Assessment of cephalometric parameters and correlation with the severity of the obstructive sleep apnea syndrome.

BACKGROUND: In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. METHODS: We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. RESULTS: Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. CONCLUSION: Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Difficult-To-Treat and Severe Asthma: Can Real-World Studies On Effectiveness of Biological Treatments Change the Lives of Patients?

Many different phenotypes that characterize severe asthma are supported by intricate pathomechanisms called endotypes. The latter are driven by molecular interactions, mediated by intercellular networks. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, real-world studies have confirmed the positive effects of currently available antibodies directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, as well as the receptors of interleukins-4 (IL-4) and 13 (IL-13). The best way to treat severe asthma should be chosen based on the peculiar phenotypic and endotypic traits of each patient. This will lead to relevant improvements in both clinical and functional outcomes. In particular, biological therapies can change the lives of asthma patients with a strong impact on quality of life. Unfortunately, patients with severe non-type-2 asthma, who continue to have pertinent unmet needs, are not receiving satisfactory advances within the context of biological treatments. It is also hopeful that in the next future new therapeutic strategies will be specifically implemented for these people, perhaps offering them the opportunity to improve their current, mostly inadequate asthma management.

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP.

Real-Life Effects of Omalizumab on Chronic Rhinosinusitis with Nasal Polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease of the nasal and sinus mucosa. This inflammatory process is supported by a multitude of cytokines, including IL-4, IL-5, and IL-13 produced by Th2 cells, as well as by IgE produced by B lymphocytes in response to a stimulus. Omalizumab is an anti-IgE monoclonal antibody with well-recognized roles in allergic asthma and chronic spontaneous urticaria. The aim of this study was to evaluate the clinical efficacy of omalizumab in a cohort of 13 patients suffering from chronic rhinosinusitis with CRSwNP. The inclusion criteria considered were as follows: 18 years of age, with a diagnosis of chronic rhinosinusitis with severe nasal polyposis expressed by an NPS greater than or equal to 5 and/or a SNOT-22 greater than or equal to 50. In addition, in the enrolled patients, the classic treatment with corticosteroids had to have been suspended due to recurrence after surgery or lack of response. Our results highlighted that omalizumab treatment for 16 weeks improved the parameters analyzed: SNOT-22, NPS, NRS, and NCS. The clinical efficacy of omalizumab was further strengthened by a significant improvement in respiratory function as well as reductions in the nasal polyps' size and in the associated symptoms.

Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence.

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.

Cellular and Biochemical Characterization of Mesenchymal Stem Cells from Killian Nasal Polyp.

Killian's (antrochoanal) polyp is a unilateral nasal polypoid lesion of the maxillary sinus especially affecting children and young adults with unilateral nasal obstruction, pus discharge, and headache. Although its etiology is unclear, chronic inflammation, autoreactivity, allergies, and viral infections are implicated in its formation and development, causing nasal tissue remodeling. In this context, we isolated and cultured mesenchymal stem cells from surgical biopsies of three patients with Killian nasal polyp (KNP-MSCs) while healthy nasal tissue (HNT-MSCs) was used as control. Our results demonstrated that KNP-MSCs exhibited reduced cell proliferation compared to HNT-MSCs, and migrated less than the control, showing a partial epithelial phenotype with low mRNA levels of I-CAM and a significant increase of E-cad. Subsequently, both MSCs were induced to osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs underwent to differentiate into osteoblasts but exhibited reduced ALP activity and calcium deposits and low mRNA levels of osteogenesis-associated genes compared to osteogenic induced-HNT-MSCs. Conversely, KNP-MSCs and HNT-MSCs have shown the same adipogenic differentiation potential, with a similar lipid droplet amount, adipocyte gene expression, and triacylglycerols content. Taken together, these results first demonstrated the cellular and molecular characterization of MSCs derived from the Killian nasal polyp.

Short-Term Evaluation of Dupilumab Effects in Patients with Severe Asthma and Nasal Polyposis.

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.

Primary Mucosal Melanoma Presenting with a Unilateral Nasal Obstruction of the Left Inferior Turbinate.

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.

Deficit in Adipose Differentiation in Mesenchymal Stem Cells Derived from Chronic Rhinosinusitis Nasal Polyps Compared to Nasal Mucosal Tissue.

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.

Real-life effects of benralizumab on allergic chronic rhinosinusitis and nasal polyposis associated with severe asthma.

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.

Intrinsic Laryngeal Lipoma Treated with Transoral CO2 Laser Microsurgery: An Unusual Case Report.

BACKGROUND Lipomas, the most common soft tissue tumors, represent almost half of all benign mesenchymal neoplasms and are characterized by the absence of symptoms. However, if they grow in a laryngeal site, they can cause dyspnea and dysphonia which represents one of the major symptoms of benign laryngeal diseases (such as polyps or nodules); these symptoms are often the first symptom of neoplastic diseases. CASE REPORT We present a case of a 28-year-old female patient with a rounded pseudocyst neoformation located in the left aryepiglottic fold that partially hid the homolateral vocal cord and limited its mobility. Due to the site of the lesion and MRI images showing a well-capsulated neoformation without contrast enhancement, we decided to surgically remove it with a micro-laryngoscopic approach after an evaluation of the patient's upper airway by an anesthetist. This case demonstrates that a micro-endoscopic approach using transoral laser microsurgery for surgical excision was useful for removing the entire mass and avoiding relapses. CONCLUSIONS Laryngeal lipomas are benign and rare lesions, in particular intrinsic lipomas are uncommon, but, if they grow, they can cause life-threatening symptoms. In our case, a lipoma reached a size of around 2 centimeters and was not pedunculated, only a histopathological examination of the surgical specimens could provide a differential diagnosis against a lipoma-like liposarcoma. The use of Transoral Laser CO2 Micro-laryngoscopy (TLM) provided good management of a small intrinsic lipomas of the larynx, minimizing the potential for relapses.

Maxillary sinus mucocele with orbital complications.

INTRODUCTION: Maxillary sinus mucocele is an unusual clinic entity (incidence of 3-10%), represented by mucous secretion lined by respiratory stratified pavemented epithelium and its origin is mainly secondary to infections, inflammations, surgery, trauma or neoplasia. CASE REPORT: We present a case of maxillary sinus mucocele. Subject of the study is a 74 aged patient referring positive anamnesis for nasal cavity surgery. His symptoms appeared six months ago and he complainted vertical ocular diplopia and ocular tension sensation, without rhinologic complaints. Oculistic examination confirmed an isolated left inferior rectus palsy, and CT showed mucous secretion occupying left maxillary sinus, with bone erosion to the orbital floor until orbital muscles. MRI is the gold standard for differential diagnosis with neoplastic lesions but the patient refused to perform this radio-diagnostic exam. He underwent to Endoscopic sinus surgery, consisting in middle meatal antrostomy and removal of the mucocele. Four months later the endoscopic follow-up showed regular maxillary cavity and regular ocular motility. CONCLUSION: In our opinion the rebuilding of the eroded bone is not mandatory if the integrity of the maxillary upper wall mucosa is respected, and antrostomy with drainage allows to recover ocular and paranasal sinus function. KEY WORDS:, Diplopia, Endoscopic sinus surgery.