Allergy最新文献

{"title":"Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways","authors":"Hui Wen,&nbsp;Tessa Kole,&nbsp;Orestes A. Carpaij,&nbsp;Tatiana Karp,&nbsp;Victor Guryev,&nbsp;Alen Faiz,&nbsp;Kian Fan Chung,&nbsp;Pankaj Bhavsar,&nbsp;Ian M. Adcock,&nbsp;Salman Siddiqui,&nbsp;Andy Lan,&nbsp;Katie L. Raby,&nbsp;Nazanin Zounemat-Kermani,&nbsp;Chris Brightling,&nbsp;Dave Singh,&nbsp;Janwillem Kocks,&nbsp;Monica Kraft,&nbsp;Bianca Beghé,&nbsp;Klaus F. Rabe,&nbsp;Alberto Papi,&nbsp;Machteld N. Hylkema,&nbsp;Martijn C. Nawijn,&nbsp;Maarten van den Berge","doi":"10.1111/all.70283","DOIUrl":"10.1111/all.70283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Transcriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the “united airways” hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (<i>n</i> = 427).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3197-3205"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Asthma Remission a New Achievable Goal? A Review of the Current Drug-Related Evidence and Predictors","authors":"Fatma Esra Gunaydin,&nbsp;Giulia Marcassa,&nbsp;Bianca Olivieri,&nbsp;Gianenrico Senna,&nbsp;Marco Caminati","doi":"10.1111/all.70388","DOIUrl":"10.1111/all.70388","url":null,"abstract":"<p>Advances in asthma therapies have shown that clinical remission may be an achievable therapeutic goal for patients with asthma. This review discusses the current definitions of remission in asthma, the predictors of remission, airway inflammation/epithelial damage in asthma remission, airway remodeling, paradigms in defining remission and super-responders, remission criteria in severe asthma studies with biologics, and future perspectives. The terminology of asthma remission basically describes a high level of disease control, which includes the absence of symptoms and exacerbations, avoiding the use of oral corticosteroids and stability of lung function with/without continuation of treatment. Predictors associated with spontaneous remission include younger age at asthma onset, milder symptoms at diagnosis, male sex, and higher baseline lung function. Biologic therapies have shown considerable success in achieving remission in asthma; however, predictors of response to these therapies remain heterogeneous and are not consistently defined across studies.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3107-3129"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Airway Transcriptome in Type 2 Cytokine Biomarker-High and -Low Severe Asthma","authors":"Jiashu Shen,&nbsp;Rekha Chaudhuri,&nbsp;Stephen Bicknell,&nbsp;Adel H. Mansur,&nbsp;Rahul Shrimanker,&nbsp;Ian D. Pavord,&nbsp;Stephen J. Fowler,&nbsp;Vanessa Brown,&nbsp;Lorcan P. McGarvey,&nbsp;Peter H. Howarth,&nbsp;Sven-Erik Dahlén,&nbsp;Ian M. Adcock,&nbsp;Nazanin Zounemat-Kermani,&nbsp;Joseph R. Arron,&nbsp;Liam G. Heaney,&nbsp;David F. Choy,&nbsp;Timothy S. C. Hinks,&nbsp;Emanuele Marchi,&nbsp;Peter Bradding,&nbsp;the UK Medical Research Council Refractory Asthma Stratification programme (RASP-UK)","doi":"10.1111/all.70441","DOIUrl":"10.1111/all.70441","url":null,"abstract":"<p>Severe asthma is a heterogeneous disease. The mechanisms driving airway pathology when type 2 (T2) cytokine activity is suppressed remain poorly understood. This study aimed to provide insight by identifying the airway molecular pathways of T2 biomarker-high and -low severe asthma. We analysed clinical and transcriptomic data from bronchial biopsies and brushes in the UK Refractory Asthma Stratification Programme multi-centre severe asthma cohort (18 corticosteroid-resistant T2 biomarker-high [T2-high], 23 T2 biomarker-intermediate [T2-intermediate], 11 T2 biomarker-low [T2-low]) plus 20 healthy controls pre- and post-treatment with high-dose inhaled corticosteroids (ICS). Many genes dysregulated in asthma vs. health were concordantly dysregulated in healthy subjects receiving ICS. Severe asthma as a whole, independent of confounding by ICS, was characterised by upregulation of mucins, <i>CEACAM5</i>, typical T2-genes (<i>POSTN</i>, <i>CLCA1, CCL26</i>), epithelial mast cell genes, and <i>CPA4</i>. T2-high severe asthma demonstrated upregulated T2-dependent genes, epithelial barrier and keratin genes, adaptive immune responses, and impaired ciliary function. T2-low asthma showed upregulated Th1- and IL-17-associated genes (<i>IDO1</i>, <i>CXCL10</i>, <i>GBP1</i>, <i>LAG3</i>), interferon-γ signalling, neuroimmune pathways, airway smooth muscle-related genes, and neutrophil enrichment. T2-intermediate asthma exhibited a mixed molecular profile sharing features of T2-high and T2-low endotypes, with selective expression of the pathogen defence and antiviral response genes. The results were validated using bronchoscopy data from the U-BIOPRED Consortium. This study defines airway molecular endotypes of severe asthma associated with T2 biomarker high and low phenotypes, independent of corticosteroid effects. These findings offer insights for severe asthma management and the development of targeted biologic therapies.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3300-3317"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remission in Global Airway Diseases: EUFOREA Consensus Paper","authors":"J. Christian Virchow,&nbsp;Xander Bertels,&nbsp;Vibeke Backer,&nbsp;Benjamin S. Bleier,&nbsp;Marco Caminati,&nbsp;Diego M. Conti,&nbsp;Eugenio De Corso,&nbsp;Mina Gaga,&nbsp;Valerie J. Lund,&nbsp;Corrado Pelaia,&nbsp;Anju T. Peters,&nbsp;Glenis K. Scadding,&nbsp;Martin Wagenmann,&nbsp;Riyad O. Al-Lehebi,&nbsp;Guy G. Brusselle,&nbsp;Philippe Gevaert,&nbsp;Liam G. Heaney,&nbsp;Stella E. Lee,&nbsp;Florence Schleich,&nbsp;Frederik Trinkmann,&nbsp;Peter W. Hellings,&nbsp;Wytske J. Fokkens,&nbsp;Paola Rogliani","doi":"10.1111/all.70415","DOIUrl":"10.1111/all.70415","url":null,"abstract":"<p>The therapeutic goal in chronic airway diseases is shifting from symptom control to disease remission. Disease-modifying therapies, including biologics and allergen immunotherapy, have made remission achievable in patients with severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), or allergic rhinitis (AR). This EUFOREA consensus aims to establish practical guidance for inducing and maintaining remission in global airway diseases. An international panel of experts in pneumology, rhinology, and allergology convened in Rome (October 2025) to review current evidence and develop consensus statements. The panel achieved consensus on key principles: (i) remission is a therapeutic target independent of disease severity prior to treatment initiation and should not be reserved for severe cases; (ii) CRSwNP with nonallergic eosinophilic asthma, and AR with allergic asthma should be considered features of a single disease rather than comorbidities; (iii) remission should be assessed by each subspecialty separately while warranting combined approaches; (iv) pragmatic definitions prioritizing achievability and clinical utility are recommended; and (v) a 4-week recall window is preferred to assess symptom control within the evaluation of remission and a 12-month period is suggested as the minimal period to define remission. Remission represents an ambitious yet achievable goal, with practical guidance for optimizing patient outcomes.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3146-3156"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features of Cellular Senescence Pathways in Severe Asthma","authors":"Woo-Jung Song,&nbsp;Nazanin Zounemat Kermani,&nbsp;Ali Versi,&nbsp;Stephany Sánchez-Ovando,&nbsp;Jodie Louise Simpson,&nbsp;Peter A. Wark,&nbsp;Katherine Joanne Baines,&nbsp;Sven-Erik Dahlén,&nbsp;Ratko Djukanovic,&nbsp;Yike Guo,&nbsp;Ian M. Adcock,&nbsp;Kian Fan Chung,&nbsp;the U-BIOPRED Study Group","doi":"10.1111/all.70416","DOIUrl":"10.1111/all.70416","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Asthma severity increases with age, suggesting a role for accelerated biological ageing. We hypothesised that cellular senescence pathways such as the senescence-associated secretory pathway (SASP) and the p53-cellular senescence pathway are enriched in the airways of patients with severe asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilised transcriptomic data from the U-BIOPRED cohort to analyse enrichment scores (ES) of p53 and SASP pathways in different airway compartments using gene set variation analysis. Findings in bronchial biopsies were validated in the independent NOVA cohort. We examined associations between senescence ES, clinical parameters and other asthma-related gene signatures. Functional clusters of the SASP gene set were also explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the U-BIOPRED cohort, p53 and SASP ES were significantly elevated in bronchial biopsies of severe asthmatics compared to mild-to-moderate asthmatics and healthy volunteers, with SASP enrichment validated in the NOVA cohort. In bronchial biopsies, higher senescence ES correlated with frequent exacerbations, oral corticosteroid use, comorbid nasal polyps and lower FEV1%. No significant enrichment was found in other airway samples according to asthma severity. In nasal brushings, SASP ES was significantly higher in participants with comorbid nasal polyps. A distinct SASP functional cluster related to lung injury and repair (Cluster 2) was strongly associated with clinical severity and nasal polyps. Senescence signatures correlated positively with oxidative phosphorylation and macrophage activation signatures, but not with eosinophil signatures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Cellular senescence pathways are enriched in severe asthmatic bronchial tissues and correlate with disease severity, remodelling and nasal polyps. These findings warrant further investigation into their therapeutic implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>NCT01982162</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3273-3285"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Artificial Intelligence in Allergy, Asthma, and Immunology With Environmental Exposures","authors":"Thinh H. Nguyen,&nbsp;Cezmi A. Akdis,&nbsp;Andrea Baccarelli,&nbsp;Sudipto Banerjee,&nbsp;Rohan Tan Bhowmik,&nbsp;Brent Coull,&nbsp;Marissa L. Childs,&nbsp;Luigi Cao Pinna,&nbsp;Christopher D. Golden,&nbsp;Thomas Hartung,&nbsp;Benjamin Q. Huynh,&nbsp;Abhinav Kaushik,&nbsp;Oladimeji Mudele,&nbsp;Wanda Phipatanakul,&nbsp;Chirag J. Patel,&nbsp;Bernardo Sousa Pinto,&nbsp;John Quackenbush,&nbsp;Vanitha Sampath,&nbsp;Jaime Toney,&nbsp;Meiliu Wu,&nbsp;Michelle A. Williams,&nbsp;Marsha Wills-Karp,&nbsp;Mohamed H. Shamji,&nbsp;Kari C. Nadeau","doi":"10.1111/all.70401","DOIUrl":"10.1111/all.70401","url":null,"abstract":"<p>Artificial intelligence (AI) in environmental health science is revolutionizing data analysis and problem-solving approaches. These technologies facilitate the prediction of environmental exposures and disease outcomes and enable the identification of causal relationships for subsequent hypothesis testing. AI techniques improve pollution research through the analysis of satellite imagery and the modeling of pollutant dispersion, while AI advances chemical safety evaluations in toxicology by examining extensive datasets. AI is instrumental in addressing pressing environmental challenges, including remediation of polluted sites and ensuring equitable healthcare applications to mitigate biases. The expanding availability of large-scale environmental, geospatial, and health outcome databases offers unprecedented opportunities for innovative applications. Their predictive capabilities are essential in disaster management, enabling real-time analysis and optimizing resource deployment amid climate-related crises. AI-driven approaches play a critical role in carbon capture and waste management efforts aimed at reducing environmental impact. Furthermore, AI can elucidate complex relationships between the exposome—defined as the totality of exposures throughout an individual's life—and health outcomes, facilitating preventative strategies. This review examines the capabilities and limitations of AI in environmental health and safety, providing insights into its judicious and effective use for environmental management and healthcare.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3130-3145"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148147625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Airways Dysfunction and Remission in Adults With Asthma: A Longitudinal Exploratory Analysis of the AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS) Study","authors":"Akshi Kumar,&nbsp;Rory Chan,&nbsp;Nazanin Zounemat-Kermani,&nbsp;Eleanor Quek,&nbsp;Ian M. Adcock,&nbsp;Bianca Beghe,&nbsp;Christopher Brightling,&nbsp;Dave Singh,&nbsp;Janwillem Kocks,&nbsp;Alberto Papi,&nbsp;Klaus F. Rabe,&nbsp;Ulrica Scaffidi-Argentina,&nbsp;Maarten van den Berge,&nbsp;Monica Kraft,&nbsp;Salman Siddiqui","doi":"10.1111/all.70264","DOIUrl":"10.1111/all.70264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Asthma remission is a feasible treatment goal. However, remission definitions vary, and predictive biomarkers remain underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a post hoc analysis of ATLANTIS (NCT02123667), a multinational prospective study including 684 adult asthmatics. Remission was defined by 3-component (3C) and 4-component (4C) criteria. 3C remission included: (1) ACQ-6 &lt; 1.5, (2) no maintenance oral corticosteroids, (3) no exacerbations. An absolute decline &lt; 10% in pre-bronchodilator FEV₁% predicted, was added for the 4C definition. Multivariate logistic regression identified remission predictors. A novel Low Disease Activity (LDA) score was developed using factor analysis of five clinical variables (ACQ-6, FeNO, BEC, and FEV₁) including an innovative small airways dysfunction questionnaire tool (SADT). Nasal transcriptomics were analysed for differential gene expression and pathway enrichment and were replicated in U-BIOPRED (NCT01976767) using sputum transcriptomics. U-BIOPRED was included only to study omics replication of remission pathways identified in ATLANTIS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Remission occurred in 48% (3C) and 45% (4C) of patients. Predictors included male sex, better lung function, fewer previous exacerbations, and higher SADT (fewer small airways symptoms). LDA identified milder disease and was associated with remission [OR 3C 4.43 (2.80, 7.10) and 4C 3.46 (2.23, 5.43)], improved QoL [OR 2.07 (1.65, 2.60)], and fewer future exacerbations [OR 0.43 (0.22, 0.85)]. Transcriptomic analyses revealed remission-associated upregulation of interleukin 4/13 signalling and downregulation of coagulation pathways, in both ATLANTIS and U-BIOPRED.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>SAD was associated with reduced asthma remission. A novel LDA tool demonstrated clinical utility in stratifying prospective asthma risk. Key immunologic and haemostatic pathways may underpin remission, offering potential targets for future intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3185-3196"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite-Based Endotypes of Asthma Reveal Distinct Clinical Characteristics and Immune Cell Signatures","authors":"Young Jin Pyung,&nbsp;Noeul Kang,&nbsp;Jihyun Chun,&nbsp;Keesun Yu,&nbsp;Da-Jeong Park,&nbsp;Do Yup Lee,&nbsp;Deog Kyeom Kim,&nbsp;Hyun Woo Lee,&nbsp;Cheol-Heui Yun","doi":"10.1111/all.70385","DOIUrl":"10.1111/all.70385","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Asthma control is commonly defined by symptom burden and recent exacerbation history. However, symptom-based clinical stability does not necessarily reflect biological quiescence, and heterogeneity in lung function and airway structure may persist despite apparent clinical control. This study aimed to determine whether blood-based metabolomic profiling can discriminate biologically distinct subgroups within a clinically stable asthma population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective observational study of adults with clinically stable asthma, defined by sustained symptom control and absence of recent exacerbations under maintenance inhaled corticosteroid-based therapy. Untargeted plasma metabolomic profiling was performed using liquid chromatography–tandem mass spectrometry, and metabolite-derived subgroups were identified by consensus clustering. Lung function, airway structure, small-airway physiology, and peripheral immune cell profiles were compared across clusters, with associations assessed using regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three metabolite-derived subgroups were identified based on patterns in the relative abundance of selected representative metabolites. Symptom control and exacerbation history were comparable across clusters, whereas lung function, airway wall thickness, small-airway physiology, and immune cell profiles differed substantially. Cluster 1 (C1; Remodeling-prone), characterized by greater relative abundance of glycerophospholipid-related metabolites, showed lower post-bronchodilator FEV₁, thicker airway walls, and increased innate lymphoid cells. Cluster 2 (C2; Biologically stable) had preserved airway structure, with thinner airway walls and higher post-bronchodilator FEV₁. Cluster 3 (C3; T2-high) exhibited metabolite patterns associated with type 2 inflammatory features, including higher FeNO levels and blood eosinophil counts, while maintaining preserved airway structure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Metabolomic profiling reveals biologically distinct subgroups among clinically stable asthma, indicating that symptom-based stability does not necessarily reflect biological homogeneity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3250-3260"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147924978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis on the Harm of Systemic Glucocorticosteroids in Inflammatory Upper Airway Disease and Asthma: An EAACI Task Force","authors":"Sophie Scheire,&nbsp;Evelijn Lourijsen,&nbsp;Manon Blauwblomme,&nbsp;Maria Dib,&nbsp;Ioana Agache,&nbsp;Claus Bachert,&nbsp;Koen Boussery,&nbsp;Adam Chaker,&nbsp;Roos Colman,&nbsp;Stefano Del Giacco,&nbsp;Ibon Eguiluz-Gracia,&nbsp;Wytske Fokkens,&nbsp;Simon Gane,&nbsp;Peter Hellings,&nbsp;Claire Hopkins,&nbsp;Ludger Klimek,&nbsp;Miguel Maldonado,&nbsp;Juan Maza-Solano,&nbsp;Ralph Mösges,&nbsp;Joaquim Mullol,&nbsp;Charles Pilette,&nbsp;Oliver Pfaar,&nbsp;Sietze Reitsma,&nbsp;Michael Rudenko,&nbsp;Mohamed H. Shamji,&nbsp;Peter Valentin Tomazic,&nbsp;Sanna Toppila-Salmi,&nbsp;Philippe Gevaert,&nbsp;Valerie Hox","doi":"10.1111/all.70332","DOIUrl":"10.1111/all.70332","url":null,"abstract":"<p>Systemic glucocorticosteroids (sGCS) are widely used in the treatment of chronic inflammatory airway diseases such as rhinitis, rhinosinusitis and asthma. It is well-known that systemic use is linked to multiple adverse effects (AEs) both in the short- and the long-term. However, less is known about the safety of multiple short courses of sGCS. Currently there is no established agreement on the acceptable cumulative exposure to sGCS, considering the potential for various AEs. This systematic review and meta-analysis evaluated sGCS-related AEs in both upper and lower inflammatory airway disease, with a particular focus on short- and long-term risks. We further evaluated whether a dose–response relationship existed between the daily and cumulative dosages of sGCS and the occurrence of those AEs. Our meta-analysis confirmed that cumulative dosages between 500 mg and 1 g prednisolone-equivalent significantly increase the risk of most AEs, with risks increasing with incremental dose. These findings underscore the importance of: (a) judicious sGCS prescription and need for steroid stewardship, due to their potential for short- and long-term complications, occurring even with repeated short courses, and (b) prioritization of steroid-sparing approaches (e.g., biologicals) to avoid reaching a cumulative dose of 500 mg.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3071-3106"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolving Endoplasmic Reticulum-Protein Misfolding Restores Corticosteroid Sensitivity in Experimental Models of Severe Asthma","authors":"Prabuddha S. Pathinayake,&nbsp;Alexandra C. Brown,&nbsp;Nikhil T. Awatade,&nbsp;Philip M. Hansbro,&nbsp;Katherine J. Baines,&nbsp;Richard Y. Kim,&nbsp;Nathan W. Bartlett,&nbsp;Jay C. Horvat,&nbsp;Peter A. B. Wark","doi":"10.1111/all.70353","DOIUrl":"10.1111/all.70353","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>People with severe steroid-resistant asthma are refractory to treatment with the mainstay inhaled corticosteroids (ICS), emphasising the urgent need for alternative therapies. This study aimed to assess the effect of endoplasmic reticulum stress (ERS) on steroid responsiveness and to evaluate the efficacy of 4-phenylebuteric acid (4-PBA) as an add-on treatment to restore steroid responses in severe asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The relationship between ERS and steroid response was assessed by treating human airway epithelial cells (AEC) with chemical ERS inducers or TNF, IFN-γ, and IL-17, and assessing the effects of dexamethasone (Dex) and 4-PBA. The correlation between genes associated with ERS and GR-signalling was assessed in sputum cells from patients with severe asthma, and the effects of 4-PBA were assessed in two murine models of severe, steroid-resistant asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chemical ERS inducers significantly downregulated the expression of corticosteroid-responsive genes, HSD11B2 and FKBP5 and reduced GR nuclear translocation in basal AECs. Treatment with TNF, IFN-γ and IL-17 upregulated ERS and protein misfolded markers while reducing Dex-induced GR nuclear translocation. In sputum cells from patients with severe asthma, ERS genes negatively correlated with GR-signalling. In differentiated primary bronchial epithelial cells (pBECs), treatment with 4-PBA reversed TNF, IFN-γ and IL-17-induced steroid resistance by upregulating HSD11B2 and FKBP5 gene expression and downregulating inflammatory genes. 4-PBA together with Dex significantly reduced airway inflammation and/or AHR in experimental models of severe, steroid-resistant asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We provide evidence for ERS inducing steroid resistance that underpins severe asthma and demonstrate a therapeutic potential for restoring steroid sensitivity in severe asthma with 4-PBA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3221-3235"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}