Search Results (55)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Background/Objective: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with a significant impact on quality of life and is frequently associated, from a pathogenetic perspective, with type 2 inflammation. The introduction of biologic therapies has marked a turning point in the management of severe forms of the disease, offering a valuable treatment option. However, selecting the most suitable biologic agent for a specific patient remains a clinical challenge. Artificial intelligence, and, in particular, ChatGPT, has recently been proposed as a potential tool to support medical decision-making and guide therapeutic choices. To evaluate the concordance between the therapeutic recommendations provided by ChatGPT and those of a multidisciplinary expert board in selecting the most appropriate biologic therapy for CRSwNP patients, based on the analysis of their phenotype and endotype. Methods: A multicenter observational cohort study was conducted. Clinical data from 286 patients with CRSwNP were analyzed. For each case, the therapeutic choice among Dupilumab, Mepolizumab, and Omalizumab was compared between the board and ChatGPT. Concordance rates and Cohen’s Kappa coefficient were calculated. Results: Overall concordance was 59.2%, with a Cohen’s Kappa coefficient of 0.116. Concordance by drug was 62.8% for Dupilumab, 26.5% for Mepolizumab, and 9.1% for Omalizumab. Patients presented with severe clinical profiles, with an average Nasal Polyp Score of 6.22 and an average SNOT-22 score of 64.5. Conclusions: This study demonstrates that, despite its substantial theoretical potential, ChatGPT is currently not a reliable tool for the autonomous selection of biological therapies in patients with CRSwNP. Further studies are necessary to enhance its reliability and integration into clinical practice. Full article

Background: Chronic rhinosinusitis with or without nasal polyps (CRSwNPs/CRSsNPs) is an inflammatory disease that is becoming increasingly associated with laryngopharyngeal reflux disease (LPRD). Although symptom-based questionnaires, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score (RSS), are widely used, there is a lack of objective endoscopic tools for assessing the nasopharyngeal and nasal manifestations of reflux. The Nasopharyngeal Reflux Endoscopic Score (NRES) is a novel endoscopic scoring system that was developed to address this issue. Objective: The objective of this study was to evaluate the diagnostic accuracy of the NRES in identifying LPRD in patients with CRS, compared with a clinical reference standard. Methods: A prospective diagnostic accuracy cohort study was conducted at two tertiary care centers in Astana, Kazakhstan, from September 2023 to February 2025. A total of 216 adults were enrolled and divided into three groups: CRS with suspected LPRD (n = 116), CRS without LPRD (n = 69), and healthy controls (n = 31). CRS was diagnosed according to the EPOS 2020 criteria. LPRD was defined using a composite reference standard comprising clinical assessment, RSS > 13, RSI, and selective 24 h pH monitoring and gastrointestinal endoscopy. All participants underwent nasopharyngeal and laryngeal endoscopy, with NRES, L-K, RFS, RSI, and RSS assessments at baseline and at 6 and 12 months. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance, and Wilcoxon tests were used to analyze the changes in scores. Correlation and regression analyses were used to explore associations between scales and predictive factors. Results: At baseline, NRES scores were significantly higher in the CRS with LPRD group (mean: 11.59) than in the CRS without LPRD group (mean: 3.10) and the healthy control group (mean: 2.16) (p < 0.001). ROC analysis demonstrated excellent diagnostic accuracy, with an area under the curve (AUC) of 0.998 (95% confidence interval (CI): 0.994–1.000), a sensitivity of 98% (95% CI: 94–100%) and a specificity of 96% (95% CI: 91–99%) at an optimal cut-off point of 8.5. NRES scores showed strong correlations with RSI, RSS, and RFS scores (r > 0.76, p < 0.001). A longitudinal assessment revealed significant reductions in all scores after treatment with proton pump inhibitors and lifestyle modifications, with sustained improvement at 12 months. Regression analysis found no significant effect of age, gender, or GERD severity (LA classification) on NRES scores. Conclusions: The NRES is a highly sensitive and specific endoscopic tool for identifying nasopharyngeal changes associated with LPRD in CRS patients. It demonstrates strong correlations with established symptom-based and laryngoscopic reflux assessments and responds to anti-reflux therapy over time. The NRES may, therefore, be a valuable objective adjunct in the comprehensive evaluation and longitudinal monitoring of LPRD-associated CRS. Full article

Chronic rhinosinusitis with nasal polyps is a Type 2 inflammatory disease associated with a significant burden on quality of life. While biological therapies have shown efficacy in randomized controlled trials, data on long-term real-world outcomes remain limited. This retrospective cohort study evaluated the clinical efficacy, safety, and treatment dynamics of biologics, particularly anti-IL-4 (dupilumab), over a five-year period at a tertiary medical center. Fifty-two patients with CRSwNP meeting the EPOS/EUFOREA eligibility criteria were included. Clinical parameters, including nasal polyp score, SNOT-22, and olfactory function, were assessed across follow-up intervals. Anti-IL-4 therapy demonstrated the most consistent and sustained improvements in all clinical parameters, with a significant proportion of patients maintaining response beyond 36 months. A subset of patients underwent interval extension of dupilumab injections without loss of efficacy. Subdomain analysis of the SNOT-22 questionnaire revealed improvements predominantly in nasal and emotional domains. Treatment response, assessed according to the EUFOREA criteria, favored anti-IL-4 over anti-IL-5 and anti-IgE. Side effects were infrequent and mostly mild. These findings support the durable effectiveness of biologics in real-world CRSwNP management and suggest that tapering down the injection intervals may be a feasible strategy for selected patients. Further studies are needed to refine treatment response definitions and optimize patient-specific therapeutic approaches. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory disorder of the upper airways, severely impacting quality of life. Dupilumab, targeting type 2 inflammatory pathways, is effective in managing severe, uncontrolled CRSwNP. However, the comparative accuracy of endoscopic scoring systems in monitoring therapeutic response to dupilumab remains unclear. This study compared the accuracy of the nasal polyp score (NPS) and the modified Lund–Kennedy endoscopic score (M-LKS) in assessing dupilumab response. Methods: A retrospective cohort analysis included 66 severe CRSwNP patients treated with dupilumab at Padua University. Endoscopic scores (NPS and M-LKS), patient-reported outcome mesures (PROMs), and clinician-reported outcome measures (CROMs), including peak nasal inspiratory flow (PNIF) and the Sniffin’ Sticks test, were evaluated at baseline and over 24 months. Results: Both NPS and M-LKS showed significant reductions over time (p < 0.001), significantly correlating with PNIF (p < 0.001). Given time and patient, PNIF emerged to be the only covariate related to endoscopic scores. No significant differences were observed between NPS and M-LKS regarding clinical outcome associations, suggesting equivalent accuracy. PNIF was identified as a critical predictor of endoscopic improvement, highlighting its clinical utility. These findings reinforce the role of standardized endoscopic metrics in assessing the efficacy of biologic therapies for CRSwNP. Full article

Background: Olfactory recovery plays an important role in improving the quality of life in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP), and Dupilumab therapy shows promising results. The Nasal Polyp Score (NPS), Visual Analog Scale (VAS) for olfactory disorders (ODs), and the Sniffin’ Sticks 16-item identification test (SS-I) are three of the main indices of efficacy in CRSwNP treatment. Although mechanical obstruction appears to be a major cause of olfactory disorders in this condition, the three indices can often vary with different trends. Aim: The aim is to assess whether there is a correlation between the sense of smell recovery and the volumetric reduction in polyps and to assess how the reduction in NPS affects the improvement in olfactory symptoms. Methods: An observational monocentric retrospective cohort study was conducted on a sample of 50 patients, enrolled in treatment with Dupilumab for 12 months at the ENT Unit of Rodolico Hospital. We investigated the relationship between NPS changes and olfactory recovery using the Sniffin’ Stick 16-item identification test and the VAS for ODs at baseline and follow-up endpoints (1-, 3-, 6-, 9-, and 12-month assessments). Results: During the follow-up, according to the data in the literature, the patients showed a faster improvement in terms of SS-I and VAS for ODs than expressed in terms of NPS variation. Conclusions: This study shows that, in patients treated with Dupilumab, there is no strong correlation between the reduction in NPS and the recovery of the sense of smell evaluated by an improvement in the SS-I and VAS for ODs in the 12 months of follow-up, suggesting that, in patients with CRSwNP, the improvement in olfactory symptoms following treatment with Dupilumab is mainly related to its anti-inflammatory effects and not to the reduction in mechanical obstruction caused by nasal polyps. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are mutually correlated with Type-2 inflammation. Dupilumab is effective in uncontrolled and relapsing CRSwNP. However, the precise characterization of Type-2 inflammation and the impact of previous surgery on clinical outcomes need clarification. Methods: We present a prospective observational study on a 38 CRSwNP-patient cohort, whose Type-2 endotype was confirmed after a multidisciplinary approach shared among ENTs, pneumologists and allergologists. Patients were treated with dupilumab and evaluated at 15 days and 1-3-6-12-18-24-30 months, focusing on clinical (VAS, nasal polyp score—NPS), radiological (Lund-Mackay) and quality of life (SNOT-22) parameters, as well olfactory function, asthma control, variation of Type-2 markers and number and extent (ACCESS score) of previous surgeries. Results: We confirmed the efficacy of dupilumab in total and sub-items VAS, NPS, SNOT-22 and sniffing score, as well as Lund–Mackay score improvements, observable and significant after 2 weeks of treatment (p < 0.0001) and long-lasting over 30 months. Good to excellent response criteria to biologic treatment at 6 months was observed in 30/32 patients. Comorbid asthma reached rapid control (p < 0.0001) and exhaled nitric oxide normalization was achieved. One single “not adequate” surgery showed a trend to milder improvement, as well as a higher ACCESS score to better olfactory outcome. Conclusions: The accurate selection of uncontrolled relapsing CRSwNP in terms of Type-2 endotyping by multidisciplinary approach can maximize dupilumab efficacy. The number and extent of previous surgeries may differentiate the response, although this effect is difficult to catch in real life. “Adequate” ESS surgery before dupilumab may drive mostly effective disease control. Full article

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) poses significant therapeutic challenges. The introduction of Mepolizumab, an anti-interleukin-5 monoclonal antibody, offers a new therapeutic option for patients with severe, uncontrolled CRSwNP. This prospective observational study aims to assess the efficacy and safety of Mepolizumab for treating severe CRSwNP in Italy. Methods: A single-center prospective observational study conducted in real-life settings with the patients of our center. Prior to enrollment, each patient underwent an interdisciplinary evaluation involving a pulmonologist and an allergologist if deemed necessary. All patients who were referred for treatment with Mepolizumab in compliance with the AIFA guidelines and the EPOS/EUFOREA update were included in the study population: (1) subjects who were over the age of 18, (2) who had severe CRSwNP, (3) whose condition was not successfully managed with standard therapies alone, and (4) whose blood eosinophil counts were greater than 150 cells/mL. Mepolizumab was administered subcutaneously through a 100 mg injection once every four weeks in addition to the standard-of-care therapy. Results: At the end of the enrollment process, 20 patients with severe CRSwNP were enrolled. Significant improvements were observed in Nasal Polyp Score, quality of life (SNOT-22; p < 0.05), and nasal obstruction and rhinorrhea (p < 0.05), while no significant improvements were seen in olfactory function (p < 0.05). Eosinophil levels also significantly decreased (p < 0.05). Conclusions: Mepolizumab effectively manages severe CRSwNP, showing improvements in symptom control and quality of life with an acceptable safety profile. Full article

Background: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are chronic respiratory conditions that frequently coexist. However, an integrated assessment tool for both conditions is currently lacking. This study aimed to develop and preliminarily evaluate a composite score capable of simultaneously assessing asthma and CRSwNP in comorbid patients. Methods: An expert panel comprising three pulmonologists, one allergist/clinical immunologist, and four ear, nose and throat (ENT) specialists developed a tool to capture asthma and CRSwNP severity. The tool (D’Amato-De Corso score, or DAMADECO score) incorporates eight parameters, four specific to asthma and four specific to CRSwNP, to assign individual scores for each condition. A composite score is then calculated to reflect the overall disease burden (ranging from −8: poor control and +8: optimal control). A retrospective pilot study was conducted to evaluate the tool. Results: The DAMADECO composite score was applied to 21 comorbid patients. The mean partial scores for asthma and CRSwNP were −1.57 and −1.67, respectively, with a mean total composite score of −3.24. A total of 13 out of 21 patients had uncontrolled domains in both diseases, while fewer patients had only uncontrolled domains in asthma (1/21) or CRSwNP (6/21). The DAMADECO score also allows researchers to track disease progression and monitor treatment effectiveness. Conclusions: The preliminary results suggest that the DAMADECO score is a promising tool for simultaneously assessing asthma and CRSwNP, addressing the unmet need for an integrated approach to comorbid respiratory diseases. Further validation studies are needed to validate the tool in larger patient populations. Full article

Sinonasal squamous cell carcinoma (SNSCC) is a rare tumor with high mortality and recurrence rates. However, SNSCC carcinogenesis mechanisms and potential therapeutic drugs have not been fully elucidated. This study investigated the key molecular mechanisms and hub proteins involved in SNSCC carcinogenesis using proteomics and bioinformatic analysis. Dysregulated proteins were validated by RT-qPCR in SNSCC and nasal polyp (NP) tissues. Proteomic analysis revealed that differentially expressed proteins were clustered using MCODE scores ≥ 4 into three modules. The specific hub proteins in each module were analyzed in carcinogenesis pathways using STRING, highlighting potential mechanisms of histone modification and spliceosome dysregulation. Spliceosome components SNRNP200 and SF3A3 were significantly downregulated in SNSCC by RT-qPCR. Web-based applications L1000CDS² and iLINCS were applied to identify 10 potential repurposable drugs that could reverse the gene expression pattern associated with SNSCC. Docking studies of TAF1, a protein in histone modification, with these 10 small molecule inhibitors indicated OSI-027 to be the most promising due to its strong binding interactions with key residues. These findings suggest that hub proteins involved in the underlying mechanism of SNSCC carcinogenesis may serve as valuable targets for drug development, with OSI-027 emerging as a novel candidate against TAF1 in SNSCC. Full article

Background and Objectives: Chronic rhinosinusitis (CRS) is a complex inflammatory condition of the nasal passages that severely impairs quality of life. Type 2 CRS is characterized by eosinophilic inflammation, driven by cytokines like IL-4, IL-5, and IL-13. These cytokines are key to CRS pathogenesis and contribute to a heavy disease burden, especially with comorbidities. This study assessed dupilumab, a monoclonal antibody targeting IL-4 and IL-13 signaling, to evaluate its efficacy in reducing the disease burden in patients with CRS with nasal polyps (CRSwNP). Materials and Methods: The patients received subcutaneous dupilumab for 42 weeks. The outcomes included Nasal Polyp Score (NPS); Sino-Nasal Outcome Test (SNOT-22), Numeric Rating Scale (NRS), and Visual Analog Scale (VAS) scores; total IgE; and olfactory function. Results: Significant improvements were observed across the NPS and SNOT-22, NRS, and VAS scores after 42 weeks. Their total IgE levels were reduced, though a transient increase in peripheral eosinophilia appeared at 16 weeks. The patients also reported substantial improvements in olfactory function and high satisfaction with the treatment, supporting dupilumab’s potential in reducing both symptom severity and inflammation in CRSwNP. Conclusions: These results indicate that dupilumab may be an effective treatment for CRSwNP, offering significant symptom relief, improved olfactory function, and enhanced quality of life. High satisfaction levels suggest that dupilumab may provide therapeutic advantages over the conventional CRS treatments, though further studies are warranted to confirm its long-term benefits. Full article

Background: This study aims to evaluate the efficacy and safety of mepolizumab in the treatment of severe uncontrolled CRSwNP with or without comorbid asthma in a real-life setting over the first six months of therapy. Methods: A total of 45 patients with nasal polyps with or without comorbid asthma were treated with mepolizumab (100 mg q4w) for 6 months. The following outcomes were assessed before therapy (V⁰), and after 6 months (V¹): endoscopic nasal polyp score (NPS), nasal congestion score (NCS), sinonasal outcome test (SNOT-22), visual analog scale (VAS), nasal flow rate (PNIF), olfactory test (SS-I), and asthma control test (ACT). Blood eosinophil count, oral steroid intake, and rescue surgery were also measured. Results: We found a statistically significant improvement in NPS, NCS, SNOT-22, overall VAS, PNIF, SS-I, and ACT. In addition, we observed a decrease in blood eosinophils count. Mepolizumab was well tolerated, and no patients interrupted the treatment during the follow up. Conclusions: Our real-life study confirmed the efficacy and tolerance of mepolizumab prescribed for CRSwNP with or without asthma. The safety profile of mepolizumab was consistent with previous reports. Full article

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease often resistant to standard treatments. Dupilumab, a monoclonal antibody targeting the IL-4α receptor, has shown efficacy in CRSwNP, but a significant subset of patients do not respond to this therapy. This study aims to investigate pretreatment complete blood count (CBC)-based inflammatory biomarkers as predictors of response to dupilumab in patients with CRSwNP. Methods: This mono-centric, retrospective, single-arm longitudinal cohort study included 80 patients with uncontrolled CRSwNP who received dupilumab treatment at the Medical University of Graz. Patients were classified into responder and non-responder groups based on a reduction of >1 in nasal polyp score (NPS) and a sinonasal outcome test-22 (SNOT-22) score <40 points at six months. Pretreatment CBC-derived biomarkers, including eosinophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation indices including the aggregate inflammation systemic index (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), were analyzed for their predictive value. Results: Of the 80 patients, 72.5% were classified as responders, while 27.5% were non-responders. A significant positive correlation was found between baseline eosinophil count and NPS reduction (p = 0.027), suggesting that higher eosinophil levels may predict higher NPS reduction in dupilumab treatment. However, no significant associations were observed between NLR, PLR, and systemic inflammation indices with treatment outcomes. Conclusions: Pretreatment eosinophil count may serve as a potential biomarker for predicting nasal polyp reduction in dupilumab treatment of CRSwNP. Other CBC-based inflammatory markers did not show significant predictive value. Further prospective studies are needed to validate these findings and explore additional, reliable biomarkers to optimize treatment outcomes for CRSwNP patients. Full article

Background/Objectives: Benralizumab is a monoclonal antibody that targets the interleukin-5 receptor (IL-5Rα), leading to the rapid depletion of blood eosinophils. RCTs have demonstrated efficacy in patients with severe eosinophilic asthma (SEA). The aim of this study was to assess the efficacy of benralizumab on sinonasal outcomes in a real-life setting in patients with SEA and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We included 25 patients (mean age: 57.47 years, range: 35–77, F/M = 12:13) who were prescribed 30 mg benralizumab every month for the first three administrations and then every 2 months. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test-22 (SNOT-22) and nasal polyp score (NPS) over a 24-month treatment period. Secondary endpoints included measuring the effects on nasal obstruction and impaired sense of smell. Results: The mean NPS score decreased significantly from 5.11 ± 1.84 at baseline to 2.37 ± 1.96 at 24 months. The mean SNOT-22 decreased from 57 ± 15.30 at baseline to 26 ± 16.73 at 24 months. The SSIT-16 mean score improved with an increase in olfactory performance from 5.23 ± 2.58 at baseline to 7 ± 3.65 at 24 months. Moreover, 8/25 patients (32%) required rescue treatment with systemic steroids and 2 patients required endoscopic sinus surgery. Conclusions: While the improvement may not seem optimal at 12 months, a progressive enhancement was noted during the second year of treatment. Despite our data showing an improvement in quality of life and a reduction in the size of nasal polyps, no significant improvement in olfactory sensitivity was observed. In addition, in several patients, rescue treatments were required to maintain control of nasal and sinus symptoms. A careful risk–benefit assessment is therefore needed when deciding to continue treatment, weighing the potential for further improvement against the risks of complications. Such decisions should always be made in the context of a multidisciplinary team. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impacts quality of life and often presents therapeutic challenges, with biologics like dupilumab showing promise in managing severe, uncontrolled cases. The aim of this study was to assess the influence of overweight on the effectiveness of dupilumab in patients with uncontrolled CRSwNP. This retrospective study analyzed treatment outcomes of 75 CRSwNP patients receiving dupilumab, categorizing them into underweight/normal-weight (BMI ≤ 24.9 kg/m²) and overweight/obese (BMI ≥ 25 kg/m²) groups. Outcome measures included changes in nasal polyp score (NPS) and sinonasal outcome test (SNOT-22) scores. Results demonstrated that the underweight/normal-weight group experienced significantly greater improvements in NPS and a higher rate of total NPS improvement compared to the overweight/obese group. While SNOT-22 scores improved in both groups, no significant differences were observed. Among patients with comorbid asthma, the underweight/normal-weight subgroup also showed significantly better outcomes, including greater reductions in both NPS and SNOT-22 scores. Multiple regression analysis identified BMI as an independent prognostic factor for NPS outcomes. The findings suggest that overweight/obesity adversely affects the response to dupilumab in CRSwNP, emphasizing the need for personalized treatment strategies considering BMI. Full article