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Purpose: Antibody therapy for chronic rhinosinusitis with nasal polyps (CRSwNP) has been established in Germany since 2019. With limited long-term data on biologic treatment for CRSwNP, we conducted a comprehensive evaluation of our 4-year data. This monocentric study aims to assess the real-world effects of this treatment on clinical course, quality of life, treatment adherence, biologic switching, dual therapy, and comorbidities., Methods: We retrospectively analysed biologic therapy data in patients with severe chronic rhinosinusitis with nasal polyps. 191 patients with CRSwNP treated with Dupilumab, Mepolizumab, or Omalizumab were observed for up to 4 years in a real-life setting., Results: We observed clear symptom improvements with few side effects. No loss of efficacy or tolerability was noted during the 4-year period. Patients reported high satisfaction compared to previous therapies, with overall improved quality of life. Revision surgery or oral steroid use during biologic therapy was rare. Some patients prolonged injection intervals or discontinued steroid nasal spray. Biologic switching occurred infrequently due to side effects or inadequate response and was generally well tolerated. Many patients reported additional positive effects such as asthma or allergy symptom improvement and reduced medication intake., Conclusion: In summary, this study confirms the potency and tolerability of biologics for CRSwNP treatment, with sustained efficacy over 4 years. Biologic switching is a viable option for inadequate response or intolerable side effects. Therapy positively impacts Th2 comorbidities, corticosteroid requirements, surgery need, and overall compliance remains high., Clinical Trial Registration: Project No.: 22-0802. Registry name: Biologika bei Patient*innen mit chronischer Sinusitis mit Nasenpolypen., (© 2024. The Author(s).)

Objective: Evaluating the possibility of predicting chronic rhinosinusitis with nasal polyps (CRSwNP) disease course using Artificial Intelligence., Methods: We prospectively included patients undergoing first endoscopic sinus surgery (ESS) for nasal polyposis. Preoperative (demographic data, blood eosinophiles, endoscopy, Lund-Mackay, SNOT-22 and depression PHQ scores) and follow-up data was standardly collected. Outcome measures included SNOT-22, PHQ-9 and endoscopy perioperative sinus endoscopy (POSE) scores and two different microRNAs (miR-125b, miR-203a-3p) from polyp tissue. Based on POSE score, three labels were created (controlled: 0-7; partial control: 8-15; or relapse: 16-32). Patients were divided into train and test groups and using Random Forest, we developed algorithms for predicting ESS related outcomes., Results: Based on data collected from 85 patients, the proposed Machine Learning-approach predicted whether the patient would present control, partial control or relapse of nasal polyposis at 18 months following ESS. The algorithm predicted ESS outcomes with an accuracy between 69.23% (for non-invasive input parameters) and 84.62% (when microRNAs were also included). Additionally, miR-125b significantly improved the algorithm's accuracy and ranked as one of the most important algorithm variables., Conclusion: We propose a Machine Learning algorithm which could change the prediction of disease course in CRSwNP., (© 2024 The Author(s). Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent chronic inflammatory condition affecting the nose and paranasal sinuses, posing a significant socio-economic impact with substantial challenges in management. Biologics targeting type 2 inflammation such as dupilumab, have emerged as promising options. This study addresses a critical knowledge gap by comprehensively evaluating the 3-year impact of sustained dupilumab therapy in CRSwNP., Methods: A multicentric, retrospective collection of real-world data from five tertiary referral centers in Germany was conducted, enrolling 150 adult patients. The study investigated patient-reported outcomes, disease-specific indices and clinical measures, focusing on therapeutic response persistence, adverse events, and factors influencing treatment continuity., Results: Results indicate significant improvements in clinical parameters from baseline (n = 150) with sustained effectiveness after 36 months (n = 138) as indicated in mean score ± standard deviation. Dupilumab treatment significantly improved overall disease-related impairment (VAS score: 7.5 ± 2.5 to 1.6 ± 1.3) and rhinosinusitis symptoms (SNOT-22: 59.4 ± 19.4 to 18.0 ± 15.0). Nasal Polyp Scores (NPS) decreased (5.3 ± 1.8 to 0.7 ± 1.1), and olfactory function improved (3.2 ± 2.5 to 8.4 ± 2.8), with three out of four patients achieving normosmia or hyposmia after 36 months. An "Excellent" treatment response according to EUFOREA23 criteria was observed in 76.5% of patients after 36 months. Sixteen patients discontinued Dupilumab, 12 permanently. Adverse events totaled 69 in 48 patients, commonly self-limiting., Conclusion: The study highlights the enduring effectiveness and lack of habituation to dupilumab after a sustained therapy of 3 years, providing valuable insights into its long-term therapeutic implications for CRSwNP patients., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: To analyze recurrence patterns of chronic sinusitis with nasal polyposis (CRSwNP) in patients who underwent complete FESS and identify predisposing factors for different patterns of recurrence., Methods: Retrospective analysis of patients with CRSwNP who underwent complete FESS at our tertiary medical center. Recurrence patterns were classified into edema, polyp and normal endoscopy, as well as into early (within 6 months) and late recurrence. Statistical analysis to identify risk factors for recurrence included univariate, multivariate logistic regression and cox regression models., Results: 114 patients were included with an average follow-up of 27 months. 91% were categorized as type-2 inflammation. Recurrence was observed in 65.8% of patients within a mean of 12.9 months. 46.7% had polyp recurrence while 53.3% had edema recurrence. Early recurrence was observed in 41%. Serum eosinophilia > 500 cells/uL was found to be significantly associated with recurrence (RR = 1.62, p-value = 0.046), and particularly with polyp recurrence (RR = 3.9, p-value = 0.001). No predictive factors for early recurrence were identified. Edema recurrence was managed with intranasal corticosteroids while polyp recurrence required systemic therapy including biologic therapy., Conclusions: In this study, two thirds of patients experienced post operative recurrence, either mucosal edema or nasal polyps, with similar frequency during an average follow up of over 2 years. Early recurrence was noted in 41% of recurrent cases. Serum eosinophils > 500 cells/uL was the only risk factor for recurrence on multivariate analysis, more accurate markers are needed for improved treatment allocation to CRSwNP patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Dupilumab exerts clinical effects, including improved sinus opacification, olfactory function, and quality of life, in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNPs). Meanwhile, only a few studies have reported its effects on nasal airway resistance and olfactory function, particularly in the Japanese population. Predictors of response remain unclear., Objective: To assess the comprehensive efficacy and therapeutic response to dupilumab in patients with severe CRSwNP with comorbid asthma., Methods: In 16 adult patients with severe CRSwNP with comorbid asthma, the efficacy of 48-week dupilumab treatment, including olfactory function measured by a T&T olfactometer, nasal airway resistance measured by rhinomanometry, nasal polyp score, Lund-Mackay computed tomography score, and 22-item Sinonasal Outcome Test (SNOT-22), was assessed. Regarding asthma, the annualized rate of exacerbations, 7-item Asthma Control Questionnaire (ACQ-7), and spirometry were assessed. Treatment responsiveness was analyzed., Results: With 48-week dupilumab treatment, olfactory function, nasal airway resistance, nasal polyp score, Lund-Mackay computed tomography score, and SNOT-22 scores improved significantly. Regarding comorbid asthma, the annualized rate of exacerbations decreased, and ACQ-7 scores and lung function improved significantly. According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020/European Forum for Research and Education in Allergy and Airway Diseases criteria, 15 patients (94%) were moderate-to-excellent responders at 48 weeks of treatment. Patients with higher SNOT-22 scores, ACQ-7 scores, the rate of asthma exacerbations in the previous year, and blood eosinophil counts benefited more from the treatment., Conclusion: Dupilumab improved upper and lower airway outcomes especially in patients with severe CRSwNP with comorbid, poorly controlled asthma., Trial Registration: UMIN Clinical Trials Registry: UMIN000038669., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

To investigate disparities in sensitisation to Staphylococcus aureus enterotoxin A/B (SEA/SEB) and olfactory function in patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), those with CRS without nasal polyps (CRSsNP), and healthy controls who underwent septoplasty only. We retrospectively reviewed the medical records of 388 subjects aged ≥ 8 years, collected between January 2021 and June 2023. We analysed patient demographics, medical history, serum IgE levels against staphylococcal enterotoxins (SEs), and serum total IgE levels against inhalant allergens. We performed olfactory and taste function tests in the participants to evaluate the relationship between olfactory function and SEs. Of 388 patients enrolled, 145 were healthy controls, 111 had CRSsNP, and 133 had CRSwNP. The prevalence of SEA/SEB positivity was significantly higher among the patients with CRSwNP than among those in the CRSsNP and healthy controls. The olfactory test results showed significant differences among the groups; anosmia was observed in 9.7% of healthy controls, 22.7% of patients with CRSsNP, and 45.1% of patients with CRSwNP. Olfactory threshold deterioration was evident in patients with CRS. Distinction and identification were more impaired in patients with CRSwNP than in those of the other groups. Finally, the olfactory function scores decreased as the serum levels of SEs increased. Sinusitis patients seem to suffer from perceiving odours, and patients with CRSwNP have difficulty distinguishing odours. Olfactory function test scores decreased in patients with a history of asthma, and as serum levels of staphylococcus enterotoxin and blood eosinophil percentage increase. Furthermore, our result suggests a potential role for SE sensitisation and eosinophil percentage in deteriorating olfaction, especially in patients with CRSwNP., (© 2024. The Author(s).)

Background: Anti-IL-4 receptor α antibody (dupilumab) has demonstrated favorable sinonasal outcomes for chronic rhinosinusitis with nasal polyps (CRSwNP), which is mainly caused by type 2 inflammation. Although increased blood eosinophil levels and injection site symptoms are frequently observed as acute adverse events (AEs) of dupilumab, limited knowledge is available regarding the late AEs of dupilumab for CRSwNP., Objectives: We investigated the late AEs following the initiation of dupilumab treatment for CRSwNP., Material and Methods: Fifty-one patients with CRSwNP treated with dupilumab for > 3 months were enrolled, and their clinical data were collected from their medical records., Results: Six (11.8%) patients experienced late AEs. One case of eczema with pruritus, one case of psoriasis-like dermatitis, two cases of severe rash, one case of malignant lymphoma, and one case of alopecia areata were observed. Skin disorders were the most common late AEs in this study. It is a Th1-inflammatory disease, and its mechanism is thought to be due to the immune imbalance caused by dupilumab. We could not confirm whether malignant lymphoma in our case was caused by dupilumab use., Conclusions and Significance: Skin disorders are often late AEs associated with dupilumab; therefore, careful monitoring after dupilumab initiation should be considered.

Purpose: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a common disease, which was previously approached with sinus surgery or systemic corticosteroids. The advent of biological therapies radically changed the approach to this disease. On the other hand, there is scarce scientific evidence of how specific subsets of patients respond to this treatment., Methods: this is a monocentric, prospective study investigating the long-term efficacy on biweekly 300 mg dupilumab therapy in CRSwNP, prescribed to 61 patients. Patients were evaluated at baseline and every 2 months for the first 6 months, then at 9, 12, 16, 20 and 24 months., Results: dupilumab proved to be an effective treatment, neatly improving both subjective and objective measurements in CRSwNP. The main finding of the study is the difference between specific subgroups of patients: while the overall response is similar, patients with Th2 comorbidities such as asthma and atopy tend to reach a stable response later, with the improvement ongoing even after 6 months of therapy, while non-asthmatic, non-atopic patients attain an earlier stability in response., Conclusions: dupilumab provides an excellent long-term control of CRSwNP, but the response in asthmatic and atopic patients appears to be different and delayed when compared to non asthmatic and non atopic ones., (© 2024. The Author(s).)

Acute invasive fungal sinusitis (AIFS) classically presents as an aggressive fungal infection that can spread beyond its origin in the sinuses in immunocompromised patients. Although there have been reports of AIFS in immunocompetent, non-diabetic patients, it is extremely rare and the true mechanism behind it is unknown. A thirty-eight year old immunocompetent, non-diabetic woman underwent bilateral ESS for chronic rhinosinusitis with nasal polyps at a tertiary care center and post-operatively developed AIFS. Patient underwent uncomplicated ESS, was packed with foam containing triamcinolone and discharged on steroid rinses and a prednisone taper. Surgical pathology demonstrated left-sided colonization with non-invasive fungal elements consistent with a mycetoma. She presented on post-operative Day 11 with headache and left-sided retro-orbital pain. A culture of her left nasal cavity grew Rhizopus spp and MRI demonstrated evidence of invasive fungal infection of left sphenoid mucosa as well as inflammatory changes in the left orbit centered at the orbital apex. She was started on amphotericin and underwent a left-sided debridement with biopsies which demonstrated angioinvasive fungal disease. Her vision in her left eye worsened to 20/800 and she was treated with transcutaneous retrobulbar injection of amphotericin B. After stable interval imaging she was discharged on a long-term course of antifungals. Extensive immunologic work-up was unremarkable. We describe a case of an immunocompetent patient who developed AIFS after sinus surgery for CRS and a mycetoma likely as a result of local immune suppression and post-surgical trauma. Laryngoscope, 134:4213-4216, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

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/m 2 ) and overweight/obese (BMI ≥ 25 kg/m 2 ) 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.

Background: The clinical phenotypes of CRS, such as the presence or absence of polyps, cannot well reflect the pathophysiological mechanisms and characteristics of patients. Only by distinguishing the different internal types of CRS can we individualize patients more accurately., Objective: To investigate the clinical characteristics of chronic rhinosinusitis with different cell types (CRSwNP), and to provide a reference for the diagnosis and treatment of CRSwNP., Materials and Methods: The cytological endotypes of CRSwNP were divided into five groups by cluster analysis., Results: There was a significant difference in the proportion of CRSwNP with different endotypes. There were significant differences in peripheral blood eosinophils, cerebrovascular disease, and unilateral and bilateral nasal polyps among CRSWNP patients with different cytological types., Conclusions: Mixed CRSwNP and eosinophilic CRSwNP are the most common, while neutrophilic CRSWNP is the least common. Eosinophilic CRSwNP is more common in bilateral nasal polyps, with a high recurrence rate and a high probability of olfactory dysfunction. Neutrophilic CRSwNP is more common in elderly patients with cardiovascular and cerebrovascular diseases. Compared with total serum IgE, the percentage of eosinophils in peripheral blood is more helpful for the diagnosis of eosinophilic CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent medical condition. Type 2 inflammation signs CRSwNP in western countries. Type 2 inflammation leads to nasal airflow limitation. Budesonide aqueous nasal spray (BANS) is an intranasal corticosteroid (INCS); it has been launched in the early 1980s. BANS is indicated for treating allergic rhinitis, nonallergic rhinitis, and nasal polyps (both as treatment and prevention after surgery). Consolidated evidence documented its efficacy in treating CRSwNP. In addition, BANS is safe with negligible local and systemic side effects. Recent guidelines for patients with CRSwNP recommend using INCS as the first line in many situations. In particular, patients may assess the perception of symptoms' severity using the Visual Analog Scale (VAS). A score >5/10 means uncontrolled symptoms in both diseases and requires adequate treatment. BANS could appropriately be used in patients with uncontrolled symptoms and/or moderate/severe nasal obstruction. In addition, BANS may adequately integrate surgery and biologics for CRSwNP management. In conclusion, BANS represents a valuable option in managing patients with type 2-mediated CRSwNP.

Background: 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., Materials and Methods: 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)., Results: 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., Conclusions: 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.

Objectives: Dupilumab, an anti-IL-4 receptor monoclonal antibody (mAb), was recently approved for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP). The main objective of this study was to assess whether previous exposure to biological treatment affected the clinical outcomes in CRSwNP and asthma patients, treated with dupilumab over time. A collateral secondary objective was to analyse the effects over time of dupilumab in patients with and without aeroallergen sensitization., Methods: Single-centre retrospective observational study on severe CRSwNP patients treated with dupilumab. Nasal polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), aeroallergen sensitization, total serum IgE levels, and blood eosinophil counts were assessed at baseline and after 4, 6 and 12 months., Results: 42 patients were included, 40 (95.2%) had asthma. Twenty-one (50%) patients received dupilumab without prior biological treatment (Group A: naive) and 50% switched to dupilumab from previous biological treatment (Group B: pre-treated). NPS, VAS symptoms, SNOT-22 improved significantly after 12 months treatment in both groups of patients ( p  < 0.001). After 12 months, VAS overall symptom score showed a significant reduction from 6 (IQR, 4.6-8.6) and 6 (IQR, 3.8-7.1) for Group A and Group B patients respectively, to 1.2 (IQR, 0.8-2.7) and 1.2 (IQR, 0.2-2.5); NPS from 6 (IQR, 4.0-7.0) and 5 (IQR, 3.5-6.0), respectively, to 1 (IQR, 0.0-2.0) and 0 (IQR, 0.0-3.0) and SNOT-22 from 64 (IQR, 56-78) and 71 (IQR, 47.5-76.0) respectively, to 5.5 (IQR, 4-21) and 6 (IQR, 4-15). IgE reduced from 57 to 22.1 and from 46.9 to 30.2 in Group A and Group B respectively ( p  < 0.001)., Conclusions: Dupilumab improves symptom severity, polyp size, and health-related quality of life, regardless of the presence or absence of comorbid aeroallergen sensitization and previous administration of biologic therapy.

Background: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus., Methods: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses., Results: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each., Conclusions: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Objective: This study evaluated the expression of TIM-3 and its influence on macrophage polarisation in recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: We detected TIM-3 expression in serum and tissue samples of healthy controls (HC), primary CRSwNP, and patients with recurrent CRSwNP. Macrophage markers were detected among three groups, and their correlations with TIM-3 levels were examined. Macrophages from circulating blood were collected and used to examine the impact of TIM-3 on polarisation in vitro ., Results: TIM-3 levels were enhanced in the CRSwNP group compared to the HC group. Tissue immunofluorescence revealed elevated TIM-3 expression in patients with CRSwNP, and patients with multiple recurrences exhibited higher TIM-3 levels compared to their first recurrence and baseline levels. Tissue CD163 and CD206 levels were higher in recurrent CRSwNP in comparison with primary cases and HCs, and had a positive correlation with TIM-3 levels. TIM-3 overexpression promoted M2 polarisation and enhanced TGF-β1 and IL-10 secretion., Conclusions: TIM-3 expression was enhanced in patients with CRSwNP, especially in those undergoing revision surgeries. TIM-3 may be a novel biomarker for recalcitrant CRSwNP. TIM-3-driven M2 polarisation might be involved in the mechanisms of recurrent CRSwNP., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Purpose: To compare the effects of doxycycline (DOX) and conventional management in patients with refractory chronic rhinosinusitis and nasal polyps (CRSwNP)., Methods: Six databases were searched to September 2023. We retrieved studies that compared improvements in refractory chronic sinusitis-related symptoms between DOX-treated and control groups., Results: DOX significantly reduced the Lund-Kennedy (LK) score [- 0.3670 (range - 0.6173; - 0.1166); I 2  = 92.8%], the nasal polyposis score [- 0.9484 (- 1.2287; - 0.6680); I 2  = 92.5%], the patient-reported Sinonasal Outcome Test (SNOT) score [- 0.3141 (- 0.4622; - 0.1660); I 2  = 91.2%], and the nasal obstruction score [- 0.1813 (- 0.3382; - 0.0243); I 2  = 86.2%]. On subgroup analyses by the measurement timepoints, the extent of nasal polyposis was significantly lower in the DOX group during treatment, at the end of treatment, and 4 and 8 weeks later. The LK scores also indicated improvements during treatment and at the end of treatment. The SNOT score tended to decrease with time in the treatment group. Nasal obstruction symptoms improved during treatment and 4 weeks later., Conclusion: DOX enhances the postoperative endoscopic outcomes of refractory CRSwNP patients by reducing recurrent polyposis and inflammation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial., Methods: Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators., Results: Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL -1 ); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm -2 at baseline to 0 cells mm -2 at week 56 (P < .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil-derived neurotoxin was significantly reduced at weeks 24 and 56 (P < .001) and interleukin-17 at week 56 (P < .05) with benralizumab., Conclusion: Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP., (© 2024 AstraZeneca. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To measure the inflammatory cytokines of middle ear effusion (MEE) in otitis media (OM) associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) with or without nonsteroidal anti-inflammatory drug (NSAID) sensitivity to strengthen our assumption that OM is part of the same inflammatory entity. The potential individual differences between MEE inflammatory cytokines could be used in clinical practice for more individual characterization of the inflammation., Study Design: Case-control study., Setting: Tertiary referral center., Patients: Convenience sample of 24 case patients with otitis media with effusion (OME) or chronic otitis media (COM), asthma, and CRSwNP, 14 of whom had NSAID intolerance, and 8 controls with OME but no history of asthma, CRSwNP, or NSAID intolerance., Intervention: Diagnostic., Main Outcome and Measure: Inflammatory cytokines including interleukins (IL)-4, IL-5, IL-6, IL-13, and interferon gamma (IFN-γ) in middle ear effusion., Results: The MEE mass fractions of IL-5 ( p = 0.003) and IFN-γ ( p = 0.048) were higher among our case patients with OME/COM than among the controls. For IL-4 and IL-13, the mass fractions were also higher among the case patients than the controls, but this difference was not statistically significant ( p = 0.199 and p = 0.617, respectively). We found no difference between the IL-6 mass fractions of the groups. We found notable heterogeneity in individual patients' cytokine levels., Conclusions: According to our findings, OM, when present, should be considered part of the respiratory inflammatory process associated with asthma and CRSwNP. The individual differences in MEE cytokine levels could be useful as biomarkers., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently leads to olfactory dysfunction. This study aimed to assess the impact of dupilumab on CRSwNP patients, focusing on olfactory outcomes and potential correlations with other clinical factors., Methods: CRSwNP patients eligible for dupilumab therapy received subcutaneous Dupixent® injections every two weeks (300mg/2ml dupilumab). The 12-item Sniffin' Sticks Test (SST-12), fractional exhaled nitric oxide (FeNO) and Nasal Polyp Score (NPS) were assessed at baseline and after one, three, and six months. Patients also completed the Sino-Nasal Outcome Test (SNOT-22) weekly., Results: 26 CRSwNP patients were included. After one month, dupilumab led to substantial reductions in FeNO, SNOT scores, andNPS, whereas SST-12 scores improved significantly only after three months. A shift toward normosmia occurred, with 81% achieving normosmia after six months, and a drop in anosmia prevalence to 9.5%. Significant negative correlations between olfaction (SST-12) and polyp severity (NPS) at baseline and after six months were found, while no significant correlations were observed between SST-12 and FeNO or SNOT scores. Age did not correlate with olfaction., Conclusions: Dupilumab demonstrated efficacy in restoring olfaction in CRSwNP patients. Reaching normosmia in over 80% ofpatients after six months of treatment underscores the drug's effectiveness in managing this challenging symptom.

Introduction: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile evidence on the impact of medical, surgical, and biological treatment on olfactory outcomes in patients with CRSwNP., Methods: This review was conducted by 2 reviewers according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence of all the studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP)., Results: Forty-four studies were included in the qualitative synthesis. These assessed sinonasal surgery (n=23), biologics (n=15), and conventional medical treatment (n=6). The methodological quality was moderate-to-high in most. Overall, significant improvements in the sense of smell were detected with all the interventions analyzed and measured using an objective tool, a subjective tool, or both. However, most studies used different outcome measures, thus hindering comparisons between interventions, and data on clinically relevant changes were missing., Conclusion: Oral corticosteroids, biologics, and sinonasal surgery improve the olfactory impairment associated with CRSwNP. However, the heterogeneous nature of existing studies does not allow accurate comparisons.

Chronic sinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition characterized by recurring nasal polyps, often necessitating repeated interventions. Blood eosinophilia has emerged as a potential biomarker for predicting disease recurrence. The present study aims to assess the predictive significance of blood eosinophilia for the recurrence of nasal polyps. To accomplish this objective, we employed the appropriate search keywords to explore international databases such as Web of Science, PubMed, Embase, and Scopus. Through this process, we extracted scholarly articles that assessed the prognostic value of blood eosinophilia in the recurrence of nasal polyps. The statistical software STATA (version 15) was employed, along with random and fixed-effects models, to appraise the compiled data. Nine articles met inclusion criteria, with a total sample size of 1279 individuals (569 recurrent polyp individuals and 710 non-recurrent polyp individuals). Cumulative Odds ratio analysis revealed that CRSwNP is associated with high blood eosinophile percentage compared to the non-CRSwNP group (p=0.01, OR=1.26, 95%Cl (1.15,1.36). The cut-off value of blood eosinophil percentage (>0.78) had relatively good, and statistically significant predictive potential. No significant publication bias was observed for the included studies. Our findings indicate that the utilization of blood eosinophils holds significant predictive value and can serve as a valuable tool for detecting recurrence in patients with CRSwNP. Based on the outcomes of our comprehensive analysis, we propose a threshold of >0.78 as a reliable indicator for assessing the probability of recurrence in CRSwNP patients.

Objective: To investigate the frequency and nature of adverse events related to type 2 biologic use in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including dupilumab and mepolizumab., Methods: This is a single-institution retrospective study of real-world patient data. Patients were included if they have a diagnosis of CRSwNP, have undergone at least one endoscopic sinus surgery, and have taken at least two doses of dupilumab or mepolizumab between January 1, 2016, and July 1, 2023. Data collected include clinicodemographic information and past medical/surgical history. The primary outcomes are the incidence and types of adverse events. Adjusted odds ratio was calculated to compare the biologics using logistic regression. Risk factors for developing adverse events were investigated., Results: Eighty-seven patients on dupilumab and 51 patients on mepolizumab were included. Thirty-nine (45%) and 10 (20%) patients respectively encountered adverse events, which differed from phase 3 trial data. The adjusted odds ratio for adverse event rates between these two treatment groups was 3.8 (95% CI, 1.5-10.5). The most common adverse events for dupilumab were arthralgia (16%), rash (14%), and conjunctivitis or xerophthalmia (10%). The main adverse events for mepolizumab were headache (6%) and fatigue (6%). Seven dupilumab and three mepolizumab patients discontinued therapy due to adverse events. The average duration of treatment was 22.5 (range: 1-77) months for mepolizumab and 15.9 (range: 1-35) months for dupilumab., Conclusion: Dupilumab and mepolizumab have distinct adverse event profiles. This study contributes to informing clinicians' decisions regarding the use of type 2 biologics in CRSwNP patients., Level of Evidence: 3 Laryngoscope, 134:3054-3059, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS)., Methods: In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology., Results: ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%)., Conclusions: Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS., (© 2024 John Wiley & Sons Ltd.)

Introduction: Interleukin (IL)-4 and IL-13 are considered key drivers of type 2 inflammatory diseases. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both cytokines., Case Study: We report a case of a patient with uncontrolled severe asthma and other T2 inflammatory diseases (atopic dermatitis, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis) treated with dupilumab., Results: After one year of treatment, dupilumab improved asthma control together with lung function parameters and airway inflammation. Additionally, a positive impact on quality of life (QoL), evaluated by validated questionnaires, across all the diseases was observed., Conclusion: In this case report, a positive and objectively measurable of global improvement on QoL across all four T2 comorbidities was observed after treatment with dupilumab, demonstrating the important role of IL-4 and IL-13 and the existence of a unifying pathological mechanism in T2 diseases.

Background: In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2 weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24 weeks, reducing the dose of dupilumab to once every 4 weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended., Methods: The course of 29 patients with severe CRSwNP, type‑2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4 weeks, thereafter up to 6 weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany)., Results: All patients showed an excellent improvement within the first 3 months. The dupilumab application interval was extended to 4 weeks after 7-31 months (median 13 months) and to 6 weeks (n = 9) after 17-35 months (median 23 months). No recurrent polyps or symptoms were subsequently observed., Conclusion: In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to 4 and potentially 6 weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential., (© 2024. The Author(s).)

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) often alters sleep quality. Dupilumab emerged as an innovative and effective therapy for refractory/recurrent severe CRSwNP. The aim of this observational retrospective study was to evaluate the sleep quality in patients with CRSwNP who underwent treatment with dupilumab., Materials and Methods: Forty-five patients treated with dupilumab for CRSwNP were enrolled. Clinical parameters (age, sex, comorbidities, Nasal Polyp Score - NPS, Asthma Control Test - ACT), nasal cytology, quality of life (Sino Nasal Outcome Test 22 - SNOT-22), sleep quality (Pittsburgh Sleep Quality Index - PSQI, Epworth Sleepiness Scale - ESS), and risk of sleep apnea (STOP-BANG) were recorded before treatment (T0), and after 3 (T1), 6 (T2), and 12 months (T3)., Results: NPS, ACT and SNOT-22 total score improved during treatment (p < 0.05). Meanwhile, all sleep parameters evaluated with SNOT-22, ESS and PSQI improved over time (p < 0.001), expect for PSQI Use of sleeping medications. Indeed, sleep drugs are rarely used before and during the treatment. The global sleep quality was classified as poor in 88.9 % of cases at T0 and decreased to 5.7 % at T3. A high risk of sleep apnea was revealed by the STOP-BANG in 68.9 % of cases at T0 and 2.8 % of patient at T3 (p < 0.001)., Conclusions: Dupilumab improves the sleep quality and reduce the risk of sleep apnea in patients with severe CRSwNP. Its favorable effect occurs within 3 months and is maintained during the treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation. Mepolizumab was approved for the treatment of CRSwNP in 2021, it may be useful to evaluate its safety profile in a real-world setting., Aim: This work aimed to prospectively highlight the effectiveness and safety profile of Mepolizumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina., Methods: An observational cohort study was carried out considering all patients treated with Mepolizumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions., Results: A total of 30 patients were treated with Mepolizumab, one patient discontinued the treatment. A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, -33 and - 43, p < 0.001 for both comparisons; NPS, 0 and - 1, p < 0.001 for both comparisons). The median (Q1-Q3) sniffin' sticks test score increased from 7 (6-8) at the 6th month to 11 (10-13) at the 12th month. Seven patients (24.1 %) reported pain at the injection site, accompanied by redness, warmth, and tenderness within the first 24 h post-injection with a median duration of three days from the onset., Conclusions: Given the optimal treatment response and the minimal adverse effects observed, clinicians should consider Mepolizumab a safe and effective treatment in CRSwNP patients. Further studies in real-life setting are necessary to better understand the long-term effects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.

Background: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP)., Methodology: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed., Results: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo., Conclusions: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Purpose: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally., Methods: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology., Results: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia., Conclusions: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy., (© 2024. The Author(s).)

Objective: Our previous study revealed that serum amyloid A (SAA) levels in polyp tissues could serve as a biomarker for the prediction of corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, their association with disease control status in the patients after endoscopic sinus surgery remains to be assessed., Methods: Polyp tissues and control uncinate process mucosa were collected from 48 patients with CRSwNP and 10 healthy control subjects. SAA expression was examined using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of SAA in nasal polyps. The clinical characteristics of 2 CRSwNP subtypes (SAA high and SAA low ) were evaluated., Results: The SAA expression levels in polyp tissues were significantly elevated both in non-eosinophilic and eosinophilic CRSwNP as compared to the healthy controls. In patients with CRSwNP, the tissue SAA level was significantly higher in the disease-controlled patients than those of the partly controlled and uncontrolled. ROC curve analysis revealed that a cut-off value of 114.9 ng/mL for the tissue SAA level predicted the patients with disease-controlled status with 93.33% sensitivity and 63.64% specificity (AUC = .8727, P < .001). Furthermore, The SAA high subgroup showed higher tissue eosinophil numbers and percentage of the disease-controlled patients compared to the SAA low subgroup., Conclusions: Our findings suggest that measurements of SAA in polyp tissues may provide useful information for evaluating CRSwNP conditions, especially identifying the CRSwNP patients with disease-controlled status after endoscopic sinus surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also affect CRSwNP regardless of asthma. We aimed to assess the effect of omalizumab treatment on CRSwNP accompanying severe allergic asthma (SAA) patients. Clinical data including spirometry measurements, serum/nasal secretion biomarker levels were collected. NP scores and CRS scores (Lund-Mancay [LM] scores) were also recorded before omalizumab treatment, as well as at the 4th and 12th months of omalizumab treatment. Twenty-one patients with both CRSwNP and SAA who underwent omalizumab therapy were assessed. There was a significant difference among forced expiratory volume (FEV1), ACT scores, NP scores, LM scores, serum IgE, and blood eosinophil levels of the patients before omalizumab therapy at the 4th and 12th months of omalizumab treatment. A significant negative correlation was observed between ∆FEV1 and ∆NP scores (r=-0.485), between ∆ACT and ∆NP scores (r=-0.469), and ∆ACT and ∆LM scores (r=-0.436). When we grouped the patients who benefited from 1 year of omalizumab therapy and those who did not in terms of NP, there was no difference between the two groups related to local eosinophil and local IgE levels in the nasal polyp biopsy. Omalizumab treatment is effective for asthma and CRSwNP in patients with CRSwNP accompanied by SAA. Improvement in asthma is associated with improvement in CRSwNP. The efficacy of omalizumab on NP in patients with CRSwNP accompanied by SAA is independent of local IgE and eosinophil counts.

Introduction: Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications., Objectives: The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private., Results: We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses., Conclusions: This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme., (Copyright © 2024 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.)

Objectives: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test., Methods: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS., Results: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS., Conclusion: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS., Level of Evidence: 3 Laryngoscope, 134:2341-2348, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Backgroud: Presently, the impact of Chronic rhinosinusitis with nasal polyps (CRSwNP) on asthma onset is unknown., Aims: To evaluate the role of CRSwNP in asthma onset., Materials and Methods: A total of 3107 CRSwNP patients were retrospectively screened from 1 January 2018, to 31 May 2021; 624 patients were enrolled. Clinical data regarding nasal symptoms, Lund-Mackay scores, blood eosinophil percentage, and onset of asthma were analyzed. Patients were divided into different groups according to past history of nasal polyps, Lund-Mackay score, and the extent of blood eosinophilia. Asthma-free rates between these subgroups were analyzed by Kaplan-Meier curves and Cox regression models., Results: The prevalence of asthma was 10.90% in patients with CRSwNP, and new-onset asthma occurred in 3.14% of these patients. Higher Lund-Mackay scores for ethmoid sinus and maxillary sinus (E/M) and blood eosinophil percentages were two independent risk factors for new-onset asthma, with hazard ratios of 1.267 (95%CI, 1.155-1.390) and 1.224 (95%CI, 1.054-1.422), respectively. CRSwNP patients with an E/M ratio > 2.33 or a blood Eos percentage > 5.5% were at risk for asthma onset., Conclusions and Significance: Blood eosinophilia and a higher E/M score ratio were associated with new-onset asthma in patients with CRSwNP.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Chronic rhinosinusitis (CRS) is heterogeneous and contains diverse pathogenesis including type 1, type 2, and/or type 3 inflammation. For severe type 2 CRS especially CRS with nasal polyps (CRSwNP), biologics that target inflammatory molecules have recently been applied along with further changes in the treatment algorithm for CRS. Currently, a completed phase 3 clinical trial for biologics for severe CRSwNP with inadequate response to surgery and/or intranasal corticosteroids, including omalizumab (anti-IgE), mepolizumab (anti-IL-5), benralizumab (anti-IL-5Rα), and dupilumab (anti-IL-4Rα), have all shown efficacy. Similar phase 3 clinical trials for tezepelumab (anti-TSLP) and etokimab (anti-IL-33) are now underway and completed, respectively. Further studies need to evaluate how to optimally and cost-effectively use biologics for CRS and determine if any biomarkers are indicative of which biologics should be administered. A definition of complete and/or clinical remission of CRS is also needed to determine when to reduce or discontinue biologics. In addition, more precise basic research on CRS, such as endotyping and genotyping, will need to be undertaken in order to determine novel targets for biologics., Competing Interests: Declaration of Competing Interest MO received honoraria from Sanofi. The authors have no funding source relevant to this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures., Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund-Kennedy endoscopic score (LKES)., Results: A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (-28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures., Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes., (© 2023 ARS‐AAOA, LLC.)

Purpose: Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype., Methods: We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24 weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration., Results: Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24 weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration., Conclusion: Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Guidelines recommend that the vast majority of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) should have at least one endoscopic sinus surgery (ESS) prior to starting biologics. Because ESS can be performed with a variable extension, the aim of this study would be to evaluate the association between surgical extensiveness, as measured by ACCESS score, and outcomes collected in patients treated with Dupilumab., Materials and Methods: This is a multicentric retrospective study; patients affected by CRSwNP who were subjected to Dupilumab therapy and who underwent at least one ESS prior to Dupilumab initiation were included. ACCESS score was assigned to each patient's pre-Dupilumab CT scan. Subjective and objective parameters (SNOT-22, NPS, VAS scores, Sniffin' Sticks) were collected before and during the administration of therapy. Statistical correlations between ACCESS scores and clinical outcomes were investigated., Results: A total of 145 patients were included; mean time from last previous ESS was 68.6 months, and on average, patients were subjected to 2.2 surgeries. Many correlations with ACCESS scores were demonstrated: better NPS at all timepoints and subjective scores (30-days SNOT-22, VAS nasal obstruction, and rhinorrhea) were achieved in patients with low ACCESS score (more extensive ESS). On the other hand, significantly worse VAS loss of smell values were demonstrated in patients with lower ACCESS scores., Conclusion: Dupilumab patients subjected to a prior extensive ESS may have reduced size of polyps and improved subjective indicators, together with a decreased chance to recover smell, when compared with patients who underwent a minimal excision., Level of Evidence: 3 Laryngoscope, 134:1556-1563, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols., Methods: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart., Results: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP., Conclusions: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To assess the severity of the top 5 22-item Sino-Nasal Outcome Test (SNOT-22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures., Study Design: Post hoc analysis of the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) clinical trials., Setting: Multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies., Methods: Patients ranked the SNOT-22 items most affecting their health at baseline. Item symptom severity (0-5 scale) was assessed at baseline, Week 24 (W24), and Week 52 (W52). Changes in nasal polyps score (NPS) and Lund-Mackay (LMK) scores were assessed in patients with/without SNOT-22 items improvements of at least 1 severity group point at W24 and W52., Results: The SNOT-22 items ranked most important at baseline were "decreased sense of smell/taste" (87% of patients), followed by "nasal blockage" (82%), "postnasal discharge" (40%), "thick nasal discharge" (37%), and "wake up at night" (26%); 82%, 61%, 32%, 40%, and 26% of patients reported severe symptoms (score 4 or 5) for these items, respectively. Dupilumab improved score severity for all top 5 items versus placebo at W24 and W52. Improvements in NPS and LMK scores were numerically greater in patients with improvements in the SNOT-22 top 5 items., Conclusion: Loss of smell/taste was ranked as the most important symptom by patients with CRSwNP. Dupilumab reduced the severity of the top 5 most important SNOT-22 items versus placebo, in parallel with improvements in objective disease measures., Clinical Trial Registration: SINUS-24 and SINUS-52 clinical trials were registered with ClinicalTrials.gov, identifiers NCT02912468 and NCT02898454, respectively., (© 2023 The Authors. Otolaryngology‐Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Objective: To review the literature comparing functional endoscopic sinus surgery to dupilumab for the treatment of chronic rhinosinusitis with nasal polyps, in terms of symptom control, cost-effectiveness and complications., Method: A literature review was conducted using PubMed, ScienceDirect and Cochrane databases. Data were extracted manually., Results: A total of six papers relevant to the main objective were found., Conclusion: Chronic rhinosinusitis with nasal polyps has a significant impact on patients' quality of life. Both functional endoscopic sinus surgery and dupilumab achieve comparable disease control and result in good symptom relief. Dupilumab is far more expensive than functional endoscopic sinus surgery and is not considered cost-effective for the time being. This is expected to change after 10 years when the drug patent expires. More research is needed to compare the complications of both treatment modalities.

Background: Increased blood eosinophil count (BEC) is common in patients under dupilumab treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). This study investigated the prevalence and consequences of hypereosinophilia and to help define patients at risk., Methods: Real-life, prospective observational cohort study of patients treated with dupilumab for severe CRSwNP. Eligible patients were adult and biological-naive (N=334). All BEC values at baseline and during treatment were reported. Patients with a follow-up of >= 1 year were included to define patients at risk for hypereosinophilia by comparing baseline BEC values (N=218). Furthermore, clinical characteristics and therapeutic consequences for patients with BEC >= 3.0 were noted., Results: Hypereosinophilia developed in a minority of patients, with a peak at week 12 (16.2% with BEC >= 1.5, and 1.7% >= 3.0) in cross-sectional analysis. BEC >= 1.5 developed in 28.9% and BEC >=3.0 in 4.6% of cases with a minimal 1-year follow-up. Baseline BEC was significantly higher for patients developing BEC >= 1.5 and BEC >=3.0, with an optimal cut-off point of 0.96 to predict developing BEC >= 3.0., Conclusions: Blood eosinophil count (BEC) >= 1.5 is transient and usually abates with no therapeutic interventions and BEC >= 3.0 is rare. Hypereosinophilic syndrome did not occur and switching to a different biological was rarely employed. A baseline BEC of >=1.0 can be a reason for extra caution.

Problem: To assess the efficacy of budesonide intrapolyp injection in chronic rhinosinusitis with nasal polyps., Method: Ninety patients were divided into three groups; group A was given oral prednisolone, group B was given budesonide intrapolyp injection weekly for five consecutive weeks and group C was given budesonide as nasal irrigation for one month. Patients were assessed using Sino-Nasal Outcome Test 22 score, total nasal polyp score, serum immunoglobulin E, absolute eosinophilic count, and morning cortisol level before treatment, one week and three months after completing their treatment., Results: Total nasal polyp score decreased significantly in all groups compared to those at baseline. Reduction in the oral and injection groups was greater than the wash group ( p 2 = 0.004), ( p 3 < 0.001), and the same trend concerning Sino-Nasal Outcome Test 22 score ( p 2 < 0.001), ( p 3 < 0.001)., Conclusion: Budesonide is an effective agent used in intrapolyp injection with no documented systemic or visual side effects that has comparable results with oral steroids.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use., Methods: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE&gt;=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC&gt;=0.39x10(9) cells/L., Results: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up., Conclusion: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.