Rush Immunotherapy (RIT) can reach the maintenance dose rapidly; however, it has more risks than conventional Immunotherapy (CIT). Adding anti-IgE antibody to allergen-specific immunotherapy (AIT) can enhance the safety of AIT. This study aimed to investigate the adverse reactions, clinical efficacy, and alterations in immunological marker in RIT combined with anti-IgE pretreatment. A retrospective study was conducted on patients with allergic rhinitis, with or without mild-to-moderate asthma, who received subcutaneous immunotherapy for one year at the First Affiliated Hospital of Guangzhou Medical University from July 2022 to January 2024. In the RIT group, patients received one dose of anti-IgE treatment within three weeks prior to therapy. We collected and analyzed adverse events, combined symptom and medication scores (CSMS), results of allergic blood tests, pulmonary function parameters, and other immunological markers before and after the treatment. All statistical analyses were performed using SPSS version 26.0. A total of 110 patients were analyzed, with 50 in the RIT group (37 males and 13 females) and 60 in the CIT group (43 males and 17 females). During the up-dosing phase, the RIT group had a significantly lower incidence of local adverse reactions compared to the CIT group (40% vs. 68.3%, P<0.01), while there was no significant difference in systemic reactions. The RIT group also had a significantly lower incidence of respiratory symptoms (0.7% vs. 2.1%, P<0.05). After one year treatment, both groups showed a significant reduction in CSMS compared to pre-treatment levels (P<0.001), with no significant difference in treatment efficacy. In the RIT group, the efficacy group had a significantly higher baseline IgE specific to house dust mites than the non-efficacy group (P<0.05). RIT combined with one dose of anti-IgE pre-treatment significantly reduces adverse reactions and demonstrates similar clinical efficacy comparable to that of CIT, suggesting that it is a safe and effective approach for accelerated immunotherapy.

The trends in allergic comorbidities secondary to the environmental variations in China remain unclear. We aimed to determine the variation of allergic comorbidities and polysensitization among asthma and/or rhinitis patients in the past decade. We assessed two nationally representative cross-sectional datasets from 2008 to 2009 and 2018 to 2019, which enrolled 2322 and 2353 patients, respectively. Over the present 10-year study period, the prevalence of allergic symptoms and allergen sensitivity among patients with multiple sensitivities in the 2018-2019 cohort was significantly higher than that in the 2008-2009 cohort, especially for mites, pollen, and animal allergens. The comorbidity rates of asthma, allergic rhinitis, conjunctivitis, and eczema were significantly increased in the 2018-2019 cohort. Also in that cohort, IgE polysensitization was significantly associated with the coexistence of asthma and rhinitis, and the number of IgE-reactive allergens was significantly associated with the number of multimorbidities. Use of an air-conditioner and carpet in the home, and keeping pet were linked to the risk of polysensitization. Our findings suggest an increase in the comorbidity rate and multimorbid polysensitized phenotype of allergic diseases in China. Asthma occurred in both cohorts more frequently with coexisting allergies than as a single entity.

Background While allergen-specific immunotherapy (AIT) is recognized as an effective treatment, its efficacy varies widely. However, whether clinical response trajectories to AIT differ among individuals and influence its effectiveness has not been investigated. Objective This study aimed to characterize real-world clinical response trajectories to three-year AIT (3y-AIT). Methods We conducted a retrospective multicenter study across 53 centers to identify clinical response trajectories in patients with house dust mite allergic asthma and rhinitis undergoing three-year AIT. The efficacy of AIT was primarily assessed using the Visual Analog Scale (VAS) for allergic symptoms at 4 time points: baseline (before AIT), and at 1, 2, and 3 years of treatment. Clustering analysis based on VAS changes at these time points was used to define response trajectories. Initial analysis was performed using data from 52 centers (Alliance cohort), and validation was conducted using data from a separate center (Guangzhou cohort). Results In the Alliance cohort, 4 distinct clinical response trajectories were identified. Cluster 1 showed symptom worsening in the first year, with no improvement by year 3. Cluster 2 exhibited symptom deterioration in the second year, followed by significant recovery and a positive response by year 3. Clusters 3 and 4, characterized by higher and lower baseline symptom severity, respectively, demonstrated marked improvement after 3 years of AIT. In the Guangzhou cohort, a similar pattern of 4 response trajectories was observed: higher baseline symptom severity and family tobacco exposure were key features of Cluster 1 (p < 0.001), while Cluster 2 had the highest rate of respiratory infections (>1/year, p < 0.001). Despite these distinct trajectories, first-year effectiveness emerged as an ideal predictor of the 3-year AIT response, with an AUC of 0.75. Conclusion This study identified 4 primary treatment response trajectories to 3-year AIT in daily clinical practice, highlighting the heterogeneous nature of AIT responses among individuals. Notably, first-year effectiveness appears to be an ideal predictor of the 3-year AIT outcome.

Background Asthma is a heterogeneous syndrome shaped by complex genetic and environmental interactions. We aimed to characterize shared and subtype-specific genetic architectures and possible parent-of-origin differences in offspring asthma risk. Methods Genetic correlations between five asthma-related phenotypes and over 1,900 traits were examined using Linkage Disequilibrium Score Regression (LDSC) and genome-wide association study (GWAS) data. Bidirectional two-sample Mendelian Randomization (TSMR) was used to investigate potential causal relationships between asthma and genetically correlated traits. Furthermore, maternal versus paternal asthma associations with offspring asthma risk were evaluated using TSMR and multivariable Mendelian Randomization (MVMR). Finally, parental asthma associations were also examined in a Chinese multicenter outpatient cohort (N = 7,135). Results We identified widespread, predominantly positive genetic overlap among asthma-related phenotypes, uncovering 23 core shared traits. Significant heterogeneity was observed between childhood-onset and adult-onset asthma. MR analyses supported a possible maternal-origin effect, with maternal asthma showing a stronger association with offspring asthma risk. This association persisted after adjustment for being breastfed as a baby in MVMR. A directionally consistent stronger maternal association was observed in the Chinese cohort (Mother-only asthma aOR 2.93 vs. Father-only aOR 1.59). Conclusions This study maps shared and subtype-specific asthma comorbidity genetics and supports a stronger maternal association with offspring asthma risk. Genetic findings based mainly on European-ancestry data should not be directly generalized to other ancestries, and findings from the Chinese outpatient cohort should not be generalized to the general population.

Atopic dermatitis (AD) involves complex metabolic-immune dysregulation, but the molecular links remain unclear. This study integrates a multilevel analytical framework to systematically investigate the metabolic-immune crosstalk in AD. Using linkage disequilibrium score regression and a two-step Mendelian randomization approach, we established genetic correlations and inferred causal relationships between plasma metabolites and inflammatory proteins, identifying 1-palmitoyl-2-arachidonoyl-GPC (PA-GPC) as a protective metabolite that exerts its effect primarily through downregulation of interleukin-18 receptor 1 (IL-18R1). Integration of single-cell transcriptomic data further revealed elevated IL-18R1 expression in T cells within the AD microenvironment and enabled stratification of T cells based on PA-GPC-associated metabolic activity, identifying 33 differentially expressed genes. Subsequent least absolute shrinkage and selection operator (LASSO) regression, combined with machine learning models and SHapley Additive exPlanations analysis, consistently prioritized CD9 as a key regulator. Functional validation showed that PA-GPC attenuates tumor necrosis factor-alpha (TNF-α)/interferon-gamma (IFN-γ)-induced inflammatory responses in human immortalized keratinocyte (HaCaT) cells and suppresses Th2 cytokine production in T cells. IL-18R1 knockdown reduced CD9 expression and Th2 cytokine production in T cells, whereas CD9 knockdown did not affect IL-18R1 expression, indicating that IL-18R1 acts upstream of CD9. Moreover, CD9 knockdown impaired T-cell viability, activation, and Th2 cytokine production. Collectively, these findings characterize metabolic-immune crosstalk in AD and identify a PA-GPC-IL-18R1-CD9 regulatory axis with potential therapeutic implications.

BackgroundA variety of patient populations receive allergen immunotherapy (AIT), but clinicians still lack an effective electronic platform to manage them.MethodsWe designed a platform based on the framework of value set extraction standardization, integration, and structurization. Average medication scoring (AMS) and other electronic medical records were developed and stored on a MySQL database. Data storage is hosted on cloud servers, linked to a mobile application, Bluetooth lung function monitoring, and a dedicated website that acts as a front-end.ResultsSince 2015, 23,847 patients in 48 hospitals with AIT prescriptions were included. Of these patients, the median age was 15 (interquartile range, 10-27) years. Allergic rhinitis was the most common disorder and accounted for 9753 (40.9%) of the cases. Five hundred and thirty-three basic data elements and six independent modules were constructed for the platform to facilitate the physicians in establishing SCIT projects, symptom scores, AMS, lung function tests, and follow-up appointments. One hundred and twelve drugs including 10 dosage forms were identified from an internal list of the dataset. The unit score was calculated based on the action mechanism of the medicine. The AMS formula has six parameters: total dose, frequency, period, unit score, unit dose, and follow-up days. A lower AMS suggests a better treatment efficacy.ConclusionThe program presented our experience in developing, pilot testing, and evaluating an electronic AIT platform, and future research would indicate whether the template could be made more time efficient in clinical practice.

To the Editor, Allergen sensitization occurs in most patients with asthma. Our previous article had demonstrated that house dust mite remained the most important allergen in Chinese individuals with asthma.1 A raised serum IgE against Aspergillus antigens usually occurred in bronchial asthma, especially a value ≥1000 IU/mL was recommended as the serum total IgE (tIgE) cut-off to diagnose Allergic bronchopulmonary aspergillosis (ABPA).2 Therefore, we aim to describe the prevalence of sensitization to common allergens among asthmatic patients with serum tIgE >1000 IU/mL, the extent to which allergy accounts for these individuals is controversial. We retrospectively analyzed the laboratory records of 1367 physician-diagnosed asthma patients at the Department of Allergy and Clinical Immunology and Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, who had serum IgE test with a battery of common allergens performed (ImmunoCAP, ThermoFisher) during a 5-year period from January, 2018 through October, 2024. All the patients analyzed had a blood tIgE level >1000 IU/mL. The allergens tested were house dust mite (Dermatophagoides pteronyssimus), grass pollen mix, food mix, cat, dog, Alternaria alternata, Aspergillus and Penicillium notatum. For patients who had multiple measurements performed during the study period, only the first time total serum IgE and specific IgE value were included for analysis. The criteria were excluded for patients with chronic obstructive pulmonary disease, helminth infection, rheumatic disease and tumors. This study was approved by the hospital ethics committee and the need for informed consent was waived. Our study showed that all the patients were sensitized to at least two allergens and 734 (53.7%) individuals sensitized to more than 5 allergens. Allergic multimorbidities were very commonly found in nearly 98% of all patients' allergies. Details about the baseline characteristics for patients are in Appendix S1. Dermatophagoides pteronyssimus (69.4%), Aspergillus fumigatus (29.7%), and cat (24.9%) were the three most common positive reactions in the tIgE >1000 individuals. Sensitization to inhalant allergens was significantly common (97.8%) as compared with food allergens (2.2%). The respective proportions for grass pollen, dog, A. alternata and P. notatum were 7.3%, 10.3%, 17.6% and 4.9% (Figure 1). In addition, a graded effect was observed with the serum tIgE level in these patients increasing with the number of positive allergens (r = 0.34, p = 0.047), and the D. pteronyssimus sIgE level (r = 0.52, p = 0.036). However, there was no statistically significant correlation between serum tIgE and Aspergillus sIgE level (Appendix S2). Levels of sIgE against the common allergens tested in a cohort of 1367 Chinese asthmatics. sIgE titers are expressed as kU/mL. The strength of IgE reactivity toward the specific allergens tested is categorized in classes from 0 to 6 according to ImmunoCAP standards as follows: class 0 (<0.35 kU/mL), class 1 (0.35–0.70 kU/mL), class 2 (0.70–3.50 kU/mL), class 3 (3.5–17.5 kU/mL), class 4 (17.5–50 kU/mL), class 5 (50–100 kU/mL), and class 6 (>100 kU/mL). The cutoff value was set at 0.35 kU/mL. The response was defined as positive if the sIgE level was ≥0.35 IU/mL. The species of the allergen source is listed below together with the rate of individuals positive for sIgE to each allergen tested. *The median sIgE titer including minimum (min) and maximum (max) is calculated for reactive individuals. sIgE, specific immunoglobulin E. Our study focused on whether a fungal allergy must be present in asthma with elevated tIgE, and found that both house dust mites and cat dander were strong sensitizers. We observed that the D. pteronyssimus was still a major perennial allergen source and a significant cause of allergic asthma even in the high tIgE individuals. Some research found that asthmatics with atopic eczema and more allergic multimorbidities would preferentially develop strong Th2 responses against common allergens, such as mite proteases and Fel d1,3, 4 then the Th2 response promotes massive IgE release by plasma cells. Our hospital was a tertiary center of Southern China, which had enriched population of asthmatic patients from nationwide. Though ABPA was well recognized in refractory asthma, the prevalence of ABPA among asthmatics with tIgE >1000 IU/mL was 29.7% in our cohort. This finding was consistent with a similar study demonstrating that compared to non-ABPA with a tIgE level >1000 IU/mL, the coexisting atopic diseases might influence the development of ABPA.5 Further large-scale studies across different geographic regions are warranted to validate our findings. In conclusion, the current study suggests that the possibility of other allergen cosensitization should be clinically considered besides Aspergillus sensitization in these patients. Wanjun Wang: Writing—original draft; validation; data curation. Lulu Wu: Methodology; investigation; formal analysis. Jing Li: Funding acquisition; project administration; supervision. Qiurong Hu: Conceptualization; resources; writing—review and editing. Wanjun Wang and Lulu Wu shared first authorship. Jing Li and Qiurong Hu contributed equally as corresponding authors. The authors thank Prof. Jing Li (Department of Allergy and Clinical Immunology, First Affiliated Hospital of Guangzhou Medical University) for writing assistance with this report. This study was partially supported by National Natural Science Foundation of China (82161138020), Major Project of Guangzhou National Laboratory, Grant No. GZNL2024A02002, Guangdong Innovation Team Project of General College and University (2023KCXTD024). Thanks to the Biobank for Respiratory Diseases in the National Clinical Research Center for Respiratory Disease (BRD-NCRCRD, Guangzhou, Southern China). The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Objective Oxidative stress is known to play a key role in the progression of asthma. The Oxidative Balance Score (OBS), derived from an analysis of diet and lifestyle choices, provides a measure of the body’s oxidative stress levels. This study aims to investigate the clinical relevance of OBS in asthma.Methods The study included National Health and Nutrition Examination Survey (NHANES) data from 10,038 individuals between the years 2007 and 2018. We assessed associations of asthma prevalence with the OBS, Dietary Oxidative Balance Score (DOBS), and Lifestyle Oxidative Balance Score (LOBS) using logistic regression and restricted cubic spline (RCS) analyses. Lung function was evaluated through correlation analysis. The Cox proportional hazards models were employed to assess all-cause and cardiovascular-specific mortality by OBS components. Subgroup and interaction analyses were conducted to examine heterogeneity and to validate the findings.Results After adjusting for confounders, higher OBS [OR = 0.98 (0.97, 0.99), p = 0.003], DOBS [OR = 0.99 (0.97, 0.99), p = 0.016], and LOBS [OR = 0.91 (0.87, 0.96), p < 0.001] were inversely associated with asthma prevalence. A nonlinear relationship was observed between OBS and asthma prevalence (p-for-nonlinear = 0.028). OBS showed positive correlations with lung function parameters, including FEV1 (r = 0.12, p < 0.001) and FEF25-75% (r = 0.06, p < 0.001). Additionally, higher OBS was associated with reduced risks of all-cause mortality [HR = 0.92 (0.89, 0.96), p < 0.001] and cardiovascular mortality [HR = 0.86 (0.80, 0.93), p < 0.001] in asthma individuals.Conclusion Our findings suggest that an antioxidant-rich diet and lifestyle may lower the risk of developing asthma and improve the prognosis for individuals with asthma.

BACKGROUND AND OBJECTIVE:Myeloid-derived suppressor cells (MDSCs) participate in the progression of many diseases including chronic lung diseases. However, whether MDSCs are accumulated in the lung and how MDSCs orchestrate the pulmonary microenvironment in bronchiectasis remains unknown. Here, we aim to test a hypothesis that PMN-MDSCs are accumulated in the lung and play a role in creating an airway immunosuppressive milieu, thereby relating to clinical outcomes in bronchiectasis. METHODS:Flow cytometry and immunofluorescence staining were performed for analysing the frequencies and presence of PMN-MDSCs, LOX-1+ neutrophils, and ARG-1+ PMN-MDSCs in PBMCs, sputum, and lung tissues. T-cell proliferation assays were established for evaluating the immunosuppressive activities of PMN-MDSCs. RNA sequencing was performed to investigate the underlying mechanism of PMN-MDSCs-mediated immunosuppression. The relationship of PMN-MDSCs with the time to next exacerbation and treatment response to antibiotic therapy was analysed. RESULTS:PMN-MDSCs are accumulated in the lung and blood in bronchiectasis patients compared to healthy individuals. The majority of neutrophils in the lung of bronchiectasis patients are LOX-1+ PMN-MDSCs. Mechanistically, PMN-MDSCs suppress T cell proliferation via secreting high levels of the enzyme arginase-1 (ARG-1). Notably, the frequencies of PMN-MDSCs in sputum negatively correlate with the time to next exacerbation in bronchiectasis patients. Additionally, antibiotic therapy dramatically decreases PMN-MDSCs frequencies in the airway of bronchiectasis patients. CONCLUSION:These findings suggest that PMN-MDSCs accumulate and establish an immunosuppressive microenvironment in the lung via ARG-1 in bronchiectasis, which is associated with clinical outcome and response to antibiotic treatment, highlighting a potential role of PMN-MDSCs in bronchiectasis progression.

Background Cough hypersensitivity is an important clinical and pathophysiologic feature of chronic cough, which involves chemical, mechanical, and thermal stimuli and sensory dysfunction. Currently, there is a need for a comprehensive method to evaluate cough hypersensitivity. Objective To develop and validate a questionnaire to assess the degree of cough hypersensitivity. Methods The initial items of the Cough Hypersensitivity Assessment Test (CHAT) were made based on a literature review, experts’ opinions, and clinical practice. Items were reduced after investigation involving patients with chronic cough. Dimensional allocation, internal reliability, test-retest reliability, construct validity, responsiveness, and cutoff value were determined in the final stage. Results The final version of CHAT on a 5-point Likert scale (0-4) includes 18 items consisting of three dimensions: environmental triggers, daily life triggers, and tussive symptoms, with total score ranging from 0 to 72. There was significant difference in CHAT-18 scores between patients and healthy controls (P < .001). Cronbach α for CHAT was 0.832 and intraclass correlation coefficient for CHAT was 0.884. Construct validity was demonstrated with a multitrait-multimethod matrix. There was good responsiveness after treatment. The cutoff value of CHAT was 18 for cough hypersensitivity. There was a mild to moderate correlation between capsaicin cough sensitivity and tussive symptoms and the total score of CHAT. Conclusions The CHAT comprehensively covers a range of cough triggers and shows robust internal reliability, test-retest reliability, construct validity, and responsiveness. This may be useful for measuring cough hypersensitivity.

Background:Allergic diseases are a growing health concern, with house dust mites being a prevalent allergen linked to various allergies. Rush subcutaneous immunotherapy (RIT) achieves maintenance dose rapidly but carries higher risks than conventional immunotherapy (CIT). The combination of Omalizumab with allergen immunotherapy (AIT) has been shown to improve AIT safety. This study investigates the safety of RIT combined with anti-immunoglobulin E (IgE) pretreatment. Methods:This retrospective analysis compared patients with allergic rhinitis and/or allergic asthma sensitive to dust mites who underwent RIT with anti-IgE pretreatment versus CIT at our facility from July 2022 to January 2024. We collected and analyzed demographic data, adverse events, and baseline metrics including visual analog scale scores, daily medication scores, allergic blood test outcomes, and lung function parameters. Results:Our study enrolled 50 patients in the RIT group and 60 in the CIT group. The RIT group demonstrated superior safety, with significantly fewer local adverse reactions during the up-dosing phase compared with CIT (P < 0.01). While systemic reactions were analogous between groups, the RIT group had a lower incidence of respiratory symptoms (P < 0.05). Logistic regression analysis established a predictive model for systemic reactions during up-dosing phase, with receiver operating characteristic analysis indicating its predictive accuracy exceeded that of individual factors (area under the curve = 0.815). Conclusion:RIT combined with anti-IgE pretreatment demonstrated low systemic adverse reaction rates and high safety. A combined visual analogue scale scores (VASs) and maximal mid-expiratory flow at 25%-75% prediction model was more accurate in forecasting systemic reactions than individual factor. Further research is required to determine its clinical utility.

Background:While much of the evidence linking the rapid urbanization and the increasing prevalence of allergen sensitization, but little is known regarding rural-to-urban migrants. The aim of this study was to identify the disparities in allergy, the gut microbiome and factors among native urban, migrating, and native rural Chinese. Methods:We redesigned the dataset of the China Alliance of Research on Respiratory Allergic Disease secondary survey, and after stratified sampling, a subsample of 2422 subjects were enrolled for the analysis of a questionnaire, skin prick tests (SPT), and specific immunoglobulin E (sIgE) titer measurements against 8 common allergens. Fecal microbiotal composition was also sequenced by 16S rRNA and regression-based analyses with covariate adjustment applied. Results:From urban to migrant and rural populations, IgE sensitization was predominantly directed against Dermatophagoides pteronyssinus (Der p). The titers of Der p-sIgE decreased sequentially across the 3 respective populations and co-sensitization to other allergens also showed a sequential decrease. Rural-to-urban migrants showed a low prevalence of Der p-SPT and Der p-sIgE initially, but developed substantial IgE titers and their gut microbiotal diversity, as well as species richness, appeared to change along with residential time spent in the urban area. High-fat diet, using a mattress, an SPT wheal size from Der p ≥ 6 mm, and duration of immigration >5 years were significantly associated with sIgE positivity in the migrants. Conclusion:The Der p-sIgE responses and the composition of gut microbiota differs synchronously with extended living time in an urban area. Studies in immigrants provide a unique opportunities to evaluate the effects of environmental factors in the pathogenesis of allergic disorders.

Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all P < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all P ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ (P = 0.051) and RSI (P = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.

Atopic dermatitis （AD） is a common chronic inflammatory skin disease characterized by dry skin， recurrent itching， and eczema-like lesions， which can significantly reduce the quality of life. In recent years， the global prevalence of AD has been increasing， with a particularly marked rise in China. Research has shown that air pollutants can damage the skin barrier through mechanisms like oxidative stress， thereby increasing the risk of AD. Various exposure factors， including diet and allergens， also significantly influence the onset and progression of AD through different mechanisms. Furthermore， psychological factors such as anxiety and stress can exacerbate AD through neuroendocrine regulation. Obesity is closely associated with AD， particularly among children and adolescents. Given the diversity of factors and mechanisms influencing AD， a comprehensive approach to primary prevention that considers multiple factors is warranted.

BACKGROUND:The allergenic relevance of the living environment changes over the last decades is largely unknown. OBJECTIVE:We aimed to compare the factors associated with asthma and/or rhinitis between 2008 and 2018. METHODS:We assessed two nationally representative cross-sectional datasets in 2008 and 2018. Within the rigorous protocol, questionnaire and serum IgE measurement were conducted in 2322 and 2353 patients with allergic asthma (A) and/or rhinitis (R) respectively. Multivariate logistic regression analysis was used to examine the effect of different factors on sensitization. RESULTS:The prevalence of sensitization increased in rhinitis alone (A-R+, 63% in 2008 vs. 67.7% in 2018, P = 0.039) and asthma with rhinitis (A+R+, 70.6% vs. 75.1%, P = 0.014). The common factors for sensitization were male sex, using mattress and air conditioner, family history of rhinitis, building age > 30 years, and meat consumption. Compared with 2008, secondhand smoke was an additional risk factor for A+R- (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.18-7.01) and A+R+ (OR 1.72, 95%CI 1.03-3.14), and the odds of farmland or forest for pollen and mold sensitization were higher in 2018 (OR 3.61, 95%CI 2.79-4.66, and OR 1.86, 95%CI 1.34-2.58). Eating fish was inversely associated with A-R+ (OR 0.68, 95%CI 0.52-0.91, P < 0.01), while older age also showed an inverse relationship with sensitization. The OR of age 25-44 years was higher in 2018. CONCLUSIONS:Repeated surveys showed variations in the factors affecting allergic asthma and/or rhinitis. The variable factors included age of 25-44 years, secondhand smoke, farmland, forest, and fish consumption.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Background The real-world study on efficacy and safety of dupilumab in chronic obstructive pulmonary disease (COPD)with type 2 inflammation are scarce. Our objective was to assess the impact of dupilumab in such patients within a real-world setting. Methods Seventeen patients with COPD and type 2 inflammation, who underwent triple inhaled therapy in conjunction with dupilumab from January 2020 to October 2023, comprised the research group. Similarly, another 17 patients with COPD and type 2 inflammation, who received only triple inhaled therapy, were included in the control group. After a six-month treatment period, pulmonary function tests, type 2 inflammatory marker levels, and quality of life assessments were compared between the two groups to evaluate the effectiveness of dupilumab in combination with triple inhaled therapy for COPD with type 2 inflammation. Results Following treatment, the research group exhibited significant improvements in forced expiratory volume in one second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FVC) compared to the control group (P < 0.05). Notably, the FEV1 and FVC values of the research group were also notably superior to those of the control group post-treatment (P < 0.05). Additionally, the research group demonstrated a statistically significant enhancement in COPD Assessment Test scores after treatment (P < 0.05). Conclusion The combination of dupilumab with triple inhaled therapy has been shown to enhance pulmonary function, decrease immunoglobulin E levels, manage airway inflammation, and elevate the quality of life of patients with COPD and type 2 inflammation.

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multivariable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6‐2.4) to 0.4 (0.2‐0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0‐1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8‐22.5 mg/day) to 2.5 mg/day (0.0‐10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm 3 [300‐815 cells/mm 3 ] versus 560 cells/mm 3 [220‐938 cells/mm 3 ], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286‐43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25‐50 ppb (OR 35.038 [95% CI, 3.104‐395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697‐0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders.

Background:Sanfeng Tongqiao Diwan has shown the potential to alleviate acute, recurrent, and chronic rhinitis in adults based on available studies. However, the evidence for its application in upper airway cough syndrome (UACS) is unclear. The purpose of this study was thus to investigate the efficacy and safety of Sanfeng Tongqiao Diwan in the treatment of UACS. Methods:This was a single-center, randomized, double-blind, placebo-controlled clinical trial. A total of 60 patients who satisfied the inclusion criteria were randomly divided into experimental and placebo groups in a 1:1 ratio. The experimental group was given Sanfeng Tongqiao Diwan, and the placebo group was given a simulant for 14 consecutive days. The follow-up period was 15 days. The primary outcome was the total effective rate. The secondary outcomes included clinical efficacy, Visual Analogue Scale (VAS) of related symptoms, and Leicester Cough Questionnaire in Mandarin-Chinese (LCQ-MC) scores before and after the treatment. Additionally, the safety was also evaluated. Results:The total effective rate in the experimental group was 86.6% (26/30), which was significantly higher than the 7.1% (2/28) in the placebo group (difference 79.6; 95% CI: 57.0 to 89.1; P<0.001). Nasal congestion, runny nose, cough, postnasal drip, and overall symptoms in the experimental group were significantly lower than those in the placebo group after treatment (3.7±1.5 vs. 5.0±1.1, 3.6±1.3 vs. 5.9±1.1, 3.8±1.2 vs. 6.8±1.3, 3.5±1.4 vs. 6.1±1.5, 3.8±2.0 vs. 7.3±1.4, respectively; all P values <0.001). After treatment, the LCQ-MC score in the experimental group was significantly higher than that in the placebo group (all P values <0.001). The blood eosinophil count in the placebo group was significantly higher after treatment than before treatment (P=0.037). No abnormalities were found in liver or renal indicators during the treatment period in the 2 groups, and no adverse reactions occurred. Conclusions:Sanfeng Tongqiao Diwan improved the symptoms and living quality of patients with UACS and showed acceptable safety. The results of this trial represent rigorous clinical evidence for the application of Sanfeng Tongqiao Diwan and further support a new option in UACS treatment. Trial Registration:Chinese Clinical Trial Registry ChiCTR2300069302.