Nasal Polyps Research Articles

The Effects of VEGF-A and GSTM1/GSTT1 Variants in the Susceptibility to the Chronic Rhinosinusitis with Nasal Polyposis: A Pilot Genetic Study.

Nasal polyps (NPs) are usually part of chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the exact etiology of CRSwNP is still unknown. In addition, the suggested etiological causes are infection, allergy, and immunological disorders, among others, such as genetic predisposition. Moreover, it is also suggested that oxygen-free radicals play a vital role in the pathogenesis of nasal polyposis, and inflammatory cells produce free radicals during phagocytosis, which is the primary source of ROS, controlled by the glutathione S-transferase (GST) system. Although, vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, it is closely interwoven with the mobilization of inflammatory cells. This pilot study evaluated the association between genetic variant VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphism in susceptibility to CRSwNP. A case-control study was conducted with 61 individuals diagnosed with CRSwNP and 100 healthy subjects. VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphisms were genotyped by RFLP-PCR and SYBR Green real-time PCR, respectively. Individuals with allergic rhinitis carriers with AC genotype (rs28357093) presented a 4-fold increased risk to CRSwNP (OR = 4.20, 95% CI = 1.31 to 13.50; p = 0.015). This evidence shows that the increased vascular permeability probably causes an inflamed nasal area leading to extensive edema and polyp growth. On the other hand, no association was verified for each genetic variant by inheritance models. Interestingly, the GSTT1 present genotype showed a protective effect on CRSwNP. In conclusion, additional studies that have larger groups in different geographic localizations may be useful to verify and assess the association between genetic variants and CRSwNP.

Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience.

Type 2 biologics have been used increasingly for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, patterns of biologic switching are understudied, and established guidelines for sequential or simultaneous use do not yet exist. This is a Canadian multicenter retrospective study of real-world patient data. Patients were included if they had recurrent CRSwNP despite maximal medical and surgical management, and received at least one dose of a type 2 biologic. Patients who remained on their initial biologic comprised the continuous group. Patients with sequential or simultaneous use of more than one biologic comprised the switched group. We compared the characteristics of patients who continued and switched biologics. Note that 225 consecutive patients were included. Thirty-six (16%) switched biologics at least once, and six (3%) switched twice. The most common switch was from mepolizumab to dupilumab, with poor control of CRSwNP symptoms being the leading cause for this switch. Lack of efficacy was the main reason for switching off mepolizumab and omalizumab, while adverse events were the leading cause for switching off dupilumab. Additionally, mepolizumab patients were more likely to switch biologics late in their treatment, while dupilumab patients rarely switched after 12 months of therapy (p-value<0.001). Switching biologics for CRSwNP is frequent in Canadian rhinology practices, with 16% of patients switching at least once. The most common switch is from mepolizumab to dupilumab with inadequate CRSwNP control driving this switch. This study may help guide sequential or simultaneous use of biologics in CRSwNP patients.

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.

A clinical study on the relationship between chronic rhinosinusitis and bronchial asthma.

To investigate the correlation between chronic rhinosinusitis (CRS) and bronchial asthma, focusing on the CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), as well as their impact on lung function. A total of 141 patients diagnosed with chronic nasal-sinus inflammation were included in this study. Clinical data, including medical histories, nasal endoscopy scores, CT scores, symptom scores, and quality of life assessments, were collected. Among the patients with CRSsNP, 23.8% had concomitant bronchial asthma. The incidence of asthma was significantly associated with the severity of sinus involvement in CRSsNP patients (p = 0.049). Pulmonary function impairment was correlated with the severity of sinus inflammation in CRSsNP patients (p = 0.019). Quality of life was significantly affected in patients with concomitant asthma and CRSsNP or CRSwNP. Chronic rhinosinusitis, both with and without nasal polyps, is closely correlated with bronchial asthma. Pulmonary function impairment is associated with the extent of inflammatory lesions in CRSsNP. Although CRSwNP does not significantly affect pulmonary function, the treatment of sinus diseases can contribute to the control of asthma.

Dupilumab for refractory chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with refractory chronic rhinosinusitis with nasal polyps (CRSwNP), despite current treatments. Dupilumab demonstrated efficacy in the treatment of severe and uncontrolled CRSwNP, with improvements in patient-reported outcome measures and in objective measurements. This study aims to evaluate efficacy and safety of dupilumab in refractory CRSwNP in EGPA patients. A prospective observational study was conducted on EGPA patients treated with dupilumab between 2021 and 2023. Patients in a phase of prolonged remission of vasculitis manifestations but still experiencing active CRSwNP were included. Clinical, biological, and rhinologic evaluations were performed, alongside with patient-reported outcomes measures (PROMs) and nasal cytology. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤ 4 mg/day, while partial response by BVAS = 0 and prednisone dose >4 mg/day. Nine EGPA patients were included. After 3 months, 55.6% achieved complete response, increasing to 83.3% at 12 months. Nasal symptoms and patient-reported outcomes improved significantly, with sustained efficacy over 12 months. An improvement in quality of life was also observed, with a significant reduction of the AAV-PRO score. Nasal cytology revealed reductions in eosinophils and neutrophils counts. Adverse events occurred in 44.4%, including hypereosinophilia in 2 cases, which led to dupilumab discontinuation. Dupilumab is an effective treatment option for severe and refractory ENT manifestations in EGPA, as it improves symptoms, reduces inflammation, and leads to better a quality of life. However, careful patient selection and monitoring are necessary to minimize adverse events and optimize outcomes.

Changes in weight secondary to improved odor perception in chronic rhinosinusitis with nasal polyps' patients treated with Dupilumab.

The advent of biologic therapies, notably Dupilumab, has transformed therapeutic approaches to nasal polyposis. This retrospective multicentric study aimed to investigate weight changes in CRSwNP patients undergoing Dupilumab treatment and explore potential correlations with olfactory improvement. Ninety-six patients with CRSwNP were followed for at least 12 months, with assessments including BMI (Body Mass Index), olfactory function, and disease severity. Significant increases in BMI and olfactory perception were observed after 1 year of Dupilumab treatment (p < .001). Subgroup analysis showed that patients with hyposmia and normosmia at T12 (1-year follow up) experienced significant weight gain (p < .001) alongside improved olfaction (both p < .001). Conversely, patients with anosmia after 1 year of therapy and also patients with stable or worsened olfaction did not show significant BMI changes (respectively p = .201 and p = .107). While these findings suggest a correlation between olfactory improvement and weight gain/BMI, factors like improved nasal airflow and corticosteroid cessation under Dupilumab treatment may also influence weight in CRPwNP patients. The study highlights the need for further research to elucidate the causal relationship and long-term implications of Dupilumab-induced olfactory improvement on weight regulation.

Effects of Mepolizumab in the treatment of type 2 CRSwNP: a real-life clinical study.

Mepolizumab was recently approved for treating Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) unresponsive to standard treatment or recurring after endoscopic sinus surgery (ESS). To date, few studies have assessed Mepolizumab's efficacy in severe type-2 CRSwNP. Our study aimed to analyze sinonasal outcomes in type-2 CRSwNP patients treated with 100mg Mepolizumab administered subcutaneously every four weeks. We conducted a retrospective study of patients with severe, recalcitrant CRSwNP treated with Mepolizumab. Demographic and clinical characteristics were collected, including age, sex, and comorbidities such as asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), and allergic rhinitis (AR), as well as the number of previous ESS procedures and the interval since the last one. Patients were evaluated at baseline and after one year for blood eosinophil count, nasal polyp score (NPS), modified Lund-Kennedy score (mLKS), olfactory function (using a VAS scale and a 16-item Sniffin' identification test), SNOT-22, and sinus opacification on CT scans. The need for rescue ESS or systemic corticosteroids (SCS), response to treatment, and side effects were also recorded. Data from 27 patients were collected. After one year, all scores showed significant improvement. NERD was the only factor associated with a less favorable improvement in olfactory function. There were no side effects reported, although 2 patients discontinued Mepolizumab as they were considered "non-responders." Mepolizumab is safe and effective in reducing the clinical, endoscopic, and radiological burden of disease, as well as in decreasing the need for salvage ESS or systemic steroids.

Impact of Sinus CT Severity Score on the Outcomes of Endoscopic Sinus Surgery in Eosinophilic CRSwNP.

Eosinophilic chronic rhinosinusitis with nasal polyps (eos-CRSwNP), especially those with diffuse disease as indicated by CT scans, has high recurrence rate and low control rate after endoscopic sinus surgery (ESS). Most of them are difficult to treat. This study sought to identify if eos-CRSwNP patients were to undergo surgery earlier, while the disease is still limited on CT, they might achieve better postoperative outcomes. This study enrolled eos-CRSwNP patients with different degree of sinus involvement who underwent primary ESS and compared the surgical outcomes of the patients exhibiting mild sinus involvement with those displaying severe sinus involvement. The demographic data, preoperative disease severity, and surgery outcomes at 1 year postoperatively were collected. CRS control status was the primary endpoint to evaluate the outcomes. This study included 118 patients with at least one-year follow-up. The overall uncontrolled rate was 33.1% at 1 year postoperatively. The best cut-off value for CT Lund-Mackay (L-M) score was 13 to predict the uncontrolled status (AUC = 0.67). Then, patients were divided into the mild group (L-M < 13, n = 70) and the severe group (L-M ≥ 13, n = 48) according to L-M score. The follow-up data indicated that 24.3% of patients (17/70) in the mild group and 45.8% of patients (22/48) in the severe group were uncontrolled (p = 0.015). Postoperative endoscopic score in the mild group was significantly better than those in the severe group (p = 0.002). ESS performed on eos-CRSwNP patients with mild sinus involvement have better postoperative outcomes at 1 year than patients with severe sinus involvement. Level 3 Laryngoscope, 2024.

Effectiveness and Outcomes of Endoscopic Sinus Surgery for Nasal Polyps: A Systematic Review

Objectives: To investigate the effectiveness and outcomes of endoscopic sinus surgery (ESS) in patients with nasal polyps. Methods: A thorough search was conducted for pertinent literature using PubMed, SCOPUS, Web of Science, Science Direct, and Wiley Library. Rayyan QRCI was used throughout this extensive procedure. Results: Our results included nine studies with a total of 780 patients, and 490 (62.8%) were males. The follow-up duration ranged from 4 months to 24 months. All of the included patients underwent ESS for chronic sinusitis with nasal polyps (CRSwNP). Patients with CRSwNP and refractory CRSwNP reported better self-evaluated olfactory function after using ESS, experienced a higher reduction in polyp load, and better quality of life. Conclusion: Patients with CRSwNP reported significant improvements in quality of life and major symptoms when using ESS. The quality of the available data, as established in this evaluation, is low enough to make firm recommendations for the best course of surgical therapy. From a precision medicine perspective, high-quality studies are needed to phenotype these patients in order to identify which ones will benefit most from each type of medicinal and surgical therapy, including a combination of both, with long-term efficiency being a crucial result.

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.

Additive Effect of Blood and Tissue Eosinophilia on ChronicRhinosinusitis With Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with varied clinical features and treatment effects. This study aimed to investigate the additive effect of blood and tissue eosinophilia on patients with CRSwNP. Based on the blood eosinophil (Beos) count and tissue eosinophil (Teos) count, we divided 144 CRSwNP patients into four groups, analysed their clinical features and histopathologic changes, and investigated their postoperative control. Patients in the Beos+Teos+ (blood eosinophil count > 0.3 × 109/L, tissue eosinophil count > 10/HPF) group had a higher incidence of allergic rhinitis (AR) and asthma. Lund-Mackay (LM) scores, hyposmia visual analogue scale (VAS) scores and Global Osteitis Scoring Scale (GOSS) scores were higher in the Beos+Teos+ group than those in the other groups. Tissue remodelling, such as connective tissue oedema and basement membrane thickening was more severe in the Beos+Teos+ group compared with other groups. There were more uncontrolled patients after surgery in Beos+Teos+, Beos+Teos- (blood eosinophil count > 0.3 × 109/L, tissue eosinophil count ≤ 10/HPF)and Beos-Teos+ (blood eosinophil count ≤ 0.3 × 109/L, tissue eosinophil count > 10/HPF)groups compared with the Beos-Teos- group. Eosinophilic inflammation both in blood and tissue was accompanied by more severe clinical features and tissue remodelling. Eosinophilia in blood or tissue indicated poorer disease control after surgery.

Orthonasal and retronasal olfactory function in patients with chronic rhinosinusitis without nasal polyps undergoing endoscopic sinonasal surgery.

Olfactory dysfunction (OD) is a key symptom of chronic rhinosinusitis (CRS). Although extensively studied in CRS with nasal polyps (CRSwNP), OD in CRS without nasal polyps (CRSsNP) remains under-researched. This study aims to assess the prevalence of OD and its evolution in surgically naïve patients with CRSsNP undergoing endoscopic sinus surgery (ESS). This prospective study included 97 participants with CRSsNP (mean age, 46.5 years; 70.1% men) and 97 healthy controls (mean age, 46.5 years; 70.1% men). Participants underwent psychophysical evaluations of orthonasal (using the Sniffin' Sticks test) and retronasal olfaction (using powdered aromas) at enrolment and 6 months post-ESS. Out of 97 patients, 81 (83.5%) completed all assessments. At enrolment, 23 (28.4%) CRSsNP patients had OD based on composite threshold, discrimination, identification scores, compared with 7 (8.6%) controls (absolute % difference, 19.8% [95% CI, 8.2-31.4]). Retronasal olfactory function was also significantly worse in CRSsNP patients. Six months post-ESS, 30 patients (37.0%) experienced a clinically significant improvement in olfactory, whereas nonsignificant changes were observed in retronasal olfactory score, and 3.7% of patients experienced a deterioration of the olfactory function. In conclusion, although 37% of patients experienced a clinically significant improvement in their sense of smell following ESS, the overall prevalence of OD in this surgically naive population appears relatively low, especially when compared to that observed in patients with CRSwNP. Therefore, ESS may offer some benefits for enhancing orthonasal olfactory function, but the extent of these improvements appears to be limited.

Distinct trajectories of treatment response to mepolizumab toward remission in patients with severe eosinophilic asthma.

Patients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission.Data from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6, and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations, and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis.We identified three trajectory groups: group 1, responsive asthma with less OCS use (n=170); group 2, responsive late-onset asthma (n=58); and group 3, obstructed and less responsive asthma (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to group 3 with 5.7% (p <0.001). Baseline predictors for assigned groups included lower OCS dose in group 1; greater FEV1% predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose, and nasal polyps in group 2; with group 3 as the reference.Treatment response to mepolizumab in severe eosinophilic asthma follows 3 trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.

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.

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

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

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience.

Patients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking. In this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test-22 (SNOT-22, 0 - 110), Visual Analog Scale symptom scores (VAS, 0-10), and Asthma Control Test (ACT, 5-25) and the proportion of patients meeting the minimal clinically important difference (MCID). Disease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0-52 vs 10, IQR:0-30 vs 0, IQR:0-15 vs 0, IQR:0-12, p < 0.001, VAS score: 1, IQR: 0-5 vs 0, IQR:0-3 vs 0, IQR:0-2 vs 0, IQR 0-1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline. The study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease.The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the "X International Workshop on Lung Health - Respiratory Disease and Immune Response", held in Nice on 19-21 January 2023.

Practice Patterns of Biologics Prescriptions and Surgery in Chronic Rhinosinusitis With Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) remains challenging to manage effectively, with high symptom recurrence rates and significant impacts on quality of life, prompting a need to evaluate the real-world use of biologics and optimize treatment strategies. To assess the real-world application and perspectives of American Rhinologic Society (ARS) members on biologic treatments and surgical interventions for CRSwNP, focusing on clinical practice patterns, adoption of biologics, and their impact on surgical practices. A standardized questionnaire evaluated clinical practice patterns of biologics prescriptions and surgery in treating CRSwNP between July 2022 and August 2023. Data collected from 162 ARS members were analyzed. Of 162 participants, a substantial majority (95.06%, n = 154) reported prescribing biologics in their practice. Notably, 45.45% (n = 70) found biologics easily accessible, although accessibility challenges remained for some. The impact of biologics on surgical practices was significant, with 36.36% (n = 56) observing a marked reduction in revision sinus surgeries. Among the participants, 47.16% (n = 71) agreed that aspirin-exacerbated respiratory disease (AERD) was the highest phenotype that tended to increase the possibility of biological treatment by more than 20%. Adopting Patient-Reported Outcome Measures (PROMs) was prevalent, with 57.79% (n = 89) utilizing them in patient management. The study highlights the evolving landscape in managing CRSwNP, with a marked trend toward integrating biological treatments into clinical practice. It underscores the necessity for continued research, updates to clinical guidelines, and enhanced practitioner education to optimize treatment outcomes for CRSwNP patients.

Role of glucocorticoid receptor beta in the development of steroid resistance

Glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs for the treatment of inflammatory diseases, despite the fact that the resistance to them is increasing due to various circumstances. GC insensitivity is an important clinical issue that is associated with life-threatening disease progression. Currently, there is no reliable biomarker that can be used to define steroid resistance. According to several studies, increased expression of the glucocorticoid receptor beta (GR-β) isoform is associated with steroid resistance. The purpose of this review is to analyse the correlation between GR-β expression and the occurrence of steroid therapy-resistant diseases and to determine its potential as a biomarker. This review summarizes studies that point out increased GR-β expression in steroid-resistant groups of patients compared to steroid-sensitive groups. Articles included in the review focus on asthma, nasal polyposis, ulcerative colitis, and other chronic inflammatory diseases in which resistance to steroid therapy is observed. GR-β levels have also been shown to be elevated in patients with allergic rhinitis, Crohn's disease and rheumatoid arthritis. In most studies, higher levels of GR-β were detected in peripheral blood mononuclear cells (PBMC) by reverse transcription polymerase chain reaction (RT-PCR). Increased expression of GR-β is mostly associated with steroid resistance. Thus, it can potentially be used as a biomarker of steroid resistance-related disorders.

Effectiveness and safety of biologics in patients with chronic rhinosinusitis with nasal polyps

Effectiveness and safety of biologics in patients with chronic rhinosinusitis with nasal polyps

S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp.

Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS). Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed. GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r=0.294, p=0.022) and Lund-Mackay scores (r=0.348, p=0.006). S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.