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Purpose: There are many specific instruments for assessing the quality of life (QoL) in patients with chronic rhinosinusitis. Of all these tests, the Sino-Nasal Outcome Test–22 (SNOT-22) is the most widely used internationally. The purpose of the study was linguistic adaptation and validation of the SNOT-22 scale in the Polish language. Methods: The SNOT-22 was adapted into Polish and was administered to 148 subjects (108 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and 40 asymptomatic controls. Seventy-one patients completed the SNOT-22 a second time to evaluate test-retest reliability. The Polish SNOT-22 was assessed for internal consistency, test-retest reliability, discriminant validity, criterion validity, and sensitivity and specificity. Results: The Polish SNOT-22 exhibited satisfactory psychometric properties. A high Cronbach's alpha coefficient (α = 0.89) was obtained. Significantly higher scores (p < 0.01) were revealed in the Study Group with a median score of 32 (range 15–53) points in comparison with controls: 5 (range 0–20). A moderate correlation was found between SNOT-22 and the Lund-Kennedy test score (r = 0.334; p < 0.001) and a strong correlation between SNOT-22 and the Lund–Macay test score (r = 0.469; p < 0.001). The best cut-off point was set at a 16 score with a sensitivity of 0.981 and a specificity of 0.995. The determined Area Under Curve (AUC = 0.997; p < 0.001) confirms the diagnostic accuracy of the Polish SNOT-22. Conclusions: The Polish version of the SNOT-22 is a valid and reliable tool for measuring health-related quality of life in patients with CRSwNP in the Polish-speaking population. [ABSTRACT FROM AUTHOR]

Asthma, characterized as a chronic heterogeneous airway disease, often presents with common comorbid conditions. The concept of "one airway, one disease" was coined more than 20 years ago, emphasizing the connection between asthma and upper airway comorbidities (UACs) such as allergic or nonallergic rhinitis, chronic rhinosinusitis with or without nasal polyps, and aspirin/nonsteroidal anti-inflammatory drug–exacerbated respiratory disease. Since then, numerous studies have demonstrated that UACs are closely related and affect asthma phenotypes. Recognizing these UACs and managing them are crucial aspects of comprehensive asthma care. Addressing these conditions as part of asthma treatment can lead to better control of symptoms, improved lung function, and better quality of life. Moreover, it is important to explore the field of respiratory biologics, which represents the latest advancements in medical treatment options for patients with asthma and UACs. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusion\nPLAIN LANGUAGE SUMMARYLoss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP. This post hoc analysis investigated the effect of dupilumab on olfaction using UPSIT smell impairment categories.Patients with baseline smell impairment (UPSIT ≤34/≤33 [women/men; score range 0–40] AND LoS score ≥1 [0–3] AND smell/taste item of the 22-item Sinonasal Outcome Test >0 [SNOT-22; 0–5]) treated with dupilumab 300 mg or placebo once every 2 weeks on background intranasal corticosteroids were analyzed.Of 724 patients, 665 (91.9%) had smell impairment at baseline; most had anosmia (UPSIT 0–18) (dupilumab/placebo: 80.9%/79.8%). At week 24, the proportion of dupilumab-treated patients with anosmia decreased to 28.5%, while 14.9% achieved normosmia; most placebo-group patients (79.2%) remained anosmic and only 1.2% achieved normosmia (odds ratio = 17.3; 95% confidence interval = 5.1–59.0; p <.0001); results were similar at week 52. Improvements in Nasal Polyp Score, nasal congestion, and SNOT-22 total score were moderately correlated with improvements in UPSIT at weeks 24 and 52 (r = −.38 to −.50).Most patients with severe CRSwNP had anosmia at baseline. Dupilumab treatment significantly improved smell versus placebo, with 14.9% achieving normosmia by week 24. There was a trend for better clinical outcomes in patients with greater smell improvement.Chronic rhinosinusitis with nasal polyps (CRSwNP) is a condition that causes partial or complete blockage of the nose, making it difficult to breathe. This has a negative effect on many aspects of a person’s life, with loss of sense of smell one of the most common and troublesome symptoms. A drug called dupilumab, which is injected under the skin every other week, has been approved for use in people with CRSwNP. This article presents results from two studies where dupilumab was tested to see if it helped people with CRSwNP, including whether it could improve sense of smell. At the start of the trial, about 80% of people had completely lost their sense of smell, known as anosmia. After 24 weeks, fewer people taking dupilumab had no sense of smell (28.5%) and more had a completely normal sense of smell (14.9%) compared with people who took a placebo (79.2% had no sense of smell; 1.2% had a normal sense of smell). Smell was assessed again after 52 weeks and dupilumab continued to provide a similar benefit. Dupilumab also improved other aspects of CRSwNP, including reducing polyp size, clearing nose blockage, and improving quality-of-life. In summary, most people with CRSwNP at the start of the dupilumab studies had completely lost their sense of smell, and dupilumab improved smell for most people within 24 weeks. This shows the benefit of dupilumab in dealing with this bothersome and difficult-to-treat symptom of CRSwNP. [ABSTRACT FROM AUTHOR]

Objectives: to evaluate our real-world data on the efficacy and safety of switching between two monoclonal antibodies in biologic treatment of uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: All patients receiving biologic treatment for uncontrolled CRSwNP between April 2020 and March 2024 at a tertiary referral center who needed transitioning between biologic agents were retrospectively analyzed. The following parameters were investigated: patient's clinical characteristics, wash-out periods, treatment outcome, and switching-related side effects. Results: Out of 91 CRSwNP patients who received biologic treatment, 4 patients (4.4%) necessitated switching to an alternative biologic agent. Three patients were switched to a different antibody because of insufficient symptom control with the initially prescribed biologic, while the other patient required switching to an alternative agent due to a side effect. Switching resulted in all four patients achieving a significant improvement in all outcome parameters. There were no switching-related side effects, and the switching procedure was performed in three cases without a wash-out period. Conclusion: CRSwNP patients under biologic therapy with an insufficient response or medication-related side effect may benefit from switching to an alternative biologic agent. Larger, prospective multicenter studies are warranted to further validate the effectiveness and safety of switching agents in the biologic treatment of CRSwNP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Chronic rhinosinusitis (CRS) is a long-lasting inflammatory condition affecting the sinonasal mucosa, which is likely triggered by a dysfunctional immune response. Vitamin D is recognized as an immunomodulator influencing both innate and adaptive immunity. Recently, this mechanism of action has sparked interest regarding the possible role of vitamin D in CRS pathogenesis and/or course of the disease. Aim: The aim of this study was to investigate the association between preoperative serum vitamin D levels and an early outcome of endoscopic sinus surgery (ESS) as well as its influence on the severity of CRS. Materials and methods: This prospective observational study included 25 patients with CRS with nasal polyps undergoing ESS and 18 healthy controls. The disease was confirmed clinically and radiologically. Demographic and clinical data for each subject were collected. Preoperatively, disease severity was evaluated by the patient using the Visual Analog Scale (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22), and by a researcher using the Lund-MacKay (LMS) and Lund-Kennedy (LKS) scoring systems. On the day of surgery, serum 25-hydroxyvitamin D was measured with the use of electrochemiluminescence binding assay. Six weeks postoperatively, reassessment was performed, including the VAS, SNOT-22, and LKS. Results: Serum 25-hydroxyvitamin D level was not significantly lower in CRS patients compared to healthy controls. Subjective and objective measures of CRS severity showed no correlation with vitamin D status. However, participants with higher vitamin D levels presented better outcomes 6 weeks postoperatively. Conclusions: Contradicting numerous previous studies, these findings failed to confirm the correlation between the occurrence or severity of CRS and vitamin D status. Nevertheless, vitamin D status seems to affect ESS early outcomes. [ABSTRACT FROM AUTHOR]

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

Key points: Unilateral or destructive sinonasal disease should raise suspicion for tumor.Patients receiving biologic therapy for CRSwNP should be carefully selected.Tissue diagnosis should be considered prior to starting biologics for nasal polyposis. [ABSTRACT FROM AUTHOR]

Key points: CRSwNP‐specific mean total annual spending ranged from $5,837 (EDS‐FLU) to $28,058 (dupilumab).Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery.While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS‐FLU. [ABSTRACT FROM AUTHOR]

Introduction: The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. Materials and methods: A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. Results: 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. Conclusion: Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered. [ABSTRACT FROM AUTHOR]

Background and Objectives This study aimed to evaluate whether preoperative oral prednisolone improves the intraoperative parameters and postoperative outcomes over a 3-month period in patients of sinonasal polyposis who undergo functional endoscopic sinus surgery. Methods In a triple-blind, randomized controlled study, 43 patients diagnosed with sinonasal polyposis in the Department of ENT, AIIMS, Jodhpur, were enrolled. After obtaining institutional ethics clearance and registering the clinical trial, randomization was conducted to assign participants into experimental and control groups. Preoperatively, patients were assessed using the clinical severity score (Sino-nasal Outcome Test; SNOT-22), radiological severity score (Lund-Mackay score), and endoscopic severity scores (discharge-inflammation-polyp [DIP] score and Lund-Kennedy score). Intraoperative assessment was done using the Perioperative Sinus Endoscopy (POSE) score, the duration of surgery, intraoperative blood loss, and visual analog scale for visual field during surgery and for the ease of disease removal. Postoperatively, at 3 months all the preoperative parameters were reassessed, and, using independent t-test, comparison was made between the two groups. Results Twenty-one patients were included in the experimental group (48%), and 22 in the control group (51%). Although the mean duration of surgery in the experimental group was shorter than in the control group, the difference was not statistically significant. Similarly, although the postoperative SNOT-22 score was lower in the experimental group compared to the control group, there was no statistically significant difference in outcomes between the two groups across any of the parameters assessed. Conclusion Although the role of oral steroids has been established in the treatment of sinonasal polyposis, our study did not find any significant difference between the group that received oral steroids prior to surgery and the group that received placebo.

Objective: To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss. Methods: This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0−8), nasal congestion/obstruction (NC, 0−3), Lund-Mackay CT-scan score (LMK-CT, 0−24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0−110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0−3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks. Results: Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%). At baseline, severe versus moderate LoS was associated with 1-point greater severity of NC (odds ratio [OR] 6.01 [95% confidence interval, (CI) 3.95, 9.15]), 5-point greater severity of LMK-CT (OR 2.19 [1.69, 2.85]), and 8.9-point greater severity of SNOT-22 (OR 1.35 [1.20, 1.49]). At Week 24, least squares mean differences (95% CI) dupilumab versus placebo in change from baseline were: NPS −1.90 (−2.56, −1.25) and −1.95 (−2.20, −1.70) in the moderate and severe baseline LoS subgroups, respectively; NC −.35 (−.64, −.06) and −1.00 (−1.13, −.87); LMK-CT −6.30 (−7.88, −4.72) and −6.22 (−6.82, −5.63); RS-VAS −1.18 (−2.20, −.16) and −3.47 (−3.90, −3.03); and SNOT-22 −7.52 (−14.55, −.48) and −21.72 (−24.63, −18.82); all nominal P <.05 versus placebo. Improvements with dupilumab in NC, RS-VAS, and SNOT-22 were statistically greater in patients with severe versus moderate baseline LoS. Conclusion: Significant smell impairment in severe CRSwNP is associated with significant disease (NC, RS-VAS, LMK), health-related quality of life impairment (SNOT-22), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease. Dupilumab significantly improved NPS, NC, LMK-CT, RS-VAS, and SNOT-22 in subjects with moderate and severe baseline smell loss. [ABSTRACT FROM AUTHOR]

Purpose of Review: Olfactory dysfunction significantly impacts quality of life that affects a majority of the patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of this review is to explore the impact of various treatment regimens on olfactory dysfunction in patients diagnosed with CRSwNP. Recent Findings: Accurate assessment of olfactory dysfunction remains challenging and should incorporate both psychophysical tests and patient-reported outcomes. Patients with CRSwNP appear capable of reliably evaluating their olfactory function. Summary: Standard treatment such as intranasal corticosteroids and surgery have limited capability of restoring the sense of smell. Oral corticosteroids have a far greater potency, albeit short-lived and at the cost of adverse events and side effects. Recent studies on registered biological agents– specifically dupilumab, mepolizumab, and omalizumab– indicate their effectiveness in restoring olfactory function in severe CRSwNP. According to meta-analyses and indirect comparisons, dupilumab shows superiority; however, direct comparative studies are necessary. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Purpose: Since its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12 months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings. Methods: The follow-up was performed with 104 patients retrospectively up to 22 months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed. Results: There was substantially improvement in all clinical parameters up to 1 year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5 billion/L) had a trend of better SNOT-22 development after 1 year (− 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events. Conclusion: Dupilumab has considerably reduced symptoms and disease severity even beyond 1 year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings. [ABSTRACT FROM AUTHOR]

Background: Dupilumab, a monoclonal antibody targeting IL-4 and IL-13, has demonstrated its efficacy in several clinical trials. However, to date, real-life data remains limited. Objective: The aim of our study was to assess the real-life impact of dupilumab on patients with severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) quality of life. Materials and methods: This was a retrospective, monocentric, observational, real-life study, conducted in accordance with the STROBE guidelines. The following parameters were collected before treatment and at 1, 4, and 12 months: Sino-Nasal Outcome Test-22 (SNOT-22), nasal polyp score (NPS), Sniffin' Sticks-16 (SST-16), visual analog scale (VAS) for loss of smell, nasal congestion score (NCS), gustatory VAS, asthma control, oral corticosteroid usage, surgery rates, and occurrence of side effects. Results: The study included 47 patients. SNOT-22 scores decreased from 52.4 ± 24.3 to 12.7 ± 10.5 at 12 months (p < 0.001). NPS decreased from 6.15 ± 1.71 to 1.57 ± 1.40 at 12 months (p < 0.001). SST-16 scores increased from 1.6 ± 2.83 to 9.1 ± 5.4 at 12 months (p < 0.001). NCS decreased from 2.45 ± 0.72 to 0.38 ± 0.63 at 12 months (p < 0.001). Prior to treatment, 72.3% were using oral corticosteroids, compared to 17.0% at 12 months (p < 0.01). Two patients required additional surgery, and 17% reported completely uncontrolled asthma, compared to 0% at 12 months (p < 0.01). Conclusion: Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose of Review: To present current evidence in long-term (> 5 years) results after endoscopic sinus surgery (ESS) focusing on Patients Reported Outcome Measures (PROMs) and other sinonasal outcomes while assessing the role of ESS in the treatment of CRSwNP, and identifying outcomes which affect the results of ESS and defining recommendations for future studies. Recent Findings: Long-term results of ESS in CRSwNP can be branched in PROMs and other objective measurements. Despite the heterogeneity of reported outcomes make it difficult to perform comparisons and meta-analysis, ESS improves PROMs, including symptoms, QOL and olfaction. Objectives outcomes such as NPS, LMS, type of surgery, or recurrence and revision surgery don't have a clear role in long-term results. Clustering patients suggest asthma, N-ERD, allergy, eosinophil count and IL-5 could have a role in predicting recurrence and severe disease. Summary: Long-term studies of CRSwNP treated with ESS are scarce. There is a significant need to standardize the report of results. The use of tools as SNOT-22, NPS, validated smell tests, defined criteria for disease recurrence and control and ESS extension in a unified systematic way could allow better comparisons between treatments in the new era of biologics. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) have been implicated in the pathogenesis of asthma, however, how EVs contribute to immune dysfunction and type 2 airway inflammation remains incompletely understood. We aimed to elucidate roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID‐exacerbated respiratory disease (N‐ERD), a severe type 2 inflammatory condition. Methods: EVs were isolated from induced sputum or supernatants of cultured nasal polyp or turbinate tissues of N‐ERD patients or healthy controls by size‐exclusion chromatography and characterized by particle tracking, electron microscopy and miRNA sequencing. Functional effects of EV miRNAs on gene expression and mediator release by human macrophages or normal human bronchial epithelial cells (NHBEs) were studied by RNA sequencing, LC–MS/MS and multiplex cytokine assays. Results: EVs were highly abundant in secretions from the upper and lower airways of N‐ERD patients. N‐ERD airway EVs displayed profoundly altered immunostimulatory capacities and miRNA profiles compared to airway EVs of healthy individuals. Airway EVs of N‐ERD patients, but not of healthy individuals induced inflammatory cytokine (GM‐CSF and IL‐8) production by NHBEs. In macrophages, N‐ERD airway EVs exhibited an impaired potential to induce cytokine and prostanoid production, while enhancing M2 macrophage activation. Let‐7 family miRNAs were highly enriched in sputum EVs from N‐ERD patients and mimicked suppressive effects of N‐ERD EVs on macrophage activation. Conclusion: Aberrant airway EV miRNA profiles may contribute to immune dysfunction and chronic type 2 inflammation in N‐ERD. Let‐7 family miRNAs represent targets for correcting aberrant macrophage activation and mediator responses in N‐ERD. [ABSTRACT FROM AUTHOR]

Key points: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA).Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%.Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%–60%. [ABSTRACT FROM AUTHOR]

Abstract Background Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types. Methods and analysis This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People’s Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients’ pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches. Discussion This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP. Systematic review registration PROSPERO ChiCTR2100041646.

Basic research on chronic rhinosinusitis (CRS) has advanced significantly in the past two decades, yet a comprehensive understanding of its pathogenic mechanisms remains elusive. Concurrently, there is a growing interest among scientists in exploring the involvement of autophagy in various human diseases, including tumors and inflammatory conditions. While the role of autophagy in asthma has been extensively studied in airway inflammatory diseases, its significance in CRS with or without nasal polyps (NPs), a condition closely linked to asthma pathophysiology, has also garnered attention, albeit with conflicting findings across studies. This review delves into the role of autophagy in CRS, suggesting that modulating autophagy to regulate inflammatory responses could potentially serve as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. Methods: A retrospective data analysis was jointly conducted at the Otolaryngology–Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow–up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. Results: Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. Conclusions: Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients' response to biological treatment in CRSwNP. [ABSTRACT FROM AUTHOR]

Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types. Methods and analysis: This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People's Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients' pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches. Discussion: This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP. Systematic review registration: PROSPERO ChiCTR2100041646. [ABSTRACT FROM AUTHOR]

Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation. Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity. Results: The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-g. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants. Conclusion: Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration. At baseline (T0) and at each follow-up, patients underwent NPS, Sinonasal Outcome Test (SNOT)-22, Visual Analogue Scale (VAS) for smell, and Sniffin' sticks identification test (SSIT). The SNOT-22 domains for function and emotion were also analysed separately. Two hundred and seventeen patients with at least 6 months of follow-up were included. All parameters have improved during treatment (p < 0.0001). Noticeably, both the function and emotion SNOT-22 domains have improved within 6 months of treatment and have continued to progress during every interval within 12 months from the baseline, positively influencing patients' emotivity and augmenting their social and economic performances. Dupilumab improves the QoL of CRSwNP patients with good effects on the reported productivity and emotional health. Clinicians should pay attention to these two aspects when dealing with patients affected by severe CRSwNP. [ABSTRACT FROM AUTHOR]

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP. [ABSTRACT FROM AUTHOR]

[Display omitted] Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP level was higher in patients undergoing extensive surgery. ESS decreased levels of IL-13 and periostin in the middle meatus. T2 inflammation after ESS was correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients. [ABSTRACT FROM AUTHOR]

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders. [ABSTRACT FROM AUTHOR]

Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) represents a condition mainly caused by the type 2 inflammation presence and marked by the existence of polyps within the nasal and paranasal sinuses. The standard of care includes intranasal steroids, additional burst of systemic steroids, if needed, and surgery. However, recurrence is common, especially among patients with comorbid type 2 inflammatory diseases. Recently, biological drugs, addressing the underlying cause of the disease, have been approved in Italy (dupilumab, omalizumab, and mepolizumab). A Health Technology Assessment was conducted to define multidimensional impact, assuming Italian NHS perspective and a 12-month time horizon. The EUnetHTA Core Model was deployed, using the following methods to analyze the domains: (i) literature evidence; (ii) administration of semi-structured questionnaires to 17 healthcare professionals; (iii) health economics tools to define the economic sustainability for the system. Evidence from NMA and ITC showed a more favorable safety profile and better efficacy for dupilumab compared with alternative biologics. All the analyses, synthesizing cost and efficacy measures, showed that dupilumab is the preferable alternative. Specifically, the cost per responder analysis for dupilumab, exhibiting a 67.0% response rate at Week 52, is notably economical at 14,209EUR per responder. This presents a more economical profile compared with the cost per responder for omalizumab (36.2% response rate) at 24,999EUR and mepolizumab (28.5% response rate) at 31,863EUR. These results underscore dupilumab's potential, not merely in terms of clinical outcomes, but also in terms of economic rationality, thereby solidifying its status as a valid and preferrable alternative in the management of CRSwNP, in the context of the Italian NHS. [ABSTRACT FROM AUTHOR]

Introduction and objective: Nowadays, treatment proposals for patients with recurrent sinonasal polyposis are based on the use of local intranasal corticosteroid therapy based on topical inhalers, cycles of systemic corticosteroids and endoscopic nasal surgery. Biological therapy is gaining more and more prominence in the treatment of this pathology. The objective of this work is based on determining which biological treatment of those administered today for this disease is more effective in managing symptoms and in its evolution. Method: Retrospective study of 21 patients with chronic rhinosinusitis with sinonasal polyposis and asthma under treatment with biological therapy at the University Hospital of Fuenlabrada. Using a Wilcoxon signed-rank study, we will analyze the efficacy of the different biological treatments administered. Results: A statistical significance with p = <0, 001 was evidenced in terms of the improvement of the symptoms suffered by the study patients (with the exception of smell) as well as an improvement in the Nasal Polyp Score of 3 points. The Wilconxon test result was statistical significance with p = <0, 001. Discussion: The data obtained in this study agree with those obtained in studies on biological therapy in CRSwNP. Remarkable reductions in the disease burden of CRSwNP have been documented objectively and subjectively. This is consistent with the fact that our patients required fewer reinterventions throughout the procedure. Conclusions: In our study, the efficacy of biological therapy has been corroborated in practically all the data analyzed. However, it has not been possible to demonstrate the relevance of one type of therapy over another. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Yakun Wang,1,&ast; Xinyu Song,2,&ast; Mulan Jin,1 Jun Lu1 1Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mulan Jin; Jun Lu, Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Email jinmulan2022@126.com; Lujun11101@126.comPurpose: Chronic rhinosinusitis is a prevalent condition in the field of otorhinolaryngology; however, its pathogenesis remains to be elucidated. The immunological defense of the nasal mucosa is significantly influenced by dendritic cells (DCs). We identified specific biological indicators linked to DCs and explored their significance in cases of chronic rhinosinusitis with nasal polyps (CRSwNP).Patients and Methods: We categorized cells using single-cell RNA (scRNA) sequencing, and combined transcriptome sequencing was used to identify potential candidate genes for CRSwNP. We selected three biomarkers based on two algorithms and performed enrichment and immune correlation analyses. Biomarkers were verified using training and validation sets, receiver operating characteristic curves, immunohistochemistry, and quantitative real-time reverse-transcription PCR (qRT-PCR). Variations in biomarker expression were validated using pseudotime analysis. The networks of competing transcription factor (TF)-mRNA and competing endogenous RNA (ceRNA) were established, and the protein drugs associated with these biomarkers were predicted.Results: Both scRNA-seq and transcriptome data showed that DCs immune infiltration was higher in the CRSwNP group than in the control group. Three DC-related biomarkers (NR4A1, CLEC4G, and CD163) were identified. In CRSwNP, NR4A1 expression decreased, whereas CLEC4G and CD163 expression increased. All biomarkers were shown to be involved in immunological and metabolic pathways by enrichment analysis. These biomarkers were associated with γδ T cells, effector memory CD4 + T cells, regulatory T cells, and immature DCs. According to pseudotime analysis, NR4A1 and CD163 expression decreased from high to low, whereas CLEC4G expression remained low.Conclusion: We screened and identified potential DC-associated biomarkers of CRSwNP progression by integrating scRNA-seq with whole transcriptome sequencing. We analyzed the biological pathways in which they were involved, explored their molecular regulatory mechanisms and related drugs, and constructed ceRNA, TF-mRNA, and biomarker–drug networks to identify new CRSwNP treatment targets, laying the groundwork for the clinical management of CRSwNP.Keywords: CRSwNP, dendritic cell, single-cell sequencing, transcriptomic sequencing, biomarker

The article discusses two studies on the effects of dupilumab and nasal allergen provocation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid seasonal timothy grass pollen allergic rhinitis. The first study found that dupilumab improved symptoms and biomarkers in patients with both conditions, suggesting it may be an effective treatment. However, the study had limitations and further research is needed. The second study found that patients with nasal polyps had a reduced response to grass allergen provocation compared to those without polyps. This research provides valuable insights into the relationship between these conditions and grass sensitization. [Extracted from the 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 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.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with multifactorial etiopathogenesis. This study investigated the recurrence rate and risk factors predicting recurrence in patients subjected to Functional Endoscopic Sinus Surgery (FESS) for CRSwNP. Methods: Patients affected by CRSwNP who underwent FESS between January 2015 and March 2020 were enrolled. The recurrence rate and the influence of risk factors were assessed. Results: A total of 154 patients were included, 100 males and 54 females, aged 14–82 years (mean age 51.96 ± 16.27; median 52 years). Of 154 patients, 28 presented CRSwNP recurrence in a follow-up period ranging from 6 months to 69 months, with a recurrence rate of 18.2%. The recurrence rate was higher in patients aged between 31 and 50 years and between 51 and 70 years at the time of surgery than in those aged between 14 and 30 years and over 70 years. Furthermore, most patients with recurrence were men (61%), while 39% were women. A higher recurrence rate was observed between non-smokers (50%) and ex-smokers (36%), while only 14% declared themselves habitual smokers. Only four subjects (14%) had a positive family history of CRSwNP. Conclusion: To date, no specific biomarkers have been identified in order to determine the appropriate therapy for the patients affected by CRSwNP. Based on our results, we suggest that it is necessary for an accurate assessment of the CRSwNP patients to identify which phenotype/endotype each subject manifests based on medical history, endoscopy, computed tomography, and a laboratory evaluation. [ABSTRACT FROM AUTHOR]