Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the upper airway, and its underlying pathogenesis remains incompletely understood. In this study, endoplasmic reticulum stress (ERS)-related gene sets were employed as the analytical starting point to systematically screen and identify core genes closely associated with CRSwNP. Through the integration of weighted gene co-expression network analysis (WGCNA), differential expression analysis, and multiple machine learning algorithms, 4 hub genes (ALOX5, HMOX1, PXDN, and CARD9) were identified, all of which exhibited favorable diagnostic performance for CRSwNP (AUC = 0.863-0.962, P < 0.05). RT-qPCR, Western blotting, and immunohistochemistry were performed to validate the aberrant expression of these hub genes in CRSwNP tissues. Notably, the expression level of ALOX5 was significantly positively correlated with the clinical severity of CRSwNP (R = 0.40-0.41, P < 0.01). Single-cell transcriptomic analysis further revealed that ferroptosis-related signatures were significantly enriched in nasal epithelial cells from patients with CRSwNP. Immunofluorescence staining and primary nasal epithelial cell experiments indicated that ALOX5 expression was negatively correlated with epithelial tight junction proteins and that targeting ALOX5 effectively modulated the ferroptosis process. Collectively, this study identified hub genes with potential diagnostic value and functional relevance in CRSwNP and elucidated the potential involvement of ALOX5-mediated epithelial ferroptosis in disease progression, thereby providing novel insights into the precise diagnosis and targeted therapy of CRSwNP.

BackgroundEosinophilic otitis media (EOM) is a refractory type 2 inflammatory disease of the middle ear, frequently associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Conventional otologic treatments often provide incomplete or transient benefit. Because EOM and CRSwNP may share a type 2 inflammatory pathway involving the nasal, Eustachian tube, and middle-ear compartments, biologic therapy may offer benefit beyond sinonasal disease control. Long-term multicenter real-world data on dupilumab in patients with concomitant EOM and severe CRSwNP remain limited.ObjectiveTo evaluate the 12-month effectiveness of dupilumab on subjective and objective otologic outcomes in adults with EOM and severe CRSwNP.MethodsIn this multicenter observational cohort, 48 adults with severe CRSwNP and concomitant EOM, diagnosed according to Iino criteria, received dupilumab 300 mg every 2 weeks. Otologic outcomes included the Chronic Otitis Media Outcome Test 15 (COMOT-15; range 0-75) and tympanometry. Sinonasal outcomes, including Nasal Polyp Score, SNOT-22, and visual analog scale of nasal congestion, were secondary measures. Outcomes were evaluated at baseline, 6 months, and 12 months.ResultsDupilumab was associated with progressive improvement in EOM-related outcomes. Median COMOT-15 decreased from 49 at baseline to 20 at 6 months and 15 at 12 months (P < 0.0001). Tympanometry improved from 32 type B and 16 type C patterns at baseline to predominantly type A patterns at 12 months. Sinonasal outcomes also improved: median NPS decreased from 6 to 3 and 2, SNOT-22 from 68 to 28 and 22, and VAS nasal congestion from 8 to 2 and 1 at 6 and 12 months, respectively (all P < 0.0001). Peripheral eosinophil counts did not significantly decrease.ConclusionIn patients with severe CRSwNP and concomitant EOM, dupilumab was associated with sustained 12-month improvement in EOM-related quality of life and tympanometric patterns, supporting further investigation within a one-airway-one-ear type 2 framework.

Myasthenia crisis is a lethal complication of myasthenia gravis, and about 20% of patients with myasthenia gravis may present for the first time in crisis. We present a case in which underlying, undiagnosed myasthenia gravis presented in crisis as acute-onset dysphagia. We would like to discuss the role of acute exacerbation of chronic rhinosinusitis and the administration of high-dose oral corticosteroids in the precipitation of the myasthenia crisis in this patient.

NSAID-exacerbated respiratory disease (N-ERD) is characterized by asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and intolerance to NSAIDs (including aspirin). In N-ERD, CRSwNP often remains refractory to standard medical and surgical treatment, necessitating escalation. Aspirin therapy after desensitization (ATAD) is an established option for CRSwNP in N-ERD, but its use is limited by adverse effects, non-response, and safety issues associated with aspirin desensitization. This narrative review focuses on newer developments in ATAD for N-ERD, including shortened desensitization schedules, lower aspirin maintenance doses, and use of intranasal preparations of aspirin such as intranasal lysine-aspirin. The developments in use of biomarkers for distinguishing the different underlying endotypes and phenotypes of N-ERD, and subsequent potential for individualization of treatment are also discussed. The availability of biologics for the treatment of CRSwNP may provide further treatment escalation options in N-ERD patients who do not tolerate or respond to ATAD; however, there is an absence of direct comparative evidence for ATAD versus biologics. Further, the conjunctive use of ATAD and biologics provides an interesting avenue of research. Finally, following a discussion of the recent advancements in ATAD and biologics in N-ERD, clinical recommendations for treatment options and pathways are made.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly debilitating airway disease primarily characterized by type 2 inflammation and eosinophilic infiltration. Among the key cytokines involved, Interleukin-5 (IL-5) plays a relevant role in eosinophil biology and contributes, together with other mediators of type 2 inflammation, to epithelial barrier dysfunction, immune dysregulation, mucus hypersecretion, and tissue remodeling. Therapies targeting this cytokine have demonstrated both efficacy and safety in patients with CRSwNP. This narrative commentary summarizes current evidence in understanding IL-5's role in CRSwNP, integrating insights from an Italian otolaryngology expert panel, with a particular focus on the patient journey in Italy. Available evidence suggests that IL-5 is associated with disease severity and may contribute to multiple aspects of CRSwNP pathophysiology beyond eosinophilia. Targeting the IL-5 pathway has been shown to improve clinical outcomes, including nasal polyp burden, symptom control, olfactory function, and quality of life, in selected patients. From a clinical perspective, the expert panel highlighted several critical unmet needs in the Italian setting, including diagnostic delay, heterogeneous implementation of care pathways, suboptimal patient selection, and limited adherence to long-term management strategies. The importance of structured diagnostic work-up, endotyping, multidisciplinary management, and patient awareness was emphasized. The implementation of shared Diagnostic and Therapeutic Care Pathways (PDTA) and network-based models may support more standardized and timely management, although further evidence is needed to define their impact on clinical outcomes. Overall, improving the understanding of IL-5-driven mechanisms and addressing organizational gaps may contribute to optimizing the management of CRSwNP in clinical practice.

PurposeTo identify independent risk factors for chronic rhinosinusitis with nasal polyps (CRSwNP) and develop a clinical risk scoring system for its prediction.MethodsThis retrospective study included 420 patients categorized into CRSwNP and CRSsNP groups. Demographic, clinical (asthma), and hematologic parameters-including blood eosinophil count (BEC) and inflammatory markers-were analyzed. Subgroup stratification focused on inhalant allergen sensitization (single vs. multiple) at different BEC levels (cut-off: 0.15 × 10[9]/L). Independent risk factors were identified via multivariate logistic regression, and an integer-based scoring system was developed.ResultsCRSwNP patients showed significantly higher BEC, asthma prevalence, and multiple sensitization rates (p < 0.05). In the low-BEC population (<0.15 × 10[9]/L), multiple inhalant sensitization-but not single sensitization-was associated with higher polyp incidence (p < 0.05). Multivariate analysis confirmed asthma (OR = 4.914), elevated BEC (OR = 2.364), and multiple inhalant allergen sensitization (OR = 2.298) as independent risk factors. A scoring system (0-4 points) based on these factors demonstrated good predictive efficacy with an area under the ROC curve (AUC) of 0.770.ConclusionMultiple inhalant allergen sensitization is a key independent predictor for CRSwNP, particularly in non-eosinophilic patients. The proposed scoring system provides a practical tool for early identification and intervention in high-risk patients.

An older adolescent immunocompetent male with a 2 month history of progressive frontal headaches, congestion and worsening vision, culminating in right optic neuropathy, was referred to our emergency department by ophthalmology. MRI revealed extensive sinus disease, though without direct optic nerve compression; CT scan identified a fungal ball extending into the right clinoid process, with bony erosion and involvement of the deep pneumatised optico-carotid recess. The patient underwent emergency endoscopic sinus surgery, where mucopus, polyps and fungal debris consistent with an infected fungal ball were found in the right nasal cavity and sphenoid sinus. Residual fungal material remained in the deep optico-carotid recess post-washout due to difficult access and dehiscent bony coverings of the optic nerve and carotid. Postoperatively, he was treated with voriconazole and intravenous co-amoxiclav. His vision returned to baseline 3 days postoperative and 3 months later, a second-look surgery confirmed no residual fungal material. Now fully recovered and discharged from follow-up.