Allergy最新文献

{"title":"Longer Asthma Duration Is Associated With Elevated Non-T2 Sputum Biomarkers and Reduced T2 Inflammation in Severe Asthma","authors":"Freda Yang,&nbsp;Sujin Seo,&nbsp;Takehiro Hasegawa,&nbsp;Chloe I. Bloom,&nbsp;Nazanin Zounemat-Kermani,&nbsp;Pankaj K. Bhavsar,&nbsp;Katie Raby,&nbsp;Ian M. Adcock,&nbsp;Sungho Won,&nbsp;Tae-Bum Kim,&nbsp;Kian Fan Chung,&nbsp;the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) Consortium","doi":"10.1111/all.70436","DOIUrl":"10.1111/all.70436","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Longer asthma duration predicts non-remission in Type-2 (T2) biologic-treated severe asthma, but underlying mechanisms remain unclear. We investigated associations between asthma duration and inflammatory biomarkers that may explain differential biologic response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed cross-sectional data from adults with severe asthma in U-BIOPRED. Asthma duration was defined as years from diagnosis to study entry. T2 and non-T2 biomarkers were measured in blood and sputum. Identical assays were performed in PRISM, a validation cohort of biologic-initiators. Multivariable regression models adjusted for age, sex, ethnicity, BMI, smoking and oral corticosteroid dose. Associations between duration-related biomarkers and 12-month biologic remission were explored in PRISM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In U-BIOPRED (<i>n</i> = 411), median asthma duration was 23 years (IQR 12–38). Longer duration was associated with higher non-T2 biomarkers including sputum CXCL9 (<i>β</i> = 0.024, 95% CI 0.011–0.038), sputum IL-6 (<i>β</i> = 0.024, 95% CI 0.011–0.037) and sputum neutrophils (<i>β</i> = 0.009, 95% CI 0.001–0.017), but lower T2 biomarkers including plasma periostin (<i>β</i> = −0.006, 95% CI −0.009 to −0.003), eosinophils (blood: <i>β</i> = −0.002, 95% CI −0.003 to −0.001; sputum: <i>β</i> = −0.023, 95% CI −0.035 to −0.011), sputum EDN (<i>β</i> = −0.032, 95% CI −0.049 to −0.014) and FeNO (<i>β</i> = −0.006, 95% CI −0.010 to −0.001). PRISM (<i>n</i> = 474) confirmed these associations. Higher sputum CXCL9 was associated with reduced remission in anti-IL-4Rα-treated patients with asthma duration ≥ 20 years (<i>β</i> = −1.73, 95% CI −3.180 to −0.276).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Longer asthma duration was associated with elevated airway non-T2 inflammation and reduced systemic and airway T2 inflammation. This highlights the importance of airway biomarker sampling and suggests combined T2 and non-T2 therapeutic strategies may be needed to achieve remission in long-standing asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT05164939</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3286-3299"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408530","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":"Targeting Airway Remodeling in Severe Asthma: Is There a Window of Opportunity for Biologic Therapy Predicting Effects Using Causal Artificial Intelligence?","authors":"Sebastiano Gangemi,&nbsp;Sara Manti,&nbsp;Johann Christian Virchow,&nbsp;Giorgio Walter Canonica","doi":"10.1111/all.70468","DOIUrl":"10.1111/all.70468","url":null,"abstract":"<p>Airway remodeling is increasingly recognized as a major determinant of asthma progression, fixed airflow limitation, and long-term morbidity, particularly in severe disease. Although biologic therapies have transformed outcomes by reducing exacerbations and systemic corticosteroid exposure, their potential to modify structural airway trajectories—and whether a time-sensitive “window of opportunity” exists—remains uncertain. Here, we provide a progressive landscape integrating mechanistic remodeling pathways with measurable structural readouts (biopsy-derived indices and quantitative imaging) and emerging digital biomarkers derived from connected respiratory technologies. We propose an operational framework linking mechanism → biomarker → remodeling readout → timing decision, and we outline a 1-, 3-, and 5-year research roadmap in which advanced artificial intelligence (AI) methods (multimodal learning, causal inference, federated learning, and digital-twin architectures) evolve in parallel with wearable and smart-inhaler ecosystems. This landscape aims to standardize endpoints, sharpen trial design, and accelerate a shift from symptom control toward credible disease modification in severe asthma.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3157-3170"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823524","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":"Adipokines in Obese Asthma: A Complex Relationship Influenced More by Sex, Weight, and Oral Steroid Treatment Than Disease Severity","authors":"Lars I. Andersson,&nbsp;Maciej Kupczyk,&nbsp;Barbro Dahlén,&nbsp;Kenji Izuhara,&nbsp;Mina Gaga,&nbsp;Nikos M. Siafakas,&nbsp;Alberto Papi,&nbsp;Bianca Beghe,&nbsp;Guy Joos,&nbsp;Klaus F. Rabe,&nbsp;Elisabeth H. Bel,&nbsp;Sebastian L. Johnston,&nbsp;Pascal Chanez,&nbsp;Mark Gjomarkaj,&nbsp;Peter H. Howarth,&nbsp;Ewa Niżankowska-Mogilnicka,&nbsp;Roelinde Middelveld,&nbsp;Sven-Erik Dahlén,&nbsp;Apostolos Bossios,&nbsp;Anna James,&nbsp;the BIOAIR (Longitudinal Assessment of Clinical Course and BIOmarkers in Severe Chronic AIRway Disease) and ChAMP consortia","doi":"10.1111/all.70318","DOIUrl":"10.1111/all.70318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity-related asthma (OBA) is a distinct asthma phenotype, with increased severity. Adipokine release from excessive adipose tissue is suggested to be a key feature of OBA pathophysiology. However, it is unclear how the clinical characteristics of severe asthma associate with adipokine mediators. We examined systemic adipokine levels and evaluated relationships with disease severity, weight, sex, and steroid treatment in asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multiplex immunoassay for nine adipokines with proposed involvement in obesity-related inflammation (adiponectin, adipsin, BAFF, chemerin, FGF-21, leptin, lipocalin-2/NGAL, osteonectin and resistin) was designed. Plasma adipokines were measured in 127 patients with mild-to-moderate asthma (MMA) or severe asthma (SA) from the European BIOAIR cohort at baseline and after a controlled 2-week oral corticosteroid (OCS) intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Leptin and chemerin were significantly increased in patients with SA vs. MMA. Leptin, adiponectin, adipsin, and NGAL were affected by sex, whereas leptin and adipsin were strongly affected by weight. OCS increased leptin and adiponectin, decreased adipsin and BAFF, and did not affect osteonectin, resistin, or chemerin. No adipokines showed positive associations with exhaled NO, blood or sputum eosinophils, although certain correlations with serum CRP, blood, and sputum neutrophils were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, we observe variable relationships between the nine adipokines, obesity and asthma severity. There were no relationships between adipokine levels and type-2 airway inflammation, yet associations with systemic neutrophilic inflammation were seen. Although one adipokine, chemerin, was independently associated with asthma severity, deciphering the role of adipokines in OBA is complex due to the influence of sex, BMI, and OCS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3206-3220"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615675","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":"IL-33 Drives Inflammatory Changes and Extracellular Trap Formation in Eosinophils Involving Oxidised LDL and Complement Pathways","authors":"Emiko Matsuyama,&nbsp;Jun Miyata,&nbsp;Takao Mochimaru,&nbsp;Ryuta Onozato,&nbsp;Yo Otsu,&nbsp;Hisashi Sasaki,&nbsp;Keeya Sunata,&nbsp;Shinichi Okuzumi,&nbsp;Katsunori Masaki,&nbsp;Hiroki Kabata,&nbsp;Keinosuke Hizuka,&nbsp;Yoshinori Hasegawa,&nbsp;Ryo Konno,&nbsp;Yusuke Kawashima,&nbsp;Makoto Arita,&nbsp;Shigeharu Ueki,&nbsp;Koichi Fukunaga","doi":"10.1111/all.70313","DOIUrl":"10.1111/all.70313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>IL-33 levels are elevated in the airways of patients with eosinophilic diseases, and IL-33 receptor expression on eosinophils is upregulated in type 2-high environments. However, the role of IL-33 in the regulation of human eosinophils remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To elucidate the inflammatory effects of IL-33 on the cellular function of human eosinophils.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood eosinophils were stimulated with IL-33, TNF-α, oxidised low-density lipoprotein (oxLDL) and complement fragments (C3a and C5a). Multi-omics analyses, including transcriptomics and proteomics, were performed. Extracellular trap formation (ETosis) was assessed by SYTOX nucleic acid staining and was visualised by immunofluorescence and transmission electron microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multi-omics analyses revealed an IL-33- and TNF-α-induced inflammatory gene signature characterised by the upregulation of cell surface markers (oxLDL receptor 1, CD22, CD4 and ICAM-1) and inflammatory mediators (C3, CCL3/4 and IL1A/B). CD22 upregulation was specific to IL-33 stimulation. Eosinophils derived from nasal polyps exhibited a gene expression profile similar to that of IL-33-stimulated eosinophils. Functional assays demonstrated that oxLDL and complement fragments differentially prolonged eosinophil survival and altered the expression of adhesion molecules. OxLDL- and complement fragment-induced gene signatures were partly detected in eosinophils derived from nasal polyps. Furthermore, IL-33 triggered ETosis via NADPH oxidase, mitogen-activated protein kinase and phosphoinositide 3-kinase pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IL-33, in conjunction with oxLDL and the complement cascade, induces inflammatory changes in eosinophils, promoting an ETosis-prone phenotype. These pathways represent potential therapeutic targets in refractory eosinophilic diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3171-3184"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506680","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":"MAIT Cells Suppress IgE-Mediated Asthma via IFNγ-Dependent B Cell Regulation","authors":"Angela M. Cannata,&nbsp;Jaclyn W. McAlees,&nbsp;Julie M. Hargis,&nbsp;Archana Shankar,&nbsp;Shouxiong Huang,&nbsp;Senad Divanovic,&nbsp;Ian P. Lewkowich","doi":"10.1111/all.70384","DOIUrl":"10.1111/all.70384","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes enriched in mucosal tissues, but their role in allergic asthma pathogenesis remains poorly defined. In this study, we sought to elucidate the role of MAIT cells in a T cell-dominant model of allergic asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used a murine model of house dust mite–induced asthma and a selective MAIT cell antagonist (Acetyl-6-formylpterin, A6FP) to inhibit MAIT cell activation in vivo. Airway hyperresponsiveness, lung inflammation, serum IgE, and cytokine profiles were assessed. In vitro co-culture experiments evaluated the direct impact of MAIT cells on B cell IgE production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pharmacologic inhibition of MAIT cells exacerbated airway hyperresponsiveness and elevated circulating IgE without altering airway eosinophilia or T helper type 2/type 17 cytokine production. MAIT cell antagonism failed to increase AHR in IgE-deficient mice. In vitro, activated MAIT cells directly suppressed B cell IgE production through IFNγ signaling. IL-4 was sufficient to enhance IFNγ production by MAIT cells, suggesting that allergic inflammation may induce a counter-regulatory response from MAIT cells to limit IgE-mediated pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MAIT cells limit airway hyperresponsiveness by suppressing IgE production through IFNγ–dependent B cell regulation. These findings define a previously unrecognized immunoregulatory function of MAIT cells in allergic asthma and suggest that enhancing MAIT cell activity may represent a therapeutic strategy for IgE-mediated diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3236-3249"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831231","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":"Spatial Transcriptomics Identifies Characteristic Immunological Niches in Atopic Dermatitis","authors":"Lina Gross, Lukas Bäriswyl, Erik Kupschke, Alexandra Wallimann, Hanne Hillen, Philipp Kirchner, Jivko Kamarashev, Martin Wartenberg, Claudio Rhyner, Christoph Schlapbach, Stephan Traidl, Mirjam Schenk","doi":"10.1111/all.70513","DOIUrl":"https://doi.org/10.1111/all.70513","url":null,"abstract":"Background Atopic dermatitis (AD) is primarily driven by a Type 2 immune response, with T helper (T <jats:sub>H</jats:sub> 2) cells producing IL‐4 and IL‐13, thereby promoting inflammation, itch, and a compromised skin barrier. Yet, the spatial organization of pathogenic immune cells and their interactions with stromal and epithelial compartments in human AD skin remain incompletely understood. Methods We performed 10× Genomics Visium spatial transcriptomics on FFPE skin biopsies from patients with AD ( <jats:italic>n</jats:italic> = 6), psoriasis ( <jats:italic>n</jats:italic> = 2), and healthy controls ( <jats:italic>n</jats:italic> = 5). Data were integrated with AD single‐cell RNA sequencing (scRNA‐seq) datasets and complemented by imaging mass cytometry (IMC) and multiplex immunofluorescence (IF) to validate the spatial localization of immune cells. Cell–cell communication analysis revealed putative signaling interactions within immune niches. Results Spatial clustering resolved tissue compartments and demonstrated transcriptional dysregulation in keratinocytes in AD and psoriasis. AD lesions showed a conserved spatial organization of immune aggregates within the superficial dermis. Integration of scRNA‐seq signatures revealed spatially organized co‐localization of T cells and mature migratory dendritic cells (mmDCs). We developed a ring‐based neighborhood analysis to characterize the cellular organization of the immune‐stromal niches, revealing T cell‐enriched regions surrounded by inflammatory fibroblasts and activated keratinocytes. Intercellular communication analysis further identified putative signaling within mmDC‐T cell niches that may promote pathogenic T cell recruitment and activation. Application of tertiary lymphoid structure (TLS) signatures indicated the presence of TLS‐like regions. IMC and IF validated the close spatial proximity between activated T <jats:sub>H</jats:sub> 2 cells and mmDCs. Conclusion AD lesions contain spatially organized TLS‐like immune niches at the dermal‐epidermal junction, characterized by the close association of T cells and mmDCs and coordinated interactions with surrounding stromal and epithelial compartments. These mmDC‐T cell niches may represent potential targets for future therapeutic strategies aimed at disrupting persistent local inflammatory pathways and improving long‐term disease control.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"21 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922754","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":"Cumulative Vulnerability to Particulate Matter and Incident Asthma: Joint Effects of Urbanicity, Poverty, and Age in a Nationwide Cohort","authors":"Hyun Lee, Jihye Heo, Jihee Nam, Suna Kang, Jin Lee, Hwamin Woo, Danbee Kang, Sung Won Kang, Hye Yun Park, Ji Ye Jung, Woo Jin Kim, Tai Joon An, Youlim Kim, Juhee Cho","doi":"10.1111/all.70502","DOIUrl":"https://doi.org/10.1111/all.70502","url":null,"abstract":"Background Long‐term exposure to ambient fine and coarse particulate matter (PM <jats:sub>2.5</jats:sub> and PM <jats:sub>10</jats:sub> ) is a major risk factor for asthma development. However, how urbanicity, poverty, and age jointly modify this association and contribute to disparities in asthma incidence remains unclear. Methods We conducted a nationwide retrospective cohort study of 8,252,498 adults in South Korea using the Korean National Health Insurance Service database. Health records were linked to 1km <jats:sup>2</jats:sup> resolution estimates of long‐term PM <jats:sub>2.5</jats:sub> and PM <jats:sub>10</jats:sub> exposure. Asthma incidence was assessed using Cox proportional hazards models adjusted for demographic, clinical, and environmental covariates. Stratified analyses were performed by age, Medical Aid status, and residential area. Results Long‐term exposure to PM <jats:sub>2.5</jats:sub> and PM <jats:sub>10</jats:sub> was significantly associated with an increased risk of new‐onset asthma. Each 10 μg/m <jats:sup>3</jats:sup> increase in PM <jats:sub>2.5</jats:sub> was associated with a hazard ratio (HR) of 1.33 (95% confidence interval [CI], 1.32–1.34), while a comparable increase in PM <jats:sub>10</jats:sub> was associated with an HR of 1.38 (95% CI, 1.37–1.38). Stratified analyses demonstrated progressive risk amplification across age, Medical Aid status, and residential area, with HRs ranging from 1.16 (95% CI, 1.14–1.18) among younger adults without Medical Aid living in rural areas to 1.80 (95% CI, 1.66–1.94) among older adults and receiving Medical Aid residing in urban areas ( <jats:italic>p</jats:italic> for interaction &lt; 0.001). Conclusion Long‐term PM exposure significantly increased asthma risk, with the greatest disparities observed among socioeconomically disadvantaged older adults residing in urban areas. Urgent, targeted strategies are needed to mitigate the disproportionate asthma burden attributable to these inequities.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"52 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922755","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":"Plasma Metabolomes Identify Distinct Asthma Metabotypes: Findings From the COREA Cohort","authors":"Woori Chae,&nbsp;Jin An,&nbsp;Chae Eun Lee,&nbsp;Seo-Young Kim,&nbsp;Eunse Kim,&nbsp;Hyouk-Soo Kwon,&nbsp;Woo-Jung Song,&nbsp;You Sook Cho,&nbsp;Joo-Youn Cho,&nbsp;Tae-Bum Kim","doi":"10.1111/all.70469","DOIUrl":"10.1111/all.70469","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Phenotype-based asthma classification has limitations that have motivated endotype-based approaches grounded in pathophysiology. However, existing biomarkers offer limited specificity and clinical accessibility. Plasma metabolomics, which reflects disease-specific metabolic states, offers a promising strategy for asthma classification. This study aimed to identify metabolic subgroups (metabotypes) of adult asthma using plasma metabolomics, with potential implications for personalized treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma samples from 407 patients with asthma in the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) were analyzed using Biocrates AbsoluteIDQ p400 HR kit with liquid chromatography-mass spectrometry. After preprocessing, 281 metabolites were natural-log-transformed, standardized, and partitioned by k-means clustering. The number of clusters was determined by a multi-criteria assessment combining cluster validity indices, consensus clustering, stability analysis, and cross-algorithm agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four metabotypes with distinct lipid-class signatures were identified. Group 1 (<i>n</i> = 123) was characterized by elevated ether-linked phosphatidylcholines, comprising younger patients with the earliest symptom onset and female predominance. Group 2 (<i>n</i> = 53) showed elevated lyso-phosphatidylcholines and altered amino acid metabolism (elevated glutamate, reduced glutamine), representing a metabolically intermediate, non-T2-high subgroup. Group 3 (<i>n</i> = 158) exhibited globally reduced sphingomyelins and broadly lower phosphatidylcholines in middle-aged, non-obese patients. Group 4 (<i>n</i> = 73) showed markedly elevated triacylglycerols (TG) and diacylglycerols (DG) with the highest body mass index (BMI), consistent with a non-T2, obesity-related metabotype. The TG/DG signature of Group 4 remained robust after adjustment for BMI, age, and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma metabolomics identifies clinically meaningful asthma metabotypes, supporting integration of metabolomic profiling into personalized asthma management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3318-3327"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672942","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":"Decalogue of the Declaration of Salamanca: Advancing Undergraduate Education in Allergy and Clinical Immunology Across Europe","authors":"Maria Jose Torres,&nbsp;Mohamed Shamji,&nbsp;Stefania Arasi,&nbsp;Marta Ferrer,&nbsp;Radoslaw Gawlik,&nbsp;Marta Vazquez-Ortiz,&nbsp;Carmen Vidal,&nbsp;Asli Gelincik,&nbsp;Cezmi A. Akdis,&nbsp;Ozlem Ceylan,&nbsp;Gulfem Çelik,&nbsp;Tomas Chivato,&nbsp;Stefano del Giacco,&nbsp;Ibon Eguiluz-Gracia,&nbsp;Maria Marta Escribese,&nbsp;Lene Heise Garvey,&nbsp;Aspasia Karavelia,&nbsp;Ludger Klimek,&nbsp;Paul Lavender,&nbsp;Andre Moreira,&nbsp;Norbert Mülleneisen,&nbsp;Constantinos Pitsios,&nbsp;Ingrid Terreehorst,&nbsp;Sophia Tsabouri,&nbsp;Arantza Vega,&nbsp;Ignacio Davila","doi":"10.1111/all.70445","DOIUrl":"10.1111/all.70445","url":null,"abstract":"&lt;p&gt;The “Declaration of Salamanca” emerges from the meeting hosted by European Academy of Allergy and Clinical Immunology (EAACI) on 17–18 October 2025 in Salamanca, Spain, a city selected for its profound academic heritage as home to the University of Salamanca, founded in 1218 and recognized as Spain's oldest university and one of the oldest in Europe. In this historically resonant setting, leading experts, educators, and patient advocates gathered to address one of Europe's most pressing yet underestimated health challenges: the need to secure a strong and unified presence of allergology and clinical immunology in undergraduate medical education.&lt;/p&gt;&lt;p&gt;Allergic diseases and related immune disorders have reached unprecedented prevalence worldwide. Today, up to 30%–40% of the global population suffers from at least one allergic condition, and these diseases are among the leading causes of outpatient visits in children and young adults. Emergencies related to anaphylaxis, severe asthma, food allergy, drug hypersensitivity, skin allergy, and complex immunological disorders are increasing year after year, yet the healthcare workforce often remains underprepared to address them [&lt;span&gt;1&lt;/span&gt;]. In this context, national healthcare systems must prepare their professionals to face this growing noninfectious disease burden, particularly in light of the still limited awareness of allergic diseases among medical students, physicians, the public, and policymakers [&lt;span&gt;2, 3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;During the meeting, professionals emphasized that allergology is unique in its ability to affect multiple organs and systems, requiring an integrative and holistic, multidisciplinary approach. Yet in many countries, allergy is not recognized as a medical specialty, meaning that access to undergraduate teaching in allergy is not possible.&lt;/p&gt;&lt;p&gt;The work of Sociedad Española de Alergología e Inmunología Clínica (SEAIC) in trying to establish allergy as a core academic subject in Spain served as an inspiration for extending similar efforts across Europe.&lt;/p&gt;&lt;p&gt;In this editorial, we present the Decalogue of the Declaration of Salamanca, which outlines 10 guiding principles to harmonize education, strengthen advocacy, and prepare the next generation of specialists in Allergy and Clinical Immunology. A forthcoming Position Paper will provide a more detailed analysis of the current situation, based on the survey conducted by the EAACI Tailored Education Committee, and will describe the operational aspects and implementation pathways of the Decalogue, including the integration of digital tools and artificial intelligence into undergraduate teaching.&lt;/p&gt;&lt;p&gt;The Declaration of Salamanca stands as a collective commitment to action. Through the Decalogue, we urge universities, national societies, European institutions, and healthcare leaders to ensure that allergology takes its rightful place in medical curricula, ultimately enhancing patient care, reducing healthcare burden, and sh","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3035-3038"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428692","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":"Update on Non-Biological and RNA-Based Therapeutics in Chronic Inflammatory Diseases: Precision Medicine Through Small Molecules: An EAACI Position Paper","authors":"Franziska Roth-Walter,&nbsp;Ian M. Adcock,&nbsp;Cristina Benito-Villalvilla,&nbsp;Rodolfo Bianchini,&nbsp;Leif Bjermer,&nbsp;Gaetano Caramori,&nbsp;Luigi Cari,&nbsp;Kian Fan Chung,&nbsp;Zuzana Diamant,&nbsp;Ibon Eguiluz-Gracia,&nbsp;Edward F. Knol,&nbsp;Milos Jesenak,&nbsp;Francesca Levi-Schaffer,&nbsp;Giuseppe Nocentini,&nbsp;Liam O'Mahony,&nbsp;Oscar Palomares,&nbsp;Frank Redegeld,&nbsp;Milena Sokolowska,&nbsp;Betty Van Esch,&nbsp;Marco Zurlo,&nbsp;Cristiana Stellato","doi":"10.1111/all.70235","DOIUrl":"10.1111/all.70235","url":null,"abstract":"<p>In the last decades, critical advancements in research technology and knowledge on disease mechanisms steered therapeutic approaches for chronic inflammatory diseases towards unprecedented target specificity. For allergic and chronic lung diseases, biologic drugs pioneered this goal, acquiring on the way—through the clinical use of monoclonal antibodies—a deeper understanding of how inflammatory and immune pathways are configured in disease-specific patterns. In this biomarker-driven approach, synthetic small molecule drugs (SMDs) were perceived as lagging behind in innovation for their relative lack of specificity. This was, however, mostly due to a shift in focus towards biologics rather than true obsolescence of SMDs. In the same timeframe, in fact, advances in structural biology and medicinal chemistry, bioinformatics and artificial intelligence held steadily SMDs' innovation and relevance. The use of kinase inhibitors, well established in the treatment of cancer and rheumatological diseases, is now approved for some allergic skin diseases and is approaching asthma and COPD with several clinical trials; moreover, new therapeutics targeting mast cell receptors and molecules involved in innate immunity are entering preclinical and clinical testing. Alongside, the portfolio of biologics is harboring the expansion of RNA therapeutics, which gained global recognition during the COVID-19 pandemic due to RNA vaccines. Different types of RNA therapeutics, including those based on different non-coding RNAs, are advancing to agency approval and market, thanks to improvements in molecule stability and delivery systems. In summary, the evidence presented in this position paper illustrates that precision medicine is becoming a goal shared between synthetic SMDs and biologics, both protein/antibody-based and RNA therapeutics. We review the current state, unmet needs and opportunities within this evolving landscape, highlighting how small molecular species, both synthetic as SMDs and biologic in nature as RNA, can contribute to the precision medicine approach along with protein and antibody-based biologics and cell therapies.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 9","pages":"3039-3070"},"PeriodicalIF":11.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136949","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}