FERMT1 contributes to the epithelial-mesenchymal transition of chronic rhinosinusitis with nasal polyps via PI3K/Akt signaling.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a key process of chronic rhinosinusitis with nasal polyps (CRSwNP). The molecular mechanism of EMT in CRSwNP remains unknown. In this study, we aimed to investigate the role of FERMT1 during the EMT process in CRSwNP. METHODS: Western blotting, qRT-PCR, and immunohistochemistry (IHC) were performed to examine the expression of related proteins and mRNAs. The migration ability of human nasal epithelial cells (HNEpCs) was evaluated with wound scratch assay. RNA sequencing was performed to investigate the downstream genes of FERMT1. The CRSwNP mouse model was established to study the effect of FERMT1 in vivo. RESULTS: We found that FERMT1 was increased in nasal polyp tissues and correlated with the symptom scores of CRSwNP patients. Knockdown of FERMT1 inhibited the EMT process and cell migration induced by TGF-ß1 through the PI3K/Akt pathway, and Akt inhibitor partially blocked the EMT induced by FERMT1 overexpression. In the CRSwNP mouse model, FERMT1 knockdown reduced nasal polyp formation and reversed the EMT process. CONCLUSIONS: Our data indicate that knockdown of FERMT1 inhibits migration and EMT process of HNEpCs via PI3K/Akt signaling pathway, suggesting that FERMT1 may be a novel and potential therapeutic target for CRSwNP treatment.

The role and mechanism of extracellular traps in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nose that affects millions of individuals worldwide. Recent research has introduced the concept of an immunologic endotype based on the pathological characteristics of CRS and the types of inflammatory cell infiltration. This endotype concept is conducive to understanding CRS pathology and guiding further targeted therapy. Eosinophils and neutrophils infiltrate different proportions in different CRS endotypes and release extracellular traps (ETs) as a response to the extracellular immune response. The mechanisms of formation and biological roles of ETs are complex. ETs can trap extracellular microorganisms and limit the range of inflammation to some extent; however, excessive and long-term ETs may be related to disease severity. This review summarises and explores the mechanism of ETs and the advances in CRS research and proposes new insights into the interaction between ETs and programmed cell death (including autophagy, pyroptosis, and necroptosis) in CRS, providing new ideas for the targeted therapy of CRS.

Real-world effectiveness of dupilumab in a European cohort of CRSwNP (CHRINOSOR).

BACKGROUND: Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score (NPS), symptom and quality of life scores in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary care centres. METHODOLOGY: NPS, SinoNasal Outcome Test (SNOT)-22 score, visual analogue scale (VAS) for total sinus symptoms, loss of smell (LoS) and nasal blockage (NB), and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline, 24 and 52 weeks of treatment of dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities and blood eosinophil counts (BEC). Treatment response was evaluated according to EUFOREA 2021 criteria. RESULTS: All patient outcomes improved at 24 and 52 weeks of treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, NSAID exacerbated respiratory disease (NERD), allergy or baseline BEC. 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks respectively. 54.4% and 68.2% reached all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks respectively. CONCLUSIONS: Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks of treatment. Favourable treatment response was independent of the number of sinus surgery procedures, major comorbidities or baseline systemic levels of type 2 inflammation.

Efficacy of Clarithromycin Combined with Fluticasone Propionate on Nasal Function, Nasal Mucociliary Transport Function, and Serum Inflammatory Markers in Chronic Rhinosinusitis Patients After Functional Endoscopic Sinus Surgery.

Objective: This study aims to assess the efficacy of clarithromycin (CAM) combined with fluticasone propionate (FP) in patients with chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS), focusing on nasal function, nasal mucociliary transport (MCT) function, and serum inflammatory markers. Methods: The control group (n = 48) was treated with FESS alone, while the study group (n = 48) was treated with FESS plus CAM combined with FP. The clinical effects, symptom scores, nasal function, nasal MCT function, serum inflammatory marker levels, and the occurrence of adverse reactions were compared. Results: The total efficacy rate of the study group (95.83%) was significantly higher than that of the control group (83.33%). After treatment, the study group showed lower symptom scores for nasal congestion, runny nose, sneezing and dizziness, and headache compared to those in the control group. The study group also had lower nasal airway resistance, shorter distance from the minimal cross-sectional area to the nostril, and lower T&T olfactory scores. In contrast, their nasal cavity volume and minimal cross-sectional area were higher than those of the control group. Additionally, the nasal mucociliary clearance and MCT rates were higher in the study group. Serum levels of interleukin-6, interleukin-8, tumor necrosis factor-α, and procalcitonin were significantly lower in the study group compared to the control group (all P < .05). Conclusion: The use of CAM combined with FP in patients after FESS for CRS is effective, leading to the relief of clinical symptoms, improvement of nasal function, enhancement of MCT function, and reduction of inflammatory response, without increasing the incidence of adverse reactions.

Causal Effects of Gastroesophageal Reflux on Chronic Rhinosinusitis: A Bidirectional Two-Sample Mendelian Randomization Study.

INTRODUCTION: Observational studies have shown a bidirectional association between gastroesophageal reflux (GER) and chronic rhinosinusitis (CRS) or chronic rhinitis (CR), but it is not clear whether this association is causal. OBJECTIVES: This study was to investigate the causality between GER and CRS or CR using bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Using pooled data from large genome-wide association studies (GWAS), genetic loci independently associated with GER, CRS and CR in populations of European and American ancestry were selected as instrumental variables (IVs). The inverse variance weighted (IVW) method was used to analyse the random effects model of MR, and the odds ratio (OR) was used as the evaluation index to explore the bidirectional causality between GER and CRS or CR. Single nucleotide polymorphism (SNP) outliers were detected using MR-pleiotropy Residual Sum and Outliers (MR-PRESSO). The MR-Egger intercept test examined the horizontal pleiotropy of SNPs. The "leave-one-out" sensitivity analysis examined whether MR results were affected by a single SNP. RESULTS: The main results of IVW showed that GER increased the risk of CRS (OR = 1.3795, 95% CI = 1.188-1.603, p < 0.0500) and CR (OR = 1.3941, 95% CI = 1.1671-1.6652, p < 0.0500). The obtained SNPs as IVs for GER, CRS and CR had no significant horizontal pleiotropy, heterogeneity or bias. Regarding the reverse directions, no notable associations could be found. CONCLUSION: This MR analysis revealed that genetically predicted GER had a causal effect on an increased risk of CRS or CR, but not vice versa. These results have great implications for the management of CRS (especially for refractory CRS) or CR in clinical practice.

Investigation and Characterization of the RAS/RAF/MEK/ERK Pathway and Other Signaling Pathways in Chronic Sinusitis with Nasal Polyps.

BACKGROUND: The clinical outcomes of drug treatments and surgical interventions for chronic sinusitis with nasal polyps (CRSwNPs) are suboptimal, and the high recurrence rate remains a significant challenge in clinical practice. Targeted therapies such as biologics provide new perspectives and directions for treating CRSwNP. SUMMARY: With the continuous investigation of signaling pathways, RAS/RAF/MEK/ERK signaling pathway and other signaling pathways including Hippo, JAK-STAT, Wnt, TGF-ß, PI3K, Notch, and NF-κB were confirmed to play an important role in the progression of CRSwNP. Among them, the abnormality of RAS/RAF/MEK/ERK signaling pathway is accompanied by the abnormality of this apoptotic component, which may provide new research directions for targeting the components of signaling pathways to mediate apoptosis. KEY MESSAGES: Abnormalities in signaling pathways are particularly important in studying the pathogenesis and treatment of CRSwNP. Therefore, this review summarizes the ongoing investigation and characterization of RAS/RAF/MEK/ERK signaling pathway and other signaling pathways in CRSwNP, which provides constructive ideas and directions for improving the treatment of CRSwNP.

Effect of hot saline irrigation on the operative field during endoscopic sinus surgery: a randomized controlled trial.

BACKGROUND: Control of bleeding is very important during endoscopic sinus surgery. Saline heated up to 50 °C causes dilatation of vessels and edema without nasal mucosa necrosis. It also promotes the clotting cascade so helps in having a bloodless procedure. METHODS AND MATERIALS: This randomized controlled trial was conducted on 60 patients divided into two groups (30 each). Group A was the interventional group in which patients were irrigated with saline of 50 °C during surgery. Group B was the control group where room-temperature saline was used. The operative field was assessed using the Boezaart score, duration of surgery, and bleeding in ml. RESULTS: The Boezaart score in group A came out to be 2.23 ± 0.72 whereas it was 3.43 ± 0.72 in group B. Most of the patients who were in the interventional group had their surgery completed within 60 min with comparatively less bleeding (mean bleeding = 221.83 ml). Patients of the control group had increased duration of surgery mostly and bleeding (mean = 265.67 ml). Our study showed a strong correlation amongst the Boezaart score, duration of surgery, and bleeding in ml with a p value of < 0.001 where all three variables significantly improved in the interventional group due to a good operative field provided by warm saline heated up to 50 °C. CONCLUSION: Normal saline heated up to 50 °C is a cost-effective way to achieve a bloodless operative field during endoscopic sinus surgery. Reduced bleeding also decreases the duration of surgery.

Causal Relationship Between Gastroesophageal Reflux Disease and the Risk of Chronic Rhinosinusitis: Insights from Multivariable and Mediation Mendelian Randomization Analysis.

Background: Previous studies have shown an association between chronic rhinosinusitis (CRS) and gastroesophageal reflux disease (GERD). However, the findings of these studies are controversial, and evaluating this association could help in the treatment of CRS. Thus, we aimed to clarify the relationship between GERD and CRS. Methods: We conducted a Mendelian randomization (MR) study. Pooled data on CRS, GERD, and their associated risk factors were extracted from large genome-wide association studies. Independent single-nucleotide polymorphisms were rigorously screened as instrumental variables. Causal associations between GERD and CRS were assessed, and mediation analyses were performed using multivariate and 2-step MR. Asthma served as a mediator because of its association with both CRS and GERD. Sensitivity tests were also performed. Results: MR analysis showed that genetically predicted GERD was associated with an increased risk of CRS (P < .001). Multivariate MR analysis showed that the effect of GERD on CRS was relatively independent. Mediation analysis showed that asthma mediated the association with a mediation effect of 21.07% (95% CI, 2.70%-40.18%). Sensitivity analyses did not reveal any significant effects of pleiotropy and heterogeneity. Conclusions: We found a causal relationship between genetically predicted GERD and an increase in the risk of CRS. As a mediator, asthma contributed to the effect of GERD on CRS. This study provides high-quality causal evidence for the prevention of CRS.

Chronic Rhinosinusitis Management: A Narrative Review Comparing Interventional Treatment With Osteopathic Manipulation.

Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the nasal cavity and paranasal sinuses. Diagnosis of CRS typically requires two of the following four symptoms to persist for a minimum of 12 weeks: anterior or posterior nasal drainage, hyposmia or anosmia, facial pain or pressure, or nasal obstruction. Additionally, diagnosis necessitates the visualization of inflammation on physical examination or diagnostic imaging. This review aims to compare the outcomes of CRS patients who undergo interventional treatment via functional endoscopic sinus surgery (FESS) to those who opt for noninterventional treatment with osteopathic manipulation. FESS is not the sole interventional method utilized for CRS, but it is the focus of this review since it is the gold standard surgical treatment, encompassing a variety of techniques. Although there is limited literature discussing the use of osteopathic manipulative treatment (OMT) to remedy CRS, some evidence indicates OMT can alleviate symptoms for individuals seeking non-surgical alternatives. Moreover, osteopathic manipulation for CRS may be beneficial for patients unresponsive to previous medical or surgical management. Pharmacologic treatment is typically the initial approach to CRS and is discussed briefly herein, though it largely falls beyond the scope of this review.

Identification of Potential Feature Genes in CRSwNP Using Bioinformatics Analysis and Machine Learning Strategies.

Purpose: The pathogenesis of CRSwNP is complex and not yet fully explored, so we aimed to identify the pivotal hub genes and associated pathways of CRSwNP, to facilitate the detection of novel diagnostic or therapeutic targets. Methods: Utilizing two CRSwNP sequencing datasets from GEO, differential expression gene analysis, WGCNA, and three machine learning methods (LASSO, RF and SVM-RFE) were applied to screen for hub genes. A diagnostic model was then formulated utilizing hub genes, and the AUC was generated to evaluate the performance of the prognostic model and candidate genes. Hub genes were validated through the validation set and qPCR performed on normal mice and CRSwNP mouse model. Lastly, the ssGSEA algorithm was employed to assess the differences in immune infiltration levels. Results: A total of 239 DEGs were identified, with 170 upregulated and 69 downregulated in CRSwNP. Enrichment analysis revealed that these DEGs were primarily enriched in pathways related to nucleocytoplasmic transport and HIF-1 signaling pathway. Data yielded by WGCNA analysis contained 183 DEGs. The application of three machine learning algorithms identified 11 hub genes. Following concurrent validation analysis with the validation set and qPCR performed after establishing the mouse model confirmed the overexpression of BTBD10, ERAP1, GIPC1, and PEX6 in CRSwNP. The examination of immune cell infiltration suggested that the infiltration rate of type 2 T helper cell and memory B cell experienced a decline in the CRSwNP group. Conversely, the infiltration rates of Immature dendritic cell and Effector memory CD8 T cell were positive correlation. Conclusion: This study successfully identified and validated BTBD10, ERAP1, GIPC1, and PEX6 as potential novel diagnostic or therapeutic targets for CRSwNP, which offers a fresh perspective and a theoretical foundation for the diagnostic prediction and therapeutic approach to CRSwNP.

Effect of Dupilumab on Radiological Remission in Patients with Chronic Rhinosinusitis with Nasal Polyp: A One Step Forward Toward Clinical Remission.

Background and Objectives:  While achieving complete radiological improvement in patients with nasal polyps is often observed following surgical resection, the impact of biologic therapy, specifically dupilumab, on polyp size is an area of great interest. The objective of this study was to assess the effect of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by assessing nasal polyps using the computed tomography (CT) staging system, Lund-Mackay score (LMS). Methods:  A two-year prospective cohort study was conducted on 29 patients diagnosed with CRSwNP and asthma and eligible for dupilumab as an add-on therapy. The study involved comprehensive assessments of patients before biologic initiation and after the study. These assessments included clinical, laboratory, and radiological evaluations. Results: Dupilumab treatment reduces LMS across sinuses (p<0.001) and improves nasal obstruction (p=0.001). Blood eosinophil count (BEC) predicts persistent sinus obstruction, doubling the likelihood per unit increase (odds ratio: 1.67, p=0.02). BEC levels identify persistent nasal obstruction (AUC: 76%, p=0.04), with a cutoff point above 255.5 cells per microliter, revealing a sensitivity of 100% and a specificity of 42%. The probability of persistent nasal obstruction at the 20th month is 55%, regardless of prior nasal polyp surgery (p=0.41). Conclusion: Dupilumab led to significant radiological improvements in patients with CRSwNP, demonstrating a potential role of radiological remission, irrespective of prior nasal polyp surgery. Additionally, BEC levels may guide the likelihood of persistent nasal obstruction.

Assessing the Use of Patient-Reported Outcome Measures in the Routine Clinical Care of Chronic Rhinosinusitis Patients: A Canadian Perspective.

IMPORTANCE: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the paranasal sinuses with significant quality of life impairments. There is a need to implement outcome-based metrics to evaluate the outcomes of CRS treatment with endoscopic sinus surgery or biologics. OBJECTIVE: We aimed to understand Canadian otolaryngologists' opinions on patient-related outcome measures (PROM) for CRS and identify potential barriers to implementation. DESIGN: Qualitative research. SETTING AND PARTICIPANTS: A cross-sectional survey was distributed via the Canadian Society of Otolaryngology-Head and Neck Surgery and direct emailing. MEASURES: Participants' demographics, practice information, and opinions on PROM were collected. RESULTS: Of 346 (23%) Canadian otolaryngologists, 78 responded to the survey (26 rhinology fellowship-trained, 51 non-fellowship-trained, and 1 missing data). Thirty-eight responded that they collect PROM (69% with fellowship-trained, 39% non-fellowship-trained, P = .029). Regarding opinions on PROM, 74% of respondents agreed that it helps patients report their symptoms, 42% agreed that it improves the efficiency of the patient encounter, 54% agreed that it is easy for patients to understand, 62% agreed that it improves management and monitoring of clinical outcomes, and 71% disagreed that PROM is not helpful. Fellowship-trained otolaryngologists were 4 times more likely to agree that PROM improves management and monitoring of clinical outcomes (P = .014), and no other differences in opinions were significant. The most-frequently-identified barriers to PROM usage were lack of time for 67% of respondents, difficulty integrating into clinical workflow for 64%, and lack of integration into the electronic medical record for 47%. If these barriers were addressed, 86% of respondents said they would use PROM in their practice. CONCLUSIONS AND RELEVANCE: Despite the low uptake of PROM among otolaryngologists without rhinology fellowship, opinions were generally favorable. We identified barriers that, if addressed, may increase their use in clinical practice. As resource-limited therapies such as biologics become more prevalent in CRS management, PROM may find more applications in shared clinical decision making.

Upper Airway Comorbidities of Asthma.

Asthma, characterized as a chronic heterogeneous airway disease, often presents with common comorbid conditions. The concept of 'one-airway-one-disease' was coined, emphasizing the connection between asthma and upper airway comorbidities (UACs) such as allergic or non-allergic rhinitis, chronic rhinosinusitis with or without nasal polyps, and aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease more than 20 years ago. Since then, numerous studies demonstrate that UACs are closely related and affect asthma phenotypes. Recognizing and managing these UACs are crucial aspects of comprehensive asthma care. Addressing these conditions as part of asthma treatment can lead to better control of symptoms, improved lung function and the quality of life. Moreover, it is important to explore the field of respiratory biologics that represent the latest advancements in medical treatment options for asthma patients with UACs.

Predictive value of tooth and sinuses radiological characteristics in managing odontogenic sinusitis of endodontic origin.

BACKGROUND: One of the most common causes of bacterial odontogenic sinusitis (ODS) is endodontic disease with periapical lesions (PAL). Referrals between otolaryngologists and dental specialists are indispensable for proper diagnosis and treatment. If the disease does not resolve after medical and root-canal treatment (RCT), tooth extraction, endoscopic sinus surgery (ESS) or both are the ways of management.The aim was to clarify the predictive value of disease's radiological characteristics for the further surgical intervention. METHODOLOGY: 68 symptomatic patients evaluated by an otolaryngologist and dental specialist were included to this prospective observational cohort study. Patients who failed medical treatment of sinusitis (intranasal steroids, saline rinses and antibiotics) and RCT were treated either with ESS, tooth extraction or both at the same time. RESULTS: 87% of patients required surgical intervention. 12% improved after tooth extraction alone, 47% after ESS and 31% required both procedures. The degree of maxillary sinus' (MS) opacification was not correlated with the need of invasive procedures implementation, as opposed to ostiomeatal complex' patency (p<0.001). Cortical bone destruction towards the MS and multiple tooth roots involvement suggested ODS resolution only after combined surgical approach (p=0.041). CONCLUSIONS: Radiological characteristics of causative tooth and patency of ostiomeatal unit correlate with the evolution of ODS and need for either ESS and/or tooth extraction. Patients with multiple roots affected, shorter distance to the MS floor and PAL's with visible bone destruction may require tooth extraction and ESS to resolve ODS completely. CLINICAL IMPLICATIONS: Radiological data may help in earlier diagnosis and treatment of ODS with PALs for both otolaryngologists and dental specialists.

Reduced Sense of Smell in Patients with Severe Chronic Rhinosinusitis and its Implications for Diagnosis and Management: A Narrative Review.

Reduced sense of smell is a common symptom in patients with chronic rhinosinusitis (CRS). Although it is often under-diagnosed by healthcare providers, reduced sense of smell can have a substantial negative impact on patient's quality of life as measured by health-related quality of life (HRQoL) assessments and patient-reported outcomes. This narrative review describes current smell loss diagnosis and management guidelines in CRS, and the relationship between smell loss and CRS. Reduced sense of smell can be an indication of CRS disease severity in patients with (CRSwNP) and without nasal polyps (CRSsNP), and recovery of smell can be an indicator of successful CRS treatment. The current first-line therapeutic options for smell loss are intranasal corticosteroids and nasal irrigation, and second-line therapeutic options include systemic steroids and surgery. Shared decision-making between patient, caregiver, and healthcare provider is important when choosing the most appropriate CRS treatment option. Emerging biologic therapies that target type 2 inflammation signaling pathways, such as dupilumab, omalizumab, and mepolizumab, have been shown to improve smell and taste in randomized controlled trials of patients with CRSwNP.A graphical abstract and video abstract are available with this article.

Chronic rhinosinusitis (CRS) is an inflammatory condition often associated with a loss of smell and taste. Patients with CRS and a loss of smell often rate their quality of life as poor and are more likely to also suffer from depression and anxiety than patients without smell loss. Patients with severe smell loss are also more likely to have increased severity of CRS disease by other measures. Standard treatments for smell loss include topical steroids, corticosteroids absorbed into the whole body system (systemic), and/or sinonasal surgery, but the effects may not last, and patients may experience side effects when they use repeated short bursts or long-term treatment with systemic corticosteroids. A newer treatment option for CRS is biologic therapy, which targets the immunologic pathways associated with inflammation. Biologic therapies have been shown to be effective in the treatment of CRS with nasal polyps including improvement in sense of smell. Here, we review the most common diagnostic tests and treatment options for CRS-associated smell loss and show how severity of smell loss is linked to severity of CRS. Supplementary file1 (MP4 60193 kb).

Quantifying corticosteroid burden in chronic rhinosinusitis with nasal polyps: A retrospective US database study.

BACKGROUND: Real-world burden data on systemic corticosteroid (SCS) use in chronic rhinosinusitis with nasal polyps (CRSwNP) are limited. OBJECTIVE: This study's objective was to describe the real-world burden of SCS in CRSwNP. METHODS: This retrospective cohort study included commercial/Medicare Advantage with Part D health plan members from the Optum Research Database with a first medical claim (index) for CRSwNP (January 2015 to July 2020). Primary outcomes/variables included SCS use, healthcare resource utilization (HCRU) and costs during the 12-month follow-up period. Outcomes were analyzed overall (N=21,172) and stratified by baseline comorbid asthma status and sinus surgeries during follow-up. RESULTS: Overall, 64.7% and 41.0% of patients used all-cause and CRSwNP-related SCS respectively, and 36.0% had ≥1 oral corticosteroid (OCS) burst (≥20 mg for 3-28 days); SCS use was higher in patients with asthma and those with a NP-related surgery (1, 2, ≥3) versus without. The mean (SD) all-cause cumulative OCS dose was 303.3 (675.0) mg/year and 23.5% had a cumulative annual dose ≥400 mg; these values were higher (p<0.001) in patients with versus without comorbid asthma (514.9 [956.1] vs. 247.5 [567.0]; 36.9% vs. 19.9%). All-cause and CRSwNP HCRU and costs increased with increasing number of surgeries; mean (SD) all-cause total medical costs were $14,472 (38,915), $26,909 (40,800), $29,816 (41,677), and $31,558 (37,143) with 0, 1, 2, and ≥3 surgeries, respectively. CONCLUSION: These data highlight the significant burden of SCS use in CRSwNP, particularly in patients with comorbid asthma and suggest a need to reduce SCS exposure.

Sinus Pathophysiology of Odontogenic Sinusitis.

Odontogenic sinusitis (ODS) is distinct pathophysiologically from nonodontogenic rhinosinusitis. ODS refers to bacterial sinusitis secondary to infectious dental pathology or procedures. Sinus mucosal inflammation in ODS is severe, mostly lymphocytic, and is driven by Th1 or Th17 inflammation. The sinus's respiratory mucosa maintains its structure and function, contrary to significant epithelial barrier dysfunction seen in some forms of chronic rhinosinusitis. The severe inflammation and infection of ODS help explain certain unique clinical features like foul-smelling drainage, frequent purulence, and papillary edema on nasal endoscopy. Appreciating the unique pathophysiology of ODS facilitates its recognition and selection of optimal interventions.

Correlation between Lund-Mackay computed tomography score and subjective symptoms in Chinese patients with nasal polyps.

BACKGROUND: The association between objective imaging findings and subjective symptoms remains undefined. AIMS: To investigate the correlation between objective imaging findings and symptom severity in the overall chronic rhinosinusitis with nasal polyps (CRSwNP) population as well as its subendotypes according to the eosinophilic inflammation. METHODS: Patients with CRSwNP undergoing endoscopic sinus surgery were included. All participants completed the Sino-Nasal Outcome Test (SNOT-22) questionnaire. The Lund-Mackay (LM) CT scores was also obtained. Spearman correlation analysis was performed to evaluate the correlation between CT scores and SNOT-22 scores. RESULTS: Forty-four non-eosinophilic CRSwNP(neCRSwNP) and 93 eosinophilic CRSwNP (eCRSwNP) patients were recruited. There was significant association between LM total score and nasal subdomain of SNOT-22 in the overall CRSwNP patients. The nasal symptom of SNOT-22 was significantly associated with maxillary, frontal, sphenoid, anterior drainage, and posterior drainage in all CRSwNP patients. In eCRSwNP and neCRSwNP patients, the sense of smell/taste was associated with sphenoid and posterior drainage. Thick nasal discharge was positively correlated with maxillary, frontal, and anterior drainage only in eCRSwNP patients. CONCLUSIONS: The high score of sphenoid and posterior drainage may suggest the occurrence of loss of sense of smell/taste, while high score of maxillary sinus may indicate suffering from thick nasal discharge in eCRSwNP patients.

Biologics in Chronic Rhinosinusitis: Current and Emerging.

Chronic rhinosinusitis (CRS) is categorized phenotypically into CRS with and without nasal polyps (CRSwNP, CRSsNP). Endotyping categorizes the disease based on immune cell activity and inflammatory mechanisms into Type 1, Type 2, and Type 3. The Type 2 endotype is the most researched and associated with asthma, atopic disease, and severe CRSwNP. For patients with poorly controlled CRSwNP, there are 3 approved biologic treatments: omalizumab, dupilumab, and mepolizumab. Many other biologics are being tested in Type 2, non-Type 2, and mixed endotypes in CRSwNP and CRSsNP. These studies will play a significant role in shaping the future of CRS management.

High M2/M1 Macrophage Ratio Observed in Nasal Polyps Formed in Allergic Fungal Rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) shares similarities with eosinophilic chronic rhinosinusitis (ECRS), both characterized by intractable nasal polyps. The key distinction lies in the presence of fungal infection within the nasal cavity. While ECRS nasal polyps are known for significant infiltration of M2 macrophages and eosinophils, as well as an increase in high endothelial venule (HEV)-like vessels, these features are less commonly reported in AFRS. This study compared clinicopathological findings between AFRS (n=10), ECRS (n=12), and non-ECRS (n=10) patients' nasal polyps using immunohistochemical analysis for CD163 and CD68 to assess the M2/M1 macrophage ratio, and peripheral lymph node addressin (PNAd) and CD34 to evaluate the proportion of HEV-like vessels. AFRS showed a significantly higher number of CD163-positive M2 macrophages and an increased M2/M1 ratio compared with ECRS. However, the percentage of HEV-like vessels and the number of eosinophils infiltrating the nasal polyps were similar in both AFRS and ECRS. The observed increase in M2 macrophages in AFRS nasal polyps is presumed to be induced by fungal infection in the nasal cavity, in comparison with ECRS. These results highlight the distinctive immunological profiles of AFRS and ECRS, emphasizing the role of macrophage polarization in their pathogenesis.