Eosinophilic Chronic Rhinosinusitis Research Articles

ALOX15+ M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps

BackgroundEpithelial remodeling is a prominent feature of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP), and infiltration of M2 macrophages plays a pivotal role in the pathogenesis of eCRSwNP, but the underlying mechanisms remain undefined. ObjectiveWe aimed to investigate the role of ALOX15+ M2 macrophages in the epithelial remodeling of eCRSwNP. MethodsDigital spatial transcriptome and single-cell sequencing analyses were used to characterize the epithelial remodeling and cellular infiltrate in eCRSwNP. Hematoxylin and eosin staining, immunohistochemical and immunofluorescent staining were used to explore the relationship between ALOX15+ M2 (CD68+CD163+) macrophages and epithelial remodeling. A co-culture system of primary human nasal epithelial cells (hNECs) and the macrophage cell line THP-1 was used to determine the underlying mechanisms. ResultsSpatial transcriptomics analysis showed that upregulation of epithelial remodeling-related genes, such as VIM and MMP10, and enrichment of epithelial-mesenchymal transition (EMT)-related pathways, in the epithelial areas in eCRSwNP, with more abundance of epithelial basal, goblet and glandular cells. Single-cell analysis identified ALOX15+, rather ALOX15-, M2 macrophages were specifically highly expressed in eCRSwNP. CRSwNP with high ALOX15+ M2THP-1-IL-4+IL-13 macrophages had more obvious epithelial remodeling features and increased genes associated with epithelial remodeling and integrity of epithelial morphology versus that with low ALOX15+ M2THP-1-IL-4+IL-13 macrophages. IL-4/13-polarized M2THP-1-IL-4+IL-13 macrophages upregulated expressions of EMT-related genes in hNECs, including VIM, TWIST1, Snail, and ZEB1. ALOX15 inhibition in M2THP-1-IL-4+IL-13 macrophages resulted in reduction of the EMT-related transcripts in hNECs. Blocking CCL13 signaling inhibited M2THP-1-IL-4+IL-13 macrophage-induced EMT alteration in hNECs. ConclusionALOX15+ M2 macrophages are specifically increased in eCRSwNP and may contribute to the pathogenesis of epithelial remodeling via production of CCL13.

The value of combined detection of specific immunoglobulin E, interleukin-6 and regulatory T cells in predicting the risk of postoperative recurrence in patients with eosinophilic chronic rhinosinusitis and nasal polyps

Background: To investigate the predictive value of specific immunoglobulin E (sIgE), interleukin-6 (IL-6) and regulatory T cells (Treg) on the risk of postoperative recurrence in patients with eosinophilic chronic sinusitis with nasal polyps (EcRswNP). Methods: A total of 198 patients with EcRswNP collected to our Hospital from January 2019 to December 2021 were selected as the research subjects. All patients underwent functional endoscopic sinus surgery. The patients were selected to recurrence group (RG, n = 48) and non-recurrence group (NRG, n = 150) on the basis of the recurrence after 1 year of follow-up. The related factors of postoperative recurrence of EcRswNP were analyzed.. The ROC was used to analyze the dangerous of sIgE, IL-6 and Treg in predicting postoperative recurrence of EcRswNP patients. Results: The proportion of asthma patients, nasal congestion VAS score and peripheral blood Eos% content in the RG were exceed than the NRG, and the Organization Neu % and peripheral blood Neu% levels were less than those in the NRGp (P all < 0.05). The serum sIgE and serum IL-6 in the RG were exceed than the NRG, and the level of peripheral blood Treg was less than the NRG (P < 0.05). Logistic regression analysis showed that high levels of serum sIgE, serum IL-6 and low Treg levels were risk factors for postoperative recurrence (P < 0.05). ROC showed that the AUC of peripheral blood sIgE level, IL-6 and Treg levels alone in predicting the dangerous of postoperative recurrence in patients with EcRswNP were 0.786, 0.707 and 0.636, respectively (all P < 0.05); The AUC of combined prediction of peripheral blood sIgE, IL-6 and Treg levels for postoperative recurrence dangerous in patients with EcRswNP was 0.973, indicating that the efficacy of jointed prediction was exceed than that of single prediction (P < 0.05). Conclusions: The high levels of sIgE, IL6 and low Treg levels in patients with EcRswNP before operation will increase the risk of postoperative recurrence, which is a risk factor affecting postoperative recurrence, and the three indicators have good predictive value for predicting postoperative recurrence in patients with EcRswNP, and the combination of the three indicators has better value in predicting postoperative recurrence.

Predictive Value of Nasal Nitric Oxide for Diagnosing Eosinophilic Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis.

The primary aim of this study was to assess disparities in nasal nitric oxide (NO) levels between individuals diagnosed with eosinophilic chronic rhinosinusitis (ECRS) and those without ECRS. The second aim was to ascertain the comparative predictive efficacy of these nasal NO levels for the presence of ECRS. A systematic analysis was conducted on relevant studies that compared nasal NO levels in individuals with ECRS and those without. Furthermore, the discriminatory capacity of nasal NO in distinguishing ECRS from non-ECRS cohorts was quantified. The risk of bias across studies was evaluated utilizing the Newcastle-Ottawa scale. The comprehensive review encompassed a total of 5 studies involving 470 participants. Findings revealed that patients diagnosed with ECRS exhibited significantly higher levels of nasal NO, as measured in parts per billion (ppb), compared to their non-ECRS patients. The mean difference was 130.03 ppb (95% confidence interval: [66.30, 193.75], I2 = 58.7%). The diagnostic odds ratio for nasal NO in identifying ECRS was 9.29 ([5.85, 14.75], I2 = 26.4%). The area under the summary receiver operating characteristic curve was 0.82. The correlation between sensitivity and false positive rate was 0.53, suggesting a lack of heterogeneity. Sensitivity, specificity, negative predictive value, and positive predictive value were 69% ([0.55, 0.79], I2 = 77.0%), 83% ([0.73, 0.90], I2 = 68.5%), 77% ([0.69, 0.83], I2 = 50.1%), and 75% ([0.67, 0.82], I2 = 41.5%), respectively. Nasal NO has the potential as a noninvasive diagnostic measure and endotype tool for ECRS.

Increased SERPINB2 potentiates 15LO1 expression via STAT6 signalling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling. SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA. SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs invitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1. SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.

Butyrate inhibits type 2 inflammation in eosinophilic chronic rhinosinusitis

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.

[Correlation study of NCF2 in chronic rhinosinusitis with nasal polyps].

Objective:After selecting NCF2 based on bioinformatics, clinical experiments were conducted to verify the expression of NCF2 in chronic rhinosinusitis with nasal polyps to study its correlation. Methods:The differentially expressed genes（DEGs） between CRSwNP and non-CRS patients were explored using the CRS-related dataset from the gene expression omnibus GEO database. The weighted gene co-expression network（WGCNA） was used for cluster analysis. The expression and cell distribution of NCF2 in the tissues were determined by single gene enrichment analysis（GSEA）, immune inflammatory infiltration analysis, and principal component（PCA） analysis. The expression degree of NCF2 in the tissues of the subjects was determined by immunohistochemistry, and the percentage of EOS in the peripheral blood of the subjects was detected and the correlation was analyzed. EOS in the tissues of the subjects were counted under a microscope and compared. Results:①The Venn diagram was obtained by crossing the module with the highest correlation between DEGs and WGCNA to determine the core gene NCF2. ②GSEA analysis showed that NCF2 was significantly related to the immunological processes such as allogeneic rejection and asthma. ③The area under the ROC curve was 1, indicating that NCF2 had diagnostic value for CRSwNP. ④NCF2 was highly expressed in nasal polyps, mainly distributed in monocytes and eosinophils. ⑤HE staining showed that the number of EOS in ECRSwNP tissues and the percentage of eosinophils in peripheral blood were higher than those in nonECRSwNP and control groups. ⑥The immunohistochemistry results showed that NCF2 was significantly expressed in the nasal polyps of ECRSwNP patients, which was higher than that in the nasal mucosa of nonECRSwNP group and control group. ⑦The expression of NCF2 in tissues was positively correlated with EOS count in ECRSwNP group and EOS expression in peripheral blood. Conclusion:The expression of NCF2 is increased in eosinophilic chronic rhinosinusitis with nasal polyps, and it is significantly correlated with the expression of eosinophils in peripheral blood and tissues, suggesting that NCF2 may be used as a basis for the intrinsic classification of ECRSwNP and a reference index for clinical diagnosis and treatment.

Clinical features of responders to mepolizumab in eosinophilic chronic rhinosinusitis and the outcomes post treatment cessation

Clinical features of responders to mepolizumab in eosinophilic chronic rhinosinusitis and the outcomes post treatment cessation

Benralizumab in Severe Eosinophilic Asthma and Chronic Rhinosinusitis with Nasal Polyps: The Real-World, Multi-Country RANS Observational Study.

Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.

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.

Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation.

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPGA )-coated TiS2 nanosheets (TLPGA ) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPGA exhibited higher cfDNA affinity than the TiS2 nanosheets coated with dendritic polyglycerol-amine (TDPGA ). TLPGA reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPGA displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment.

Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction

BackgroundChronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies. ObjectiveThe aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter timeframe using intranasal ovalbumin (OVA) and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb. MethodsMale BALB/c mice were intranasally administered OVA and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histological assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. ResultsThe developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model. ConclusionThis study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRSwNP and olfactory dysfunction.

Validation and shortcomings of the most common mouse model of chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis (CRS) is a highly prevalent airway disease worldwide. Whereas eosinophilic CRS with nasal polyps (eCRSwNP) represents its most severe phenotype, pathogenic mechanisms remain poorly understood despite a wide spectrum of in vitro and in vivo experimental models. A mouse model of experimental ovalbumin (OVA)-induced airway allergy with coadministration of Staphylococcus aureus enterotoxin B (SEB) has been widely used to study eosinophilic eCRSwNP. This study revisits the features of this model and its suitability for studying eCRS. We implemented the most used eCRSwNP mouse model based on OVA+SEB intranasal challenges. Readouts including inflammatory features by (immuno)histology of the sinonasal epithelium (NP formation, eosinophils, epithelial and basement membrane thickness, fibrosis, goblet cells, Charcot-Leyden crystals (CLC)-like, tight junctions) and IgE production by enzyme-linked immunosorbent assay (ELISA), were compared to features of the corresponding human disease. The OVA+SEB model induced eosinophilic inflammation of upper and lower airways, with epithelial and basement membrane thickening, goblet cell hyperplasia and subepithelial fibrosis in the sinuses, along increased IgE production. Except local IgE in nasal lavage (NL), which was only increased in OVA+SEB group, all other features did not differ between OVA and OVA+SEB groups. Macro- or microscopic NP were not detected. With the notable exception of local IgE production, the addition of SEB did not induce additional inflammatory or structural change in the sinuses from mice exposed to and challenged with OVA. This model might represent a model for severe upper airway allergy rather than a specific model of human eCRSwNP.

Eosinophil extracellular traps in eosinophilic chronic rhinosinusitis induce Charcot-Leyden crystal formation and eosinophil recruitment.

Eosinophil extracellular traps (EETs) are implicated in various eosinophil-associated diseases; however, their role in chronic rhinosinusitis (CRS) remains unclear. In the present study, 57 CRS patients were enrolled, and immunofluorescence was used to analyze EETs in eosinophilic (eCRS) and non-eosinophilic (Non-eCRS) tissues. MSD was used to examine IL-4, IL-5, and IL-13 concentrations in tissue homogenates. Charcot-Leyden crystals (CLCs) protein expression was detected in PMA, PMA+DNase I, and blank control eosinophils using ELISA. Eotaxin-3 mRNA and protein levels were measured in human nasal epithelial cells (HNECs) cultured with EETs, EETs+DNase I, DNase I, and unstimulated eosinophils using PCR and ELISA. EETs were significantly increased in eCRS tissues compared with Non-eCRS (P<0.001), and correlated with VAS and Lund-Mackay CT scores. IL-5 expression was related to EETs formation (r = 0.738, P<0.001). PMA-stimulated eosinophils exhibited higher CLCs protein levels (P<0.01). Co-culturing HNECs with EETs significantly increased eotaxin-3 mRNA and protein levels (P<0.0001, P<0.001) compared with other groups. The study suggests EETs formation is elevated in eCRS patients and is involved in CLCs formation and chemokine secretion, promoting eosinophilic inflammation.

Correlation of Kennedy Osteitis Score with the Tissue and Peripheral Eosinophil Counts in Patients of Eosinophilic Chronic Rhinosinusitis

Correlation of Kennedy Osteitis Score with the Tissue and Peripheral Eosinophil Counts in Patients of Eosinophilic Chronic Rhinosinusitis

Apoptosis and turnover disruption of olfactory sensory neurons in eosinophilic chronic rhinosinusitis.

Olfactory dysfunction (OD) is one of the important and difficult-to-treat symptoms of eosinophilic chronic rhinosinusitis (CRS), which is typically associated with type 2 inflammation where eosinophils (EOSs) function as both effectors and initiators. Eosinophilic infiltration in the olfactory mucosa (OM) is associated with severe OD, mucosal erosion, and more loss of olfactory sensory neurons (OSNs). Active EOS-derived cytokines, chemokines, and eosinophil granule proteins may lead to aggravation of inflammation, tissue damage, and impairment of the survival and regeneration of OSNs. Recent studies show that EOSs can lead to apoptosis of OSNs through axonal and neural body damage, turnover disorder of OSNs through the loss of immature OSNs and globose basal cells (GBCs), changed proliferative activity of horizontal basal cells (HBCs), and dysfunction of OSNs through the breakdown of neuroepithelial integrity and alteration of ion concentration in OSNs and mucin. In this review, we outline the current progress on the role of EOSs on OD in patients with eosinophilic CRS and the mechanism of EOS-associated injury of the OM and OSNs in experimental animal models with sinonasal inflammation. Further investigations on the molecular mechanisms of tissue eosinophilia-induced injury of OSNs are warranted to obtain new therapeutic targets and achieve better restoration of olfactory function.

THE IMPACT OF PREOPERATIVE STEROIDS ADMINISTRATION ON ENDOSCOPIC SINUS SURGERY: A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Chronic rhinosinusitis (CRS) is one of the most common diseases in the world, affecting approximately 14 of people in the USA. It is defined as chronic inflammation of nasal and sinus cavities lasting longer than 12 weeks, it can be with or without nasal polyposis (CRSwNP or CRSsNP), primary and secondary, localized or diffuse disease regarding anatomic distribution, either type 2 or non-type 2, considering the endotype dominance, eCRS, and non-eCRS for eosinophilic and non-eosinophilic CRS. The aim: This study aims to show about the impact of preoperative steroids administration on endoscopic sinus surgery. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 51 articles, whereas the results of our search on SagePub brought up 74 articles. The results of the search conducted for the last year of 2014 yielded a total 24 articles for PubMed and 48 articles for SagePub. The result from title screening, a total 5 articles for PubMed and 12 articles for SagePub. In the end, we compiled a total of 8 papers. We included five research that met the criteria. Conclusion: Low dose preoperative systemic steroid (PSS) does not seem to have an effect on the long term outcome after endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) with nasal polyposis (NP). Eosinophilic infiltration and presence of asthma are important predictors of surgical outcome in such cases.

Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa with distinct endotypes including type 2 (T2) high eosinophilic CRS with nasal polyps (eCRSwNP), T2 low non-eosinophilic CRS with nasal polyps (neCRSwNP), and CRS without nasal polyps (CRSsNP). Given the heterogeneity of disease, we hypothesized that assessment of single cell RNA sequencing (scRNA-seq) across this spectrum of disease would reveal connections between infiltrating and activated immune cells and the epithelial and stromal populations that reside in sinonasal tissue. Here we find increased expression of genes encoding glycolytic enzymes in epithelial cells (EpCs), stromal cells, and memory T-cell subsets from patients with eCRSwNP, as compared to healthy controls. In basal EpCs, this is associated with a program of cell motility and Rho GTPase effector expression. Across both stromal and immune subsets, glycolytic programming was associated with extracellular matrix interactions, proteoglycan generation, and collagen formation. Furthermore, we report increased cell-cell interactions between EpCs and stromal/immune cells in eCRSwNP compared to healthy control tissue, and we nominate candidate receptor-ligand pairs that may drive tissue remodeling. These findings support a role for glycolytic reprograming in T2-elicited tissue remodeling and implicate increased cellular crosstalk in eCRSwNP.

Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps.

The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP. We assessed the expression of INPP4A in human and mouse nasal mucosal tissues via immunofluorescence staining. THP-1 cells were cultured and exposed to various cytokines to investigate the regulation of INPP4A expression and its functional role. Additionally, we established a murine nasal polyp (NP) model and administrated an INPP4A-overexpressing lentivirus evaluate its impact on NP. The percentage of INPP4A + CD68 + macrophages among total macrophages decreased in the E-CRSwNP group compared to the control and the non-eosinophilic CRSwNP (NE-CRSwNP) groups, exhibiting an inverse correlation with an increased percentage of CD206 + CD68 + M2 macrophages among total macrophages. Overexpression of INPP4A led to a reduced percentage of THP-1 cells polarizing towards the M2 phenotype, accompanied by decreased levels of associated chemotactic factors including CCL18, CCL22, CCL24, and CCL26. We also validated the involvement of the PI3K-AKT pathway in the function of INPP4A in vitro. Furthermore, INPP4A overexpression in the murine NP model resulted in the attenuation of eosinophilic inflammation in the nasal mucosa. INPP4A deficiency promotes macrophage polarization towards the M2 phenotype, leading to the secretion of chemokines that recruit eosinophils and Th2 cells, thereby amplifying eosinophilic inflammation in E-CRSwNP. INPP4A may exert a suppressive role in eosinophilic inflammation and could potentially serve as a novel therapeutic strategy.

Olfaction and Quality of Life in Patients with Eosinophilic CRS Undergoing Endoscopic Sinus Surgery.

Introduction  Chronic rhinosinusitis (CRS) is a common inflammatory disease. This high prevalence leads to high direct and indirect public health costs, which include medical visits, laboratory tests and imaging, pharmacotherapy, hospitalizations, and surgical treatment. Furthermore, CRS has a substantial impact on patient quality of life, affecting productivity and being a common cause of absence from work CRS-associated olfactory dysfunction is highly prevalent, the actual effectiveness of surgical intervention remains inconsistent. Although there are studies evaluating the postoperative course of patients with eosinophilic Chronic rhinosinusitis (eCRS) treated with high-volume budesonide irrigation, there is little objective information regarding the impact of this intervention on olfactory status and quality of life. Objective  To conduct a pre- and postoperative analysis of olfaction and quality of life in patients with eCRS treated with surgical intervention followed by high-volume budesonide nasal irrigation. Methods  Prospective, descriptive, uncontrolled study of patients with eCRS. All patients underwent pre- and postoperative nasal endoscopy, SNOT-22 questionnaire, and the University of Pennsylvania Smell Identification Text (UPSIT), always by the same previously trained examiner. The SNOT-22 questionnaire and the UPSIT were readministered to all patients at 3 months, 6 months, and 1 year postoperatively, and scores compared with those obtained preoperatively. Results  Twenty patients were included in the study, 13 males and 7 females, between the ages of 23 and 65; 8 patients had comorbid asthma. Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). There was no significant association between eosinophil concentrations in polypoid tissue and postoperative SNOT-22 and UPSIT results. Patients with tissue eosinophils >50 had a lower preoperative UPSIT score. As early as 3 months postoperatively, a significant improvement in quality of life was already noticeable, as represented by a decrease in SNOT-22 values, which persisted through the 1-year postoperative follow-up evaluation (p = 0.0005). Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). Conclusion  Surgery effectively controlled eCRS in patients who adhered to high-volume budesonide nasal irrigation postoperatively. There were significant improvements in quality of life and olfaction, which persisted at least up to one year postoperatively.

Severe Type 2 Inflammation Leads to High Platelet-Activating-Factor-Associated Pathology in Chronic Rhinosinusitis with Nasal Polyps-A Hierarchical Cluster Analysis Using Bulk RNA Barcoding and Sequencing.

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) (n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) (n = 3), and controls with a normal uncinate process mucosa (n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP.