The aim of this study has been to evaluate the efficacy of the IL-5 receptor blocker benralizumab on chronic rhinosinusitis with nasal polyposis (CRSwNP), associated with severe eosinophilic allergic asthma. Ten patients with severe eosinophilic allergic asthma and CRSwNP were enrolled. Sino-nasal outcome test (SNOT-22), numerical rating scale (NRS), endoscopic nasal polyp score, Lund Mackey CT (computed tomography) score, and blood eosinophil count were measured at baseline and after 24 weeks of treatment with benralizumab. All the above clinical, endoscopic, imaging, and hematological parameters significantly improved after 24 weeks of treatment with benralizumab. In particular, SNOT-22 decreased from 61.10 ± 17.20 to 26.30 ± 19.74 ( P < 0.001), NRS decreased from 7.20 ± 1.55 to 3.40 ± 2.22 ( P < 0.001), the endoscopic polyp nasal score decreased from 4.20 ± 1.32 to 2.50 ± 1.78 ( P < 0.001), the Lund-Mackay CT score decreased from 16.60 ± 5.50 to 6.90 ± 5.99 ( P < 0.001), and blood eosinophil count decreased from 807.3 ± 271.1 cells/μL to 0 cells/μL ( P < 0.0001). These results strongly suggest that benralizumab exerted a very effective therapeutic action on CRSwNP associated with severe asthma, thus improving nasal symptoms and decreasing polyp size.
We report the case of a primitive nasal melanoma in an 82-year-old patient, showing how this rare malignancy, with non-specific signs and symptoms, can represent a challenging diagnosis for the physician. A 82-year-old Caucasian patient presented for unilateral nasal obstruction and occasional epistaxis. Computerized tomography (CT) and magnetic resonance imaging (MRI) of the facial massif revealed turbinate hypertrophy and a polypoid phlogistic tissue isointense in T1 with an intermediate signal in T2 and Short-TI Inversion Recovery (STIR)-T2, occupying the middle meatus and the anterior upper and lower left meatus with partial obliteration of the ostium and the infundibulum of the maxillary sinus. The Positron emission tomography (PET) exam was negative for metastases. Conservatory surgery in the left anterior video rhinoscopy was performed, allowing a radical 4-cm tumor excision. Histology reported epithelioid cell melanoma, PanK−, CD45−, and PanMelanoma+. Adjuvant radiotherapy was suggested, even considering a complete resection as the result of surgery. No local or systemic relapse was noticed at the 2-month follow-up visit. Although mucosal melanoma is a rare and aggressive malignancy characterized by a poor prognosis, early diagnosis allows a more conservative approach, with little surgical difficulty and no aesthetic effect. Our case raises awareness of the importance of early intervention even in those cases where the clinic symptoms and diagnostic images show uncertain severity.
Background Having been approved for biological treatment of atopic dermatitis, dupilumab has also been recently licensed as add-on therapy for severe asthma and nasal polyposis. With regard to the latter diseases, few real-life clinical investigations have been carried out to date. Objective The primary end point of this single-center observational study was to evaluate in a real-life setting the short-term therapeutic effects of dupilumab in patients with severe asthma and nasal polyposis. Methods At baseline and after 4 weeks of add-on therapy with dupilumab, several clinical and functional parameters were assessed in 20 patients with severe asthma and nasal polyposis, including both allergic and nonallergic subjects. Results After 4 weeks of treatment with dupilumab, all patients experienced remarkable improvement in both severe asthma and nasal polyposis. In particular, asthma-control test and sinonasal outcome test 22 scores had significantly increased ( p <0.0001) and decreased ( p <0.0001), respectively. Oral corticosteroid intake got to zero within 4 weeks ( p <0.0001). Moreover, in week 4, significant increases were detected with regard to both prebronchodilator forced expiratory volume in the first second ( p <0.01) and forced vital capacity (FVC; p <0.05). At the same time point, dupilumab had significantly reduced residual volume ( p <0.0001) and total lung capacity ( p <0.001), whereas it had enhanced forced midexpiratory flow of 25%–75% FVC ( p <0.01) and peak expiratory flow ( p <0.01). After 4 weeks of treatment, dupilumab had also lowered levels of fractional exhaled nitric oxide ( p <0.0001). Conclusion The results of this real-life study suggest that dupilumab can be utilized in both allergic and nonallergic patients with severe asthma and nasal polyposis as a valuable add-on biological therapy with rapid onset of action.
Chronic rhinosinusitis of the nasal mucosa is an inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion, and hyposmia, and in some cases, it can result in the development of nasal polyposis. Nasal polyps are benign lobular-shaped growths that project in the nasal cavities; they originate from inflammation in the paranasal mucous membrane and are associated with a high expression of interleukins (IL)-4, IL-5, IL-13, and IgE. Polyps derive from the epithelial–mesenchymal transition of the nasal epithelium resulting in a nasal tissue remodeling. Nasal polyps from three patients with chronic rhinosinusitis as well as control non-polyp nasal mucosa were used to isolate and cultivate mesenchymal stem cells characterized as CD73+, CD90+, CD105+/CD14−, CD34−, and CD45−. Mesenchymal stem cells (MSCs) cultures were induced to differentiate toward adipocytes, where lipid droplets and adipocyte genes PPARγ2, ADIPO-Q, and FABP4 were observed in control non-polyp nasal mucosa-derived mesenchymal cells but were scarcely present in the cultures derived from the nasal polyps, where apoptosis was evident. The modulation of the response to adipogenic stimulus in polyps represents a change in the molecular response that controls the cascade required for differentiation as well as possible means to specifically target these cells, sparing the normal mucosa of the nasal sinuses.
Already used for the treatment of some allergic and inflammatory diseases, such as asthma or atopic dermatitis, dupilumab has also been approved as add-on therapy for patients with CRSwNP, and it could represent the keystone to reducing the remission time as well as to improve healing and quality of life. On the other hand, the role of miRNAs as potential biomarkers of immune modulation is emerging. We analyzed the effects of a short-time treatment with dupilumab in patients with CRSwNP, analyzing the immune response modification as well as miRNAs modulations. First, in this early observation stage, all patients experienced remarkable improvement and were clinically stable. Indeed, we observed a significant decrease in CD4+ T cells and a significant reduction in total IgE (p < 0.05) and serum IL-8 levels (p < 0.01), indicating a reduction in the general inflammatory condition. In addition, we analyzed a panel of about 200 circulating miRNAs. After treatment, we noted a significant downregulation of hsa-mir-25-3p (p-value = 0.02415) and hsa-mir-185-5p (p-value = 0.04547), two miRNAs involved in the proliferation, inflammation, and dug-resistance, in accordance with the clinical status of patients. All these preliminary data aimed to identify new biomarkers of prognosis, identifiable with non-invasive procedures for patients. Further, these patients are still under observation, and others with different levels of responsiveness to treatment need to be enrolled to increase the statistical data.
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