeneous inflammatory condition. It has been reported that mitophagy may provide a new therapeutic option for CRSwNP. The GSE136825 (training dataset) and GSE179265 (validation dataset) were scoured from the Gene Expression Omnibus database. The candidate genes related to mitophagy were identified by differential expression analysis. Subsequently, the biomarkers were selected from the machine learning, Receiver Operating Characteristic curves, and expression level verification. A backpropagation (BP) neural network was generated to evaluate the diagnostic ability of biomarkers. In addition, the infiltration abundance of immune cells, potential drugs, and related ear-nose-throat (ENT) diseases were analyzed based on the biomarkers. Finally, qPCR analysis was performed to verify these biomarkers. A total of 8 candidate genes were identified by overlapping 3,400 differentially expressed genes (DEGs) and 72 mitophagy-related genes Subsequently, TFE3 and TP53 were identified as biomarkers of CRSwNP, and the area under the curves (AUC) of the BP neural network was 0.74, which indicated that the biomarkers had excellent abilities. TFE3 and TP53 were co-enriched in the cancer pathway, cell cycle, endocytosis, etc. What's more, Macrophage and Immature dendritic cells had significant correlations with biomarkers. The drugs (Doxorubicin, Tetrachlorodibenzodioxin, etc.) and the ear-nose-throat diseases (hearing loss, sensorineural, tinnitus, etc.) related to biomarkers were predicted. Ultimately, qPCR results showed that the expression levels of TFE3 and TP53 in polyp tissue of CRSwNP were increased. Overall, TFE3 and TP53 could be used as biomarkers or potential therapeutic targets to diagnose and treat CRSwNP.

A mini-update on chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses and the nasal cavity lasting longer than 12 weeks. This disease is a common clinical syndrome with significant monetary burden due to the high costs of medical visits, diagnostic tests, medications, and surgical therapies. CRS without nasal polyposis (CRSsNP) is the most common subtype of CRS, accounting for about 70% of all patients. Other subtypes include CRS with nasal polyposis (CRSwNP) and allergic fungal rhinosinusitis (AFRS). CRSwNP has the worldwide prevalence of 2% to 4% and is often accompanied by type 2 inflammation and asthma as a comorbid condition. Pediatric chronic sinusitis is distinct from adult chronic sinusitis and is currently considered an infectious process, characterized by persistent inflammation representing an exaggerated immune response to an external stimulus. The medical and surgical management of CRS has been remarkably modified in the past two decades. The aim of this study was to present an update on CRS based on the recent years’ literature.

Supersulfide formation in the sinus mucosa of chronic rhinosinusitis.

Disruption of the oxidative stress defense system is involved in developing various diseases. Sulfur compounds such as glutathione (GSH) and cysteine (CysSH) are representative antioxidants in the body. Recently, supersulfides, including reactive persulfide and polysulfide species, have gained attention as potent antioxidants regulating oxidative stress and redox signaling. However, their involvement in the pathogenesis of chronic rhinosinusitis (CRS) remains unclear. To clarify the changes in sulfur compounds within the sinus mucosa of each CRS subtype, we measured sulfur compound levels in the sinus mucosa of control individuals (n = 9), patients with eosinophilic CRS (ECRS) (n = 13), and those with non-ECRS (nECRS) (n = 11) who underwent sinus surgery using mass spectrometry. GSH and CysSH levels were significantly reduced, and the glutathione disulfide (GSSG)/GSH ratio, an oxidative stress indicator, was increased in patients with ECRS. Despite the absence of notable variations in supersulfides, patients with ECRS and nECRS exhibited a significant reduction in glutathione trisulfide (GSSSG), which serves as the precursor for supersulfides. This study is the first quantitative assessment of supersulfides in normal and inflamed sinus mucosa, suggesting that sulfur compounds contribute to the pathogenesis of CRS. N/A.

Exploring Sociodemographic Factors in Allergic Fungal Rhinosinusitis in a Northern California Patient Population.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis (CRS) that has previously been associated with younger age and Black patients. However, the role of demographic and socioeconomic factors in AFRS severity remains to be fully elucidated. The objective of this study was to determine whether demographic and socioeconomic factors are associated with incidence of AFRS, as well as with disease severity in Northern California. A retrospective cohort study was conducted of adult patients with AFRS and CRS from 2010 to 2019. AFRS was determined by the Bent and Kuhn criteria, and severity was assessed by radiographic evidence of cranioorbital invasion and other clinical parameters. Chi-square and t-test were used to assess demographic and socioeconomic differences between AFRS and CRS cohorts, and multivariable logistic regression was used to assess risk factors for severe AFRS. Black patients represented 26.2% (55/210 patients) of the AFRS group and 4.9% (842/17,300 patients) of the CRS group, with pairwise comparison of race/ethnicity categories showing that the AFRS group had significantly higher proportions of Black race/ethnicity compared with other race/ethnicities (p < 0.01). AFRS and CRS groups differed significantly by age, with mean ages of 48.7 and 51.0 years, respectively (p = 0.04). There were no significant differences in gender, Medicaid status, comorbidities, and socioeconomic status measures. Multivariate logistic regression showed that Black patients had higher odds of having severe AFRS (adjusted odds ratio = 2.29; 95% confidence interval: 1.18-4.45). AFRS has a unique predilection for Black patients, and severe disease is also more likely in this population.

Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

Development and validation of the Sinonasal Endoscopic Score (SiNES) for chronic rhinosinusitis.

Although there are several endoscopic grading systems for chronic rhinosinusitis (CRS), they are limited in their range and applicability. We developed a SiNonasal Endoscopic Score (SiNES) that builds upon the strengths of previous systems while addressing their limitations. The SiNES system was developed by consensus after multiple rounds of guided discussions. Face, content, and convergent validity were investigated. It was validated using an independent sample of 79 CRS individuals from two referral centres from September 2021 to February 2022. Each patient underwent a sinonasal endoscopy and filled PROM questionnaires. Three independent rhinologists graded endoscopic videos using the SiNES and modified Lund-Kennedy (MLK) scores. Inter-rater and test-retest reliability were assessed via the intraclass correlation coefficient (ICC). SiNES and MLK scores were correlated with PROMs using a Spearman correlation and canonical correlation analysis (CCA). The SiNES system evaluates five anatomical spaces regarding edema, discharge, and scarring. Face, content, and convergent validity were deemed satisfactory by the study authors and an independent panel of Otolaryngologists. Inter-rater reliability was excellent for the SiNES and good for the MLK score. Test-retest reliability was excellent for both systems. Total SiNES was correlated with self-reported smell loss. The SiNES system is an accurate and reliable grading framework applicable to all CRS subtypes. It can be utilized in clinical and research settings and improves upon previously published systems.

Comparison of Long-Term Postoperative Outcomes of the Subtypes of Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition that significantly impacts the health-related quality of life (HRQOL) of patients. This study aims to investigate the disparities in preoperative examination findings, postoperative HRQOL, and disease control status based on CRSwNP subtypes. (2) Methods: A retrospective analysis was conducted on 202 patients who underwent endoscopic sinus surgery for CRSwNP. The study assessed clinical characteristics, blood eosinophil and immunoglobulin E (IgE) levels, modified Lund-Kennedy and Lund-Mackay scores, and Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scores. HRQOL was evaluated using the Sino-nasal Outcome Test (SNOT-22) scores, and disease control status was assessed based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 guidelines. (3) Results: Of the 202 patients, Eosinophilic CRSwNP patients exhibited significantly higher preoperative peripheral blood eosinophil ratios and IgE levels, and JESREC scores (p < 0.05). Two years postoperatively, patients in the non-eosinophilic group showed significantly improved SNOT-22 scores compared to preoperative scores (p = 0.007). Notably, the proportion of patients with uncontrolled disease was significantly higher in the eosinophilic group (p = 0.035). Logistic regression analyses identified preoperative SNOT-22 scores and eosinophilic CRSwNP subtype as influential factors on disease control status (p < 0.05). (4) Conclusions: Patients with more severe preoperative symptoms and eosinophilic CRSwNP demonstrated poorer long-term treatment outcomes.

Endoscopic and Radiologic Central Compartment Disease as Predictors of Perennial Inhalant Allergen Sensitization in Chronic Rhinosinusitis.

Central compartment atopic disease (CCAD) is a recently described variant of chronic rhinosinusitis (CRS) strongly associated with atopy. The association between central compartment disease (CCD) and inhalant allergy is not well established in South-East Asia, where perennial allergic rhinitis is common. The primary objective was to evaluate endoscopic and radiologic CCD as predictors of perennial allergen sensitization in primary CRS. The secondary objective was to compare clinical characteristics of CCAD with other CRS subtypes (CRSwNP and CRSsNP). A retrospective study of consecutive patients with primary CRS who underwent endoscopic sinus surgery at our institution was performed. Allergen sensitization was confirmed by skin or serum testing. Endoscopy records and computed tomography scans of paranasal sinuses were reviewed for CCD. The diagnostic accuracy of endoscopic and radiologic CCD in predicting atopy was calculated. There were 104 patients (43 CCAD, 30 CRSwNP and 31 CRSsNP). Endoscopic CCD was significantly associated with aeroallergen sensitization (odds ratio (OR) 3.99, 95% confidence interval (CI) 1.65-9.67, P = 0.002). Endoscopic CCD predicted atopy with 57% sensitivity, 72% specificity, 69% positive predictive value and positive likelihood ratio of 2.05. Radiologic CCD was not associated with aeroallergen sensitization (OR 0.728, 95%CI 0.292-1.82, P = 0.496). There were more CCAD patients who reported hyposmia (86% vs 42%, P < 0.001) and had anosmia on olfactory testing than CRSsNP (65% vs 14%, P = 0.015). The prevalence of atopy was significantly higher in CCAD than CRSwNP and CRSsNP (70% vs 37% and 42%, P = 0.015 and P = 0.05, respectively). Median serum total immunoglobulin E was higher in CCAD (283 IU/ml) and CRSwNP (127 IU/ml) than CRSsNP (27 IU/ml, P = 0.006 and P = 0.042, respectively). Endoscopic CCD was a better predictor of inhalant allergy than radiologic CCD in primary CRS, in a locale of perennial allergic rhinitis.

Decoding chronic rhinosinusitis: A metabolomics-based approach.

Chronic rhinosinusitis (CRS) is a common and intractable disease in otorhinolaryngology, laying a heavy burden on healthcare systems. The worldwide researchers are making efforts to find solutions to this disease. Metabolomics has recently gained more and more traction, and might become a promising tool to unravel the complexity of CRS. This paper provides an overview of current studies on the metabolomics of various CRS subtypes. We conducted a comprehensive literature search in PubMed, Web of Science, EMBASE, Google Scholar, and Cochrane Library, up to May 25, 2023. Search strategies incorporated key terms such as "chronic rhinosinusitis" and "metabolomics" with relevant synonyms and MeSH terms. Titles and abstracts of 86 screened articles were assessed for relevance to CRS and metabolomics. Methodological robustness, data reliability, and relevance were considered for shortlisted articles. After the refined process, a total of 26 articles were included in this study and sorted out by research themes, methodology and pivotal discoveries. These included studies identified the metabolic pathways and markers related to the pathophysiology in each subtype of CRS. Metabolomics helps to shed light on the complexity of CRS. The mentioned findings highlight the importance of specific metabolic pathways and markers in understanding the pathophysiology of CRS. Despite that, challenges and future directions in metabolomics research for CRS would be worth being further explored.

Clinical and Radiological Characteristics of Central Compartment Atopic Disease in Korea

Background and Objectives Central compartment atopic disease (CCAD) has been studied with increasingly more importance as a distinct subtype of chronic rhinosinusitis with nasal polyp (CRSwNP). Studies have shown that CCAD in Western populations show a strong association with allergy and typical features of medial nasal structure and sinus involvement. The purpose of this study was to evaluate the clinical characteristics of CCAD and compare them to those of other subtypes of CRS in Korea.Subjects and Method A chart review was performed retrospectively at two tertiary rhinologic centers for patients who were treated with bilateral endoscopic sinus surgery for CRS with or without nasal polyp from January 2019 to December 2021. Patients were divided into three groups, namely CCAD, CRSwNP, and CRS without nasal polyps (CRSsNP), and demographics, clinical characteristics, and imaging data were compared among the three groups.Results A total of 150 patients were included in this study (50 patients in each group). CCAD showed similar nasal symptoms with CRSwNP, but higher rates of olfactory impairment than CRSsNP did. Allergy prevalence, serum total immunoglobulin E, and serum eosinophil were significantly higher in CCAD than in CRSwNP or CRSsNP. In CT scans of paranasal sinuses, CCAD showed significantly less haziness of maxillary sinus and higher ethmoid/maxillary score ratio than the other two groups. In addition, CT scans showed mucosal involvements of central compartment in CCAD.Conclusion CCAD has characteristic endoscopic and imaging findings, showing a high prevalence of allergy and a strong association with the markers of type 2 inflammation. Therefore, CCAD is a distinct disease of CRSwNP and its allergic etiology should be considered in the management of patients with CCAD phenotype.

Incidence Rates and Risk Ratios of Normal Tension Glaucoma in Patients with Chronic Rhinosinusitis: A Population-Based Longitudinal Follow-Up Study.

Several studies have investigated the association between chronic rhinosinusitis (CRS) and ophthalmological complications. However, it remains uncertain whether CRS is independently associated with the development of normal tension glaucoma (NTG). Therefore, this retrospective cohort study aimed to investigate the prospective association between CRS and the increased incidence and risk of NTG using a representative population-based dataset. The selection of both the CRS and comparison groups was meticulously conducted through the propensity scoring method. The incidence and risk ratios of NTG were measured using person-years at risk and a weighted Cox proportional hazards model. We enrolled 30,284 individuals without CRS (comparison group) and 15,142 individuals with CRS. The NTG incidence rates were 1.19 and 0.81 in the CRS and comparison groups, respectively. The CRS group showed a significantly increased risk of subsequent development for NTG (adjusted hazard ratio = 1.41, 95% confidence interval = 1.16-1.72), regardless of the CRS subtype. Additionally, the risk of developing NTG was relatively higher in the first 2 years after CRS diagnosis. Moreover, a subgroup analysis revealed a higher risk of NTG in elderly female individuals with CRS. The present findings underscore the importance of monitoring and managing NTG risk in individuals with CRS, especially in elderly female patients.

Integrative analysis of immune-related signature profiles in eosinophilic chronic rhinosinusitis with nasal polyposis.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of chronic rhinosinusitis (CRS) that is associated with the nasal cavity and sinus polyps, elevated levels of eosinophils, and dysregulated immune responses to environmental triggers. The underlying cause of ECRSwNP is not well understood, and few studies have focused on the unique features of this subtype of CRS. Our study integrated proteomic and transcriptomic data with multi-omic bioinformatics analyses. We collected nasal polyps from three ECRSwNP patients and three control patients and identified 360 differentially expressed (DE) proteins, including 119 upregulated and 241 downregulated proteins. Functional analyses revealed several significant associations with ECRSwNP, including focal adhesion, hypertrophic cardiomyopathy, and extracellular matrix (ECM)-receptor interactions. Additionally, a protein-protein interaction (PPI) network revealed seven hub proteins that may play crucial roles in the development of ECRSwNP. We also compared the proteomic data with publicly available transcriptomic data and identified a total of 1077 DE genes. Pathways enriched by the DE genes involved angiogenesis, positive regulation of cell motility, and immune responses. Furthermore, we investigated immune cell infiltration and identified biomarkers associated with eosinophil and M2 macrophage infiltration using CIBERSORT and Weighted Gene Correlation Network Analysis (WGCNA). Our results provide a more complete picture of the immune-related mechanisms underlying ECRSwNP, which could contribute to the development of more precise treatment strategies for this condition.

Induction of a type 2 inflammatory chronic rhinosinusitis in C57BL/6 mice

Background: Eosinophilic chronic rhinosinusitis (CRS) has been widely studied for its intractability and high recurrence rate. It can be divided into pure and mixed type 2 CRS subtypes. Mouse models that reflect pure type 2 inflammation of CRS are lacking. Objective: This study aims to establish a relatively pure type 2 CRS mouse model and compare it with 2 mixed type 2 CRS models. Methods: Three mouse CRS models were constructed: (1) aerosol ovalbumin (OVA) + aspergillus oryzae-derived protease (AP); (2) intranasal OVA + AP; (3) Intraperitoneal then intranasal OVA + AP (n = 10 per group). Nasal, lung symptoms, IgE, inflammatory cells, cytokines, and remodeling factors were evaluated. Results: Histological and micro-computed tomography showed inflammation, polyps, and opacification in all 3 experimental groups. The aerosol group had significantly increased local eosinophils and type 2 cytokines, while other types of cytokines showed no noticeable change. The nasal instillation groups also showed elevated other inflammatory factors and tissue polypoid changes were more pronounced. More severe pulmonary inflammation was observed with aerosol delivery. Conclusion: Aerosol inhalation mouse model is superior for studying nasal relatively pure type 2 inflammation and lower airway comorbidities.

Central Compartment Atopic Disease as a Pathophysiologically Distinct Subtype of Chronic Rhinosinusitis: A Scoping Review

Central compartment atopic disease (CCAD) is a distinct phenotype within chronic rhinosinusitis with nasal polyps (CRSwNP) with a pathophysiology that bridges the gap between allergy and CRSwNP, an association that was previously ambiguous. Understanding this endotype and its link to allergic disease is crucial for improved CCAD management. Using a systematic search and an independent dual-reviewer evaluation and data extraction process, this scoping review examines the clinical features, management options, and treatment outcomes of CCAD. Central compartment (CC) polypoid changes of the MT predominantly correlate with allergic rhinitis, increased septal inflammation, oblique MT orientation, and decreased nasal cavity opacification and Lund–Mackay scores compared to other CRSwNP subtypes. CCAD patients also exhibit higher rates of asthma, allergen sensitization, and hyposmia or anosmia. Surgical outcomes, including revision rate and SNOT-22 improvement, are favorable in CCAD as well. In conclusion, CCAD primarily affects atopic individuals and is managed using endoscopic sinus surgery combined with treating the underlying allergy. Continued research is needed to further refine understanding and develop optimal treatment strategies of this emerging CRS subtype.

Comprehensive analysis of mitophagy-related genes in diagnosis and heterogeneous endothelial cells in chronic rhinosinusitis: based on bulk and single-cell RNA sequencing data.

Background: Chronic rhinosinusitis (CRS) is a complex inflammatory disorder affecting the nasal and paranasal sinuses. Mitophagy, the process of selective mitochondrial degradation via autophagy, is crucial for maintaining cellular balance. However, the role of mitophagy in CRS is not well-studied. This research aims to examine the role of mitophagy-related genes (MRGs) in CRS, with a particular focus on the heterogeneity of endothelial cells (ECs). Methods: We employed both bulk and single-cell RNA sequencing data to investigate the role of MRGs in CRS. We compiled a combined database of 92 CRS samples and 35 healthy control samples from the Gene Expression Omnibus (GEO) database and we explored the differential expression of MRGs between them. A logistic regression model was built based on seven key genes identified through Random Forests and Support Vector Machines - Recursive Feature Elimination (SVM-RFE). Consensus cluster analysis was used to categorize CRS patients based on MRG expression patterns and weighted gene co-expression network analysis (WGCNA) was performed to find modules of highly correlated genes of the different clusters. Single-cell RNA sequencing data was utilized to analyze MRGs and EC heterogeneity in CRS. Results: Seven hub genes-SQSTM1, SRC, UBA52, MFN2, UBC, RPS27A, and ATG12-showed differential expression between two groups. A diagnostic model based on hub genes showed excellent prognostic accuracy. A strong positive correlation was found between the seven hub MRGs and resting dendritic cells, while a significant negative correlation was observed with mast cells and CD8+ T cells. CRS could be divided into two subclusters based on MRG expression patterns. WGCNA analysis identified modules of highly correlated genes of these two different subclusters. At the single-cell level, two types of venous ECs with different MRG scores were identified, suggesting their varying roles in CRS pathogenesis, especially in the non-eosinophilic CRS subtype. Conclusion: Our comprehensive study of CRS reveals the significant role of MRGs and underscores the heterogeneity of ECs. We highlighted the importance of Migration Inhibitory Factor (MIF) and TGFb pathways in mediating the effects of mitophagy, particularly the MIF. Overall, our findings enhance the understanding of mitophagy in CRS, providing a foundation for future research and potential therapeutic developments.

Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence

Objectives Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown. The breathing pattern assessment tool (BPAT) can identify BPD. Our objective was to thus investigate the prevalence of BPD, nasal airflow obstruction and measures of airway disease severity in CRS with (CRSwNP) and without nasal polyps (CRSsNP) in severe asthma. Methods We determined whether CRS status, peak nasal inspiratory flow (PNIF) or polyp disease increased BPD prevalence. Demographic factors, measures of airway function and breathlessness in relation to BPD status and CRS subtypes were also evaluated. Results 130 Patients were evaluated (n = 69 had BPD). The prevalence of BPD in CRS with severe asthma was 53.1%. There was no difference between BPD occurrence between CRSwNP and CRSsNP. The mean polyp grade and PNIF were not statistically different between the BPD and non-BPD group. The presence of nasal polyps did not increase breathlessness. Conclusions BPD and CRS are commonly co-associated. CRS status and nasal obstruction per se does not increase BPD prevalence.

Fungal and Bacterial Microbiome in Sinus Mucosa of Patients with and without Chronic Rhinosinusitis.

Dysbiosis of the sinonasal microbiome has been implicated in the pathogenesis of chronic rhinosinusitis (CRS). However, the mycobiome remains largely understudied, and microbial alterations associated with specific CRS subtypes have yet to be delineated. The objective of this study is to investigate the fungal and bacterial microbiome of sinus mucosa in CRS patients with and without nasal polyposis (CRSwNP and CRSsNP) versus healthy controls. Sinus mucosa was obtained from 92 patients (31 CRSsNP, 31 CRSwNP, and 30 controls) undergoing endoscopic sinus/skull base surgery. Data regarding demographics, Lund-MacKay scores, and histopathology were collected. Fungal and bacterial microbiome analysis was performed utilizing internal transcribed spacer amplicon and 16S rRNA sequencing. Beta diversity of the sinonasal mycobiome differed significantly between CRS and controls (p = 0.001) and between CRSwNP and controls (p = 0.049), but not between CRSwNP and CRSsNP (p = 0.32) nor between CRSsNP and controls (p = 0.06). With respect to the bacterial microbiome, significantly lower alpha diversity was observed between CRS and controls (p < 0.001), CRSwNP versus controls (p < 0.001), and CRSsNP versus controls (p < 0.001). Beta diversity was also significantly different at the genus level between CRSwNP and CRSsNP (p = 0.019), CRSwNP and controls (p = 0.002)), and CRSsNP and controls (p < 0.001). However, alpha and beta diversity did not differ significantly between CRS patients with/without eosinophils or correlate with Lund-MacKay scores. Differences in mycobiota diversity in CRS patients in comparison with controls suggest that alterations in the mycobiome may contribute to disease pathogenesis. Our findings also confirmed that diminished diversity among bacterial communities is associated with CRS and that significant differences are present in microbial composition between CRSwNP and CRSsNP. 3 Laryngoscope, 134:1054-1062, 2024.

Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report

BackgroundAbrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties.Case presentationA 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient’s clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus.ConclusionsIn cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.