Dupilumab: a delayed response in asthmatic and atopic patients treated for chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a common disease, which was previously approached with sinus surgery or systemic corticosteroids. The advent of biological therapies radically changed the approach to this disease. On the other hand, there is scarce scientific evidence of how specific subsets of patients respond to this treatment. METHODS: this is a monocentric, prospective study investigating the long-term efficacy on biweekly 300 mg dupilumab therapy in CRSwNP, prescribed to 61 patients. Patients were evaluated at baseline and every 2 months for the first 6 months, then at 9, 12, 16, 20 and 24 months. RESULTS: dupilumab proved to be an effective treatment, neatly improving both subjective and objective measurements in CRSwNP. The main finding of the study is the difference between specific subgroups of patients: while the overall response is similar, patients with Th2 comorbidities such as asthma and atopy tend to reach a stable response later, with the improvement ongoing even after 6 months of therapy, while non-asthmatic, non-atopic patients attain an earlier stability in response. CONCLUSIONS: dupilumab provides an excellent long-term control of CRSwNP, but the response in asthmatic and atopic patients appears to be different and delayed when compared to non asthmatic and non atopic ones.

An adjoint-based approach for the surgical correction of nasal septal deviations.

Deviations of the septal wall are widespread anatomic anomalies of the human nose; they vary significantly in shape and location, and often cause the obstruction of the nasal airways. When severe, septal deviations need to be surgically corrected by ear-nose-throat (ENT) specialists. Septoplasty, however, has a low success rate, owing to the lack of suitable standardized clinical tools for assessing type and severity of obstructions, and for surgery planning. Moreover, the restoration of a perfectly straight septal wall is often impossible and possibly unnecessary. This paper introduces a procedure, based on advanced patient-specific Computational Fluid Dynamics (CFD) simulations, to support ENT surgeons in septoplasty planning. The method hinges upon the theory of adjoint-based optimization, and minimizes a cost function that indirectly accounts for viscous losses. A sensitivity map is computed on the mucosal wall to provide the surgeon with a simple quantification of how much tissue removal at each location would contribute to easing the obstruction. The optimization procedure is applied to three representative nasal anatomies, reconstructed from CT scans of patients affected by complex septal deviations. The computed sensitivity consistently identifies all the anomalies correctly. Virtual surgery, i.e. morphing of the anatomies according to the computed sensitivity, confirms that the characteristics of the nasal airflow improve significantly after small anatomy changes derived from adjoint-based optimization.

Early increase in eosinophil count may predict long-term hypereosinophilia during dupilumab treatment: a 2-year observational study.

KEY POINTS: In a limited subset of patients, dupilumab-induced hypereosinophilia is persistent. Two-month follow-up eosinophil count may predict long-lasting hypereosinophilia.

Comparison of guidelines for prescription and follow-up of biologics for chronic rhinosinusitis with nasal polyps.

PURPOSE: To compare international and regional guidelines for prescription and monitoring of response to biologics in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A literature review was performed to identify publications reporting indications for biologic therapy in CRSwNP. A full-text reading identified specific issues for comparison: prior surgery, evidence of type 2 inflammation (T2I), smell function, comorbidities, use of systemic corticosteroids, impact on quality of life, and endoscopic and CT findings were compared for the prescription, while the monitoring of the treatment was described in relation to timing, classification of response and criteria for withdrawal. RESULTS: Ten publications were found. Prior surgery was strictly necessary in five guidelines, while in all the remaining it was variably recommended. A confirmation of T2I was considered necessary in one publication, unnecessary in two, and recommended or constituted only one of the factors to consider in seven. All the other issues analyzed were variably considered. Reevaluation was suggested at 4-6 months and 1 year, mostly assessing improvement in the same criteria used for prescription. CONCLUSIONS: A combination of subjective and objective findings is used for the identification of patients with CRSwNP who are indicated for biologic therapy. Major debate has developed on the need for previous surgery, which is generally recommended, or strictly necessary for some authors. Confirmation of T2I is generally suggested, but compulsory only in a minority of guidelines. Smell function, use of systemic corticosteroids, and the impact on quality of life are the other factors most frequently considered.

Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results.

PURPOSE: Biological therapies are gaining relevance in the management of CRSwNP with few adverse events reported. Among these, dupilumab, an anti-IL4-Ra monoclonal antibody, is frequently associated with hypereosinophilia (HE) which usually remains silent and progressively resolves, although some cases of systemic involvement occurs. The aim of this paper is to describe our experience and propose a management flowchart for HE during therapy with dupilumab. METHODS: Patients with CRSwNP who satisfied EPOS2020 criteria for biological therapies were included in this prospective study. Each case was discussed in a multidisciplinary meeting with subsequent prescription of dupilumab; all patients were candidates to follow-up bi-monthly for 6 months, while additional blood tests were scheduled in the event of HE. RESULTS: A total of 21 patients with a mean age of 48.4 years were enrolled. Of these, 15 of 21 presented an asthma comorbidity and 9 of 21 ASA sensitivity. Four patients (19%) developed HE with AEC > 1.5 × 109/L, whereas it occurred in 9.5% (two patients) if considered AEC > 3 × 109/L. No cases of hypereosinophilic syndrome were recorded. Following our decision-making flowchart, two patients received short-term corticosteroid therapy, whereas the other two were only eligible for closer follow-up. CONCLUSIONS: During dupilumab therapy, HE may occur and should be considered benign when < 3 × 109/L in the absence of organ involvement. Conversely, in case of HE ≥ 3 × 109/L, an empirical approach with short-term corticosteroid therapy should be considered to debulk the blood from eosinophils and prevent potential organ involvement.

A prospective study on the efficacy of dupilumab in chronic rhinosinusitis with type 2 inflammation.

Objective: Treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) includes endoscopic sinus surgery and topic and/or systemic corticosteroids, which have only temporary effects. The development of biologic therapies has provided a new treatment paradigm for CRSwNP. Dupilumab is the only biological approved in Italy for CRSwNP, but its efficacy in a real-life context is still scarce. Methods: We carried out a monocentric prospective study at our institution with a 6-month follow-up on patients administered biweekly 300 mg dupilumab therapy for CRSwNP, prescribed according to EPOS 2020 criteria. Patients were evaluated at baseline and every 2 months. Results: Median values at baseline and 6 months were, respectively, 3/12 and 8/12 for the Brief Smell Identification Test (p = 0.005), 5/8 and 2/8 for the Nasal Polyp Score (p < 0.001), 10/20 and 6/20 for the Lund-Kennedy score (p < 0.001), 65/110 and 14/110 for the Sinonasal Outcome Test (p < 0.001), and 15/25 and 23/25 for the Asthma Control Test score (p = 0.009). Adverse events were mild, consisting mainly in discomfort at the site of injection. Four patients developed asymptomatic hypereosinophilia. The treatment was not discontinued in any patient. Conclusions: Dupilumab was confirmed to be an effective and safe treatment for CRSwNP, as previously seen in registrational studies.

The importance of clinical presentation on long-term outcomes of external dacryocystorhinostomies: Our experience on 245 cases.

PURPOSE: External dacryocystorhinostomy (EXT-DCR) is a surgical approach commonly used to treat post-canalicular acquired lacrimal obstruction whose success rate has been described, equally with endoscopic DCR, to be superior to other available treatments. METHODS: At San Raffaele Hospital, Milan (Italy), from January 2008 to December 2020, 245 EXT-DCRs were performed. All patients underwent routine pre-operative work-up including Jones tests and probing and irrigation of the lacrimal pathway; when necessary, a multidisciplinary approach with nasal endoscopy was performed. The surgical approach was followed by positioning of a bicanalicular stent which was left in place for 6 months. Success was defined as resolution of clinical signs/symptoms and free lacrimal flow on functional test. RESULTS: Of the cases enrolled, 26.9% were treated for recurrent epiphora (group 1), and 73.1% for epiphora associated with chronic dacryocystitis (group 2). After a median follow-up of 71 months, group 1 had success at T0 (1 month) and T1 (long-term) of 81.8% and 60.6%, respectively, compared to 93.8% and 77.7% in group 2. Statistical analysis showed a significant association with surgery both at T0 (p = 0.018) and T1 (p = 0.012) with group 2 showing better outcomes. Additionally, the cosmetic outcome of the external scar was defined as invisible in 91.8% of cases and slightly visible in 8.2%. CONCLUSIONS: External dacryocystorhinostomy provides long-term reliable results particularly in case of chronic dacryocystitis. Moreover, the optimal esthetic outcome of the external scar should be no longer considered the only guiding principle of treatment modality, particularly in the elderly.