Search Results (194)

Nasal polyposis is a multifactorial disorder arising from complex interactions among cellular, molecular, and inflammatory mechanisms. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and other ion channels are essential for epithelial ion transport, mucosal hydration, and barrier integrity in the nasal airway. Prostaglandin E₂ (PGE₂) acts not only as an inflammatory mediator but also as a regulator of ion exchange through CFTR-dependent and CFTR-independent pathways. Ionocytes, specialized epithelial cells that regulate ion balance and fluid secretion in the respiratory tract, are closely associated with CFTR function. Both eosinophilic and non-eosinophilic inflammation may alter ionocyte abundance and function, thereby reducing normal CFTR activity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also characterized by diminished PGE₂ production. The I³PGE₂ hypothesis proposes that CRSwNP results from the combined effects of ion channel dysfunction, persistent inflammation, altered ionocyte number and function, and impaired PGE₂ synthesis. Together, these abnormalities disrupt nasal physiology and promote polyp formation. We hypothesize that corticosteroids and biologic therapies may improve CRSwNP by reducing inflammation, restoring ion channel activity, improving ionocyte function, and recovering PGE₂ production. These effects enhance hydration and mucociliary clearance, limit mucus accumulation, restore epithelial homeostasis and mucosal host defense, and ultimately contribute to the reduction or resolution of nasal polyps. Full article

Background/Objective: Previous studies on the association between chronic rhinosinusitis (CRS) and allergic rhinitis (AR) have mostly focused on the general population, and much less on patients with CRS requiring surgical treatment. This study aimed to investigate the frequency of perennial and seasonal AR (PAR and SAR, respectively) among CRS patients in whom it was necessary to apply surgical treatment, including those with nasal polyps (CRSwNP) and those without (CRSsNP). Methods: A three-year retrospective study from a single center included CRS patients with indications for surgical treatment. The patients were not previously treated surgically. Several clinical parameters were considered: frequency of AR, PAR, SAR, SAR+PAR, asthma, and gastroesophageal reflux disease (GERD). Total serum IgE, percentage of eosinophils in peripheral blood, and Lund–Mackay computed tomography (CT) score (LMS) were also determined. Correlation analyses were performed to assess the relationships among the clinical parameters, while multivariable binary logistic regression analysis was performed to determine their independent associations with the outcome and to identify the best independent predictor. Results: A total of 155 patients with CRS were considered. Over 70% were patients with CRSwNP. AR was significantly more prevalent in patients with CRSwNP (p = 0.049), with PAR being the more common form (p = 0.035). Also, GERD and asthma were more common in CRSwNP (p = 0.01 and p = 0.001, respectively). The strongest correlation was found between total serum IgE and percentage of eosinophils (rho = 0.776; p < 0.001), then between percentage of eosinophils and LMS (rho = 0.760; p < 0.001), as well as between total IgE and LMS (rho = 0.695; p < 0.001). Binary logistic regression analysis identified LMS as the only independent statistically significant predictor for CRSwNP (OR = 1.381, p < 0.001) among all numerical parameters. Conclusions: The results suggest a better association between PAR and CRS, especially with CRSwNP. Asthma and GERD are also highly associated, primarily with CRSwNP. LMS is the best independent predictor for the presence of CRSwNP. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which type 2 inflammation predominates in most patients in Western populations. Galectin-10 (Gal-10) and Charcot-Leyden crystals (CLCs), linked to eosinophil activation, cytolysis and eosinophil extracellular trap cell death (EETosis), have emerged as potential biomarkers and mediators of eosinophilic inflammation. This narrative review summarises current evidence on their biological role and clinical relevance in CRSwNP. The literature was identified through searches of PubMed/MEDLINE, Web of Science and Google Scholar, with emphasis on mechanistic studies, clinical investigations and recent evidence concerning type 2 inflammatory airway diseases. Available evidence suggests that Gal-10 and CLCs are associated with eosinophil activation and may contribute to persistent type 2 inflammation through epithelial injury, increased mucus viscosity, impaired mucociliary clearance, tissue remodelling and inflammatory amplification. Gal-10/CLCs may have value as investigational biomarkers of disease activity, postoperative recurrence and response to biologic therapy. Current biologics may indirectly modulate the Gal-10/CLC pathway by reducing eosinophil survival, recruitment or activation, although direct evidence remains limited. Gal-10 and CLCs are promising investigational biomarkers and mechanistically plausible therapeutic targets in CRSwNP. However, clinical application is limited by the lack of standardised analytical methods, validated cut-off values and prospective studies demonstrating incremental value beyond established biomarkers. Further research is required to clarify their role in stratification, prognosis and monitoring of biologic therapy. Full article

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by type 2 inflammation, including M2 macrophage infiltration. Baicalein is a flavonoid with anti-inflammatory properties. This study aimed to investigate the therapeutic effect of baicalein in a papain-induced eosinophilic rhinosinusitis model and to determine whether it acts through arachidonate 15-lipoxygenase (ALOX15)-dependent M2 macrophage function. Clinical nasal samples from controls, non-eosinophilic CRSwNP (neCRSwNP), and eCRSwNP were analyzed for ALOX15 expression and localization. THP-1 cells were differentiated and polarized toward M2 macrophages, and the effects of baicalein on ALOX15 expression, lipid peroxidation, cytokine secretion, and transcriptomic profile were examined. The ALOX15 inhibitor PD146176 was used for target validation. A murine eosinophilic rhinosinusitis model was established by intranasal papain instillation, followed by baicalein treatment. Mucosal inflammation, IgE levels, proteoglycan 2 (PRG2)/ALOX15 expression, and immune cell infiltration were evaluated. ALOX15 was upregulated in eCRSwNP tissues and localized to CD68⁺CD206⁺ M2 macrophages. In vitro, M2 polarization increased ALOX15 expression and lipid peroxidation. Baicalein suppressed ALOX15 expression, lipid peroxidation, and the secretion of CCL22, CCL2, CXCL12, FGF-2, and IL-15. PD146176 produced similar effects, and baicalein showed no additional effect after ALOX15 blockade. RNA sequencing revealed transcriptional remodeling in M2 macrophages after baicalein treatment. In vivo, papain increased ethmoid sinus mucosal thickening, serum IgE, PRG2/ALOX15 positive cells, and infiltration of CD45⁺ immune cells, CD170⁺ eosinophils, F4/80⁺ macrophages, and B220⁺ B cells. Baicalein significantly alleviated all these pathological changes. In conclusion, baicalein attenuates papain-induced eCRSwNP-like inflammation by inhibiting lipid peroxidation and ALOX15-associated M2 macrophage secretory function. The ALOX15/M2 macrophage axis may represent a potential therapeutic target for eCRSwNP. Full article

Background: Olfactory dysfunction (OD) is a key symptom of chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab improves clinical outcomes, including patient-reported olfactory function. This study aimed to analyze correlations between patient-reported olfactory improvement, quality of life, and endoscopic outcomes in patients treated with dupilumab. Methods: A real-life, single-center retrospective study included 35 patients with severe, uncontrolled CRSwNP treated with dupilumab. Patient-reported olfactory function was assessed using a visual analog scale (VAS-olfaction), quality of life with the Sinonasal Outcome Test-22 (SNOT-22), and polyp size with the Nasal Polyp Score (NPS) at baseline, 6 months, and 12 months. Changes from baseline were analyzed using the Wilcoxon signed-rank test, whereas correlations were evaluated using Spearman’s rank correlation coefficient. Results: Dupilumab was associated with significant improvements in patient-reported olfactory function, quality of life, and polyp size at 6 and 12 months. Improvements in VAS-olfaction correlated significantly with SNOT-22 at 6 months (p = 0.035) and 12 months (p = 0.024). In a sensitivity analysis excluding the smell/taste item from the SNOT-22, these correlations were attenuated and no longer reached statistical significance. No significant correlation was observed between patient-reported olfactory improvement and NPS. Conclusions: Patient-reported olfactory improvement correlated with quality of life but not with reductions in global polyp burden. These findings suggest that this improvement may not be fully explained by changes in polyp size alone. Full article

Kartagener syndrome (KS) is a rare form of primary ciliary dyskinesia (PCD) characterized by chronic respiratory infections, bronchiectasis, chronic rhinosinusitis, and situs inversus. Evidence regarding biologic therapies in this setting is currently lacking. We report the case of a patient with KS and severe refractory chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab after failure of conventional medical and surgical management. Treatment resulted in marked improvements in symptom burden, olfactory function, endoscopic findings, and quality of life, with sustained benefit throughout the 12-month follow-up. This observation suggests that type 2 inflammation may contribute to disease burden in selected patients with PCD and supports further investigation of biologic therapies in this challenging clinical setting. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which type 2 inflammation, epithelial dysfunction, and tissue remodeling determine severity, recurrence, and treatment response. Although molecular biomarkers have clarified disease endotypes, their routine use remains limited by cost, availability, and invasiveness. Nasal cytology offers a simple, repeatable, and minimally invasive method to assess—at the mucosal surface—both epithelial morphology and the dominant inflammatory infiltrate, whether neutrophilic, eosinophilic, mast cell, or mixed. Clinical-Cytological Grading (CCG) integrates the dominant cytological pattern with selected comorbidities, including asthma, allergy, and NSAID-exacerbated respiratory disease (N-ERD), into a weighted clinical-cytological framework. In the founding cohort, the highest relapse association was observed when mixed eosinophil–mast cell inflammation coexisted with asthma and N-ERD. This review discusses the rationale, clinical relevance, and translational applications of CCG in CRSwNP, addressing eosinophilic and mixed mast cell–eosinophilic inflammation, epithelial morphology, disease recurrence, difficult-to-treat phenotypes, biologic monitoring, and the operative dialogue between nasal cytology and histopathology. By linking cytological findings with selected clinical comorbidities, CCG may support biologically informed patient characterization and may prompt targeted mast cell assessment in tissue. However, its prognostic accuracy, incremental clinical value, and role in therapeutic decision-making require independent external validation. Full article

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory condition that significantly impairs health-related quality of life (HRQoL), particularly sleep quality. Beyond mechanical nasal obstruction, type 2 cytokines (IL-4, IL-13) are thought to directly disrupt sleep architecture. Dupilumab, an IL-4Rα antagonist, is approved for severe CRSwNP, but its specific effect on sleep quality remains under investigation. This systematic review aims to evaluate the impact of dupilumab on sleep quality in patients with severe, uncontrolled CRSwNP. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Google Scholar, and Web of Science up to June 2026. We included adult studies (≥1 month of dupilumab 300 mg every 15 days) reporting sleep outcomes using validated tools (Epworth Sleepiness Scale [ESS], Pittsburgh Sleep Quality Index [PSQI], Insomnia Severity Index [ISI], or the SNOT-22 sleep domain). Risk of bias was assessed using ROBINS-I and RoB 2 tools. Results: Seven studies (n = 2164 patients) met inclusion criteria. Across observational and post hoc RCT analyses, dupilumab consistently improved the SNOT-22 sleep domain (mean reduction up to −7.02 points at 24 weeks; p < 0.001), PSQI, ESS, and ISI scores. One study reported a decrease in poor global sleep quality from 88.9% at baseline to 5.7% at 12 months. However, most observational studies had a serious risk of bias due to unaddressed confounding and lack of blinding. No polysomnographic data were reported. Conclusions: Dupilumab was associated with significant improvements in patient-reported sleep quality in CRSwNP patients across seven included studies. However, the evidence is limited by the absence of objective sleep measures, the serious risk of bias in most observational studies, and the lack of comparative head-to-head data. High-quality randomized controlled trials with prespecified sleep endpoints and polysomnographic assessments are needed before definitive conclusions can be drawn. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous type 2 inflammatory disease characterized by frequent postoperative recurrence despite endoscopic sinus surgery (ESS). Reliable biomarkers capable of predicting recurrence remain insufficiently validated. This study evaluates the prognostic utility of circulating biomarkers for recurrence prediction in CRSwNP, in addition to the predictive performance of the blood eosinophilia. Materials and Methods: A prospective cohort of 69 patients with CRSwNP undergoing primary ESS was followed for up to 3 years. Periostin, eotaxin-3, procalcitonin and IL-33 were taken from blood before surgery and analyzed by ELISA technique. Clinical outcomes were assessed using SNOT-22 and Perioperative Sinus Endoscopy (POSE) scores. Statistical analyses included Spearman’s correlation, the Mann–Whitney U test, the Kruskal–Wallis test, Cox proportional hazards regression, multivariable binary logistic regression, ROC analysis, and longitudinal MANCOVA. Results: Blood eosinophilia remained the strongest clinical predictor of recurrence (OR = 4.55, p = 0.001). Serum periostin, eotaxin and procalcitonin significantly correlated with postoperative disease severity and recurrence, particularly with POSE scores at 1 and 3 years (p < 0.05). Patients with recurrence demonstrated significantly higher serum levels of these biomarkers compared with controlled patients (all p < 0.001). Multivariate Cox regression identified periostin (HR = 1.033, p = 0.010), eotaxin (HR = 1.554, p < 0.001) and procalcitonin (HR = 1.183, p < 0.001) as significant predictors of recurrence. Procalcitonin demonstrated the highest predictive performance in ROC analysis (AUC = 0.805). Longitudinal MANCOVA confirmed significant associations between periostin, eotaxin, procalcitonin, and persistent postoperative inflammatory burden over 3 years. Conclusions: Circulating periostin, eotaxin and procalcitonin are promising predictors of CRSwNP recurrence and appear to contribute to prognostic accuracy. Integration of serum biomarker profiling into clinical practice may improve personalized postoperative management and risk stratification in CRSwNP. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with a complex pathogenesis that significantly affects patients’ quality of life. Type 2 inflammation plays a dominant role in its course and is associated with the activation of immune pathways involving interleukins IL-4, IL-5 and IL-13, eosinophils, and immunoglobulin E. Standard treatment methods, including corticosteroids and surgical interventions, despite their proven efficacy, often fail to provide sustained disease control and are associated with a high rate of recurrence. The aim of this review is not only to summarize the available evidence on biological therapies in CRSwNP, but also to critically evaluate their current position within treatment algorithms, with particular emphasis on patient selection, integration with endoscopic sinus surgery, comparison of available biologic mechanisms, and remaining challenges in personalized treatment strategies. The paper discusses available monoclonal antibodies, such as dupilumab, omalizumab, mepolizumab, and benralizumab, which act by selectively inhibiting key mediators of type 2 inflammation. Analysis of clinical trial results indicates that biological therapies lead to a significant reduction in nasal polyp size, improvement in nasal patency, restoration of olfactory function, and enhancement of quality of life as measured by the SNOT-22 scale. Furthermore, they demonstrate a favourable safety profile and may represent an effective therapeutic option for patients with severe, treatment-resistant disease, particularly in cases with coexisting eosinophilic asthma. Biological therapies represent a breakthrough in the treatment of CRSwNP and align with the concept of personalised medicine. Their role in clinical practice continues to expand; however, further research is required to optimise patient selection and assess long-term treatment outcomes. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which identifying simple biomarkers reflecting disease severity remains challenging. This study aimed to evaluate the relationship between systemic inflammatory indices and radiological disease severity assessed by the Lund–Mackay (LM) score. This retrospective study included 90 adult patients with CRSwNP who underwent endoscopic sinus surgery. Preoperative computed tomography findings were scored using the LM system, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-monocyte ratio (NMR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and eosinophil/leukocyte ratio, were calculated from complete blood count parameters. Spearman correlation and univariate logistic regression analyses were performed. ELR (r = 0.49, p < 0.001) and eosinophil/leukocyte ratio (r = 0.46, p < 0.001) showed moderate positive correlations with LM score, whereas other indices were not significantly associated. In logistic regression analysis, both ELR (OR = 5.44 × 10⁴, p < 0.001) and eosinophil/leukocyte ratio (OR = 4.99 × 10¹², p = 0.001) were significantly associated with high disease burden (LM ≥ 15). These findings suggest that eosinophil-based inflammatory indices may better reflect radiological disease severity in CRSwNP compared to traditional systemic inflammatory markers. Full article

Staphylococcus aureus frequently colonizes the skin and upper airways and produces a broad repertoire of immunomodulatory molecules. In asthma, the most consistent evidence concerns staphylococcal enterotoxins (SEs), which can act both as superantigens and as allergens, and IgE sensitization to SEs (SE-sIgE). SE-sIgE is associated with severe asthma, type 2 inflammation, chronic rhinosinusitis with nasal polyps (CRSwNP), exacerbations, and, in some longitudinal studies, persistent airflow obstruction. However, this relationship is not necessarily causal: SE-sIgE may reflect exposure, an immune response, or a biologically active endotype, whereas colonization, local toxin production, and systemic sensitization are not equivalent. SEs simultaneously bind class II MHC molecules and Vbeta regions of the T-cell receptor, activating large fractions of T lymphocytes; they also promote IL-4, IL-5, and IL-13 production, polyclonal B-cell activation, local IgE synthesis, mast-cell degranulation, eosinophilia, and IL-8/neutrophil circuits. Alpha-toxin (Hla) and SEB can damage the epithelial barrier, facilitating allergen penetration and alarmin signalling. These observations support an interaction model in which dysbiosis, barrier dysfunction, and type 2 immunity mutually reinforce one another along the nasobronchial axis. Corticosteroids and antibiotics may modify selected nodes in this circuit, but current evidence is insufficient to recommend decolonization or antitoxin therapy in stable asthma. Biologics interrupt downstream pathways potentially fuelled by toxins: omalizumab neutralizes free IgE; mepolizumab and benralizumab reduce the eosinophilic axis; dupilumab blocks IL-4/IL-13 signalling; and tezepelumab acts upstream on TSLP. Nevertheless, randomized trials stratified by SE-sIgE are lacking, and no evidence demonstrates that these treatments eliminate colonization or toxin production. SE-sIgE therefore appears to be a promising biomarker, particularly in severe asthma with CRSwNP, but it is not yet an autonomous criterion for biologic selection. A broader barrier-organ analysis also identifies nasal, cutaneous, and intestinal colonization as distinct ecological states; atopic dermatitis as a complementary model of toxin-amplified type 2 inflammation; and biofilms and extracellular vesicles as candidate mechanisms of persistent toxin delivery. These data increase biological plausibility but remain indirect for asthma. Full article

Background: Bacteria colonizing the nasal cavity contribute to mucosal homeostasis, and altered sinonasal bacterial communities have been associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Whether routine, culture-based microbiology can distinguish the cultivable bacterial profile of CRSwNP patients from that of controls remains unclear. Methods: In this single-center observational pilot study, middle-meatus swabs from 30 patients with CRSwNP and 30 controls were cultured on four media, and isolates were identified with the VITEK 2 system. For each species, presence or absence per subject was compared between groups using Fisher’s exact test with Benjamini–Hochberg correction for multiple comparisons; the number of cultivable species per subject was compared with the Mann–Whitney test. Results: The two groups were comparable in age and sex. Patients yielded more cultivable bacterial species per subject than controls (mean 4.4 vs. 2.9; Mann–Whitney p < 0.001). Several species were numerically more frequent in patients (e.g., Staphylococcus hominis, S. lugdunensis) and others in controls (e.g., S. epidermidis, S. aureus), but no individual species difference remained significant after correction. Conclusions: Using routine culture, CRSwNP was characterized chiefly by a higher number of cultivable bacterial species, whereas individual species differences were not statistically robust. These hypothesis-generating findings warrant confirmation in larger, sequencing-based studies. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal and paranasal sinus mucosa, associated with significant impairment in quality of life, frequent postoperative recurrence, and repeated need for systemic glucocorticosteroid therapy. Despite the availability of biologics targeting IL-4/IL-13, IL-5, and IgE, a subset of patients shows incomplete or insufficient clinical response. In this context, upstream targeting of epithelial alarmins, particularly thymic stromal lymphopoietin (TSLP), has emerged as a potential therapeutic strategy. To critically review current evidence on the role of TSLP in CRSwNP and to evaluate available data on the mechanism of action, clinical efficacy, and therapeutic potential of tezepelumab in severe and recurrent disease. Materials and Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies published between 2016 and 2026 were included, comprising experimental research, phase II–III clinical trials, systematic reviews, and international guidelines. Results: TSLP functions as an epithelial alarmin that initiates and amplifies type 2 inflammation via dendritic cell activation, Th2 polarization, and activation of type 2 innate lymphoid cells (ILC2). Data suggests that tezepelumab, a monoclonal antibody targeting TSLP, may reduce inflammation and regulate the immune system. Evidence from asthma populations and relevant CRSwNP subgroups indicates potential improvements in nasal polyp score, congestion, olfactory function and quality of life. It is our understanding that the safety profile appears comparable to placebo, with no new safety concerns having been identified in long-term studies. Conclusions: Tezepelumab is a promising biologic that targets inflammation in CRSwNP. It may benefit severe, recurrent, treatment-resistant disease by modulating immune pathways. However, evidence is indirect and limited, and more trials are needed to define its efficacy, identify biomarkers, and clarify its role in treatment algorithms. Full article

Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa whose pathogenesis is characterized by complex interactions of immunological and environmental factors. The maintenance of normal sinonasal function requires a balance of sinus ostial patency, mucociliary clearance, and mucus secretion, and disruption of this balance can lead to CRS. Although many studies have examined the pathophysiology of CRS, the role of reactive oxygen species (ROS) remains incompletely understood. In this review, we analyzed 22 studies of CRS that examined the effects of ROS on epithelial barrier function, local immune responses, and tissue remodeling. The results from in vitro studies, animal models, and human tissue analyses suggest that ROS are not merely by-products of inflammation, but appear to function as key mediators in the pathophysiology of CRS, particularly in the formation and persistence of the CRS phenotype with nasal polyps (CRSwNP). In particular, CRSwNP is characterized by increased activity of enzymes in the dual oxidase (DUOX) and NADPH oxidase (NOX) families, mitochondrial dysfunction, and decreased activity of superoxide dismutase (SOD) and peroxiredoxin 2 (PRDX2). At the molecular level, these alterations increase the generation of ROS and impair antioxidant defense. At the cellular level, these alterations disrupt the epithelial barrier, activate inflammasomes, increase pyroptosis, and induce the formation of neutrophilic and eosinophilic extracellular traps. These changes culminate in the epithelial–mesenchymal transition (EMT), with the formation of nasal polyps and tissue remodeling. Increased oxidative stress can also occur in CRS without nasal polyps (CRSsNP), but this phenotype appears to have relatively preserved antioxidant defense systems, which may partly explain the more limited structural remodeling. External stimuli, such as fungal proteases, bacterial toxins, and certain antibiotics, can also increase the production of ROS and may contribute to disease chronicity. Taken together, the level and pathophysiological roles of ROS differ in the two primary phenotypes of CRS. Further mechanistic studies are needed to clarify the specific alterations of redox pathways in these two phenotypes and to develop novel therapeutic strategies that target ROS. Full article