Xing Gong,1,* Li Wei,1,* Yunshu Xu,2 Changdi Xu,3 Yi Zhang,1 Fengxia Sun,1 Man Tian,3 Liya Wang,4 Hengxue Wang,5 Ming Ge,1 Feng Liu,3 Lilin Xiong,1 Wei Pan61Department of Environment Health Promotion, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3Department of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Physical and Chemical Inspection, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 5Department of Acute Infectious Diseases Control and Prevention, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 6Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lilin Xiong, Department of Environment Health Promotion, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China, Email hzxionglilin@163.com Wei Pan, Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China, Email panwei303303@sina.comPurpose: Extreme cold exposure may trigger respiratory morbidity in children, but whether concurrent ambient air pollution modifies cold-related risks of pediatric asthma remains unclear. This study evaluated associations between extreme cold events and pediatric asthma outpatient visits and assessed whether these associations differed according to ambient pollutant concentrations.Patients and methods: We conducted a time-series study of 62,167 pediatric asthma outpatient visits among children diagnosed with asthma at a tertiary children’s hospital in Nanjing, China, from 2019 to 2024. Daily asthma visits were linked with meteorological variables and ambient concentrations of PM10, PM2.5, NO2, SO2, CO, and O3. Extreme cold events were defined as ≥ 2, ≥ 3, or ≥ 4 consecutive days with daily mean temperature ≤ 4.5°C (the 10th percentile of the study-period distribution). Quasi-Poisson distributed-lag non-linear models were used to estimate cumulative relative risks over lag 0– 14 days. Pollutant-related effect modification was evaluated using stratified analyses and interaction measures.Results: Overall, extreme cold events were not significantly associated with pediatric asthma outpatient visits. However, stronger associations were observed during periods with higher CO and SO2 concentrations. For lag 0– 14 days, cumulative relative risks for ≥ 2-day cold events were 2.60 (95% CI: 1.13– 5.95) in the higher-CO stratum and 3.41 (95% CI: 1.15– 10.11) in the higher-SO2 stratum. Similar patterns were observed for longer cold-event definitions. Multiplicative interactions were identified for both CO and SO2, whereas additive interaction evidence was clearer for CO. Other pollutants showed less consistent modification patterns.Conclusion: The association between extreme cold events and pediatric asthma outpatient visits may depend on concurrent gaseous pollutant conditions. Relatively elevated CO and SO2 may help identify cold-event periods with greater pediatric asthma outpatient burden.Keywords: pediatric asthma outpatient visits, extreme cold events, ambient air pollutants, distributed-lag non-linear models, effect modification
Chun-Tse Hung,1 Chen-Yen An,2 Chi-Won Suk,3 Ting-Wei Lee,4,5 Shun-Hsing Hung61Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 2Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan; 3Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Division of Urology, Department of Surgery, Chi Mei Hospital, Chiali, Tainan, TaiwanCorrespondence: Chun-Tse Hung, Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, 1007 E. Huron St, Ann Arbor, MI, 48104, USA, Email chuntseh@umich.eduBackground: While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise in improving respiratory outcomes, the comparative effectiveness of dual glucose-dependent insulinotropic polypeptide/GLP-1 RA versus GLP-1 RA alone remains unclear.Objective: To assess the association of tirzepatide versus semaglutide with the risk of asthma exacerbation among patients with asthma and type 2 diabetes (T2D).Methods: Data from the TriNetX US Collaborative Network were used. Adults with asthma and T2D who initiated tirzepatide or semaglutide between June 01, 2022, and December 31, 2024, were included. The study period ended on December 1, 2025. The primary outcome was time to first asthma exacerbation over a 12-month follow-up. Secondary outcomes included systemic corticosteroid and short-acting beta-agonist (SABA) use. Propensity score matching was used to balance baseline covariates. Kaplan-Meier curves and Cox regression models were used to estimate comparative effectiveness.Results: After 1:1 matching, 8176 patients were included in each group. The risk of asthma exacerbation was similar between tirzepatide and semaglutide (11.0% vs 11.1%; HR, 1.00; 95% CI, 0.91– 1.10). This finding remained consistent across sensitivity and subgroup analyses. For secondary outcomes, tirzepatide was associated with a lower risk of SABA use (HR, 0.92; 95% CI, 0.88– 0.96) and a similar risk of systemic corticosteroid use (HR, 1.01; 95% CI, 0.96– 1.05) compared with semaglutide.Conclusion: Among patients with asthma and T2D, no difference in the risk of asthma exacerbation between tirzepatide and semaglutide was observed. Further investigation through randomized controlled trials is warranted to clarify the potential role of GLP-1 RA-based therapies in patients with asthma and T2D.Keywords: asthma, asthma exacerbation, type 2 diabetes, glucagon-like peptide-1 receptor agonist, glucose-dependent insulinotropic polypeptide, tirzepatide, semaglutide, real-world evidence
Purpose:The study aimed to evaluate differences in cough variant asthma (CVA) management and physician-reported pulmonary function testing resources across hospital tiers in Zhejiang, China. Methods:From October 12 to November 15, 2025, a cross-sectional online questionnaire survey was conducted among physicians engaged in respiratory or chronic cough care in Zhejiang, China. The survey assessed physicians' knowledge of CVA diagnosis and treatment, awareness of prognosis, and reported access to pulmonary function testing resources. Responses were compared across hospital tiers. Results:A total of 550 submitted questionnaires were received, and 522 valid responses were included after data cleaning. Physicians in tertiary hospitals were most accurate in diagnosing CVA according to guideline criteria (85.79%), compared with those in secondary (70.59%) and primary hospitals (51.53%). Reported access to key tests, especially bronchial provocation testing, was lower in secondary and primary hospitals. The proportion of physicians who intended to use bronchial provocation testing exceeded the proportion who actually performed it (41.57% vs 23.75%). For initial treatment, 91.05% of tertiary hospital physicians selected inhaled corticosteroids (ICS) combined with long-acting beta2 agonists (LABA). This was significantly higher than the proportions in secondary and primary hospitals (69.12% and 37.24%, respectively). Physicians in tertiary hospitals also showed greater awareness of CVA prognosis. Conclusion:Clear differences exist in CVA care across hospital tiers in Zhejiang, China. Lower-tier hospitals showed gaps in diagnosis, access to bronchial provocation testing, and ICS/LABA selection. In addition, the gap between intended and performed use of bronchial provocation testing may reflect a potential barrier to objective CVA diagnosis.
Jiangying Guo,1,* Xi Zhang,1,* Jianxing Lai,1,* Jian Wang,2 Linfeng Shen,2 Yonghong Zhong,2 Huaqiong Huang11Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zhejiang University School of Medicine Second Affiliated Hospital Linping Campus, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huaqiong Huang, Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 15005818703, Email zr_hhq@zju.edu.cnPurpose: The study aimed to evaluate differences in cough variant asthma (CVA) management and physician-reported pulmonary function testing resources across hospital tiers in Zhejiang, China.Methods: From October 12 to November 15, 2025, a cross-sectional online questionnaire survey was conducted among physicians engaged in respiratory or chronic cough care in Zhejiang, China. The survey assessed physicians’ knowledge of CVA diagnosis and treatment, awareness of prognosis, and reported access to pulmonary function testing resources. Responses were compared across hospital tiers.Results: A total of 550 submitted questionnaires were received, and 522 valid responses were included after data cleaning. Physicians in tertiary hospitals were most accurate in diagnosing CVA according to guideline criteria (85.79%), compared with those in secondary (70.59%) and primary hospitals (51.53%). Reported access to key tests, especially bronchial provocation testing, was lower in secondary and primary hospitals. The proportion of physicians who intended to use bronchial provocation testing exceeded the proportion who actually performed it (41.57% vs 23.75%). For initial treatment, 91.05% of tertiary hospital physicians selected inhaled corticosteroids (ICS) combined with long-acting beta2 agonists (LABA). This was significantly higher than the proportions in secondary and primary hospitals (69.12% and 37.24%, respectively). Physicians in tertiary hospitals also showed greater awareness of CVA prognosis.Conclusion: Clear differences exist in CVA care across hospital tiers in Zhejiang, China. Lower-tier hospitals showed gaps in diagnosis, access to bronchial provocation testing, and ICS/LABA selection. In addition, the gap between intended and performed use of bronchial provocation testing may reflect a potential barrier to objective CVA diagnosis.Keywords: cough variant asthma, chronic cough, pulmonary function test, hospital tiers, guideline adherence, clinical practice
Background:Acute urticaria (AU) is common and often considered self-limiting in children; however, a subset may progress to chronic spontaneous urticaria (CSU) or develop recurrent AU. Clinical characteristics associated with these unfavorable outcomes remain poorly characterized. Methods:In this single-center retrospective cohort study, 475 children (<18 years) with AU presenting to dermatology settings were included. Demographic, clinical, and laboratory data were extracted from electronic medical records. Personal and family histories of atopy were confirmed, and 1-year outcomes were assessed via structured telephone follow-up. Independent risk factors were identified using Firth penalized multivariable logistic regression. Results:Follow-up was completed for 358 of 475 (75.4%) patients. Median age was 4.25 years, with 51% being male. At 1 year, 50 patients (14.0%) progressed to CSU and 37 patients (10.3%) experienced recurrent AU. Firth penalized multivariable analysis identified non-first-episode presentation (CSU: aOR 7.89, 95% CI 3.54-17.92; recurrent AU: aOR 6.73, 95% CI 2.57-17.31) and family history of CSU (CSU: aOR 4.35, 95% CI 1.27-13.65; recurrent AU: aOR 8.85, 95% CI 2.76-27.19) as independent predictors of both adverse outcomes. Family history of asthma was associated with CSU progression (aOR 32.26, 95% CI 1.67-477.76), and family history of chronic inducible urticaria was associated with recurrent AU (aOR 9.07, 95% CI 2.02-40.99); however, these estimates were imprecise because of small exposed case numbers. Notably, systemic corticosteroid use was not independently associated with either adverse outcome. Conclusion:Recurrent AU, in addition to CSU progression, is an important 1-year outcome after pediatric AU. Non-first-episode AU and family history of CSU are readily ascertainable predictors that enable early risk stratification and follow-up. The single-center retrospective design and loss to follow-up should be considered when interpreting the generalizability of these findings.
Lina HM Ahmed,1 Safa Noor,1 Mohannad N AbuHaweeleh,2 Harshita Shailesh,1 Antonisamy Belavendra,1 Haneen Aldulaimi,2 Amal Al-Naimi,3 Ibrahim Janahi1,3,41Department of Medical Services, Sidra Medicine, Doha, Qatar; 2College of Medicine, Qatar University, Doha, Qatar; 3Department of Pediatric Pulmonology, Sidra Medicine, Doha, Qatar; 4Clinical Pediatrics, Weill Cornel Medicine–Qatar (WCM-Q), Doha, QatarCorrespondence: Ibrahim Janahi, Department of Pediatric Pulmonology, Sidra Medicine, P.O. Box. 26999, Doha, Qatar, Email ijanahi@sidra.orgBackground: Childhood asthma, obesity, and vitamin D deficiency are all highly prevalent in Qatar, and children with concurrent asthma and obesity experience greater disease severity and poorer treatment response than those with asthma alone. Although vitamin D deficiency has been linked to asthma, the combined effect of co-existing asthma and overweight/obesity on vitamin D status has not been characterized in this population, warranting further investigation.Methods: This cross-sectional observational study assessed serum 25-hydroxyvitamin D levels in children aged 6– 17 years, residing in Qatar. A total of 364 children were divided into four groups: children with normal weight and asthma (NW-A), children with overweight/obesity and asthma (OO-A), children with overweight/obesity and no asthma (OO), and children with normal weight and no asthma (NW). Between-group differences were assessed using chi-square, Dunn (Bonferroni-corrected), and Spearman correlation tests, and a multivariable logistic regression model adjusted for age, sex, BMI, and atopy was used to examine the association between asthma and vitamin D status.Results: Children in all the four groups demonstrated a high prevalence of vitamin D deficiency (< 50 nmol/L), regardless of asthma or BMI. Vitamin D deficiency was present in 81.1% of OO, 73.9% OO-A, 68.3% of NW, and 66.3% of NW-A, with no statistically significant difference across groups. Vitamin D levels were similar between NW-A and OO-A, but OO group had significantly lower levels. A negative correlation between BMI and vitamin D levels was observed in OO-A (ρ=– 0.279, p=0.008) and OO (ρ=– 0.266, p=0.009), but not in normal-weight children. Multivariable logistic regression showed no significant association between vitamin D levels and asthma status.Conclusion: Higher BMI was associated with lower serum vitamin D levels in overweight/obese children, independent of asthma status, whereas asthma was not independently associated with vitamin D deficiency. Given the cross-sectional design, these findings indicate associations rather than causal relationships. The high prevalence of vitamin D deficiency across all study groups highlights a substantial public-health concern and supports the value of routine screening, nutritional and lifestyle measures, and where indicated, vitamin D supplementation, in pediatric health management in Qatar, pending confirmation from longitudinal and interventional studies.Keywords: 25‑hydroxy vitamin D, body mass index, childhood asthma, pediatric
Hai-Ling Yang, Ya-Jia Chen, Xue-Qiong Mai, Xiao-Ling Zou, Wenwen Ding, Shao-Zhu WuDepartment of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shao-Zhu Wu, Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, Email shaozhuwu@163.comAbstract: Biologics have revolutionized the treatment of severe asthma, yet their clinical efficacy assessment has focused primarily on exacerbation reduction and symptom control, often overlooking the comprehensive evaluation of lung function improvement. Traditionally, forced expiratory volume in one second (FEV1) has been the cornerstone metric for assessing airflow limitation. However, accumulating evidence highlights small airway dysfunction (SAD) as a critical driver of asthma symptoms, exacerbation risk, and heterogeneity in treatment response. This review explores the existing tools and metrics and their clinical relevance for assessing the impact of biologics on lung function, with a particular emphasis on small airway function in asthma patients. Methodologically, we appraise the physiological validity, repeatability, feasibility, responsiveness, and current regulatory readiness of small-airway endpoints for biologic trials and real-world effectiveness studies. We propose that these measures complement, rather than replace, FEV1 within a multidimensional endpoint framework. We explore the application of techniques ranging from conventional spirometry (FEV1, FEF25–75, ie, forced expiratory flow at 25– 75% of forced vital capacity) to more advanced methods such as impulse oscillometry (IOS), body plethysmography, multiple-breath nitrogen washout (MBNW), and novel imaging modalities. Our analysis reveals the differences in the effects of various biologics (anti-IgE, anti-IL-5/5Rα, anti-IL-4Rα, anti-TSLP, etc.). on large and small airways. Furthermore, we also discuss the methodological frameworks, challenges, and future directions for integrating small airway function assessment into both clinical trial design and real-world effectiveness evaluations.Keywords: asthma, biologics, small airway dysfunction, lung function, FEV1, impulse oscillometry, methodology, efficacy evaluation
Purpose:Asthma is a heterogeneous disease, and identifying phenotypes associated with an increased exacerbation burden is clinically important. Preserved ratio impaired spirometry (PRISm) has been linked to adverse health outcomes; however, its clinical impact on asthma remains incompletely defined. The aim of this study was to determine whether asthma with PRISm represents a distinct clinical phenotype characterised by an increased exacerbation burden. Patients and Methods:We retrospectively analysed data from 1,411 adult patients with asthma. The patients were categorised into three groups according to %FEV1 and FEV1/FVC: control (n=1102), PRISm (n=133), and airflow obstruction groups (n=176). Clinical characteristics and asthma exacerbation profiles were compared among the groups. Results:Age, sex, smoking status, and body mas index (BMI) significantly differed among the groups. The PRISm group had a significantly higher frequency of severe acute exacerbations than the control group, whereas no significant difference was observed between the PRISm and airflow obstruction groups. Severe asthma was more frequent in the PRISm group than in the control group, but its frequency was comparable between the PRISm and airflow obstruction groups. In multinomial logistic regression analysis, relative to the control group, the PRISm group was characterised by higher BMI (1.08 (1.03-1.13), adjusted odds ratio (95% confidence interval)), longer asthma duration (1.02 (1.00-1.03)), and higher severe acute exacerbation (2.31 (1.46-3.64)). Relative to the airflow obstruction group, the PRISm group was characterised by higher BMI (1.15 (1.07-1.24)) and shorter asthma duration (0.97 (0.96-0.99)), while the frequency of severe acute exacerbations (1.39 (0.78-2.48)) did not differ significantly between them. Conclusion:Asthma with PRISm may represent a distinct and clinically relevant phenotype associated with a substantial exacerbation burden. Its clinical importance lies not merely in its spirometric profile, but in the identification of a subgroup of patients who may require closer surveillance and earlier optimisation of management.
Eosinophils are key immunopathological cells in respiratory diseases and contribute to airway inflammation, tissue remodeling, and disease heterogeneity. Although eosinophils have traditionally been regarded as biomarkers of type 2 inflammation, increasing evidence indicates that they also function as active mediators of lung function impairment in selected respiratory diseases, including chronic obstructive pulmonary disease, asthma, and eosinophilic pneumonia. These disorders were selected because they represent distinct yet complementary models of eosinophil-associated airway and parenchymal injury, allowing comparison of shared and disease-specific mechanisms. Mechanistically, eosinophils impair lung function through the coordinated release of cytotoxic granule proteins, reactive oxygen species, lipid mediators, and cytokines, while interacting with epithelial, immune, and structural cells to amplify inflammation, airway remodeling, and tissue injury. These advances have improved understanding of eosinophil biology and facilitated the development of clinically relevant biomarkers and targeted therapies. Blood and sputum eosinophil counts remain the most widely used biomarkers, whereas emerging biomarkers, including eosinophil-derived neurotoxin, may further improve disease stratification and treatment monitoring. Biologics targeting interleukin-5 and its receptor have demonstrated therapeutic benefit in selected eosinophilic respiratory diseases, although treatment responses differ among disease phenotypes. This review summarizes current evidence regarding the molecular mechanisms linking eosinophils to lung function impairment, discusses the evolving role of eosinophils as both biomarkers and pathogenic drivers, and highlights the biomarker and therapeutic implications for precision management of respiratory diseases.
Purpose:To assess the effects of IL-5 pathway inhibition with mepolizumab or benralizumab on circulating eosinophil-related and selected remodeling-associated biomarkers in severe eosinophilic asthma (SEA), and to determine whether these profiles differ according to four-component study-defined early clinical remission (ECR) status. Patients and Methods:This prospective, observational, single-center cohort study included 30 adults with SEA treated with mepolizumab or benralizumab. Clinical assessment, spirometry, and blood sampling were performed at baseline and after 6 months. The primary endpoint was change in circulating biomarker concentrations; secondary endpoints included clinical improvement and ECR rate. Results:IL-5 pathway inhibition improved asthma control and lung function, with OCS-treated exacerbations occurring in 4 of 30 patients during follow-up. These changes were accompanied by marked reductions in eosinophil-related biomarkers, with median decreases of 95.3% in blood eosinophils, 79.5% in eosinophil-derived neurotoxin, and 32.9% in galectin-10, respectively; false discovery rate (FDR)-adjusted p≤0.003. Significant but smaller decreases were observed in MMP-10, TGF-β1, and TGF-β2, with median reductions of 5.0%, 21.2%, and 10.9%, respectively; FDR-adjusted p≤0.002. No significant group-level changes were observed for eotaxin-1, MMP-9, TIMP-1, fibulin-1, tenascin-C, or periostin. ECR was achieved in 16 of 30 patients (53.3%). Compared with non-ECR patients, those achieving ECR had lower baseline OCS burden and fewer relevant comorbidities, whereas neither baseline biomarker concentrations nor 6-month biomarker changes differed significantly between groups. Exploratory comparisons did not show consistent differences in clinical outcomes or biomarker changes between mepolizumab and benralizumab. Conclusion:IL-5 pathway inhibition in SEA was associated with marked suppression of eosinophil-related biomarkers, more selective changes in remodeling-associated mediators, and meaningful clinical benefit after 6 months. Similar biomarker responses in patients with and without ECR should be interpreted cautiously, but suggest that incomplete clinical response may reflect broader disease burden, particularly comorbidities, rather than insufficient suppression of eosinophilic inflammation alone.
This narrative review comprehensively elaborates the complicated interleukin (IL)-macrophage polarization axis as the core pathogenesis of allergic rhinitis (AR), focusing on layered molecular regulatory mechanisms covering inflammatory signaling, metabolic reprogramming and epigenetic modulation. Pro-inflammatory IL-1β, IL-6, IL-17 and TNF-α bind to TLR receptors to activate NF-κB, NLRP3 inflammasome and PI3K/Akt cascades, triggering M1 macrophage overactivation and acute nasal congestion, rhinorrhea via robust inflammatory mediator release. By contrast, anti-inflammatory IL-4 and IL-10 predominantly activate STAT6 signaling to drive abnormal M2 macrophage accumulation, sustaining persistent type 2 inflammation and irreversible nasal tissue remodeling; notably, IL-17 presents concentration-dependent bidirectional regulation on macrophage phenotypes. Metabolic reprogramming featured with glycolysis-oxidative phosphorylation switch, together with DNA methylation, histone modification and non-cRNA-mediated epigenetic regulation, serve as vital downstream executors linking IL signals to macrophage polarization imbalance. Conventional glucocorticoids, antihistamines and monoclonal antibodies including omalizumab and dupilumab (targeting IL-4Rα) exert therapeutic efficacy via intervening this axis, while multiple natural herbal constituents and classic TCM formulas also modulate relevant inflammatory pathways to alleviate AR symptoms. For translational application, the CD206/CD86 macrophage polarization ratio is highlighted as a representative candidate biomarker for disease severity assessment. Collectively, this review integrates multi-layered regulatory evidence and lays theoretical support for developing novel precision-targeted anti-allergic therapies.
Purpose:Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods:This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV1) or percent predicted peak expiratory flow rate (ppPEFR) ≥80%, and no long-term oral corticosteroid (LTOCS) use. Results:A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤0.001), no exacerbations (p<0.001), well- or partly controlled asthma (p=0.047), a ppFEV1 or ppPEFR ≥80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion:Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.
Background:Allergic rhinitis (AR) is a prevalent condition characterized by an immunoglobulin E (IgE)-mediated immune response. T follicular helper (TFH) cells regulate B-cell differentiation and antibody production, and circulating TFH2 cells are closely associated with type 2 humoral immunity and IgE-related responses in AR. However, whether AR is marked by isolated TFH2 expansion or broader remodeling of circulating TFH (cTFH) subsets, including TFH1-related heterogeneity, remains unclear. Methods:A total of 56 participants were enrolled, including 39 patients with AR and 17 healthy controls (HC). Flow cytometry was performed in 36 patients with AR and 14 HC to quantify cTFH subsets and activation states. Single-cell RNA sequencing (scRNA-seq) was conducted in an independent exploratory cohort comprising 3 patients with AR and 3 HC to characterize TFH transcriptional heterogeneity, based on canonical transcriptional programs. Results:Flow cytometry demonstrated that cTFH2 cell frequencies were significantly increased in patients with AR and positively correlated with disease severity. Activated CCR7^low PD-1^high cTFH cells were also elevated, indicating enhanced TFH activation. Further scRNA-seq analysis identified six transcriptionally distinct TFH clusters, with TFH2-like transcriptional signatures enriched in patients with AR, consistent with flow cytometric findings. Notably, a GZMK+ TFH1 subset, enriched in cytotoxic genes, including GZMK, CCL5, and GZMA, was more abundant in patients with AR, a result corroborated by flow cytometry. Conclusion:This study demonstrates the expansion of cTFH2 and GZMK+ TFH1 subsets in patients with AR and highlights the phenotypic and transcriptional heterogeneity of cTFH cells. These findings suggest that peripheral TFH profiling may aid in characterizing systemic immune alterations in allergic inflammation. The scRNA-seq results should be interpreted as exploratory due to the limited sample size.
Background:CYP4V2 is involved in lipid metabolism, but its contribution to asthma is poorly understood. This study aimed to investigate genetic polymorphisms and regulatory features of CYP4V2 in asthma development. Methods:We performed an integrative multi-omics analysis combining transcriptomic, genetic, and epigenetic data from peripheral blood mononuclear cells (PBMCs) of individuals in the Singapore/Malaysia Cross-Sectional Genetics and Epidemiological Study (SMCSGES) cohort. The influence of CYP4V2 expression on asthma risk and expression of genes involved in arachidonic acid (AA) pathway were evaluated, followed by expression quantitative trait locus (eQTL) analysis to identify regulatory variants. DNA methylation analyses were conducted to assess epigenetic regulation of CYP4V2, and promoter reporter assays were used to functionally validate candidate regulatory CpG sites. Results:The upregulation of CYP4V2 in PBMCs was associated with an increased risk of asthma and inversely associated with PTGER2 and ALOX5AP in the AA pathway. The SNP rs2276921 was identified as the only expression quantitative trait locus (eQTL) associated with both increased CYP4V2 expression and asthma risk (FDR-adjusted p < 0.05; OR = 1.24, 95% CI = 1.10-1.40). The minor allele G of rs2276921 was associated with low methylation at cg23232844 (p = 3.94 × 10-3) and cg11969330 (p = 4.25 × 10-2), located in the promoters of the protein-coding and non-coding CYP4V2 isoforms respectively. Promoter assays indicated that these two CpG sites inhibited CYP4V2 expression, supporting the regulatory effect of rs2276921 on CYP4V2 expression may be mediated through methylation. Conclusion:This study identified rs2276921 and CpG sites cg23232844 and cg11969330 that regulate CYP4V2 expression. CYP4V2 potentially modulates the AA metabolism and contributes to asthma susceptibility. These findings suggest CYP4V2 as a potential biomarker and therapeutic target in asthma.
Purpose:Yinqiao powder (YQP) is a traditional Chinese medicine formula that has been widely used clinically to treat infectious diseases such as respiratory tract infections, influenza, and pneumonia, exhibiting anti-inflammatory and antiviral properties. This study aimed to investigate its therapeutic potential for atopic dermatitis (AD) and to identify its key target genes and active components. Methods:We performed mRNA transcriptome sequencing on blood samples collected from 15 adult patients with AD and 15 adult healthy controls. Potential targets were identified by intersecting differentially expressed genes (DEGs) with known YQP target genes. Key genes were pinpointed using protein-protein interaction networks and receiver operating characteristic (ROC) curve analysis. We estimated immune cell proportions, constructed regulatory networks, and used molecular docking to predict active ingredients. Single-cell RNA sequencing data (GSE180885) was also analyzed to identify key cell types and track gene expression. Results:Fifty-two potential target genes were identified. From these, four key genes-CTNNB1, ERBB2, TP53, and HIF1A-were highlighted, potentially involved in carbon metabolism and organelle biosynthesis. A nomogram model based on these genes showed strong predictive power for AD. Immune analysis linked resting CD4+ memory T cells with TP53 and HIF1A. Molecular docking suggested beta-carotene, aloe-emodin, and quercetin as potential active ingredients binding to these key targets. Single-cell analysis identified keratinocytes as a key population, with key gene expression varying during their differentiation. Conclusion:This study indicates that CTNNB1, ERBB2, TP53, and HIF1A are key targets of YQP in AD treatment, with beta-carotene, aloe-emodin, and quercetin as likely active components. These findings provide a theoretical basis for using YQP in AD therapy.
Wang Chun Kwok,1,* Lu Zhou,2,* Ting Fung Ma,2 Raymond Yau Hang Leung,1 Terence Chi Chun Tam,1 James CM Ho11Department of Medicine, The University of Hong Kong, Hong Kong SAR, People’s Republic of China; 2Department of Statistics, University of South Carolina, Columbia, SC, USA*These authors contributed equally to this workCorrespondence: James CM Ho, Department of Medicine, The University of Hong Kong, 4/F, Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, People’s Republic of China, Tel +852 2255 4999, Email jhocm@hku.hkBackground: Co-existing asthma and diabetes mellitus (DM) are common, and there has been a debate on whether glucagon-like peptide-1 (GLP-1)-based therapies, such as GLP-1 receptor agonists (GLP-1RA) and inhibitors of dipeptidyl peptidase-4 (DPP-4i), confer benefits in these patients due to their anti-inflammatory effects in chronic inflammatory diseases.Methods: A territory-wide retrospective cohort study was conducted in Hong Kong among adult patients with co-existing asthma and DM to examine the impact of add-on GLP-1RA or DPP-4i on asthma exacerbations, ranging from mild exacerbations managed in outpatient settings to severe exacerbations requiring hospitalization. Adult patients were prescribed DPP-4i or GLP-1RA in year 2018 and for at least 6 months in Hospital Authority of Hong Kong were included. These patients were followed till 31st December 31, 2023. Propensity score matching was performed using optimal full matching, which is a sub-classification-based approach in which treated and control subjects are assigned to matched subclasses.Results: A total of 3295 patients with both asthma and DM, 3193 treated with DPP-4i and 102 treated with GLP-1RA, were included in the study. There were 1191 (36.1%) male patients with a mean age of 68.0 ± 14.2 years. There were 2531 (76.8%) patients with moderate-to-severe asthma according to Global Initiative for Asthma (GINA) Steps 3 to 5. GLP-1RA-treated patients had significantly lower risks of hospitalized asthma exacerbation (Average Treatment Effect on the Treated (ATT) Mean Ratio of 0.513, p < 0.001), ad hoc outpatient visits with OCS (ATT Mean Ratio of 0.343, p = 0.005), emergency visits (ATT Mean Ratio of 0.378, p = 0.009), and all asthma exacerbations (ATT Mean Ratio of 0.419, p < 0.001) compared with the DPP-4i group.Conclusion: GLP-1RA, compared with DPP-4i, as an add-on treatment for patients with co-existing DM and asthma was associated with a lower risk of asthma exacerbation. The use of GLP-1RA among diabetic patients with comorbid asthma may be considered though validation in clinical trials is needed.Keywords: acute exacerbation, asthma, GLP-1 receptor antagonist, DPP-4 inhibitor
Purpose:The distribution of allergens exhibits significant geographic variation. Local epidemiological studies are essential for understanding allergic sensitization patterns, which may inform regional epidemiological reference. This study aimed to investigate the sensitization patterns among a routinely screened population in Shenzhen, a coastal metropolis in southeastern China. Patients and Methods:A total of 18,777 participants undergoing routine health examinations were included. Serum-specific IgE (sIgE) levels against 19 allergens (10 inhalant and 9 food allergens) were measured using an immunoblot assay. The prevalence of sensitization was analyzed across gender, age groups, and seasons. Results:Among 18,777 participants, overall sIgE positivity was 24.4%. Inhalant allergens (21.7%) were more common than food allergens (6.7%). House dust mite (17.7%), crab (3.5%), cat dander (2.9%) and cockroach (2.7%) were the most prevalent. An 12-allergen panel was able to detected 99% of sensitized individuals in this population. Males showed significantly higher sensitization rates than females (P < 0.05). Inhalant sensitization decreased with age, whereas food sensitization remained relatively stable Seasonal variations were significant for tree, common ragweed, mutton, and house dust (all P < 0.05). Poly-sensitization was observed in 32.5% of sensitized individuals. Strong positive correlations formed four distinct allergen modules. Conclusion:House dust mite, crab, and cat dander are major allergens in Shenzhen. Sensitization patterns vary significantly by gender, age, and season. Seafood sensitization is more common in younger adults, while peanut sensitization increases in older adults.
Yoshihito Arimoto,1 Natsue Honda,1 Kosuke Haruki,1 Yasuo To,2,3 Masako To1,21Department of Laboratory Medicine, Dokkyo Medical University, Saitama Medical Center, Koshigaya, Saitama, Japan; 2Department of Allergy and Respiratory Medicine, The Fraternity Memorial Hospital, Sumida, Tokyo, Japan; 3Department of Pulmonary Medicine, International University of Health and Welfare Narita Hospital, Narita, Chiba, JapanCorrespondence: Masako To, Department of Laboratory Medicine, Dokkyo Medical University, Saitama Medical Center, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan, Email m-to@dokkyomed.ac.jpPurpose: Asthma is a heterogeneous disease, and identifying phenotypes associated with an increased exacerbation burden is clinically important. Preserved ratio impaired spirometry (PRISm) has been linked to adverse health outcomes; however, its clinical impact on asthma remains incompletely defined. The aim of this study was to determine whether asthma with PRISm represents a distinct clinical phenotype characterised by an increased exacerbation burden.Patients and Methods: We retrospectively analysed data from 1,411 adult patients with asthma. The patients were categorised into three groups according to %FEV1 and FEV1/FVC: control (n=1102), PRISm (n=133), and airflow obstruction groups (n=176). Clinical characteristics and asthma exacerbation profiles were compared among the groups.Results: Age, sex, smoking status, and body mas index (BMI) significantly differed among the groups. The PRISm group had a significantly higher frequency of severe acute exacerbations than the control group, whereas no significant difference was observed between the PRISm and airflow obstruction groups. Severe asthma was more frequent in the PRISm group than in the control group, but its frequency was comparable between the PRISm and airflow obstruction groups. In multinomial logistic regression analysis, relative to the control group, the PRISm group was characterised by higher BMI (1.08 (1.03– 1.13), adjusted odds ratio (95% confidence interval)), longer asthma duration (1.02 (1.00– 1.03)), and higher severe acute exacerbation (2.31 (1.46– 3.64)). Relative to the airflow obstruction group, the PRISm group was characterised by higher BMI (1.15 (1.07– 1.24)) and shorter asthma duration (0.97 (0.96– 0.99)), while the frequency of severe acute exacerbations (1.39 (0.78– 2.48)) did not differ significantly between them.Conclusion: Asthma with PRISm may represent a distinct and clinically relevant phenotype associated with a substantial exacerbation burden. Its clinical importance lies not merely in its spirometric profile, but in the identification of a subgroup of patients who may require closer surveillance and earlier optimisation of management.Keywords: asthma phenotype, acute exacerbation of asthma, obesity, preserved ratio impaired spirometry
