Nasal Polyps Patients Research Articles

The expression of MUC5AC in patients with rhinosinusitis: A systematic review and meta-analysis.

To understand the connection between Muc5AC expression and the likelihood of rhinosinusitis, with the goal of providing insights into its prospective use as a biomarker. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies up to November 2023 to conduct a literature review. After screening and quality assessment, eligible studies meeting the criteria were included. Muc5AC expression and rhinosinusitis association was analyzed by STATA 14.0. Including weighted mean difference and 95% confidence interval, were reported. The meta-analysis included 16 studies with 1448 rhinosinusitis patients. MUC5AC expression was significantly up-regulated in both chronic rhinosinusitis with nasal polyps (CRSwNP; WMD: 0.52; 95% CI: 0.41-0.63) and chronic rhinosinusitis without nasal polyps (CRSsNP; WMD: 0.42; 95% CI: 0.28-0.56) patients compared to controls. IHC positive area analysis corroborated these findings, with elevated MUC5AC levels in CRSwNP (WMD: 25.61; 95% CI: 22.41-28.81) and CRSsNP (WMD: 39.74; 95% CI: 25.6-53.88) patients. Subgroup analysis based on tissue type (nasal tissue fluid and sinus mucosa) consistently supported the overall results. Our meta-analysis robustly demonstrates a significant association between elevated MUC5AC expression and rhinosinusitis risk. This finding underscores the potential of MUC5AC as a molecular marker, providing valuable insights for future research and potential therapeutic interventions in rhinosinusitis management. CRD42024518932.

Cost-utility and clinical outcome analysis of surgery or oral corticosteroids treatment in patients with chronic rhinosinusitis with nasal polyps

Background: Surgery and oral corticosteroids are recommended therapies for chronic rhinosinusitis with nasal polyps (CRSwNP) patients who are nonresponsive to intranasal corticosteroid treatment. Objective: This study aimed to compare the effectiveness of these 2 treatments in terms of improving sinus-related symptoms, enhancing quality of life, and economic costs and duration costs. Methods: This prospective study enrolled CRSwNP patients. All participants were instructed to complete the 22-item Sino-Nasal Outcome Test (SNOT-22), visual analog scale, and 36-item short-form (SF-36) questionnaire at baseline and 3 months after treatment. The nasal polyp score (NPS) was assessed via endoscopic examination. Additionally, patients were requested to maintain records of economic direct costs, other indirect costs, and duration costs throughout the 3-month period and to report them during each follow-up visit. Results: A total of 40 patients who underwent surgery or received oral corticosteroids were enrolled in this study. After 3 months of treatment, significant improvements were observed between baseline and 3 months after treatment in the NPS, total SNOT-22 score, and nasal congestion, runny nose, facial pain, olfactory function, and overall symptoms measured. Only headache and sleep order were improved in the surgery group. Both physical functioning and general health, as measured by the SF-36, improved after both treatments, and the role-physical, bodily pain, and social functioning domains of the SF-36 improved only in the surgery group. The changes in the NPS, nasal congestion, runny nose, olfactory function, and sleep disorders in the surgery group were greater than those in the oral corticosteroid group (P values = 0.0003, 0.0092, 0.0258, 0.0284, and 0.0164, respectively). Changes in the total SNOT-22 score and SF-36 subscores were not different between the 2 treatment groups. The direct economic costs and duration costs of surgical treatment were 4.5 times and 17.0 times higher, respectively, than those of oral corticosteroid treatment. Conclusions: Both surgical and oral corticosteroid treatments effectively improved clinical symptoms and quality of life in patients with CRSwNP. Patients who underwent surgery exhibited greater improvements in sinus-related symptoms. Nevertheless, oral corticosteroid treatment presented notable advantages in terms of economic cost and duration cost of disease-related care.

Differential Nasal Recolonization and Microbial Profiles in Chronic Rhinosinusitis With Nasal Polyps Patients After Endoscopic Sinus Surgery or Dupilumab Treatment: A Prospective Observational Study.

The role of microbial profiles in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) pathogenesis is increasingly recognised, with microbial imbalances perpetuating inflammation. We performed this study to associate the different nasal microbiological profile changes with the response to surgical or monoclonal treatment. This prospective observational study evaluated changes in the nasal microbial profiles of 44 patients (22 dupilumab, 22 surgery) over 6 months. Clinical assessments were performed at baseline and follow-ups, including Sino-Nasal Outcome Test-22 (SNOT-22) scores and Sniffin Sticks-Identification (SS-I) olfactory testing. Microbial profiling of nasal swabs was carried out by microbial culture and subsequent molecular identification by Polymerase chain reaction (PCR) and sequencing. Baseline characteristics of 44 patients (22 dupilumab, 22 surgery) enrolled in this study were similar between groups. In the dupilumab group, Staphylococcus epidermidis prevalence rose from 37.03% to 59.25%, while Pseudomonas aeruginosa was eradicated. Moreover, dupilumab stabilised Staphylococcus aureus at 63.64%, while its prevalence increased in the surgery group (from 22.72% to 50%). When bacterial groups were associated with clinical scores, P. aeruginosa carriers had worse SNOT-22 (21.00 ± 1.41) and SS-I (5.50 ± 0.71) scores. Instead, S. epidermidis-colonised patients exhibited significantly lower mean SNOT-22 (15.39 ± 8.54) and greater SS-I scores (8.39 ± 3.77). The best outcomes were found in the subgroup of S. epidermidis carriers undergoing the dupilumab treatment. The two treatments modulated the microbial profiles differently, and, most importantly, clinical responses might depend on the association between treatment and the dominant bacterial species colonising the nasal cavity. Further investigation into microbial-restorative strategies could enhance outcomes for better treatment of CRS.

Assessing adequacy of surgical extent in CRSwNP: The Completion of Surgery Index.

Endoscopic sinus surgery (ESS) maximized for topical steroid irrigations is highly effective for polyp disease. As extent and completeness of ESS varies widely by situation and practitioner, it is important to understand when revision surgery is appropriate, particularly in the era of biologic treatments. A Completion of Surgery Index (CoSI) was developed to assess operative changes in polyp patients using pre- and postoperative computed tomography scans. The CoSI was then applied and tested in a cohort of consecutive chronic rhinosinusitis with nasal polyps (CRSwNP) patients, and examined within the context of quality-of-life improvements. The CoSI assesses surgical extent on a scale of 0-100, with 100 representing the highest possible degree of surgical completeness. Among 100 consecutive CRSwNP patients undergoing ESS in 2021 with postoperative topical steroid irrigations, including 75 revision surgeries, SNOT-22 scores improved at 6months postoperatively, with durable and consistent improvement at 24months (p<0.001). Preoperative CoSI scores in revision surgery patients were 49.4±26.0, improving to 91.0±8.1 postoperatively. SNOT-22 scores for primary ESS patients and patients with a preoperative CoSI score of less than 70 improved by 26.4 and 28.1 points, respectively, in contrast to patients with a preoperative CoSI of 70 or greater (14.1 points, p=0.029). It is important to define extent of surgery in CRSwNP to stratify postsurgical patients based on likelihood to benefit from revision surgery or alternative medications. The CoSI can be utilized to identify patients who are likely to improve significantly with revision surgical intervention.

Risk factors investigation for different outcomes between unilateral and bilateral chronic rhinosinusitis with nasal polyps patients.

Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. Demographic information, tissue and blood cells, endoscopic scores, Lund-Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control-related symptoms at follow-up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases.

Rheumatoid Arthritis Exacerbates Eosinophilic Inflammation Contributing to Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.

To assess the impact of rheumatoid arthritis (RA) on histopathological features and the risk of postoperative recurrence in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. A retrospective cohort study of CRSwNP patients who underwent functional endoscopic sinus surgery was performed. Patients were followed up for more than two years, and classified into RA and Non-RA groups, recurrent and non-recurrent groups. The influence of RA on histopathological features and the risk of CRSwNP recurrence was explored. A total of 517 CRSwNP patients were finally recruited, including 78 RA patients. The RA group exhibited a higher recurrence rate, tissue eosinophil counts and percentages compared to the non-RA group (P < 0.05). Tissue eosinophil count and percentage, and the prevalence of allergic rhinitis were significantly higher in the recurrent group in compared to the non-recurrent group (P < 0.05). Multivariate logistic regression analysis identified tissue eosinophil count and percentage, RA, and allergic rhinitis as significant predictors of increased recurrence risk (P < 0.05). Both adjusted and unadjusted models affirmed RA as an independent risk factor for CRSwNP postoperative recurrence (P < 0.05). Kaplan-Meier curves further indicated a higher recurrence risk in CRSwNP patients with RA than those without (P < 0.05). Our findings suggest that RA significantly exacerbates tissue eosinophilic inflammation and independently heightens the risk of postoperative recurrence in CRSwNP patients. These insights underscore the need for tailored therapeutic strategies addressing the complex interplay between CRSwNP and RA to mitigate recurrence risks and improve clinical outcomes.

Aspirin hypersensitivity diagnostic index (AHDI): Invitro test for diagnosing of N-ERD based on urinary 15-oxo-ETE and LTE4 excretion.

15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E4 (LTE4) and assessed their diagnostic value to identify patients with N-ERD. The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE4 excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested. Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE4-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%. We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.

NRP1 antagonism as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis.

Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP). Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real-time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model. NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)-1β, IL-6, IL-8, and IL-33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells. These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis.

Rare presence and function of neuroendocrine cells in the nasal mucosa.

There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers CHGA and ASCL1 was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. In vitro, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.

Inflammatory Profile of Chronic Rhinosinusitis With Nasal Polyp Patients in Brazil: Multicenter Study.

To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. Multicenter cross-sectional study involving 15 centers representing different regions of Brazil. Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund-Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund-Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF-alpha and significantly higher concentrations of IFN-gamma, CCL11/Eotaxin, CCL24/Eotaxin-2/MPIF-2, and CCL26/Eotaxin-3 versus the control group (Kruskal-Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann-Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL-6 and IL-33 (Mann-Whitney test). According to ROC curve analysis the best cut-off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund-Mackay score (Mann-Whitney test). CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut-off in nasal polyps.

Artificial intelligence for automatic detection and segmentation of nasal polyposis: a pilot study.

Accurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos. Recorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation. The YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%. The study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods.

Enhanced IL-37-IL-1R8 axis is negatively associated with inflammatory and clinical severity of chronic rhinosinusitis with nasal polyps.

The importance of IL-37 and downstream signal in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) demanding further investigation. We sought to address the potential importance of the IL-37-IL-1R8 axis in regulating inflammatory response in patients with CRSwNP. Nasal polyp (NP) tissues and control sinonasal tissues were obtained from adult CRSwNP, chronic rhinosinusitis without nasal polyps patients and healthy control subjects. The mRNA and protein levels of IL-37 and IL-1R8 in nasal tissues were examined by using quantitative PCR, immunohistochemical staining, and immunoblotting. In addition, the regulation of IL-1R8 expression was evaluated in human nasal epithelial cells (HNECs) in the presence of different stimuli. The mRNA and protein levels of IL-37 and IL-1R8 were significantly elevated in nasal polyps compared with that in control tissues. IL-37 and IL-1R8 were mainly distributed in the epithelial layer and lamina propria of tissues. IL-1R8 mRNA level in nasal polys was negatively associated with eosinophil and neutrophil infiltration, as well as endoscopic score and computed tomography score. Moreover, the mRNA expression of IL-1R8 in HNECs was significantly increased by toll-like receptor agonists, but significantly inhibited by proinflammatory cytokines, which can be rescued by using steroid (DEX). Our findings showed that enhanced IL-37-IL-1R8 axis in NP tissues was negatively associated with inflammatory and clinical severity of CRSwNP patients, which could be considered as a future therapeutic target in CRSwNP patients.

The value of CT radiomics in predicting treatment outcomes in patients with nasal polyps

Objective: To evaluate the predictive efficacy of sinus CT radiomics for treatment outcomes in nasal polyp patients undergoing endoscopic sinus surgery. Methods: A retrospective cohort study was conducted at the First Affiliated Hospital of Sun Yat-sen University, including 194 patients with nasal polyps treated between January 2015 and December 2019. The cohort comprised 132 males and 62 females, aged 16 to 75 years. Patients were divided into a training set (n=135) and an internal validation set (n=59). An external validation set (n=34), consisting of 22 males and 12 females aged 16 to 59 years, was included from January 2020 to December 2021. Disease control was evaluated using the criteria from the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020). Radiomic features were extracted from sinus CT images and analyzed using the least absolute shrinkage and selection operator (LASSO) regression. Models combining radiomic and clinical features were developed to predict treatment efficacy. Results: The radiomics and combined models, based on four selected features, outperformed the clinical feature model in the training set, with AUC values of 0.901 and 0.915, versus 0.874, respectively. In the internal validation set, AUCs were 0.839, 0.832, and 0.716. Despite reduced AUCs in the external set, the radiomics model maintained good generalizability (0.748, 0.764, 0.620). Decision curve analysis showed significant clinical benefits in both radiomics and combined models. Conclusion: The CT-based radiomics model demonstrates significant predictive power in identifying refractory nasal polyps, suggesting its potential for clinical application in treatment outcome prediction.

Up-regulation of systemic and local BDNF in non-allergic Nasal Polyps in China.

Although the role of brain-derived neurotrophic factor (BDNF) in allergic rhinitis and/or nasal polyps (NPs) development has been studied, the contribution of BDNF in non-allergic NPs has not been evaluated yet. This study was to investigate the possible role of BDNF in non-allergic NPs pathogenesis. The study was carried out at The Second Hospital of Shandong University from December 2020 to November 2021. The non-allergic NPs patients (n=26) and the control group (n=22) were included. Lund-Mackay CT scores, nasal endoscopy scores, and pulmonary function testing were evaluated before surgery. Tissue and serum levels of BDNF, eosinophil cationic protein (ECP), and cytokeratins 5 (CK5) were assessed between different groups. The BDNF level in serum and tissue, CK5 count, and eosinophil infiltration in tissue were higher in non-allergic NPs. The eosinophils infiltration, ECP mRNA expression level, as well as BDNF mRNA level were increased in the BDNFhigh subgroup compared with BDNFlow subgroup. Significantly negative correlations between BDNF count and the situation of airway obstruction were found in non-allergic NPs. BDNF may have both local and systemic effects in non-allergic NPs pathogenesis. BDNF may be a possible therapeutic target or an indicator for eosinophilic NPs management.

MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3.

The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

CXCR5+TIM-3-PD-1+ stem-like cytotoxic CD8+ T cells: elevated in chronic rhinosinusitis and associated with disease severity.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease with an autoimmune background. Altered expression levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3), C-X-C chemokine receptor type 5 (CXCR5), and programmed cell death protein 1 (PD-1) are implicated in the progression of inflammatory and autoimmune diseases. Moreover, CXCR5+TIM-3-PD-1+ stem-like cytotoxic T cells function as memory stem cells during chronic disease processes and retain cytotoxicity-related gene networks. To explore the expressions of CXCR5, TIM-3, and PD-1 on T cells and their correlation with clinical parameters in CRS. Flow cytometry was used to assess the expressions and co-expressions of CXCR5, TIM-3, and PD-1 on T cells in the tissues of the paranasal sinus and peripheral blood of patients with CRS as well as healthy controls. Immunofluorescence was used to assess the co-localization of TIM-3, CXCR5, and PD-1 with T cells. The disease severity of our patients with CRS was evaluated using the Lund-Mackay score. A complete blood count was also performed for the patients with CRS. Expression levels of CXCR5 and PD-1 on T cells were significantly increased in the nasal tissues of patients with CRS. Compared with those in healthy controls, patients with CRS had high percentages of CXCR5+TIM-3-PD-1+ CD8+ and CD4+ T cells in nasal tissues, while no significant difference was observed in peripheral blood levels. Patients with CRS had a higher density of nasal CXCR5+TIM-3-PD-1+ T cells than that in healthy controls. CXCR5+TIM-3-PD-1+ CD8+ T cell levels in the nasal polyps of patients with CRS were negatively correlated with the patients' Lund-Mackay scores. The levels of CXCR5+TIM-3-PD-1+ T cells in nasal tissues were also negatively associated with disease duration and positively associated with the chronic inflammatory state of CRS. The level of CXCR5+TIM-3-PD-1+ stem cell-like T cells, especially CXCR5+TIM-3-PD-1+ CD8+ T cells, is increased in CRS. Therefore, inducing CXCR5+TIM-3-PD-1+ T cell exhaustion may be an effective immunotherapy for CRS.

Tissue-specific early and late activated lymphocytes immunophenotype inchronic rhinosinusitis with nasalpolyps.

T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.

RECENT ACHIEVEMENTS IN THE STUDY OF PATHOMECHANISMS OF RHYNOSINUSITIS ASSOCIATED WITH NON-STEROID ANTI-INFLAMMATORS INTOLERANCE (literature review)

Background. The pathomechanism of rhinosinusitis associated with the use of non-steroidal anti-inflammatory drugs is complex and still not fully understood. They are now known to be associated with genetic predisposition and environmental triggers that lead to dysregulation of fatty acid and lipid metabolism, cell transmetabolism, and chronic inflammation in the airways.&#x0D; Aim: analysis of recent advances in the study of aspirin-associated respiratory disease (AERD), summarization of already known information about the pathomechanisms of the disease.&#x0D; Materials and methods. The analysis of literary sources included publications in the international electronic scientometric databases PubMed, Scopus, Web of Science by keywords for the period 2013-2023. 46 sources were selected for analysis, of which 24 were used that met the search criteria.&#x0D; Results. The results showed that researchers are actively studying the role of immunological factors, particularly IgG4 and IgE in the pathogenesis of the disease. IgG4 was detected in nasal polyp tissue and associated with poor postoperative outcome, which may indicate its important role in chronic sinusitis. In addition, cytokines such as thymic stromal lymphopoietin, IL-4, IL-10, IL-5, IL-13, and IL-33 have been detected in eosinophilic nasal polyps in patients with aspirin intolerance, suggesting their possible role in the development AERD.&#x0D; Conclusion. The cause of severe nasal polyposis in AERD has not been definitively determined. Further research may lead to the development of more personalized treatments. Dietary modification and development of new monoclonal antibody drugs lead to reduction of AERD symptoms and improvement of patients' quality of life.

Meta-analysis of the Relationship Between Neutrophil to Lymphocyte Ratio and Nasal Polyps.

Our study aimed to enhance understanding of nasal polyp pathophysiology by reviewing the data for variations of NLR values between patients with nasal polyp and healthy controls. We searched Web of Science, PubMed, ProQuest, and Scopus up to 2 April 2023. The search strategy was not limited to any specific language. Twelve studies were included in our study. Of them, ten studies, involving 898 nasal polyp patients and 590 control patients, were included in the meta-analysis. The NLR levels in nasal polyp patients were statistically greater than in the control group (SMD = 0.56; 95%CI 0.04-1.08, P = 0.036). Subgroup analysis based on study design yielded that patients with nasal polyp exhibited significantly higher NLR levels than healthy controls in retrospective studies (SMD = 0.83; 95%CI 0.30-1.35, P = 0.002) but not in prospective studies (SMD = 0.10; 95%CI = -1.03 to 1.23, P = 0.85). Also, we found that the NLR levels in nasal polyp patients were significantly higher than healthy controls in high-quality studies (SMD = 1.00; 95%CI 0.38-1.62, P = 0.002) but not in low-quality studies (SMD = 0.11; 95%CI = -0.69 to 0.91, P = 0.79). A total of 312 patients with recurrence and 550 patients without recurrence were included in the study. The combined results revealed that NLR levels in nasal polyp recurrence patients were significantly higher than those of the nasal polyp without recurrence group (SMD = 0.06, 95% CI 0.39-0.81, P = 0.000). These results showed the relationship between the NLR in nasal polyps and can help medical doctors to predict the recurrence of the disease in such patients.

Serum metabolomics identifies uric acid as a possible novel biomarker for predicting recurrence of chronic rhinosinusitis with nasal polyps.

Metabolomics has proven to be a valuable tool in gaining new insights into disease progression and prognosis, the specific metabolic alterations in the serum of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) patients remain unknown. This study aims to explore the serum metabolomic profiles of recurrent CRSwNP and identify potential predictive biomarkers. A prospective, single-center study was conducted on CRSwNP patients prior to endoscopic sinus surgery. Serum samples were subjected to untargeted metabolomic profiling. Patients were followed up for over 2 years and categorized into recurrence and non-recurrence groups. Metabolite differences between the two groups were compared, and the identified differentially regulated metabolites were subsequently validated in a large clinical cohort. 67 CRSwNP patients completed the follow-up schedule, with 47 classified into the non-recurrent group and 20 into the recurrent group. Significant differences were found in the metabolomic profiles between both groups, and serum uric acid (SUA) showed promising predictive potential for postoperative recurrence in both positive and negative ion models. A validation cohort comprising 398 non-recurrent and 142 recurrent CRSwNP patients was recruited, and a significant elevation in SUA levels was observed in recurrent cases. Patients were stratified into tertiles based on the distribution of baseline SUA levels. Multivariate Cox regression analysis showed that higher tertiles of SUA were associated with an increased risk of CRSwNP recurrence compared to lower tertiles, even after adjusting for potential confounding factors. The receiver operating characteristic curve and Kaplan-Meier survival analysis highlighted that elevated SUA levels exhibited potential predictive values for postoperative recurrence. Serum metabolic signatures might predict postoperative recurrence in CRSwNP patients. Increased SUA concentrations were found to be associated with a higher risk of future postoperative recurrence in CRSwNP, independent of traditional risk factors.