Search Results (24)

Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP, respectively) is a chronic inflammatory disease affecting almost 5 to 12% of the population and exhibiting high recurrence rates after functional endoscopic sinus surgery (FESS). TGFβ1-related pathways contribute to tissue remodelling, which is one of the key aspects of CRS pathogenesis. Additionally, adenosine signalling participates in inflammatory processes, and CNPase was shown to elevate adenosine levels by metabolizing cyclic monophosphates. Thus, the aim of this study was to assess the expression levels of Smad2, pSmad3, TGFβ1, and CNPase protein via immunohistochemistry in sinus epithelial tissues from patients with CRSwNP (n = 20), CRSsNP (n = 23), and non-CRS patients (n = 8). The expression of Smad2, pSmad3, TGFβ1, and CNPase was observed in the sinus epithelium and subepithelial area of all three groups of patients, and their expression correlated with several clinical symptoms of CRS. Smad2 expression was increased in CRSsNP patients compared to CRSwNP patients and controls (p = 0.001 and p < 0.001, respectively), pSmad3 expression was elevated in CRSwNP patients compared to controls (p = 0.007), TGFβ1 expression was elevated in CRSwNP patients compared to controls (p = 0.009), and CNPase was decreased in CRSsNP patients compared to controls (p = 0.03). To the best of our knowledge, we are the first to demonstrate CNPase expression in the upper airway epithelium of CRSwNP, CRSsNP, and non-CRS patients and point out a putative synergy between CNPase and TGFβ1/Smad signalling in CRS pathogenesis that emerges as a novel still undiscovered aspect of CRS pathogenesis; further studies are needed to explore its function in the course of the chronic inflammation of the upper airways. Full article

Recalcitrant frontal sinusitis in patients with chronic rhinosinusitis and nasal polyps (CRSwNP) has a negative impact on their quality of life due to frontal pain and a high risk of sinus occlusion, thus necessitating antibiotics, systemic corticosteroids, and multiple surgeries. The aim of this study was to assess the efficacy of dupilumab in reducing frontal pain and the need for rescue treatments for recalcitrant frontal sinusitis in patients with CRSwNP. We enrolled a cohort of 10 patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis associated with severe facial pain measured by MIDAS score who were treated with dupilumab 300 mg every 2 weeks and followed for at least 12 months. The mean MIDAS score decreased from 45.6 ± 10.7 at baseline to 1.3 ± 2.3 at 6 months (p < 0.05). VAS craniofacial pain decreased from 7.3 ± 1.6 at baseline to 1.2 ± 1.5 at 6 months (p < 0.05). No patient needed oral corticosteroids during treatment with dupilumab (p < 0.05), and the use of analgesics decreased from 9.6 ± 3.1 NSAID pills/week in the last 2 months at baseline to 0.6 ± 1.3 at 1 year of follow-up (p < 0.05). Our results demonstrated that use of subcutaneous dupilumab can improve symptom control, including recurrent severe cranio-facial pain, and reduce the need for rescue medical treatments (systemic steroids and NSAID) in patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis. Full article

Chronic rhinosinusitis (CRS) is a complex syndrome with various inflammatory mechanisms resulting in different patterns of inflammation that correlate with the clinical phenotypes of CRS. Our aim was to use detected IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, Ki 67, HBD-2, HBD-3, and LL-37 to classify specific inflammatory endotypes in chronic rhinosinusitis with the tissue of nasal polyps (CRSwNP). Samples from 35 individuals with primary and recurrent CRSwNP were taken during surgery. The tissues were stained for the previously mentioned biomarkers immunohistochemically. A hierarchical cluster analysis was performed. The clinical parameters were compared between clusters. Five clusters had significantly different biomarkers between groups. There were no significant differences in the clinical parameters, except for the Lund–Mackay score, which was significantly higher in cluster 4 compared to that of cluster 1 (p = 0.024). Five endotypes of (CRSwNP) are characterized by different combinations of type 1, type 2, and type 3 tissue inflammation patterns. In the Latvian population, endotypes associated with neutrophilic inflammation or a combination of neutrophilic inflammation and type 2 inflammation are predominant. Increased proliferation marker Ki 67 values are not associated with more severe inflammation in the tissue samples of chronic rhinosinusitis with nasal polyps. Full article

The prevention of postoperative recurrence after endoscopic sinus surgery (ESS) relies on targeting specific pathological mechanisms according to individuals’ immunological profiles. However, essential biomarkers and biological characteristics of difficult-to-treat chronic rhinosinusitis (CRS) patients are not well-defined. The aim of this study was to explore the immunologic profiles of subgroups of CRS patients and determine the specific cytokines responsible for recalcitrant or recurrent CRS with nasal polyposis (rCRSwNP). We used 30 cytokine antibody arrays to determine the key cytokines related to recurrent polypogenesis. Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to assess the levels of these key cytokines in 78 patients. Polymorphonuclear leukocytes (PMNs) isolated from nasal polyps were challenged with specific cytokines to examine the levels of enhanced interleukin (IL)-8 production. Finally, we used immunohistochemistry (IHC) staining to check for the presence and distribution of the biomarkers within nasal polyps. A cytokine antibody array revealed that IL-8, IL-13, IL-15, and IL-20 were significantly higher in the recalcitrant CRSwNP group. Subsequent ELISA screening showed a stepwise increase in tissue IL-8 levels in the CHR, CRSsNP, and CRSwNP groups. PMNs isolated from nine CRSwNP cases all demonstrated enhanced IL-8 production after IL-15 treatment. IHC staining was labeled concurrent IL-8 and IL-15 expression in areas of prominent neutrophil infiltration. Our results suggest that IL-15 within the sinonasal mucosa plays a crucial role in promoting IL-8 secretion by infiltrating PMNs in recalcitrant nasal polyps. In addition, we propose a novel therapeutic strategy targeting the anti-IL-15/IL-8 axis to treat CRS with nasal polyposis. Full article

Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) represents a condition mainly caused by the type 2 inflammation presence and marked by the existence of polyps within the nasal and paranasal sinuses. The standard of care includes intranasal steroids, additional burst of systemic steroids, if needed, and surgery. However, recurrence is common, especially among patients with comorbid type 2 inflammatory diseases. Recently, biological drugs, addressing the underlying cause of the disease, have been approved in Italy (dupilumab, omalizumab, and mepolizumab). A Health Technology Assessment was conducted to define multidimensional impact, assuming Italian NHS perspective and a 12-month time horizon. The EUnetHTA Core Model was deployed, using the following methods to analyze the domains: (i) literature evidence; (ii) administration of semi-structured questionnaires to 17 healthcare professionals; (iii) health economics tools to define the economic sustainability for the system. Evidence from NMA and ITC showed a more favorable safety profile and better efficacy for dupilumab compared with alternative biologics. All the analyses, synthesizing cost and efficacy measures, showed that dupilumab is the preferable alternative. Specifically, the cost per responder analysis for dupilumab, exhibiting a 67.0% response rate at Week 52, is notably economical at 14,209EUR per responder. This presents a more economical profile compared with the cost per responder for omalizumab (36.2% response rate) at 24,999EUR and mepolizumab (28.5% response rate) at 31,863EUR. These results underscore dupilumab’s potential, not merely in terms of clinical outcomes, but also in terms of economic rationality, thereby solidifying its status as a valid and preferrable alternative in the management of CRSwNP, in the context of the Italian NHS. Full article

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high rate of recurrence in patients, despite therapy with local corticosteroids and functional endoscopic sinus surgery. Dupilumab, a recombinant monoclonal human IgG4 antibody directed against the IL-4 receptor α that inhibits both IL-4 and IL-13 signal transduction, is available for symptomatic therapy. Patient preference between repeated surgery and injection therapy with Dupilumab is not known. (2) Methods: Patients who had experienced at least one surgical intervention for nasal polyps and were treated with Dupilumab for at least 3 months completed a retrospective patient questionnaire. (3) Results: In a cohort of 75 previously operated CRSwNP patients, 91.5% preferred therapy with Dupilumab to repeated surgery for nasal polyps. Preference for Dupilumab in the subgroups of patients with concomitant Non-steroidal Anti-inflammatory Drugs Exacerbated Respiratory Disease (N-ERD) (n = 32), patients with concomitant asthma (n = 25), and patients without concomitant disease (n = 18) was 100%, 96%, and 72%, respectively. (4) Conclusions: Patient preference for Dupilumab over repeat surgery is strongest in previously operated CRSwNP patients with concomitant asthma or N-ERD, but remains very high in patients without concomitant disease. Full article

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with multifactorial etiopathogenesis. This study investigated the recurrence rate and risk factors predicting recurrence in patients subjected to Functional Endoscopic Sinus Surgery (FESS) for CRSwNP. Methods: Patients affected by CRSwNP who underwent FESS between January 2015 and March 2020 were enrolled. The recurrence rate and the influence of risk factors were assessed. Results: A total of 154 patients were included, 100 males and 54 females, aged 14–82 years (mean age 51.96 ± 16.27; median 52 years). Of 154 patients, 28 presented CRSwNP recurrence in a follow-up period ranging from 6 months to 69 months, with a recurrence rate of 18.2%. The recurrence rate was higher in patients aged between 31 and 50 years and between 51 and 70 years at the time of surgery than in those aged between 14 and 30 years and over 70 years. Furthermore, most patients with recurrence were men (61%), while 39% were women. A higher recurrence rate was observed between non-smokers (50%) and ex-smokers (36%), while only 14% declared themselves habitual smokers. Only four subjects (14%) had a positive family history of CRSwNP. Conclusion: To date, no specific biomarkers have been identified in order to determine the appropriate therapy for the patients affected by CRSwNP. Based on our results, we suggest that it is necessary for an accurate assessment of the CRSwNP patients to identify which phenotype/endotype each subject manifests based on medical history, endoscopy, computed tomography, and a laboratory evaluation. Full article

Different inflammatory endotypes reflect the heterogeneity of chronic rhinosinusitis with nasal polyps’ (CRSwNPs) clinical presentation. This retrospective study aimed to analyze the distribution of polyps in nasal cavities and paranasal sinuses to establish a possible association between CRSwNP endotypes, prognosis, and polyps’ extension. This study included 449 adult patients who underwent endoscopic sinus surgery for CRSwNPs between 2009 and 2022. Patients were categorized based on the number of paranasal sinuses involved by polyps. Statistical analyses, including Cox regression, were performed to identify associations between demographic, clinical, and histopathological factors and disease recurrence. CRSwNP patients were stratified into four groups based on the extent of polyp involvement. Asthma and acetylsalicylic acid (ASA) sensitivity were associated with more sinuses involved (p-values = 0.0003 and 0.0037, respectively). Blood eosinophil counts increased with the number of sinuses affected (p-value < 0.0001). The distribution of eosinophilic and non-eosinophilic histotypes varied significantly among these groups (p-value < 0.0001). The risk of CRSwNP recurrence was higher in patients with asthma, higher basophil percentages, and eosinophilic histotype (p-value 0.0104, 0.0001, 0.0118, and 0.0104, respectively). This study suggests a positive association between the number of paranasal sinuses involved by polyps and the severity of CRSwNPs, particularly in patients with eosinophilic histotype, asthma, and ASA sensitivity. Full article

Background and Objectives: Chronic sinusitis is a commonly encountered diagnosis for otorhinolaryngologists. The profound negative effect of rhinosinusitis on patients’ quality of life is frequently overlooked, and surgical lines of treatment are numerous. The aim of the study was to assess the comparative efficacy of endoscopic middle meatal antrostomy with the endoscopic prelacrimal recess approach, combined with middle meatal antrostomy in the treatment of unilateral chronic maxillary sinus lesion. Materials and Methods: Thirty patients with unilateral chronic maxillary sinus lesions enrolled in the study at Alahsa hospital. Patients were divided into two groups: 15 treated through a middle meatal antrostomy and 15 treated via a combined middle meatal antrostomy and prelacrimal recess approach. Demographic and clinical information of the patients, including the medical history, CT scan findings, diagnosis, recurrence, and complications, were gathered and analyzed. Pre- and postoperative clinical findings were graded utilizing the Lund–Kennedy Endoscopic Scoring System. Results: The enrolled patients varied in age from 18 to 56, with 60% being male and 40% being female. Antrochoanal polyp, maxillary sinus mucocele, and unilateral allergic fungal sinusitis were among the pathological diagnoses. The follow-up period averaged 14.3 months. Following surgery, two patients in Group II encountered nasal discomfort, which included synechia and epiphora. The success rate for preserving a patient’s disease-free condition was 86.7%. A statistically significant difference in disease-free incidence was observed among the patients in group II. In group I, recurrence was identified in 26.7% of the patients. The postoperative symptoms diminished considerably, and the VAS score was reduced substantially. In Group II patients, however, there was no significant difference in scarring. Clinically significant differences were observed in the mean total Lund–Kennedy Endoscopic scores when compared to their preoperative values. Conclusions: Achieving endoscopic access to the sinus’s anterior, lateral, inferior, and inferomedial regions is facilitated by operating via the prelacrimal recess, which is the most advantageous approach. This approach facilitates rapid mucosal healing by maintaining the integrity of the nasolacrimal duct and mucosal covering. The specific pathology, surgical objectives, surgeon expertise, and equipment accessibility influence the choice of endoscopic surgical technique. Full article

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. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) presently remains a difficult disease to manage. Antimicrobial and defense proteins are important factors that could help characterize the role of microorganisms in CRSwNP pathogenesis, as the concept of microbial dysbiosis in CRS is still being considered. Our aim is to investigate the complex appearance, relative distribution and interlinks of human β defensin 2 (HBD-2), human β defensin 3 (HBD-3), human β defensin 4 (HBD-4), and cathelicidin LL 37 (LL 37) in chronic rhinosinusitis with nasal polyps (CRSwNP)-affected human nasal mucosa. Materials and Methods: The study group consisted of 48 samples from patients with CRSwNP. Samples were collected during functional endoscopic sinus surgery. The control group consisted of 17 normal healthy nasal mucosa samples gathered during routine septoplasty. β-defensin-2, β-defensin-3, β-defensin-4 and cathelicidin LL 37 in tissue were detected via immunohistochemical analysis. Results: HBD-2, HBD-3 and LL 37 were significantly decreased in epithelial cells in both primary and recurrent nasal polyp samples (p < 0.001) in comparison to control samples. HBD-2 was decreased in the subepithelial connective tissue of primary nasal polyp samples when compared to both recurrent polyp (p = 0.050) and control (p = 0.033) samples. In subepithelial connective tissue, significantly more HBD-3-positive structures were observed in primary nasal polyp samples (p = 0.049) than in control samples. In primary polyp samples, moderate correlations between connective tissue HBD-3 and connective (R = 0.584, p = 0.001) and epithelial tissue LL 37 (R = 0.556, p = 0.002) were observed. Conclusions: Decreased HBD-2, HBD-3 and LL 37 concentrations in the epithelium suggest a dysfunction of the epithelial barrier in patients with nasal polyps. Decreased subepithelial connective tissue HBD-2 suggests different responses to nasal microbiota in patients with primary nasal polyps compared to recurrent nasal polyps. Increased HBD-3 in subepithelial connective tissue suggests a possible role of this antimicrobial peptide in the pathogenesis of primary nasal polyps. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a mainly type-2-driven inflammatory disease that is often refractory to medical and surgical treatment and characterized by a high rate of recurrence. Monoclonal antibodies have been approved for severe refractory CRSwNP. Randomized controlled trials (RCT) have shown significant improvement in objective and subjective parameters. The results of these RCTs cannot necessarily be transferred to daily routine. The purpose of this retrospective study is to evaluate the treatment effects of biologics in patients with CRSwNP in a real-life setting. Patients treated with one of the approved biologics since July 2020 with at least 6 months follow-up were included in the study. Changes in SNOT-22 and nasal polyp score (NPS), as well as subjective change in sense of smell, number of sinus surgeries prior to and during treatment, comorbidities, discontinuation or change of monoclonal antibody and adverse events were evaluated. Thirty-three patients were included in this study. The mean SNOT-22 score and NPS improved significantly. The subjective assessment of sense of smell showed an improvement in 81.8% of patients. The monoclonal antibody had to be changed in seven patients. No severe adverse events occurred during the initiation of the treatment and follow-up. Biologics can be a treatment option in patients with severe refractory CRSwNP, showing significant improvements in quality of life, symptoms and polyp scores in randomized controlled trials and clinical routine with rare complications. Further research is needed to evaluate possible biomarkers, interdose interval prolongation and long-term safety. Full article

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils’ values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine–acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine–acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence. Full article

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-β1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-β1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-β1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-β1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery. Full article