(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79–9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous rhinologic disease frequently driven by type 2 inflammation, yet routine clinical phenotyping remains insufficient for endotype-informed management. Conventional markers, including blood eosinophils, serum immunoglobulin E (IgE), fractional exhaled nitric oxide, tissue eosinophilia, nasal polyp score, and sinus computed tomography (CT) scores, provide useful but incomplete information. Artificial intelligence (AI) enables integration of sinus CT, radiomic features, digital pathology, biomarkers, comorbidities, and follow-up treatment outcomes. Emerging studies suggest that CT-based AI supports non-invasive identification of eosinophilic or type 2-high disease, whereas digital pathology links routine histology with inflammatory and molecular endotypes. However, published evidence remains dominated by retrospective single-modality studies or partial multi-source integration, and no model has yet jointly integrated sinus CT, digital whole-slide pathology, and biomarkers in CRSwNP. Additional limitations include heterogeneous endotype labels, insufficient external validation, and uncertain clinical utility for biologic decision-making. This Mini Review synthesizes existing single-modality artificial intelligence pipelines, contextualizes CRSwNP as a representative disease model for AI-driven type 2 inflammatory endotyping, and proposes a clinically oriented, multimodal interpretable scoring framework integrating sinus imaging and digital pathology to support precision type 2 stratification in CRS management.

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.

Objectives: We aimed to characterize the clinicopathologic features, treatment, and outcomes of three types of Switch/Sucrose Nonfermentable (SWI/SNF)-deficient sinonasal carcinomas (SDSCs), thereby expanding the spectrum of these rare entities and facilitating early diagnosis. Methods: We designed a retrospective single-center case series to analyze the clinicopathological features of 17 patients with SMARCB1-deficient sinonasal carcinoma (n = 10), SMARCA4-deficient carcinoma (n = 6) and SMARCA4-deficient sinonasal teratocarcinosarcoma (TCS) (n = 1) treated between 2018 and 2025, and reviewed the relevant literature. Results: The cohort included 14 males and 3 females, aged 26 to 69 years (mean, 47 years). SMARCB1-deficient sinonasal carcinomas predominantly involved the ethmoid sinus (6 of 8 patients), presenting epistaxis (7 of 10 patients), nasal obstruction (5 of 10 patients), and ocular symptoms (4 of 10 patients). SMARCA4-deficient sinonasal carcinomas mainly arose in the nasal cavity (3 of 4 patients), characterized by nasal obstruction (4 of 6 patients), and epistaxis or purulent rhinorrhea (4 of 6 patients); ocular symptoms were less common (2 of 6 patients). The TCS patient had left nasal cavity and ethmoid involvement with nasal obstruction and purulent rhinorrhea. Most patients presented with advanced-stage disease (T4a, n = 9), with skull base (n = 6), and orbital (n = 3) involvement. Histologically, immunohistochemical analysis confirmed complete SMARCB1 or SMARCA4 loss (complete in carcinomas and partial in TCS), diffuse CK positivity, and high Ki-67 indices. Treatment modalities included: chemotherapy and immunotherapy without surgery (n = 2), radical surgery with adjuvant chemoradiotherapy and immunotherapy (n = 2), radical surgery with chemoradiotherapy (n = 9), postoperative radiotherapy alone (n = 3), and non-radical surgery with chemoradiotherapy (n = 1). At a median follow-up of 19 months (range, 8–57 months), 2 patients were lost to follow-up, 3 died, 2 had persistent disease, and 10 remained disease-free. Conclusions: SDSC is an aggressive tumor with male predominance and advanced-stage presentation. Early recognition and appropriate immunohistochemical evaluation are essential for timely diagnosis and management. Prospective studies of novel targeted and immunotherapeutic strategies are warranted.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent type 2 inflammatory disorder that substantially impairs patient quality of life (QoL) through cardinal symptoms of nasal obstruction, olfactory dysfunction, and sleep disturbance, further compounded by frequent comorbidities including asthma and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NERD). While conventional therapies with intranasal corticosteroids, systemic corticosteroids, and endoscopic sinus surgery remain foundational, their limitations in achieving durable disease control have prompted the emergence of biologic agents targeting key type 2 inflammatory pathways. This narrative review synthesizes evidence from a targeted literature search including randomized controlled trials and complementary real-world studies to evaluate the impact of biologic therapies on patient-reported QoL outcomes in severe CRSwNP. Biologic agents targeting key mediators of type 2 inflammation have consistently demonstrated clinically meaningful improvements in disease-specific QoL, as measured by the Sinonasal Outcome Test-22 (SNOT-22), across nasal, sleep, olfactory, and emotional domains, with consistent benefits regardless of comorbidities or prior surgery. Real-world evidence corroborates trial findings, demonstrating sustained QoL benefits and reduced dependence on systemic corticosteroids and revision surgery. The integration of patient-reported outcome measures into therapeutic decision-making bridges the gap between objective clinical metrics and lived disease burden, informing patient-centered care models. Biologic therapies have redefined success in CRSwNP management by consistently delivering multidimensional, durable improvements in patient-reported QoL, head-to-head comparisons and optimized treatment sequencing warrant further research.