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.

Objective:Chronic rhinosinusitis with nasal polyps （CRSwNP） is a disease characterized by chronic inflammation of the nasal and paranasal sinus mucosa. Patients commonly experience symptoms such as nasal congestion, loss of smell, rhinorrhea, and facial pain or pressure, which significantly impair patients' quality of life. Stapokibart is an anti-interleukin-4 receptor α （IL-4Rα） monoclonal antibody. This study aimed to assess the efficacy of stapokibart on improving patients' quality of life. Methods:In the phase 3 CROWNS-2 study, patients were randomized 1︰1 to receive stapokibart or placebo once every 2 weeks for 24 weeks. Both groups then received stapokibart for 28 weeks, followed by an 8-week safety follow-up period. This post-hoc analysis of the CROWNS-2 study assessed the effects of stapokibart on 22-item sinonasal outcome test （SNOT-22） domain scores. Results:During the double-blind period, stapokibart significantly improved multiple SNOT-22 domain scores, including the Nasal, Ear/facial, Sleep, and Emotion domains, compared with placebo. These improvements were maintained and further progressed during the open-label extension and subsequent safety follow-up periods. Conclusion:Stapokibart provides significant clinical benefits across multiple dimensions of quality of life, offering important clinical evidence for the long-term management of CRSwNP.

The prevalence of allergic diseases in our country is increasing, and the impact on health is becoming more and more serious. Allergenic pollens are the main source of allergic diseases in northern China. The prevalence of pollen allergy diseases (PiAD) is high in northern China. Anaphylactic shock can be fatal. However, the standardized diagnosis and treatment rate of PiAD is low, specialized doctors and nurses are extremely few, public awareness is seriously insufficient, and misdiagnosis and mistreatment are very common. Therefore, it is urgent to improve the level of prevention and control. The "Five in One" integrated precise prevention and control system includes pollen monitoring, vegetation research, epidemiological investigation, standardized training for medical personnel, and public science popularization and education. Allergenic pollen spreads through the air and is also known as airborne allergen, its concentration in the air is related to the seasons. In spring, allergenic pollen come from trees, while grasses and weeds in summer and autumn. The purpose of pollen monitoring and vegetation investigation is to monitor the seasonal changes in the concentration of allergenic pollen in the air and the corresponding vegetation distribution, providing a decision-making basis to control the allergenic environment from the source for landscaping and grassland ecological administrations. The purpose of the epidemiological investigation is to determine the prevalence of the disease and to study the follow-up strategies. The purpose of medical training is to improve the knowledge, attitude, and behavior (KAB) of medical doctors and nurses working in primary care units in preventing and treating allergic diseases, and to enhance the standardized and systemic diagnosis and treatment level. The purpose of popular science education is to provide the public with knowledge, attitude, and behavior (KAB) on allergic diseases, prevent patients from worsening or relapsing, prevent transiting high-risk populations from developing into patients, and prevent the general population from developing into high-risk populations. Director Wang Xueyan's initiative of the "Five in One" precision prevention and control system has been widely promoted and applied in northern China for over a decade with good results and huge social benefits. It is in line with China's new era development concept of putting people at the center and promoting a healthy China and has made significant contributions to the world's prevention and control of allergic diseases. It has significant practical and far-reaching historical significance.

Allergic Rhinitis and its Impact on Asthma (ARIA) was, up until 2017, a guideline using the best evidence (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) and developed as a change management strategy. A second change management strategy-in collaboration with the European Academy of Allergy and Clinical Immunology (ARIA-EAACI)-was developed as a person-centred, digitally enabled, artificial intelligence-assisted care (person-centred care) with strong political involvement. The digital tools of ARIA are mainly based on MASK-air, an Organisation for Economic Co-operation and Development (OECD) Best Practice for integrated care for chronic diseases. Artificial intelligence was used, in particular, to approach the patients' views and expectations. The current paper describes the steps to build and achieve a new change management strategy. The future of the Change Management strategy is (i) a collaboration between ARIA and EAACI, (ii) the development of ARIA 2024-2025 guidelines, (iii) the new ARIA-MeDALL classification of multimorbid airway diseases and (iv) embedding MASK-air in a registry for severe allergic diseases. The ultimate goals of the ARIA-EAACI change management strategy will be (i) the transformation of health and care in rhinitis and asthma multimorbidity and (ii) the development of novel guidelines and policies in a cost-effective manner, improving shared-decision-making.

Type 2 (T2) immunity is classically associated with defense against helminths and environmental threats, from a physiological perspective, and with allergies and eosinophilic inflammatory diseases, in a pathological sense. However, growing evidence reveals that T2 pathways also support other essential homeostatic functions, including tissue protection and repair. There are major clues from the early evolution of T2 responses for protection against massive tissue damage and positive selection for survival against parasites starting over 500 million years ago. These responses likely co-evolved stepwise with immune-regulatory circuits, culminating in the emergence of the fully functional human-type IgG4 in the great apes (Hominidae) within the last ~10 million years. The involvement of body barriers along with the strong influence of local epithelial cells and their interaction with the microbiome and the immune system is a common characteristic of T2 inflammation. An expanding list of new T2 diseases is being reported, characterized by epithelial cell and immune system activation, epithelial barrier damage, and microbial dysbiosis, including opportunistic pathogen colonization and loss of commensals. This evolving understanding coincides with the clinical success of biologics targeting key T2 mediators such as IL-4, IL-5, IL-13, IL-31, TSLP, and IgE, which have transformed the management of severe allergic diseases and other T2-driven pathologies. However, the contribution of T2 immunity to homeostatic programs raises questions about the long-term consequences of sustained T2 suppression. In this review, we examine the dual role of T2 immunity in health and disease, revisit its evolutionary origins, highlight its protective functions beyond allergy, and discuss the potential implications of prolonged T2 pathway blockade.

Airborne pollen is a key environmental allergen affecting millions across China. As pollen levels and allergy prevalence continue to rise under rapid urbanization and climate change, developing spatially explicit, long-term pollen datasets becomes increasingly important for public health and ecological risk assessment. In this study, we developed a novel ensemble machine learning framework integrating random forest and gradient boosting models to estimate daily tree and herbaceous pollen concentrations across mainland China from 2011 to 2023. Models were trained using daily pollen data from 27 monitoring sites during 2019-2024 and a rich set of predictors, including meteorological, vegetation, land use, and spatiotemporal variables. By applying the trained models to historical environmental datasets, we reconstructed nationwide daily pollen concentrations for 2011-2023 to extend the temporal coverage beyond the observational record. The models achieved high accuracy, with R2 values of 0.90 (tree) and 0.89 (herbaceous), and root mean square errors of 0.58 and 0.49, respectively. Tree pollen peaked in early spring in eastern, northeastern, central, and southwestern regions, while herbaceous pollen peaked in late summer in northern and northwestern areas. Seasonal timing, temperature, and vegetation indices were key drivers, with short-term lagged temperature (0-7 days) strongly influencing predictions. This study provides the first nationwide, long-term, daily pollen dataset for China derived from observation-based modeling and historical reconstruction, serving as an important resource for ecological research and public health applications. The established modeling framework offers a robust foundation for pollen exposure assessment, allergy forecasting, and climate-responsive risk management of aeroallergens under changing environmental conditions.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) exhibits distinct bacterial colonization patterns between eosinophilic (ECRSwNP) and non-eosinophilic (non-ECRSwNP) subgroups. It remains unclear to what extent these differences are clinically relevant to the response to glucocorticoid (GC) treatment. Objective: This study aimed to investigate differences in nasal bacterial colonization between ECRSwNP and non-ECRSwNP patients in relation to their GC treatment response. Methods: We enrolled 347 CRSwNP patients, including 222 ECRSwNP and 125 non-ECRSwNP patients. Nasal swabs were collected from all participants, and bacterial composition was assessed via standard culture techniques. Of these, 189 patients received a 2-week course of oral GC treatment (24 mg of methylprednisolone daily), and nasal bacterial colonization was analyzed in relation to GC treatment response. Results: Of the 347 CRSwNP patients recruited, Staphylococcus was the most prevalent bacterial genus, followed by Corynebacterium and Streptococcus . Compared to ECRSwNP patients, non-ECRSwNP patients exhibited higher colonization rates of Streptococcus viridans and Haemophilus influenzae , and lower colonization rates of Klebsiella . Among the 189 patients who received GC treatment, further subgroup analysis was performed based on GC sensitivity. In GC-sensitive patients, S. viridans and H. influenzae were significantly more prevalent in non-ECRSwNP than in ECRSwNP. Conversely, among GC-resistant patients, Corynebacterium pseudodiphtheriticum was increased considerably in ECRSwNP than in non-ECRSwNP. Conclusion: Our findings indicate that there are distinct bacterial compositions in non-ECRSwNP and ECRSwNP patients. Streptococcus viridans and H. influenzae are linked to GC-sensitive non-ECRSwNP, while C. pseudodiphtheriticum is associated with GC resistance in ECRSwNP, highlighting their potential role in modulating GC treatment outcomes.

ABSTRACT Allergic Rhinitis and its Impact on Asthma (ARIA) was, up until 2017, a guideline using the best evidence (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) and developed as a change management strategy. A second change management strategy—in collaboration with the European Academy of Allergy and Clinical Immunology (ARIA‐EAACI)—was developed as a person‐centred, digitally enabled, artificial intelligence‐assisted care (person‐centred care) with strong political involvement. The digital tools of ARIA are mainly based on MASK‐air, an Organisation for Economic Co‐operation and Development (OECD) Best Practice for integrated care for chronic diseases. Artificial intelligence was used, in particular, to approach the patients' views and expectations. The current paper describes the steps to build and achieve a new change management strategy. The future of the Change Management strategy is (i) a collaboration between ARIA and EAACI, (ii) the development of ARIA 2024‐2025 guidelines, (iii) the new ARIA‐MeDALL classification of multimorbid airway diseases and (iv) embedding MASK‐air in a registry for severe allergic diseases. The ultimate goals of the ARIA‐EAACI change management strategy will be (i) the transformation of health and care in rhinitis and asthma multimorbidity and (ii) the development of novel guidelines and policies in a cost‐effective manner, improving shared‐decision‐making.

Objective:To investigate the impact of prior sinus surgery on the efficacy of stapokibart in patients with refractory chronic rhinosinusitis with nasal polyps（RCRSwNP）. Methods:This post hoc analysis was based on data from the phase III CROWNS-2 trial. A total of 179 patients with RCRSwNP who received at least one dose of stapokibart or placebo were included and categorized into two groups according to their history of prior sinus surgery（114 with prior sinus surgery and 65 without）. Intergroup differences in the efficacy of stapokibart and its ability to reduce the need for surgery were compared. Results:Of the 179 patients, 114（63.7%） had a history of prior sinus surgery. Among those with prior surgery, 77.2%（88/114） had undergone only one procedure, and 78.9%（90/114） had their most recent surgery ≥3 years before enrollment. Regardless of prior sinus surgery, number of prior surgeries, or time since the last surgery, the stapokibart group demonstrated significantly greater improvements in all efficacy endpoints at week 24 compared with the placebo group, including polyp size, nasal congestion, quality of life, olfactory function, and radiologic scores. For most endpoints, treatment effects were not influenced by surgical history; however, greater improvements in nasal congestion, quality of life, total symptom scores, and radiologic outcomes were observed among patients with a history of sinus surgery（P for interaction<0.05）. Notably, regardless of prior sinus surgery, stapokibart significantly reduced the predicted need for further surgery compared with placebo, and these treatment-by-subgroup interactions were not statistically significant. Conclusion:Regardless of prior sinus surgery, stapokibart significantly reduces nasal polyp burden, improves symptoms and quality of life, and decreases the predicted need for further surgery in patients with RCRSwNP.

KEY POINTS:The efficacy of stapokibart in seasonal allergic rhinitis (SAR) is correlated with changes in nasal brushing clc mRNA levels. Changes in blood biomarker levels may not be associated with stapokibart efficacy in SAR.

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.

Purpose:Evaluating allergen immunotherapy efficacy amidst natural pollen fluctuations is complicated by pollen variation. This study evaluates the relationship between pollen exposure and therapeutic impact of Artemisia annua sublingual immunotherapy (SLIT) in seasonal allergic rhinitis (SAR). Patients and Methods:In a two-year multicenter, controlled trial, SAR patients sensitized to Artemisia received SLIT or symptomatic medication. Daily assessments of combined symptom and medication score (CSMS), total nasal symptom score (TNSS) and daily medication score (DMS), were conducted across two pollen seasons. Linear mixed-effect models (LMMs) were utilized to evaluate treatment effects while considering pollen variability. Exploratory analyses of immunoglobulins in serum and nasal secretions were performed. Results:Pollen fluctuations correlated positively with CSMS, TNSS, and DMS in both groups. SLIT significantly reduced the mean daily CSMS (β = -0.34, q < 0.001), TNSS (β = -1.01, q < 0.001), and DMS (β = -0.09, q < 0.001) compared to the control group. These effects were consistent across both pollen seasons. During the first pollen season, a significantly negative impact of group × time × pollen interactions on the average daily CSMS was observed in SLIT group (β = -0.11, P = 0.03). LMM analyses revealed significant group × time interactions for serum Artemisia-specific IgG4 and IgA with nasal IgA showing isolated significance. Conclusion:SLIT provided early and sustained symptom relief in SAR, taking into account the annual and seasonal pollen fluctuations. SLIT efficacy may be influenced by pollen exposure, with effect size increasing in correlation with higher levels of pollen exposure. SLIT elevated allergen-specific IgG4 and IgA in systemic and local compartments.

BACKGROUND:The management of moderate-to-severe allergic rhinitis (AR) is challenging given numerous advanced therapies. A comparative, evidence-based treatment hierarchy to guide the selection of biologics, allergen immunotherapy (AIT), and advanced pharmacotherapies is critically lacking due to a paucity of head-to-head trials. This network meta-analysis established a treatment hierarchy for moderate-to-severe AR by comparing the efficacy and safety of biologics, AIT, and key pharmacotherapies. METHODS:We analyzed 28 randomized controlled trials (13,312 participants), which evaluated the efficacy and safety of biologics (anti-IgE, anti-IL-4Rα therapies), AIT (evaluated within a 6-month time frame to ensure comparability), and key pharmacotherapies (intranasal corticosteroids alone or combined with antihistamines) for moderate-to-severe AR. Efficacy was assessed by changes in the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). A treatment hierarchy was established using surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS:For the TNSS, anti-IL-4Rα therapy was most effective, followed by anti-IgE therapy and AIT, which surpassed all pharmacotherapies. The combination of intranasal corticosteroid and intranasal antihistamine ranked the highest for ocular symptoms. Anti-IL-4Rα therapy was also superior for improving the RQLQ. Overall, all treatments demonstrated a favorable safety profile. Biologics and AIT did not show a significant increase in adverse events risk compared to placebo. CONCLUSIONS:This network meta-analysis establishes the first comprehensive treatment hierarchy for moderate-to-severe AR. Our findings demonstrate that biologics, particularly anti-IL-4Rα therapy, are the most effective interventions for nasal symptom control, ranking superior to AIT and pharmacotherapies, thus providing a robust, data-driven framework to personalize patient care.

This study utilizes multi-center networked observations of hourly airborne allergenic pollen concentrations from nine cities in Northern and Northwestern China to identify the dominant meteorological mechanisms driving diurnal pollen concentration variations at a regional scale. The results reveal two distinct diurnal patterns-unimodal and bimodal-whose peak timings are closely associated with predominant pollen types (Artemisia, Chenopodiaceae/Amaranthaceae, and Humulus/Cannabis). Based on dominant biometeorological processes, the responses of each city were classified into three mechanisms: (1) diffusion-driven, where pollen concentration shows a significant positive correlation with wind, indicating that wind force is the key limiting factor for pollen transport, with Handan exhibiting a lag effect of wind speed; (2) sedimentation-inhibited, where high nocturnal humidity exerts a strong inhibitory effect and lagged effect on pollen concentration, as humidity governs concentration changes by promoting pollen hygroscopic sedimentation; and (3) release-driven, where pollen concentration is significantly positively correlated with air temperature, indicating that temperature functions as the initial rate-limiting factor for pollen release under low thermal conditions. Wind rose analyses reveal that high pollen events are associated with wind directions and often occur under moderate wind speeds.

Background: Emerging evidence indicates that the succinate–succinate receptor 1 (SUCNR1) axis promotes metabolic reprogramming and plays a pivotal role in shaping immune responses, yet the contribution of the succinate–SUCNR1 axis to eosinophilic inflammation of the nasal mucosa remains poorly understood. Objective: This study aimed to investigate the role of the succinate–SUCNR1 axis in eosinophilic inflammation of the nasal mucosa. Methods: SUCNR1 expression and cellular localization were evaluated using immunohistochemistry, immunofluorescence, and single-cell RNA sequencing in human nasal tissues. The functional role of the succinate–SUCNR1 axis was assessed in a papain-induced murine eosinophilic rhinosinusitis model using succinate administration with or without the SUCNR1 antagonist compound 7a. In addition, succinate was administered to healthy mice to evaluate its effects on normal nasal mucosa. Results: SUCNR1 + cells were significantly upregulated in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) compared with noneosinophilic chronic rhinosinusitis with nasal polyps (nonECRSwNP; fold change = 6.33, P < 0.0001) and controls (fold change = 16.89, P < 0.0001). SUCNR1 was predominantly expressed in M2 macrophages, and CD163 + SUCNR1 + M2 macrophage counts were strongly correlated with tissue eosinophil counts ( r = 0.8092, P < 0.0001). In murine eosinophilic rhinosinusitis, lamina propria SUCNR1 + cells (fold change = 6.71, P < 0.001) and serum succinate (fold change = 1.78, P < 0.01) were elevated. Succinate administration exacerbated eosinophil infiltration in nasal mucosa (fold change = 2.0, P < 0.001) and peripheral blood eosinophilia (fold change = 1.83, P < 0.01), effects that were reversed by SUCNR1 antagonist compound 7a (both P < 0.01). Meanwhile, exogenous succinate did not induce significant nasal inflammation or blood eosinophilia in healthy mice versus vehicle controls ( P > 0.05). Conclusion: SUCNR1 was significantly upregulated in nasal polyps from patients with ECRSwNP and was predominantly expressed in M2 macrophages. The succinate–SUCNR1 axis is an eosinophilic inflammatory amplification pathway in nasal mucosa.

Background: Olfactory dysfunction, ranging from mild impairment to complete loss, is a prevalent and bothersome symptom in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: This study aimed to identify risk factors associated with the severity of olfactory dysfunction in the CRSwNP population, which have been largely overlooked. Methods: A total of 282 patients with CRSwNP were enrolled and categorized into normosmia, hyposmia, and anosmia groups according to their olfactory levels examined by the smell identification test specifically for the Chinese population (CSIT). Patients' demographic characteristics, history of asthma, computed tomography (CT)-based imaging scores, blood cytology, immunoglobulin E, and serum lipid profiles were recorded for all participants. Ordinal logistic regression analysis was used to identify risk factors of gradual olfactory dysfunction, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of those factors for discriminating different degrees of olfactory dysfunction from normosmia. Results: Significant differences were observed in age, prevalence of comorbid asthma, blood eosinophils, serum lipid profiles, and CT-based imaging scores of CRSwNP among the 3 groups stratified by olfactory outcomes ( P < 0.05, respectively). Multivariate ordinal logistic regression analysis identified Lund-Mackay scores, ethmoidal-to-maxillary (E/M) sinus ratio, age, and total cholesterol as independent risk factors for gradual olfactory dysfunction in CRSwNP ( P < 0.01, respectively). Correlation analysis indicated that the 4 identified risk factors were all significantly inversely correlated with the olfactory score measured by CSIT ( P < 0.001, respectively). ROC analysis demonstrated that the combined model based on the 4 risk factors showed strong power to discriminate between anosmic and normosmia (area under the curve [AUC]: 0.893, 95% confidence interval [CI]: 0.848–0.939), and moderate accuracy in classifying hyposmia and normosmia (AUC: 0.716, 95% CI: 0.640–0.792). When compared the AUC between different models, the combined model shows a better prediction ability than E/M ratio, age, and total cholesterol alone ( P < 0.05, respectively). Conclusion: Lund-Mackay score, E/M ratio, age, and serum total cholesterol are independent risk factors for gradual olfactory dysfunction in patients with CRSwNP, which can be used to develop a predictive model for olfactory outcomes.