BACKGROUND:Chronic rhinosinusitis with nasal polyps involves mixed type 2-type 3 inflammation, associated with disease severity and treatment resistance, yet mechanisms remain unclear. OBJECTIVE:We sought to investigate the role of IL-2 and its interaction with type 3 inducers (TNF-α, IL-1β, and IL-23) in driving mixed type 2-type 3 inflammation. METHODS:IL-2 and receptor expression in nasal polyps was analyzed using tissue homogenates and public RNA-sequencing data. Dispersed nasal polyp cells were treated with IL-2/type 3 inducers, with cytokine production, proliferation, and gene expression analyzed via immunoassays, flow cytometry, and RNA sequencing. IL-2 receptor/Janus kinase (JAK) blockade studies were conducted. Furthermore, CD4+ and CD8+ T cells were magnetically isolated from nasal polyps to evaluate their response to cytokine stimulation. RESULTS:IL-2 levels were increased in chronic rhinosinusitis with nasal polyps, particularly in type 3-dominant and mixed type 2-type 3 subgroups, and correlated with type 3 cytokines. RNA sequencing supported upregulated IL-2 receptors and their coexpression with type 3 genes. IL-2 synergized with type 3 inducers to enhance both type 2 and type 3 cytokine production in dispersed nasal polyp cells. Direct functional evidence from isolated CD4+ and CD8+ T cells confirmed this synergy, with CD8+ T cells emerging as a novel source of IL-13. Flow cytometry further supported these findings, showing synergistic cytokine production across diverse cell populations, including T-cell subsets and natural killer cells. Memory T cells mediated T-cell receptor-independent cytokine production. Transcriptomic analysis identified activated type 3, type 2, and JAK-signal transducer and activator of transcription signaling pathways. IL-2 receptor blockade, particularly JAK inhibition, attenuated IL-2/type 3 inducer-mediated synergistic inflammation. CONCLUSIONS:A novel mechanism was identified whereby IL-2 synergizes with proinflammatory type 3 inducers to amplify mixed type 2-type 3 inflammation via innate-like T-cell activation, and targeted JAK inhibition was validated as a potential therapy.

ABSTRACT Objective Allergic rhinitis (AR) represents one of the most prevalent respiratory disorders. Mining workers face sustained occupational exposure to elevated airborne pollutant concentrations. However, environmental epidemiology data documenting AR prevalence among this workforce in mining‐intensive regions remain limited. This study, which focuses on mining settings within northern China cities, examines the association between occupational air pollutant exposure and AR prevalence among coal miners. Methods We implemented a cross‐sectional survey to assess AR prevalence (self‐report) and risk factors in mining workers within heavily industrialized Ordos city in northern China. A total of 538 mining workers were finally included. Subsequently, descriptive statistics characterized baseline distributions of demographic, clinical, and environmental covariates. Logistic regression modeling was employed: (a) crude association assessment via age‐ and sex‐adjusted analysis; (b) confounder‐adjusted multivariable regression to differentiate risk‐enhancing and protective exposures influencing AR prevalence. Results A total of 151 patients (28.07%) were identified with AR. Longer work duration of occupational exposure in mining settings conferred a significantly increased risk of AR [OR: 1.041(95% CI = 1.002–1.083), p = 0.0417]. Moreover, alcohol consumption habits [OR: 1.675 (95% CI = 1.028–2.728), p = 0.0384], food allergy histories [OR: 5.614 (95% CI = 1.905–16.547), p = 0.0018], and family atopy [OR: 5.511(95% CI = 2.501–12.144), p < 0.0001] significantly heightened the risk of AR development, while higher educational attainment emerged as a protective factor against AR [OR: 0.54 (95% CI = 0.325–0.897), p = 0.0174]. Conclusion Chronic occupational exposure in coal mines was related to the risk of AR. This study revealed epidemiological evidence to improve AR management in mining occupational settings. Level of Evidence 3.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 classification for chronic rhinosinusitis (CRS) hasn’t been extensively characterized in people living with HIV (PLWH), a population with a high burden of sinonasal disease. This study aimed to characterize the clinical features of surgical HIV-associated CRS and compare bilateral versus unilateral disease. This single-center, retrospective surgical cohort study included 60 consecutive patients with HIV-associated CRS requiring endoscopic sinus surgery between January 2020 and June 2025 at Beijing You’ an Hospital, a national designated center where a large proportion of HIV-associated CRS surgical cases have been managed in China. Demographic, clinical, laboratory (including eosinophil/neutrophil counts), and radiological (Lund-Mackay score, E/M ratio) factors were analyzed. Univariate comparisons were performed using the Mann–Whitney U test for continuous variables and χ2 test (or Fisher’s exact test) for categorical variables to identify factors associated with bilateral CRS. The cohort comprised 60 PLWH (median age 36.0 years; 95.0

Background: Epidemiological studies have reported sex differences in the prevalence of asthma and allergic rhinitis, suggesting a potential role of sex hormones in their pathophysiology. Methods: We performed a two-sample Mendelian randomization (MR) analysis to investigate the causal effect of testosterone on allergic diseases (ADs). Genetic instruments for TES were derived from 425,097 individuals. Summary-level data for ADs were obtained from nine discovery and thirteen validation cohorts, encompassing a total of 8.4 million participants. The inverse-variance weighted (IVW) method served as the primary MR approach, supplemented by sensitivity analyses including MR-Egger, weighted median, and MR-PRESSO to assess pleiotropy and heterogeneity. Leave-one-out analysis was conducted to examine the influence of individual variants. Multivariable MR was applied to evaluate BMI as a potential mediator. Findings: Genetically predicted higher testosterone levels (per SD) were inversely associated with allergic rhinitis (OR = 0.851, 95% CI: 0.769–0.943, P=0.002) and eczema (OR = 0.981, 95% CI: 0.966–0.996, P=0.015). After adjustment for BMI using multivariable MR, the protective effects were strengthened for allergic rhinitis (OR = 0.725, 95% CI: 0.628–0.838, P<0.001) and eczema (OR = 0.962, 95% CI: 0.934–0.990, P=0.008). A similar pattern was observed in asthma cohorts, where BMI adjustment enhanced the inverse association, suggesting partial mediation by BMI. Interpretation: This MR study supports a causal, protective role of testosterone against ADs, partly mediated through BMI. These findings offer a genetic explanation for sex disparities in ADs and suggest the potential relevance of hormone-modulating strategies in allergy prevention and management.

PURPOSE:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the mucosa, which significantly impairs patients' quality of life. Eucalyptol-Limonene-Pinene (ELP) is a plant-derived mucoactive agent used in respiratory diseases, including CRSwNP; however, its underlying mechanisms remain unclear. This study aimed to evaluate ELP's effect on CRSwNP and explore its mechanisms. METHODS:Predicted targets and pathways from network pharmacology were validated in vitro using nasal epithelial cells (NECs) and single-cell suspensions from CRSwNP patients, and in vivo using Aspergillus oryzae protease/ovalbumin-induced mouse CRSwNP model. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, Western blot, Luminex, hematoxylin and eosin staining, Alcian blue-periodic acid-Schiff staining, immunofluorescence, and immunohistochemistry were used to quantify inflammatory mediators and mucociliary changes. RESULTS:Network pharmacology revealed that epidermal growth factor receptor (EGFR), hypoxia-inducible factor 1-alpha, interleukin (IL)-2 are core targets and enriched in inflammation pathways. In vitro, ELP inhibited the overexpression of mucin 5AC induced by amphiregulin, hypoxia, IL-2 and IL-13 in NECs. ELP decreased expression of type 2 inflammatory mediators, arachidonate 15-lipoxygenase, C-C motif chemokine ligand 26, periostin and epithelial-derived alarmins thymic stromal lymphopoietin, IL-33 in NECs, reduced the concentrations of cytokines/chemokines and countered lipopolysaccharide-induced inflammation in single-cell suspensions. In vivo, ELP reduced epithelial thickness, inflammatory infiltration, goblet cell hyperplasia and cilia damage. CONCLUSIONS:ELP reduced mucus hypersecretion and inflammatory mediators in vitro and in vivo in CRSwNP by specifically inhibiting EGFR-, hypoxia-, IL-2- and IL-13-mediated pathways, suppressing inflammatory responses, and alleviating ciliary damage, suggesting its potential therapeutic value.

Allergic diseases are a major public health challenge for children. To date, a comprehensive assessment of the disease burden of major allergic diseases in Chinese children is still limited. This study aimed to analyze the epidemiological characteristics of major allergic diseases in China through the Global Burden of Disease Study 2021 (GBD 2021). The incidence and prevalence of asthma, atopic dermatitis (AD), and urticaria among children aged 0 to 14 years in China from 1990 to 2021 were assessed through data from GBD 2021. Moreover, subgroup analyses by sex, age, and China/global comparisons were performed to analyze the differences more accurately. We used Joinpoint regression analyses to quantify temporal trends, calculate annual percentage changes, and average annual percentage changes. From 1990 to 2021, China experienced significant declining trends in childhood asthma, with incidence and prevalence falling by approximately −26% and −23%, respectively. These rates were consistently higher in boys (male-to-female ratio >1.3). In contrast, AD presented a mixed pattern: a slight decrease in incidence (−6.7%) alongside a marginal rise in prevalence (+1.5%), diverging from the global decline. AD showed a consistent female predominance. Meanwhile, urticaria remained relatively stable nationally (incidence: −2.3%, prevalence: −0.4%), but exhibited a pronounced female skew, with incidence and prevalence rates about 60% higher in girls. Although the burden of asthma has decreased, the prevalence of AD has been increasing, whereas the prevalence trend of urticaria has been relatively stable. The burden of allergic diseases is still large, and there are obvious sex differences.

Chronic rhinosinusitis, with or without nasal polyps, severely impairs the quality of life and imposes heavy economic costs. Standard care, including intranasal corticosteroids and endoscopic sinus surgery, is limited by poor drug penetration into narrow recesses and high rates of postoperative restenosis and recurrence. Biodegradable steroid-eluting stents provide sustained, targeted corticosteroid delivery directly to diseased mucosa. It has been 8 years since the first fully biodegradable steroid-eluting stent was approved for the treatment of chronic rhinosinusitis in China. In clinical practice, the standardized application of the stent calls for guidance based on high-quality evidence, while its real-world use continues to broaden the exploration of its clinical utility. To standardize the clinical use of sinus stents, experts from the Rhinology Group, National Medical Quality Control Center of Otorhinolaryngology (China), convened to establish this consensus based on current clinical evidence. An analysis of 13 randomized controlled trials (2011–2025) demonstrated that these devices significantly reduced polyp formation, eosinophilic inflammation, adhesions, and the need for revision surgery or systemic steroids, while maintaining frontal-sinus patency. Office-based implantation effectively manages recurrent polyposis. Safety data demonstrated minimal systemic exposure and a rare incidence of serious adverse events. Its optimal use was reported in refractory chronic rhinosinusitis with nasal polyps (guided by T2/eosinophilic endotype), high-risk ostial stenosis, and early postoperative care to prevent middle-turbinate lateralization. Although long-term efficacy and cost-effectiveness remain variable, steroid-eluting stents integrate surgical and pharmacologic strategies for achieving durable disease control.

BackgroundPollen-induced allergic rhinitis (PIAR) is a major public health burden in high-pollen regions of northern China (e.g., Ordos, southern Inner Mongolia Plateau). However, regional variations in PIAR across ecological zones (urban, agropastoral, desert, and mining zones), dominant allergens, and key risk factors remain understudied due to prior small-sample or narrow-scope research.ObjectiveThis study aimed to investigate the prevalence, major risk factors, and current treatment patterns for PIAR in Ordos.MethodsFrom March to July 2023, a multicenter, randomized, stratified cross-sectional survey was conducted across nine areas in Ordos. Participants were recruited to complete in-person questionnaires and undergo skin prick tests (SPTs) for 16 common allergens. Pollen was collected and counted to monitor exposure levels.ResultsAmong the 4,303 participants, the prevalence rates of self-reported allergic rhinitis (SRAR), physician-diagnosed allergic rhinitis (PDAR), and PIAR were 52.89% (2,276/4,303), 34.70% (1,493/4,303), and 31.51% (1,356/4,303), respectively. The prevalence rates of PIAR in urban, agropastoral, desert, and mining areas were 30.46%, 39.55%, 29.09%, and 19.72%, respectively. Among patients with PIAR, the incidence of symptom onset was highest among urban residents and lowest among mining area residents. Poplar pollen allergen dominated in spring, whereas in autumn, Artemisia pollen was predominant. Clinical symptoms were greatest in July, preceding the autumn pollen peak in September.ConclusionPIAR is highly prevalent in northern China's grasslands, with marked zone-specific variations. Artemisia pollen exposure is the main sensitization driver, supporting targeted PIAR prevention/control.

Allergic rhinitis (AR) is a common, persistent nasal disorder that poses significant public health challenges worldwide. Current treatment options frequently fail to achieve adequate symptom control in a substantial subset of patients. Over the past two decades, biologic therapies that target type 2 inflammatory pathways have been used to treat patients experiencing poorly controlled symptoms, despite standard-of-care (SoC) treatment. Although biological treatment options for AR remain limited worldwide, the recent approval of novel agents, such as stapokibart for seasonal allergic rhinitis (SAR), has accelerated clinical research and development in this field. Evidence for biologic therapy in the management of perennial allergic rhinitis (PAR) is currently sparse. To standardise the use of biologics in AR management and promote their evidence-based application, a multidisciplinary expert panel was convened. This position paper evaluates current evidence regarding the efficacy and safety of biologic agents for AR, incorporating data from both international and regional clinical studies. Here, we provide recommendations on appropriate indications for biologic therapy and emphasise its role in patients with uncontrolled SAR, supporting clinical decision-making and facilitating the integration of biologics into routine practice.

BACKGROUND:Eosinophilic and neutrophilic inflammation, along with tissue remodeling, are key pathogenic features in chronic rhinosinusitis with nasal polyps (CRSwNP). While ADAM8 (a disintegrin and metalloproteinase 8) is implicated in inflammation and remodeling in various contexts, its specific role in CRSwNP remains unclear. OBJECTIVE:We aimed to elucidate the role of ADAM8 and its underlying mechanisms in CRSwNP pathogenesis. METHODS:Bulk RNA sequencing, single-cell RNA sequencing reanalysis, and histologic analysis were performed on human nasal tissues. Eosinophil and neutrophil migration, transendothelial migration, and adhesion were assessed in vitro.ADAM8 was overexpressed in a human nasal epithelial cell (HNEC) line (HNEpC) via transfection. Primary HNECs were stimulated with CRSwNP-related factors. In vivo, a murine CRSwNP model was treated with an ADAM8 inhibitor. RESULTS:ADAM8 expression was significantly elevated in both eosinophilic and noneosinophilic CRSwNP and was abundantly expressed by multiple inflammatory cells and epithelial cells. This elevation strongly correlates with inflammatory cell infiltration, tissue remodeling, and disease severity. ADAM8 inhibition reduced the migration, transendothelial migration, and adhesion to endothelial cells of both eosinophils and neutrophils. ADAM8 overexpression in HNEpCs activated inflammation pathways and upregulated the expression of matrix metalloproteinases (MMPs), including MMP2, MMP10, and MMP24. IL-4, IL-13, TGF-β1, and hypoxia upregulated ADAM8 in HNECs. In the murine CRSwNP model, ADAM8 inhibition reduced nasal polyp formation, eosinophil and neutrophil infiltration, and tissue remodeling. CONCLUSION:ADAM8 functions as a critical mediator of inflammatory cell infiltration and tissue remodeling in CRSwNP. Targeting ADAM8 represents a promising therapeutic strategy potentially applicable across different CRSwNP subtypes.

Pathogenic protein crystallization in vivo triggers multifactorial inflammatory cascades that ultimately lead to irreversible tissue damage, representing an unmet therapeutic challenge. Here we report ISQ, a novel self-assembling peptide that specifically targets galectin-10 (Gal-10) crystallization─a key pathological driver of airway inflammation, where Gal-10 crystal deposition activates interleukin-1β (IL-1β)-dependent pathways and promotes neutrophilic inflammation. ISQ exhibits dual functionality: it not only binds Gal-10 with nanomolar affinity (KD = 2.1 nM) to dissolve preformed crystals in vitro, but also spontaneously self-assembles into stable nanostructures with structural resilience that maintain target recognition even after thermal denaturation, demonstrating superior robustness compared to antibodies. In a Gal-10 crystal-induced murine model, intratracheal administration of ISQ assemblies significantly attenuated airway inflammation, reducing both proinflammatory cytokine production and neutrophil infiltration. The therapeutic efficacy was further confirmed in primary airway epithelial cells derived from patients with Gal-10 crystallopathies. Collectively, these findings establish ISQ as a first-in-class, self-assembling peptide therapeutic that disrupts pathogenic protein crystallization, offering a promising treatment strategy for crystallopathy inflammation currently lacking effective interventions.

Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E, with its global prevalence exhibiting a persistent upward trend. This review elucidates the pivotal role of DNA methylation, a fundamental epigenetic mechanism, in the pathogenesis of AR. Serving as a crucial interface between environmental exposures and genetic susceptibility, DNA methylation provides a molecular framework for understanding gene-environment interactions in this complex disease. The article systematically examines the multifaceted involvement of DNA methylation in AR. It details how epigenetic modifications contribute to the intergenerational transmission of disease risk, highlighting evidence for both maternal and paternal influences through specific gene methylation patterns. A significant portion is devoted to dissecting how various environmental factors, including airborne pollutants (e.g., PM2.5), microbial exposures, and allergens (e.g., pollen, house dust mites), can dynamically alter the DNA methylome. These alterations subsequently dysregulate the expression of key immune-related genes. The review further delves into the mechanistic consequences of these methylation changes. It summarizes how aberrant methylation of critical genes-such as those within the FOX family (e.g., FOXP3), cytokines (e.g., IL13, IFN-gamma), and others (e.g., LPCAT2)-disrupts immune homeostasis. This disruption predominantly manifests as a Th1/Th2 imbalance, characterized by suppressed Th1 responses and amplified Th2 activity, leading to the hallmark inflammation and symptoms of AR. Notably, the reversible nature of DNA methylation presents a promising therapeutic avenue. The potential of DNA methyltransferase inhibitors, widely used in oncology, is discussed for their capacity to reverse pathological methylation patterns, restore immune balance, and potentially treat AR. Despite the promising insights, the review acknowledges current limitations, such as relatively small-scale studies, a focus often broader than AR-specific mechanisms, and an incomplete understanding of the precise pathways linking environmental triggers to specific methylation changes. In conclusion, DNA methylation stands as a central regulator in AR pathogenesis. Profiling DNA methylation patterns holds significant promise for developing novel diagnostic biomarkers, enabling precise disease stratification, and guiding the development of targeted epigenetic therapies, ultimately contributing to improved prevention and management strategies for AR.

BACKGROUND:Staphylococcal superantigen-specific IgE (SAg-IgE) correlates with disease severity in patients with type 2 (T2) chronic rhinosinusitis with nasal polyps (CRSwNP). Although Staphylococcus aureus is recognized as a primary source of SAgs, SAg-IgE is detected even in patients with culture-negative S aureus. OBJECTIVE:We sought to identify the source of SAgs in SAg-IgE-positive patients with T2 CRSwNP with culture-negative S aureus. METHODS:Metagenomic sequencing was conducted in patients with T2 CRSwNP with repeatedly negative S aureus cultures, stratified by SAg-IgE status. We screened clinical isolates for SAg genes and evaluated SAg functionality by measuring SAg-specific T-cell receptor repertoire expansion and T2 inflammatory responses in an ex vivo infection model. RESULTS:The SAg-IgE-positive group showed significantly higher abundances of S epidermidis, S aureus, Lysinibacillus xylanilyticus, and S capitis compared with the SAg-IgE-negative group. Interestingly, in all participants in whom S aureus was detected, S capitis was also present, albeit at low abundance. Redundancy analysis demonstrated clustering of the Staphylococcus genus, SAg-IgE, and IL-5, supporting a potential link between the Staphylococcus genus and SAg-driven immune responses. Notably, a clinical S capitis isolate carried SEA (staphylococcal enterotoxin A) and SEC genes and secreted functional SAgs, which triggered the clonal expansion of SEA/SEC-specific T-cell receptors and exacerbated the T2 inflammatory response via IL-33 induction. CONCLUSIONS:Metagenomic sequencing reveals that S capitis, beyond S aureus, produces functional SAg to drive T2 response in SAg-IgE-positive patients with CRSwNP when conventional cultures fail to detect S aureus. Independent of culturable bacterial load, tissue SAg-IgE positivity reliably indicates bacterial colonization and SAg exposure in CRSwNP.

Background: Patients with moderate-to-severe allergic rhinitis (AR) often experience a heavy clinical burden and require more medications to alleviate nasal symptoms. The aim of this study was to evaluate the efficacy and safety of GSP301, a fixed-dose combination nasal spray containing olopatadine hydrochloride and mometasone furoate, in patients with seasonal AR (SAR). Methods: In this multicenter, randomized, double-blind, parallel-group study, moderate-to-severe SAR patients were assigned at a 1:1:1 ratio to receive intranasal GSP301, olopatadine hydrochloride (OLO), or mometasone furoate (MF) for 14 days. The primary endpoint was the change from baseline in the average A.M. and P.M. 12-hour reflective total nasal symptom score (rTNSS). Secondary endpoints included changes in the instantaneous TNSS (iTNSS), individual nasal symptoms, reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score (iTOSS), individual ocular symptoms, and rhinoconjunctivitis quality-of-life questionnaire (RQLQ). Exploratory endpoints and adverse events were also analyzed. Results: Among the 534 subjects, the GSP301 group demonstrated statistically significant improvements in the average rTNSS compared with the OLO group [posterior least square mean difference (LSMD) =-0.56; P < 0.0001] and the MF group (posterior LSMD =-0.43; P < 0.0001). Consistent benefits were observed across secondary endpoints, including iTNSS, rTOSS, RQLQ, and individual nasal and ocular symptoms (all P < 0.05). Additionally, GSP301 reduced the levels of interleukin (IL)-5 and eosinophilic cationic protein (ECP) in nasal secretions. Treatment-emergent adverse events (TEAEs) occurred in 11.2%, 13.5%, and 11.3% of patients in the GSP301, OLO, and MF groups, respectively. Conclusion: Compared with OLO and MF, GSP301 demonstrated superior efficacy, safety, and potential advantages in alleviating local inflammation in patients with moderate-to-severe SAR.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) features marked infiltration of diverse inflammatory cells. Cadherin-26 (CDH26) is an adhesion molecule associated with eosinophilic inflammation, but its role in CRSwNP remains undefined. Objective To investigate the expression, mechanisim, and function of CDH26 in CRSwNP. Methods Bulk and single-cell RNA sequencing and immunohistochemistry of human nasal tissues profiled CDH26 expression, localization, and its association with immune cells and inflammatory pathways in CRSwNP. Nasal epithelial cells were stimulated with cytokines to examine CDH26 expression, and were transfected to evaluate CDH26’s impact on JAK-STAT signaling. Adhesion and survival assays were conducted with isolated eosinophils and neutrophils. CDH26-/- mice were used to establish a CRSwNP model to determine CDH26’s role in disease development. Results CDH26 was elevated in eosinophilic CRSwNP (ECRSwNP) compared with control and non-eosinophilic CRSwNP (NECRSwNP) and correlated with intraepithelial infiltration of both eosinophils and neutrophils. Single-cell analysis showed its epithelial localization and co-expression with IL13RA1/STAT6 in basal cells. CDH26 was induced by IL-4/IL-13 via JAK-STAT signaling and, in turn, enhanced STAT6 phosphorylation. CDH26 mediated epithelial adhesion of eosinophils and neutrophils via integrin α4 (ITGA4) and enhanced their survival in vitro. CDH26-/- mice showed attenuated nasal polyp-like lesion formation and reduction in the infiltration of eosinophils, neutrophils, mast cells, and T cell subsets. Conclusion CDH26 is a type 2-inducible epithelial molecule that functions as an inflammatory mediator in CRSwNP by modulating JAK-STAT signaling and promoting eosinophil and neutrophil retention, thereby linking epithelial dysfunction to sustained inflammation and may represent a potential therapeutic target.

Background:The treatment of refractory chronic rhinosinusitis with nasal polyps (CRSwNP) withomalizumab has been well studied based on clinical evaluation. Nevertheless, ideal quantitative orqualitative biomarkers for predicting a different response to biologics urgently need to beexplored. We aim to identify potential biomarkers for predicting a good or poor response in pa-tients with refractory CRSwNP. Methodology:Patients received an endoscopic and radiological evaluation, a visual analoguescale (VAS) assessment, and a 22-item sinonasal outcome test (SNOT-22). Forty-eight biomarkersinvolving type 1 (T1), type 2 (T2), and type 3 (T3) inflammatory factors, chemokines, andremodeling factors were detected in nasal secretion and serum samples at baseline and after 24weeks of omalizumab treatment. Results:Eighteen patients with CRSwNP and 16 patients as control were enrolled. Patients withCRSwNP who received oamlizumab treatment with the SNOT-22 and VAS scores improved by 8.9and 2 points in 72.22% and 50%, respectively.The nasal polyp score (NPS) and Lund-Mackay scorewere significantly improved in 55.56% of patients. The concentrations of T2 inflammatorybiomarker, granulocyte-macrophage colony-stimulating factor (GM-CSF), T3 inflammatory bio-markers, granulocyte colony-stimulating factor (G-CSF), chemokine (C-X-C motif) ligand (CXCL)-1,and chemokine (C-C motif) ligand-20 (CCL-20), T1 inflammatory biomarker, IP-10 (CXCL-10), andgranzyme B in nasal secretion and serum periostin were significantly decreased. Serum CCL-3(AUC 1/40.836) and CCL-4 (AUC 1/40.909) levels predicted the improvement of SNOT-22 score,respectively. Serum IL-8 (AUC 1/40.883) predicted poor improvement in nasal congestion score.Nasal secretion CXCL-1 (AUC 1/40.812), GM-CSF (AUC 1/40.813), IgE (AUC 1/40.900) and IP-10(AUC 1/40.800) effectively predicted none or less improvement in nasal polyp score. Conclusions:Omalizumab remarkably affects inflammatory mediators in different pathways.CCL-3 and CCL-4 in serum and IgE, CXCL-1, GM-CSF, and IP-10 in nasal secretion may be considered as preferable biomarkers for predicting favorable or ineffective response to omalizu- mab therapy in patients with refractory CRSwNP comorbid with asthma, based on various clinical indicators.

The prevalence of allergic rhinitis (AR) continues to rise, severely impairing patients’ quality of life and causing enormous social and economic burdens. For refractory AR that cannot be adequately controlled by standardized firstline therapies, neurotomy has become an important secondline therapeutic option. However, due to various remaining controversial issues, there is currently a lack of internationally unified clinical guidelines, which restricts its clinical application and generalization. To better guide the clinical practice of neurotomy for AR in China, 49 experts in the field of rhinology and allergy nationwide, led by the Third Affiliated Hospital of Sun Yat-sen University, carried out the work of formulating a consensus. Using the Delphi method, we focused on seven dimensions: the purpose and significance of neurotomy for AR, relevant applied anatomy, pathophysiological basis, surgical indications and contraindications, surgical techniques, efficacy and evaluation criteria, and surgical complications and their management, ultimately generating a series of core viewpoints. This consensus is expected to further promote the standardized development of neurotomy for AR in China, and help improve the overall prevention and management of AR.

Background: The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions. Objective: Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS2020 guidelines. Methods: A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS2020 guidelines. Results: Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.4% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment. Conclusion: This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with variable manifestations, including recurrent epistaxis, telangiectasias, arteriovenous malformations, and family history. It is caused by heterozygous null alleles of ENG , ACVRL1 , SMAD4 , or BMP9 , with delayed clinical diagnosis. Genetic testing is crucial for early diagnosis. To analyze the variant distribution of HHT-related genes, expand variant databases for Chinese patients, and explore phenotype-genotype associations. Thirty-two individuals from 20 unrelated families were recruited. Coding regions of ENG , ACVRL1 , SMAD4 , and BMP9 were sequenced. Variants were identified by sequence alignment. Epistaxis severity was evaluated using the epistaxis severity score (ESS), and the ESS differences between groups were analyzed using the Mann–Whitney test. Seventeen unique variants were identified in 17 unrelated HHT families (17/20, 85%), including 5 novel variants (3 in ENG and 2 in ACVRL1 ). Eleven ACVRL1 variants were identified in 12 families (12/17, 70.6%). Six variants of ENG were detected in 5 families (5/17, 29.4%), and one patient had two variants. ACVRL1 variants were 2.4 times more prevalent than ENG variants, with 41.7% of ACVRL1 variants in exon 10. A recurrent variant, c.1435C>T, was identified in two families. Epistaxis severity increased with age. ACVRL1 variants were more common than ENG variants in Chinese HHT families, with exon 10 identified as a potential hotspot. These findings enhance understanding of HHT genetics and guide targeted genetic testing in China.