Dupilumab's impact on nasal citology: Real life experience after 1 year of treatment.

BACKGROUND: Biologic agents are considered a new revolutionized therapy for severe and recurrent forms of CRSwNP which disease burden is not sufficiently controlled by conservative and/or surgical treatments. Recent Research has focused on evaluating their real-life efficacy in CRSwNP, as only limited reports on real-life data are available. However, in most studies, the response to treatment is evaluated in terms of improvement in Nasal Polyp Score (NPS) or in Sino-Nasal Outcome test (SNOT-22) scores. However, both criteria do not consider nasal immunophlogosis, which can be easily assessed by nasal cytology. The aim of our study was to evaluate changings in the nasal inflammatory infiltrate of CRSwNP patients treated with Dupilumab for 12 months. METHODS: 27 patients suffering from severe CRSwNP treated with Dupilumab were recruited. Nasal cytology findings, NPS, SNOT-22, ACT scores and blood eosinophil count at T0 (before treatment) and at T1 (after 1 year of treatment) were compared. RESULTS: After 1 year of biological therapy with Dupilumab, NPS, SNOT-22 and, among the 17 asthmatic patients, ACT scores improved significantly. At T1, a statistically significant percentage of patients showed negative citology. Moreover, a significant reduction in the mast cell-eosinophilic pattern and an increase of neutrophils and bacteria was reported. CONCLUSIONS: The response to treatment can be considered both in the case of negative nasal cytology and in the case of the appearance of neutrophils and bacteria. In this context, eosinophils, the specific target of biological therapies, play a crucial role in regulating tissue homeostasis and, consequently, the nasal immunophlogosis.

Eosinophil-mast cell pattern of intraepithelial infiltration as a marker of severity in CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is defined as a Type 2 eosinophilic disease, while CRSsNP is considered a Type 1 neutrophilic disease. Since neutrophils are also activated in eosinophilic CRSwNP, the eosinophil-neutrophil dualism has been revaluated. Among the inflammatory cells infiltrating sinus-nasal tissues, the role of mast cells (MCs) is not already recognized, although Clinical-Cytological Grading, which defines the severity of CRSwNP, attributes to mixed eosinophil-MC forms of CRSwNP a greater risk of recurrence. We aimed to examine nasal polyps from both a cytological and histopathological point of view, to evaluate the presence and localization of MCs. Cytological and histological examination of 39 samples of nasal polyps were performed. Immunohistochemistry was used to evaluate the presence of Tryptase + CD117 + MCs, which were counted both in the epithelial layer and in the lamina propria. A statistically significant correlation was found between intraepithelial MCs and CRSwNP severity (p < 0.001) and between the total eosinophil count and the total mast cell count (p < 0.001). Cytological examination and immunohistochemistry were comparable in detecting the presence of intraepithelial MCs (p = 0.002). The histological cut-off of 6 intraepithelial MCs was identified to detect severe CRSwNP (p < 0.001). MCs have been shown to be located in the lamina propria of almost all eosinophilic nasal polyps without significantly affecting their severity. Intraepithelial MCs are associated with greater severity of CRSwNP. Histopathological criteria of the eosinophil-MC form of CRSwNP in addition to the eosinophilic one, should be defined to guarantee patients effective and tailored treatments.

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting.

INTRODUCTION: Interleukin-5 (IL-5) is the principal cytokine regulating eosinophil growth, differentiation, activation, and expression. It is a specific target of mepolizumab, an anti-IL-5 monoclonal antibody used in the treatment of severe eosinophilic asthma. This new drug can improve symptoms, reduce asthma exacerbations and steroid use. Few data are available on its efficacy for nasal symptoms. OBJECTIVE: To describe the all-round clinical impact of mepolizumab in a real-life setting, evaluating the efficacy and safety of the drug in severe eosinophilic asthma patients. POPULATION AND METHODS: We retrospectively collected the clinical and functional data on 27 patients (16 males) affected with severe eosinophilic asthma, diagnosed at the Siena Regional Referral Centre and monitored for 6 months. Clinical, immunological, and functional data at baseline and follow-up were entered in a database together with comorbidities, number of exacerbations, steroid treatment, multiple-flow exhaled nitric oxide, and validated questionnaires. RESULTS: A significant reduction in asthma exacerbations was observed in all patients after 6 months of the biological therapy (p = 0.0009), and 4/6 patients discontinued chronic oral steroids. A significant improvement in ACT, FEV1, SNOT22, and alveolar nitric oxide was observed after 1 month of mepolizumab (p = 0.003, p = 0.007, p = 0.047, and p = 0.019, respectively) and maintained after 6 months of treatment. After 6 months, FeNO 50 was reduced as well (p = 0.030). Mepolizumab was very well tolerated, and no major side effects were observed. CONCLUSIONS: Our study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma.