The primary pathogenic mechanism of Type I hypersensitivity reactions involves histamine-mediated activation of the H1 receptor (H1R) and the subsequent signaling of the phospholipase C β-inositol trisphosphate (PLCβ-IP3) pathway. The present study evaluates the in vitro efficacy of a novel nutraceutical mixture—Quercetin, Perilla frutescens, Boswellia serrata, Blackcurrant, Parthenium, Helichrysum, Lactobacillus Acidophilus (L. acidophilus) and Bifidobacterium animalis (B. animalis)—in modulating HRH1 gene expression and the activation of the intracellular second messenger inositol trisphosphate (IP3). Quantitative PCR (qPCR) analysis revealed that the mixture downregulated HRH1 expression by approximately 33% (p < 0.05) compared to the control group. Furthermore, ELISA assays demonstrated that the mixture significantly reduced IP3 release by 10.30% (p < 0.05 vs. positive control). These results indicate that the nutraceutical mixture exerts its effects by modulating the H1R-PLCβ-IP3 pathway through the reduction in both H1 receptor gene expression and IP3 release. These findings suggest a potential mechanism of action involving the modulation of the histamine H1 receptor. Consequently, the mixture emerges as a promising candidate for further investigation into the H1R-IP3 activation cascade.

Background:In recent years, treatment options for patients with uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) have been expanded with biologics. Definitions of uncontrolled severe disease differ across international recommendations and the prescription of biologics depends on national reimbursement criteria. Objective:We aimed to evaluate the indication for biologic treatment, based on international recommendations, in a real-world cohort of CRSwNP patients. Methods:CRS patients who visited the outpatient ENT clinic of 10 tertiary centres from 7 European countries were invited to use the Galenus Health mobile application monitoring their disease. The proportion of patients who fulfilled biologic indication criteria according to EUFOREA 2021 and EPOS/EUFOREA 2023 recommendations was evaluated. Results:A total of 281 CRS patients were recruited of which 227 (82.1%) were diagnosed as CRSwNP. Out of these 227 patients, 21 patients with prior biologic use were excluded, resulting in a cohort of 206 patients. A total of 28.7% (50/174) and 47.6% (81/170) of CRSwNP patients, met the EUFOREA 2021 or EPOS/EUFOREA 2023 criteria for indication for biologic treatment, respectively. Biologic treatment was initiated at the time of inclusion in the cohort in 18.9% (39/206) of CRSwNP patients. Conclusion:According to international recommendations, 29-48% of CRSwNP patients in tertiary centres may be a candidate for biologic treatment. EPOS/EUFOREA2023 criteria were more inclusive than EUFOREA 2021 criteria with respect to biologic indication for CRSwNP. National reimbursement criteria prevail over international recommendations for actual biologic prescription and are less restrictive in some countries.

Background/Objectives: The therapeutic effectiveness of chronic rhinosinusitis with nasal polyposis (CRSwNP) depends on an accurate diagnosis that identifies disease characteristics, evaluates sinus patency, and detects paranasal sinus obliteration. This study aims to assess a novel artificial intelligence (AI) system integrated with radiomic analysis for the radiological evaluation of CRSwNP, developing a reliable and predictive clinical-radiological scoring system. Methods: This study retrospectively evaluates CT scans of patients with CRSwNP. Image analysis was performed using Radiomica LifeX (Local Image Features Extraction) version 7.5. The extracted densitometric volumes were compared to the Lund-Mackay Score (LMS) to develop a novel scoring system (P-ABCD score) and assess its radiomic predictive capability. Results: Twenty patients with CRSwNP undergoing Dupilumab therapy participated in this study. The P-ABCD score, derived from sinus CT imaging data, served as a valuable objective measure of clinical improvement following CRSwNP treatment. Conclusions: Advanced radiomic imaging techniques of the sinus cavity provide precise volumetric data combined with texture analysis. These techniques offer high sensitivity by accurately quantifying the true extent of inflammatory involvement in the paranasal sinuses, enabling effective disease stratification.

BACKGROUND:The SYNAPSE phase 3 study demonstrated that mepolizumab significantly improves nasal polyp score (NPS), quality of life and symptom severity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE:We aimed to evaluate mepolizumab effectiveness in a real-world cohort from 12 tertiary centers in 6 European countries. METHODOLOGY:A retrospective analysis was conducted in 110 CRSwNP patients (comorbid asthma: 86.4%). CRS-related outcomes were analyzed at baseline, 24 and 52 weeks of mepolizumab. Treatment response was evaluated based on EUFOREA 2021 criteria. RESULTS:Significant improvements in NPS, Sinonasal Outcome Test-22 (SNOT-22), and visual analog scale (VAS) symptom scores were observed at 24 and 52 weeks compared to baseline. Further improvement between weeks 24 and 52 was observed for NPS and SNOT-22. Asthma Control Test (ACT) also improved significantly by week 24 (ACT score ≥ 20: 64.5%). At least one response criterion (change in SNOT-22 ≥ 8.9, NPS ≥ 1, VAS total sinus symptoms ≥ 20, VAS nasal blockage ≥ 20, VAS loss of smell ≥ 20) was met by 85.6% and 78.7% of patients at 24 and 52 weeks, respectively. A more stringent composite response (SNOT-22 < 30, NPS < 4, VAS total sinus symptoms < 50, and VAS nasal blockage < 50) was achieved in 18.3% and 44.6% of patients at 24 and 52 weeks, respectively. CONCLUSION:Mepolizumab demonstrated clinically meaningful benefits in a real-world CRSwNP population, with nearly half of patients achieving a beneficial composite treatment response by week 52. Notably, progressive improvements between weeks 24 and 52 underscore the value of prolonged therapy and the importance of evaluating treatment response at one year.

PURPOSE:Biologics targeting the underlying inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) not only alleviate symptoms but also provide potential disease-modifying effects. This has redefined treatment goals in CRSwNP, emphasizing the concept of achieving disease remission as proposed by the EPOS2020/EUFOREA expert panel. Remission in CRSwNP is defined as sustained control for at least 12 months, along with the absence of active disease as assessed by nasal endoscopy. The purpose of this study was to identify patients with severe CRSwNP who achieved disease remission during the first two years of Dupilumab treatment. METHODS:This real-life, observational, retrospective study evaluated the effectiveness and safety of Dupilumab in patients with severe, uncontrolled CRSwNP over two years. Remission was assessed taking into account the latest EPOS2020/EUFOREA expert panel and currently available expert opinion on the topic. Data were collected at baseline and after 1, 3, 6, 9, 12, 18, and 24 months, focusing on nasal polyp score (NPS), symptoms, olfactory function, and quality of life (QoL). Additionally, the safety profile was evaluated by monitoring side effects and eosinophil blood count. RESULTS:A total of 30 patients (19 males, 11 females; mean age 53.7 years) were included. Dupilumab treatment led to significant clinical improvements, including a reduction in NPS, relief of nasal symptoms, and notable improvements in olfactory function and QoL, as demonstrated through SNOT-22 and VAS scores. Twenty-three patients (77%) achieved disease remission. CONCLUSION:This retrospective study confirms the efficacy of Dupilumab in managing difficult-to-treat, type-2 inflammation-driven CRSwNP, with a high percentage of patients achieving remission. Further studies with larger cohorts along with universal guidelines establishing validated criteria, including specific cut-off values, for a standardized definition of remission in CRSwNP are required.

Background: Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score, symptom score, and quality-of-life score in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary-care centers. Methodology: Nasal polyp score, Sinonasal Outcome Test 22 score, visual analog scale for total sinus symptoms, loss of smell, and nasal blockage, and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline and again at 24 and 52 weeks' treatment with dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities, and blood eosinophil counts (BEC). Treatment response was evaluated according to European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) 2021 criteria. Results: All patient outcomes improved at 24 and 52 weeks' treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergy, or baseline BEC. A total of 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks, respectively; 54.4% and 68.2% met all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks, respectively. Conclusions: Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks' treatment. Favorable treatment response was independent of the number of sinus surgery procedures, major comorbidities, or baseline systemic levels of type 2 inflammation. (J Allergy Clin Immunol 2025;155:451-60.)

IntroductionFluticasone propionate (FP) is a topical corticosteroid used to treat rhinosinusitis with nasal polyposis (CRSwNP). However, the need for a consensus on its use stems from the increasing focus on optimizing topical therapies to improve clinical outcomes and minimize systemic side effects.Materials and methodsThe Butterfly Decisions AI platform facilitated the collection and integration of evaluations and feedback, facilitating an expert consensus on 13 statements.ResultsThe participants agreed highly on the different statements. The experts agreed that FP effectively reduces the need for surgery and controls the symptoms of CRSwNP. The use of advanced delivery systems significantly improved drug delivery and therapeutic outcomes. Treatment with FP was associated with a reduction in the recurrence of nasal polyps and an improvement in the patient's quality of life.ConclusionsFP, as other equal corticosteroids, represents a first-line local therapy for patients with CRSwNP without complicating comorbidities due to its high efficacy and low systemic bioavailability. The Butterfly Decisions platform has demonstrated the effectiveness of integrating AI tools into clinical decision-making, improving the transparency and objectivity of assessments.

Objective: It remains unclear whether baseline FeNO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma. Methods: We recruited 104 patients with severe eosinophilic asthma treated with anti-IL5/anti-IL5R for at least one year who had measured FeNO values before the beginning of anti-eosinophilic treatment. Population was divided into subjects with FeNO < 25 and >= 25 ppb. In each group we evaluated the changes in pulmonary function (FEV1% and FEF25-75%), clinical (ACT and exacerbations) and steroid-sparing effect, expressed as the modification of daily dosage of inhaled corticosteroids (ICS) and oral corticosteroids (OC), after anti-IL5/anti-IL5R. Results: FEV1 changes after treatment were 3.34 +/- 15,97% in subjects with low baseline FeNO, whereas 11.2 +/- 16.1% in individuals with FeNO >= 25 ppb (p = 0.012). Also, FEF25-75% variations after treatment were different in the two groups: 2.1 +/- 10.7% vs 9.6 +/- 18% in individuals with FeNO < 25 and >= 25 respectively (p = 0.05). Conversely, ACT (4.4 +/- 4.2 vs 5.9 +/- 4.6; p = 0.147), exacerbation changes (-2.46 +/- 1.5 vs -2.9 +/- 1.6; p = 0.137) after treatment were similar in both groups where ICS dosages reduction was alike. On the contrary, the percentage of subjects that reduced/stopped OC treatment after anti-IL5/anti-IL5R was 71.7% in the group with FeNO < 25 ppb whereas 94.1% in individuals with FeNO >= 25 (p = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO >= 25 and improvement in FEV1%/FEF25-75% (beta = 8.372, p = 0.013 and beta = 8.883; p = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838 [95%CI:3.159-100.730]; p = 0.001) in the high FeNO group. Conclusion: Pre-biologic FeNO might predict a greater response to treatment with anti-IL-5/5R especially in terms of lung function and OC sparing in subjects with severe eosinophilic/allergic asthma. This could likely be a biomarker that can better guide in choosing an anti-IL5/5R in severe overlapping asthma (eosinophilic/allergic) to maximize treatment effects.

Background/Objectives: MicroRNAs (miRNAs) play a crucial role in regulating immune responses and have been implicated in the pathogenesis of various nasal diseases, including chronic rhinosinusitis (CRS), allergic rhinitis (AR), and sinonasal tumors. This review comprehensively explores the emerging role of miRNAs in inflammatory and oncological nasal diseases, highlighting their diagnostic, prognostic, and therapeutic potential. Methods: A comprehensive review of the literature was conducted to summarize current findings on miRNA expression in nasal inflammatory conditions and tumors. Key studies evaluating miRNA-mediated regulatory mechanisms, potential biomarker applications, and therapeutic approaches were analyzed. Results: Altered miRNA expression profiles contribute to the pathogenesis of CRS, AR, and sinonasal tumors. Specific miRNAs, such as miR-125b and miR-155 are upregulated in CRS and AR, promoting inflammation and tissue remodeling. In sinonasal tumors, dysregulated miRNAs, including miR-126 and miR-34/miR-449 clusters, influence tumor progression and therapeutic response. Exosome-mediated miRNA delivery emerges as a promising avenue for precision medicine, offering novel strategies for miRNA-based diagnostics and therapies. Conclusions: miRNAs are key regulators of nasal diseases, with potential applications in non-invasive diagnostics and targeted therapies. Further research into miRNA-based interventions may improve treatment outcomes and contribute to the development of personalized medicine approaches for nasal inflammatory disorders and malignancies.

Respiratory and food allergy conditions are increasing internationally and the most commonly used drugs in these conditions are antihistamines, products that can interfere as histamine receptor antagonists. In accordance with the need to test new principals capable of developing fewer side effects, we preliminarily studied the therapeutic antihistamine effect in vitro and in vivo of an innovative nutraceutical blend based on Quercetin, Perilla frutescens, Boswellia serrata, Blackcurrant, Parthenium, Helichrysum, Lactobacillus acidophilus and Bifidobacterium animalis. The in vitro test demonstrated the interaction between the examined mixture and a rat leukemia cell line (RBL-2H3) widely used as a model simulating mast cells in immunological and allergological studies; this pre-clinical test demonstrated a statistically significant reduction in cell histamine degranulation (about 30%). The in vivo test demonstrated instead that the mixture interferes up to 30% in the development of histamine wheal. In addition, during the in vitro test, we also tested the effect of the mixture on allergic inflammation, so we evaluated the interference of the mixture on TNF alpha levels, determining a reduction in tested concentrations of about 13%.

This study investigated nasal cytological alterations in patients with persistent post-viral olfactory dysfunction. The primary objective was to evaluate the role of immune dysregulation and chronic local inflammation within the nasal mucosa in sustaining long-term olfactory impairment. An observational case-control study was conducted at the Otorhinolaryngology Department of the University of Rome Tor Vergata. Thirty-six patients with persistent olfactory dysfunction were compared to two control groups: one comprised subjects recovered from SARS-CoV-2 infection without olfactory impairment, and the other included individuals without a history of COVID-19 or olfactory dysfunction. Psychophysical olfactory function was assessed using the TDI (Threshold, Discrimination, and Identification) test. Nasal cytology samples were obtained via nasal brushing at the level of the olfactory cleft and stained using the May-Grunwald-Giemsa technique. Cellular alterations were evaluated using a semiquantitative grading system. Patients with persistent olfactory dysfunction exhibited increased lymphocytes and neutrophils compared to both control groups, indicating ongoing local inflammation. Ciliocytophthoria was notably present in a significant portion of the olfactory dysfunction group, while absent or minimally present in controls. Eosinophils and mast cells were rare across all groups. Persistent post-viral olfactory dysfunction is associated with sustained immune activation and epithelial damage localized to the olfactory cleft. Elevated lymphocytes, neutrophils, and ciliocytophthoria emphasize the role of chronic inflammation in the pathogenesis of prolonged olfactory deficits. These findings highlight the potential utility of targeted therapies to modulate immune responses and promote olfactory recovery in affected patients.

BACKGROUND:Primary chronic rhinosinusitis (CRS) can be classified based on the sinuses involved and the dominant endotype of the mucosal inflammation. Since the introduction of type 2 targeted biologics as treatment option for CRS, assessment of the inflammatory status has gained importance in CRS patients. We here aimed to characterize CRS patients with and without elevated markers of type 2 inflammation. METHODS:CRS patients who visited the outpatient ENT clinic in one of the 10 tertiary centers in 7 European countries were invited to use the Galenus Health mobile application for the monitoring of their disease. RESULTS:CRS patients (n = 281) were stratified according to blood eosinophil counts or BEC (< 150 cells/μL: 21.6% of patients, ≥ 150 cells/μL: 78.4%; < 250 cells/μL: 36.3%, ≥ 250 cells/μL: 63.7%) and serum total IgE (< 100 IU/mL: 59.9%, ≥ 100 IU/mL: 40.1%). BEC and serum total IgE did not correlate well (Spearman r = 0.06; p = 0.39). CRS patients with BEC ≥ 150 cell/μL or ≥ 250 cells/μL, respectively, showed increased NPS, SNOT-22, VAS for total CRS symptoms, loss of smell, nasal blockage, runny nose compared to patients with BEC below 150 or 250 cells/μL. CRS patients with increased serum total IgE (≥ 100 IU/mL) did not show differences in the outcome parameters compared to patients with levels below 100 IU/mL. CRS patients with asthma (58.9%) showed increased SNOT-22 and VAS loss of smell compared to patients without asthma. CONCLUSIONS:A significant proportion of CRS patients exhibit a type 2 endotype, characterized by blood eosinophilia (78%), increased serum total IgE (40%) and/or concomitant asthma (59%). Our results underline the usefulness of eosinophils as a marker of type 2 inflammation and severity but challenge the utility of serum total IgE since it does not correlate with any of the markers of severity.

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a debilitating disease with significant morbidity and decreased quality of life (QoL). The introduction of biologics in its management has allowed new therapeutic options, and Dupilumab represents the first approved biologic. This study aims to evaluate a possible relationship between the clinical response to biological therapy and mental health in patients with severe CRSwNP. Methods: This is a multicenter study conducted at the Otolaryngology departments of three major Italian health institutions. Participants were patients with CRSwNP treated with Dupilumab. Patients were assessed at baseline and during treatment by submitting them to a survey consisting of a dedicated questionnaire focused on psychological health and two patient-reported outcome measures (PROMs): the 22-item Sino-Nasal Outcome Test (SNOT-22) and a Visual Analogue Scale (VAS) for nasal symptoms. Results: 86 patients were included in the study (58 males and 28 females; mean age: 58.2 years). There was a significant improvement in both symptoms and QoL, with an enhanced psychological state observed in patients after the first administration and within the first months of therapy. Conclusions: This study evaluated the possible correlations between Dupilumab treatment and improvements in mental health in patients with CRSwNP, as assessed through a survey, and clinical conditions, assessed through SNOT-22 and VAS. Our findings showed that Dupilumab not only improved clinical symptoms but also had a positive impact on patients’ mental health, with benefits observed already after the first administration and the first months of therapy. This survey highlights the relevance of psychological well-being and its implications for patients with chronic diseases such as CRSwNP.

Kimura’s disease (KD) is a rare, chronic inflammatory disorder that predominantly affects young men of East Asian descent. It is characterized by painless solid masses primarily localized to the deep subcutaneous tissues of the head and neck, eosinophilia, and elevated serum immunoglobulin E (IgE). While the exact cause remains unclear, the pathogenesis is thought to involve dysregulated immune responses, particularly those mediated by T-helper cells 2 (Th2), eosinophils, and IgE production. Advances in molecular biology have suggested that genetic factors play a significant role in the development and progression of this chronic inflammatory condition. Recent studies have implicated several genes and immune pathways in its development, and understanding these genetic components may provide insights into better diagnostic tools and therapeutic strategies for KD. In this regard, biological therapies, by targeting the immune mechanisms underlying KD, have been used to treat this challenging condition with promising results, contributing to a better understanding of the pathogenesis of this rare disorder. The aim of this study was to review the literature concerning the genetic factors and immune mechanisms that contribute to the pathogenesis of KD, with a special focus on the role of biological therapies.

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.

OBJECTIVE:In professional singers, allergic rhinitis can lead to dysphonia and alterations in resonance. Each episode of laryngeal inflammation increases the risk of vocal strain or forces singers to cancel performances. This study aimed to analyze differences between allergic and nonallergic professional singers in self-evaluation of voice quality, objective examination of voice, and limitations of professional activities due to voice troubles. METHODS:Two groups, one with 30 subjects diagnosed with allergic rhinitis (the study group) and the other with 30 subjects without allergic rhinitis (the control group), were recruited from a pool of 167 professional pop singers. All subjects underwent comprehensive rhinological and phoniatric evaluations. The rhinological evaluation included nasal endoscopy, rhinomanometry, and 22-item Sinonasal Outcome Test (SNOT-22) questionnaire. The phoniatric evaluation included laryngostroboscopy, the Voice Handicap Index (VHI) and Singing Voice Handicap Index (SVHI) questionnaires, and the Dysphonia Severity Index (DSI). Statistical analysis was conducted using the Statistical Package for Social Sciences 25.0 (SPSS). RESULTS:Dust mite allergy was the main cause of symptoms in our series of allergic singers, particularly when associated with seasonal allergens. Comparing singers with allergic rhinitis to those without, the study group had significantly higher scores on the SNOT-22, VHI, and SVHI assessments. Although the median DSI value indicated a good quality of voice in all subjects, it was significantly lower in the allergic group compared with the control group. The odds ratio (OR) indicated an increased risk for allergic singers of needing to postpone performances (OR 3.7), singing with laryngeal inflammation (OR 4.4), or changing the song pitch (OR 22.2). CONCLUSIONS:Allergic singers experienced severe limitations in their professional activities. Our results suggest that careful management of allergic rhinitis is essential for singers to avoid conditions that could lead to vocal strain.

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.

Background Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score (NPS), symptom and quality of life scores in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Objective We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary care centres. Methodology NPS, SinoNasal Outcome Test (SNOT)-22 score, visual analogue scale (VAS) for total sinus symptoms, loss of smell (LoS) and nasal blockage (NB), and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline, 24 and 52 weeks of treatment of dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities and blood eosinophil counts (BEC). Treatment response was evaluated according to EUFOREA 2021 criteria. Results All patient outcomes improved at 24 and 52 weeks of treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, NSAID exacerbated respiratory disease (NERD), allergy or baseline BEC. 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks respectively. 54.4% and 68.2% reached all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks respectively. Conclusions Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks of treatment. Favourable treatment response was independent of the number of sinus surgery procedures, major comorbidities or baseline systemic levels of type 2 inflammation.

PURPOSE:Biologics represent a new therapeutic strategy for severe and recurrent chronic rhinosinusitis with nasal polyps (CRSwNP). Usually, their actual therapeutic effectiveness is assessed by reduction in nasal polyps and/or improvement in nasal symptoms and quality of life. However, these measures do not consider nasal immunophlogosis, which can be evaluated through nasal cytology. The purpose of this study was to assess not only the clinical impact but also the cellular changes in the nasal inflammatory infiltrate observed through nasal cytology of CRSwNP patients treated with Dupilumab for 24 months. METHODS:Fifty-five CRSwNP patients treated with Dupilumab were collected. Patients were evaluated before starting treatment and at one, three, six, nine months, one year, one and a half years, and two years after the first drug administration. During follow-up visits patients underwent endoscopic evaluation, nasal symptoms and quality of life assessment, complete blood count and nasal cytology. RESULTS:During follow-up, significant improvement was found in Nasal Polyps Score (NPS), nasal patency, olfaction, Sino-Nasal Outcome Test (SNOT-22) score, and Visual Analogue Scale (VAS). Regarding nasal cytology, a reduction in eosinophils and mast cells in the cellular infiltrate was observed over the two-year follow-up period compared to baseline. CONCLUSION:Dupilumab has demonstrated broad efficacy in the management of CRSwNP from both clinical and cytological findings. Further studies are needed to confirm our findings and evaluate the biologics' impact on nasal mucosal inflammatory cells by nasal cytology with the aim of better identifying each patient's endotype and predicting the response to biologics.

BACKGROUND: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics. OBJECTIVE: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology. METHODOLOGY: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion. RESULTS: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security as-pects. Up to 300 patients have already been included. CONCLUSIONS: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE. (c) 2022 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:431-8)