Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health‐related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real‐world evidence is still limited.Methods: This Phase IV real‐life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow‐up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint.Results: We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino‐Nasal Outcomes Test‐22 (SNOT‐22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21;p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent‐moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria.Conclusions: Our findings from this large‐scale real‐life study support the effectiveness of dupilumab as an add‐on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

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.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL‐5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients.Methods: This was a case–control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT‐22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT‐22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL‐5 and calprotectin in both nasal secretions and nasal polyp tissue.Results: Calprotectin and IL‐5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non‐steroidal anti‐inflammatory drugs‐exacerbated respiratory disease (NSAID‐ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID‐ERD, and IL‐5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease.Conclusions: Our data suggest that asthma, NSAID‐ERD, and IL‐5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries.

Objective. The aim of this study was to evaluate the clinical relevance of absolute eosinophil blood count and eosinophil count by nasal cytology in the context of real-life clinical practice and to determine if they correlate with the severity of symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods. We enrolled 425 patients with CRSwNP followed between January 2015 and April 2023 at the A. Gemelli Hospital Foundation-IRCCS, Rome, Italy. We gathered data on blood and local eosinophil count and correlated the results with clinical features. All patients underwent endoscopy, Visual Analogical Scale (VAS) for main symptoms, and SinoNasal Outcome Test 22 (SNOT-22). Results. We observed significantly higher mean levels of eosinophils in serum and at nasal cytology in patients with CRSwNP and comorbidities (asthma, non-steroidal anti-inflammatory drugs - exacerbated respiratory disease and allergy) compared to those without. Blood eosinophilia was not associated with severity of symptoms, whereas patients with nasal eosinophil count > 5 eosinophils per high-power field at nasal cytology had a significantly higher median specific VAS for nasal symptoms and significantly higher SNOT 22 scores. Conclusions. We demonstrated that blood eosinophil count and nasal cytology may represent useful tools in routine clinical practice to define Type 2 inflammation and that their levels are usually higher in patients with comorbidities. We also showed that blood eosinophilia was not correlated with severity of symptoms, whereas local eosinophil count was associated with high severity of symptoms and high burden on quality of life.