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Volume 11.1 July 2026 emjreviews.com

Allergy & Immunology

Review of the

EAACI Congress 2026

Interviews:

Article:

María Torres, EAACI President, and Aspasia Karavelia, Chair of the EAACI Junior Members Assembly, share the latest updates from the annual congress

Biologics in High-Risk, Non-Severe Asthma: Current Evidence and Future Studies

Contents Editorial Board 04

Foreword 09

Jacques Bouchard La Malbaie Hospital, Quebec, Canada

Congress Review

Welcome 07

Congress Review

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of the European Academy of 10 Review Allergy and Clinical Immunology (EAACI) Congress 2026, 12th–15th June

Congress Feature and Allergic Diseases: Fact or Fiction 23 Omics Villaseñor A et al.

Abstract Reviews of Tree Allergen Components 28 Clustering and Phylogenetic Analysis of Patient Profiles Reveal Key Combinations for Allergen Immunotherapy Yasniuk M et al.

Endovascular Profiles in 30 Characterising ACE Inhibitor-Induced Angioedema in a South African Cohort Pedretti S et al.

a Predictive Diagnostic 32 Testing Scale for NSAID Hypersensitivity in Paediatric Patients Falabella P et al.

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Find out more about our Allergy & Immunology content

Congress Interviews 34 María Torres 41 Aspasia Karavelia 44 Ian Adcock Interviews 50 Cezmi Akdis

Articles

54 Isabella Annesi-Maesano

72 Editor's Pick: Biologics in High-Risk,

Non-Severe Asthma: Current Evidence and Future Studies

57 Jennifer Koplin

Rahem A et al.

61 Mitchell H. Grayson

85 Pituitary Macroadenoma Mimicking

Perennial Allergic Rhinitis: A Case Report

64 Ruchi Gupta

Bakiri and Mingomataj

Spotlight on Europe Society for Allergology and 68 German Clinical Immunology (DGAKI) Association of Allergologists and 70 Serbian Clinical Immunologists (SAACI)

"EAACI highlighted the importance of maintaining a multidisciplinary approach to addressing the increasing burden of allergic diseases and immune disorders worldwide"

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Editorial Board Editor-in-Chief Prof Jacques Bouchard La Malbaie Hospital, Canada Jacques Bouchard is a distinguished family physician with over 30 years of practice in La Malbaie, Quebec, Canada, specialising in inpatient care, allergy, and respiratory physiology. An associate professor of clinical medicine at Laval University, Quebec, Canada, he is deeply committed to medical education through his work with the Federation of General Practitioners of Quebec. A recipient of the Prix Gilles-Des Rosiers and the College of Family Physicians of Canada’s Award of Excellence, he has made significant contributions to both rural healthcare and respiratory education.

Prof Igor Kaidashev

Dr Reynold A. Panettieri

Poltava State Medical University, Ukraine

Rutgers Institute for Translational Medicine and Science, USA

Dr Sarah Karabus

Prof Michael Rudenko

Red Cross War Memorial Children's Hospital, South Africa

London Allergy and Immunology Centre, UK

Dr Ting Fan Leung

Prof Stefan Wöhrl

The Chinese University of Hong Kong, Hong Kong

Floridsdorf Allergy Center, Vienna, Austria

Prof Branimir Nestorovic

Dr James Woijoo Kim

University Children's Hospital Belgrade, Serbia

Family Physician Airway Group of Canada, Canada

Dr Enrico Heffler Humanitas University, Italy

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Aims and Scope EMJ Allergy & Immunology is an open access, peer-reviewed ejournal committed to helping elevate the quality of practices in allergic and immunological diseases globally by informing healthcare professionals on the latest research in the field. The journal is published annually, six weeks after the European Academy of Allergy & Clinical Immunology (EAACI) Event, and features highlights from this event, alongside interviews with experts in the field, reviews of abstracts presented at EAACI, as well as in-depth features on sessions from this event. The journal also covers advances within the clinical and pharmaceutical arenas by publishing sponsored content from congress symposia, which is of high educational value for healthcare professionals. This undergoes rigorous quality control checks by independent experts and the in-house editorial team. EMJ Allergy & Immunology also publishes peer-reviewed research papers, review articles, and case reports in the field. In addition, the journal welcomes the submission of features and opinion pieces intended to create a discussion around key topics in the field and broaden readers’ professional interests. The journal is managed by a dedicated editorial team that adheres to a rigorous double-blind peer-review process, maintains high standards of copy editing, and ensures timely publication. EMJ Allergy & Immunology endeavours to increase knowledge, stimulate discussion, and contribute to a better understanding of practices in the field. Our focus is on research that is relevant to all healthcare professionals in this area. We do not publish veterinary science papers or laboratory studies not linked to patient outcomes. We have a particular interest in topical studies that advance knowledge and inform of coming trends affecting clinical practice in the field. Further details on coverage can be found here: www.emjreviews.com Editorial Expertise EMJ is supported by various levels of expertise: • • • •

Guidance from an Editorial Board consisting of leading authorities from a wide variety of disciplines. Invited contributors who are recognised authorities in their respective fields. Peer review, which is conducted by expert reviewers who are invited by the Editorial team and appointed based on their knowledge of a specific topic. An experienced team of editors and technical editors.

Peer Review On submission, all articles are assessed by the editorial team to determine their suitability for the journal and appropriateness for peer review. Editorial staff, following consultation with either a member of the Editorial Board or the author(s) if necessary, identify three appropriate reviewers, who are selected based on their specialist knowledge in the relevant area. All peer review is double blind. Following review, papers are either accepted without modification, returned to the author(s) to incorporate required changes, or rejected.

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Editorial staff have final discretion over any proposed amendments. Submissions We welcome contributions from professionals, consultants, academics, and industry leaders on relevant and topical subjects. We seek papers with the most current, interesting, and relevant information in each therapeutic area and accept original research, review articles, case reports, and features. We are always keen to hear from healthcare professionals wishing to discuss potential submissions, please email: editorial.assistant@emjreviews.com To submit a paper, use our online submission site: https://emj.kriyadocs.com/submissions/submit/emj/emj/login Submission details can be found through our website: www.emjreviews.com/contributors/authors Reprints All articles included in EMJ are available as reprints (minimum order 1,000). Please contact hello@emjreviews.com if you would like to order reprints. Distribution and Readership EMJ is distributed through controlled circulation to healthcare professionals in the relevant fields across Europe. Indexing and Availability EMJ is indexed on DOAJ, the Royal Society of Medicine, and Google Scholar®; selected articles are indexed in PubMed Central®. EMJ is available through the websites of our leading partners and collaborating societies. EMJ journals are all available via our website: www.emjreviews.com Open Access This is an open-access journal in accordance with the Creative Commons Attribution-Non Commercial 4.0 (CC BY-NC 4.0) license. Congress Notice Staff members attend medical congresses as reporters when required. This Publication Launch Date: 2013 Frequency: Annually Online ISSN: 2398-9130 All information obtained by EMJ and each of the contributions from various sources is as current and accurate as possible. However, due to human or mechanical errors, EMJ and the contributors cannot guarantee the accuracy, adequacy, or completeness of any information, and cannot be held responsible for any errors or omissions. EMJ is completely independent of the review event (EAACI 2026) and the use of the organisations does not constitute endorsement or media partnership in any form whatsoever. The cover photo is of Istanbul, Türkiye, the location of EAACI 2026. Front cover and contents photograph: Digitally enhanced image © AlexAnton / stock.adobe.com

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This online educational webinar is sponsored and funded by KalVista Pharmaceuticals, part of the Chiesi Group, and is intended for healthcare professionals only.

CLOSING THE GAPS in HAE MANAGEMENT: Addressing HAE Management Challenges for Adolescentss

WEBINAR OVERVIEW: Join us as expert speakers discuss defining control of hereditary angioedema (HAE) for adolescents, the updated 2026 HAE guidelines, and challenges for adolescents with HAE.

CLICK HERE TO WATCH

DISCUSSION BY:

Mauro Cancian

Emily Carne

Mar Guilarte

Markus Magerl

University Hospital of Padua, Italy

Immunology & Allergy at Cardiff and Vale University Health Board, Wales, UK

Hospital Universitari Vall d’Hebron, Barcelona, Spain

Charité – Universitätsmedizin Berlin Institute of Allergology IFA, Berlin, Germany

MAT-UNB-GLOBAL-0011 07/2026

Welcome Editorial Director Andrea Charles

Dear Readers,

Editor Sean Boyle

We are thrilled to welcome you to the 2026 issue of EMJ Allergy & Immunology, which features coverage from this year’s European Association of Allergy and Clinical Immunology (EAACI) Congress held in Istanbul, Türkiye. Focusing on ‘Vision Zero’, the Congress explored the latest advances shaping the future of allergy and clinical immunology, spanning innovative approaches in disease prevention, precision medicine, immunotherapy, diagnostics, education, and patient-centred care. The meeting highlighted emerging research and clinical developments across allergic diseases, asthma, immunological disorders, and the evolving role of environmental and societal factors in improving global health outcomes.

Managing Editor Darcy Richards Senior Copy Editor Noémie Fouarge Copy Editors Meghan Garcka, Sarah Jahncke Editorial Leads Helena Bradbury, Katrina Thornber, Aleksandra Zurowska Senior Editorial Co-ordinator Bertie Pearcy Editorial Co-ordinators Jess Nicholson, Alena Sofieva Editorial Assistants Niamh Holmes, Josh Warren Lister, Nonyelum Okonkwo, Roli Omamuli Creative Director Tim Uden Design Manager Stacey White Senior Designers Tamara Kondolomo, Owen Silcox Designers Shanjok Gurung, Fabio van Paris Junior Designers Fraser Hoey, Helena Spicer, Caleb Wylie

In our congress review, we place a spotlight on breaking research from the event, including future perspectives on peanut allergy testing. This issue also showcases multiple ground-breaking reviews of abstracts presented at EAACI 2026, highlighting an array of themes that range from polysensitisation to tree pollen allergens to non-steroidal anti-inflammatory drug hypersensitivity. We also present several interviews with leading experts in the field, as well as exclusive insights from prominent figures in the Association, including María Torres, President of EAACI. Our peer-reviewed content includes fascinating research highlighting how biologics can be applied to high-risk, nonsevere asthma. Additionally, explore a unique case showing how pituitary macroadenoma can mimic perennial allergic rhinitis. We would like to take this opportunity to thank our Editorial Board, authors, peer reviewers, and interviewees for their support and critical contributions that have helped bring this issue to life. We hope you enjoy reading! Niamh Holmes Editorial Assistant

Marketing Director Stephanie Corbett Business Unit Lead Kelly Byrne

Chief Executive Officer Justin Levett

Editorial enquiries: editor@emjreviews.com Sales opportunities: salesadmin@emjreviews.com Permissions and copyright: accountsreceivable@emjreviews.com

Chief Commercial Officer Dan Healy Founder and Chairman Spencer Gore

Reprints: info@emjreviews.com Media enquiries: marketing@emjreviews.com

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Foreword Dear Colleagues, It is with great delight that I introduce EMJ Allergy & Immunology 11.1, an edition that highlights the latest advancements in the field. This issue draws on key highlights from the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2026, held in Istanbul, Türkiye, from 12th–15th June 2026. The event united specialists from around the world to explore the latest developments in allergy and immunology research. This year’s Congress provided an insightful array of sessions, featuring a record number of plenary and thematic symposia, posters, and flash talk sessions that fostered meaningful discussion, knowledge exchange, and collaboration among experts across the field. Among the many highlights of EAACI 2026 were advances in precision allergy care, with emerging innovations in allergen immunotherapy, personalised diagnostics, biomarkers, and AI shaping the future of clinical practice. Key discussions focused on transforming the management of food and drug allergies through novel therapeutic approaches, including safer treatments, improved diagnostic pathways, and targeted interventions, while emphasising the role of multidisciplinary collaboration and scientific innovation in delivering more personalised outcomes for patients worldwide. We are delighted to share a series of interviews with key figures involved in shaping the Congress, including an interview with EAACI President, María Torres. Torres discusses the future of allergy management,

including safer food allergy therapies, drug allergy de-labelling, biologics guided by inflammatory profiles, and the need for young clinicians to combine scientific rigour, collaboration, and innovation to improve patient outcomes.

This year’s Congress provided an insightful array of sessions, featuring a record number of plenary and thematic symposia, posters, and flash talk sessions Alongside these highlights, this issue also includes peer-reviewed articles exploring a unique case in which a pituitary macroadenoma caused cerebrospinal fluid rhinorrhoea that mimicked persistent allergic rhinitis, and an analysis of how biologic therapies can be applied to non-severe, high-risk asthma. Thank you to all contributors, reviewers, and members of our EMJ Allergy & Immunology Editorial Board. We hope you find this edition informative and inspiring as we look forward to welcoming the allergy and immunology community at the next EAACI Congress in 2027.

Prof Jacques Bouchard La Malbaie Hospital, Quebec, Canada

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EAACI 2026

EAACI highlighted the importance of maintaining a multidisciplinary approach to addressing the increasing burden of allergic diseases and immune disorders worldwide

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Congress Review Review of the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2026 Location:

Istanbul, Türkiye

Date:

12th–15th June 2026

Citation:

EMJ Allergy Immunol. 2026;11[1]:11-22. https://doi.org/10.33590/emjallergyimmunol/CDYVH00Q

THE HISTORIC city of Istanbul, Türkiye, provided the backdrop for the 70th Annual Congress of the European Academy of Allergy and Clinical Immunology (EAACI), bringing together the international allergy and immunology community for a landmark meeting celebrating scientific progress, collaboration, and innovation. Reflecting the Congress theme of ‘Vision Zero’, the meeting highlighted EAACI’s ambition to reduce the global burden of allergic and immune-mediated diseases through advances in prevention, education, research, and patient-centred care. Situated between Europe and Asia, Istanbul has long been a centre of cultural exchange, science, and commerce. With a rich history shaped by the Byzantine and Ottoman eras, the city’s blend of historic landmarks and modern international influence provided a fitting setting for a Congress centred on global collaboration and the advancement of allergy and clinical immunology.

OPENING ADDRESSES AND WELCOME REMARKS The opening ceremony marked a significant milestone as EAACI celebrated 70 years of advancing allergy and immunology. President Maria Torres and Vice President Andre Moreira welcomed delegates, reflecting on the Academy’s growth into a global organisation connecting clinicians, researchers, educators, and patient communities.

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With membership approaching 20,000 professionals and strong engagement from junior members, EAACI highlighted the importance of maintaining a multidisciplinary approach to addressing the increasing burden of allergic diseases and immune disorders worldwide. Torres outlined the Academy’s continued focus on quality improvement, education, sustainability, and transparency, highlighting initiatives such as the EAACI Quality Centres programme and the EAACI Nexus platform, which support collaboration and knowledge exchange across the specialty. The ceremony also emphasised EAACI’s wider role in advocacy and healthcare policy. The Declaration of Salamanca was highlighted as an important step towards strengthening the integration of allergy and clinical immunology education within medical training programmes across Europe.

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SCIENTIFIC PROGRAMME: ADDRESSING CURRENT AND FUTURE CHALLENGES The Congress’ scientific programme showcased the breadth of modern allergy and immunology through plenary lectures, thematic symposia, oral presentations, poster sessions, flash talks, workshops, ‘Meet the Expert’ sessions, and educational activities. The hybrid format enabled wider participation through both onsite attendance and digital access. Key discussions explored emerging research, clinical advances, education, and strategies to improve patient outcomes. Sustainability was also incorporated into the Congress vision through the concept of a “healthy planet, healthier people,” highlighting the relationship between environmental factors and human health. A major highlight of the opening ceremony was the keynote lecture, which addressed the growing challenge of misinformation in healthcare, including the impact of inaccurate health information, particularly online, on public understanding and medical decision-making. There was an emphasis on the importance of trust-based communication, with the speaker introducing an empathetic refutational approach that focuses on understanding the concerns behind beliefs before addressing misconceptions with evidence-based information.

HONOURING EXCELLENCE IN ALLERGY AND IMMUNOLOGY The opening ceremony also recognised outstanding contributions to the field through the EAACI Congress 2026 awards. These honours celebrated achievements across research, clinical practice, education, and leadership. The Clemens von Pirquet Award was presented to Antonella Cianferoni, University of Pennsylvania, Philadelphia, USA; and Walter Canonica, Humanitas University, Milan, Italy, recognising their contributions to allergy and immunology. The Paul Ehrlich Award was awarded to Thomas Bieber, Bieber Dermatology Consulting, Bonn, Germany, while the Charles Blackley Award recognised Cezmi Akdis, 12

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EAACI 2026

Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland; and Rudolf Valenta, Medical University of Vienna, Austria. The Daniel Bovet Award was presented to Isabel Skypala, Royal Brompton & Harefield NHS Foundation Trust, UK. Early-career achievements were also celebrated, with the Cezmi Akdis Prize 2026 awarded to Sadhbh Hurley, Royal College of Surgeons in Ireland, Dublin, Ireland; and Katri Korpela, University of Helsinki, Finland. The EAACI Allergopharma Award 2026 recognised Mahmoud Ismael Abdel-Aziz, Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, the Netherlands, while the EAACI Early Career Research Award 2026 was presented to Juan Luis Paris Fernández de la Puente, Instituto de Investigación Biomédica de Málaga, Spain.

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EAACI also recognised new Clinical and Research Fellows, celebrating the continued development of future leaders within allergy and clinical immunology.

A CELEBRATION OF COLLABORATION The opening ceremony concluded with a performance by Fire of Anatolia, celebrating Türkiye’s cultural heritage and providing a memorable introduction to the congress week. As delegates gathered for the welcome reception, the evening reflected the central message of EAACI 2026: that continued progress in allergy and immunology depends on collaboration, innovation, and a shared commitment to improving global health.

The city’s blend of historic landmarks and modern international influence provided a fitting setting for a congress centred on global collaboration

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CD4 T Cells Drive Oesophageal Barrier Dysfunction Epithelial Changes A NEW study presented at EAACI 2026 provides further insight into how immune–epithelial interactions contribute to the development of eosinophilic oesophagitis (EoE). The research investigated the direct effects of activated cluster of differentiation (CD)4 T cells on oesophageal epithelial function using an in vitro model.1 EoE is a chronic, immunemediated disease characterised by oesophageal inflammation, epithelial barrier disruption, and immune cell infiltration. Although CD4 T cells and their Type 2 inflammatory mediators are known to play a central role in disease pathogenesis, the precise mechanisms through which they affect epithelial cells remain incompletely understood.

Bulk RNA sequencing revealed extensive epithelial reprogramming, with more than 5,000 genes differentially expressed following exposure to activated CD4 T cells

To explore this, the investigators isolated primary CD4 T cells from healthy donor blood samples and activated them through T cell receptor stimulation using anti-CD3/CD28 antibodies. These activated or non-activated CD4 T cells were then co-cultured with differentiated EPC2 oesophageal epithelial cells grown under air– liquid interface conditions, allowing assessment of epithelial barrier function, inflammatory signalling, and transcriptional changes. The findings demonstrated that activated CD4 T cells directly impaired epithelial barrier integrity. Co-culture with stimulated T cells resulted in a 25% reduction in transepithelial electrical resistance and a two-fold increase in epithelial permeability compared with non-activated controls, indicating increased barrier leakage. This functional disruption was accompanied by marked reductions in epithelial barrierassociated genes, including DSG1 and FLG, both of which have previously been linked to EoErelated epithelial dysfunction. In addition, epithelial cells exposed to activated CD4 T cells developed a pro-inflammatory secretory profile, releasing immune mediators including IL-15, granulocyte-macrophage colony-stimulating factor (GMCSF), chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10, suggesting that epithelial cells

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actively participate in sustaining inflammatory responses. Bulk RNA sequencing revealed extensive epithelial reprogramming, with more than 5,000 genes differentially expressed following exposure to activated CD4 T cells. Comparison with transcriptomic signatures from oesophageal biopsies of patients with EoE showed that 1,295 genes overlapped between the experimental model and patient disease profiles. Further analysis demonstrated enrichment of pathways associated with interferon (IFN)-γ and IFN-α responses, as well as epithelial-tomesenchymal transition, processes implicated in chronic inflammation and tissue remodelling. The authors concluded that activated CD4 T cells are capable of directly inducing epithelial barrier failure and diseaseassociated transcriptional changes resembling those observed in patients with EoE. These findings highlight immune–epithelial crosstalk as a key mechanism in EoE pathogenesis and suggest that targeting interactions between immune cells and epithelial barriers may represent a future therapeutic strategy.

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MAIT Cells Show Potent Immunomodulatory Response to IL-33 MUCOSAL-associated invariant T (MAIT) cells displayed a potent immunomodulatory phenotype when stimulated with IL-33 and IL-12, according to new research presented at EAACI 2026, highlighting the ability of MAIT cells to reshape inflammatory immune responses through enhanced production of interferon (IFN)-γ and other immune mediators.2 MAIT cells are unconventional T cells that are recognised for their rapid response to microbial infections through the detection of microbial riboflavin-derived antigens and inflammatory cytokines. While their antimicrobial functions have been well described, their response to epithelialderived inflammatory mediators, known as alarmins, remained unclear. Researchers investigated the effects of the alarmins IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), administered alone or alongside established MAIT cell stimuli, including the microbial antigen 5-OP-RU and IL-12. The investigators also examined how activated MAIT cells influenced other immune cell populations, including cluster of differentiation (CD)14 positive monocytes and CD4 positive T cells. Multiparametric flow cytometry, quantitative PCR, ELISA, and proteomic analysis were used to characterise cellular responses. The study found that IL-33, but not IL-25 or TSLP, acted synergistically with IL-12 to induce a pronounced Th1- and cytotoxicbiased MAIT cell phenotype. This response was characterised by enhanced secretion of IFN-γ and granzyme B.

TNF, vascular endothelial growth factor, leukaemia inhibitory factor, and C-C motif chemokine ligand 20. These findings suggest that MAIT cells may contribute not only to inflammatory signalling but also to vascularisation and immune cell recruitment. Conditioned media collected from MAIT cells stimulated with IL-33 and IL-12 promoted polarisation of CD14-positive monocytes towards a pro-inflammatory M1-like phenotype. In addition, exposure to alarmins and IL-12 resulted in reduced expression of the Th2-associated genes IL5 and IL13 in CD4-positive T cells. Taken together, these findings indicate that MAIT cells can adopt a broader immunomodulatory role when polarised towards a Th1 programme. The authors concluded that this phenotype has the capacity to influence multiple immune compartments and noted that ongoing studies are investigating the extent to which activated MAIT cells may shape Th2 immune responses.

Proteomic profiling demonstrated that activated MAIT cells also secreted several additional immune mediators, including

Taken together, these findings indicate that MAIT cells can adopt a broader immunomodulatory role when polarised towards a Th1 programme

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Safe Early Skin Testing After Immediate Hypersensitivity Reactions to Chemotherapy SAFE AND RELIABLE allergological evaluation of immediate hypersensitivity reaction (IHR) to chemotherapy (CHT) can be performed within an earlier period, potentially assisting in reducing treatment delays and unnecessary empiric drug desensitisations, according to a new study presented at EAACI 2026.3 Recommendations suggest that skin testing (ST) should be performed in patients 4–6 weeks to 6 months after IHR to CHT. However, oncological treatment regimens often do not align with this window and comprise predefined cycles that range from weekly to every 4 weeks. Patients who experience delayed referrals after reactions to platins are at a higher risk of receiving false-negative ST results; however, data on false negatives when performing early ST is limited. In this study, researchers looked to determine whether it was possible to safely implement early ST in IHR to CHT.

Early ST could therefore be an important clinical tool to assist in the avoidance of treatment delays and unnecessary empiric drug desensitisations

A total of 209 patients, primarily consisting of women (F=187) who experienced suspected IHR to CHT, were consecutively referred to the Immunoallergology Unit at Careggi University Hospital in Florence, Italy, from October 2019–May 2025. A drug provocation test (DPT) was provided to those patients who received a negative ST, had a mild–moderate reaction, and had no other risk factors. Patients were stratified into three groups based on time between reaction and ST evaluation: ‘early’ (within 4 weeks), ‘ideal’ (1–6 months), and ‘late’ (>6 months). ST evaluation was performed in 159 (76.1%) patients in the ‘early’ group, 35 patients (16.7%) in the ‘ideal’ group, and 15 patients (7.0%) in the ‘late’ group.

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There was no significant difference in positive ST results between the ‘early’ group (25.8%) and the ‘ideal’ group (34.3%). In the subgroup of ST-negative patients, positive DPT responses were observed in 13 individuals (12.0%) in the ‘early’ group compared with two individuals (9.5%) in the ‘ideal’ group, with no statistically significant difference between groups (p=not significant). Multivariate analysis showed no significant difference in ST or DPT results between the two groups after adjusting for confounding factors. Overall, researchers demonstrated the possibility of implementing early allergological evaluation of IHRs to CHT in a safe and reliable way. Early ST could therefore be an important clinical tool to assist in the avoidance of treatment delays and unnecessary empiric drug desensitisations. However, the authors noted that the study was limited by its cohort distribution, and that confirmation of these findings would require ST after IHR to CHT to be carried out in a more evenly distributed population.

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Novel Method for Quantifying Conjunctival Provocation Test A RETROSPECTIVE study presented at EAACI 2026 suggested that a novel synthetic symptom metric (SSM) may predict treatment efficacy after 6 months by integrating conjunctival provocation test (CPT) readouts across multiple allergen dilutions and combining subjective and objective measures into one value.4 Monitoring immunotherapy effectively requires the quantification of provocation tests. Current methods commonly use the Symptom Severity Score (SSS), which evaluates a patient’s reaction to an allergen. The SSS readout is the highest allergen dilution at which the SSS exceeds a predefined threshold, which is usually SSS ≥3. Researchers noted that the primary limitation of the SSS is that the same readout can be obtained despite substantially different symptom severity. During treatment, the highest allergen dilution at which the SSS threshold is reached may increase. However, this readout fails to account for a substantially higher symptom score at this new dilution level. As a result, the authors expressed caution when interpreting the SSS alone as evidence of reduced allergen sensitivity. To address the limitations of the conventional SSS, researchers proposed a new method that would bring together symptom scores from multiple allergen dilutions into one metric.

undergoing immunotherapy. To assess robustness, the SSM was recalculated while omitting one or more dilutions for a given CPT and comparing these values. These findings suggest that, in comparison to the traditional SSS, an SSM increases sensitivity by combining subjective and objective measures into one value and incorporating results from multiple allergen concentrations. Importantly, treatment response may be predicted as early as 6 months when the metric is applied to longitudinal immunotherapy data.

The study involved a retrospective analysis of a clinical study that validated an AI platform (AllergoEye, AI-MedImaging, Dresden, Germany) that quantifies CPTs. CPT was performed in 41 patients at multiple allergen dilutions, which enabled researchers to develop a formula that integrates five measures, including three subjective patient-reported symptoms, one semi-quantitative nurse-assessed eye-redness score, and one quantitative AllergoEye eye-redness measurement.

In comparison to the traditional SSS, an SSM increases sensitivity by combining subjective and objective measures into one value and incorporating results from multiple allergen concentrations

The efficacy of treatment could be predicted after 6 months when applying an SSM to CPT data from 41 patients CC BY-NC 4.0 Licence

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Asthma Biologics May Restore Key Immune Regulatory Cells in Children with Persistent Asthma NEW RESEARCH presented at EAACI 2026 suggests that biologic therapies may help restore levels of regulatory B cells (B reg) in children and adolescents with persistent asthma. Patients receiving biologic treatment had B reg levels comparable to healthy controls and significantly higher than those seen in patients not receiving biologics.5 B regs play an important role in controlling allergic inflammation through the production of IL-10, an immunomodulatory cytokine. Previous research has shown that children with allergic asthma have lower levels of these cells compared with healthy individuals. However, the impact of asthma biologic therapies on B reg levels has remained unclear.

asthma cohort, 42 participants were not receiving biologic treatment, while nine were being treated with the biologics dupilumab, benralizumab, or tezepelumab. Participants ranged in age from 3–21 years, with a median age of 11 years.

Researchers investigated B reg frequencies in children and adolescents with persistent asthma, comparing patients receiving biologic therapy, patients not receiving biologic therapy, and healthy age-matched controls. Blood samples were collected from participants, and peripheral blood mononuclear cells were analysed using flow cytometry to quantify IL-10-producing B regs within a previously established asthma-associated B cell subset.

Researchers found that children with persistent asthma who were not receiving biologic therapy had significantly lower levels of B regs than healthy controls (median: 0.20% versus 0.69%; p=0.002). In contrast, B reg levels in participants receiving biologic therapy were not significantly different from those observed in healthy controls (median: 0.59% versus 0.69%; p=0.590). Furthermore, B reg frequencies were significantly higher in patients receiving biologic treatment than in those not receiving biologics (median: 0.59% versus 0.20%; p=0.033).

The study included 51 participants with persistent asthma and 17 healthy controls. Among the

The findings suggest that biologic therapies targeting Type 2 inflammation may

help normalise B reg levels in paediatric asthma. According to the authors, this restoration of B regs could contribute to improved physiological control of allergic airway inflammation and may represent an additional mechanism through which biologic therapies exert their clinical benefits. The study was limited by its small sample size, particularly in the biologic therapy group, and larger studies are needed to confirm these findings. Further research will also be required to determine whether B regs could serve as a useful biomarker for disease control or treatment response in paediatric asthma. These results provide early evidence that biologic therapies may influence key immune regulatory pathways in children and adolescents with persistent asthma, highlighting a potential role for B regs in both disease pathophysiology and therapeutic monitoring.

The findings suggest that biologic therapies targeting Type 2 inflammation may help normalise B reg levels in paediatric asthma

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Oral Food Challenge Refines Infant Peanut Allergy Diagnosis ROUTINE oral food challenges may help avoid unnecessary peanut allergy treatment in infants, according to findings from Australia's nationally standardised ADAPT Oral Immunotherapy (OIT) Program presented at EAACI 2026.6 Peanut allergy is an immunemediated condition in which exposure to peanut proteins can trigger symptoms ranging from mild skin reactions to anaphylaxis. OIT aims to increase tolerance to peanut exposure, but approaches to diagnosis and treatment vary widely across healthcare systems. The study assessed infants through the ADAPT OIT Program, which introduced threshold oral food challenges (TOFC) before treatment in infants with a history of Consortium for Food Allergy Research (CoFAR) Grade 1 or 2 peanut reactions. The aim was to confirm allergy status and identify an appropriate starting dose for immunotherapy. Between April 2024–October 2025, 1,244 infants were assessed across 10 public hospital sites, with 783 (median age: 13 months) undergoing TOFC. The challenge was positive in 65.4% of infants, while 34.6% had a negative result despite a previous clinical reaction and evidence of peanut sensitisation. This suggests that more than one-third of infants who underwent TOFC could be delabelled as having peanut allergy, potentially avoiding unnecessary treatment.

7 mm) than those with negative challenges (median SPT: 5 mm). However, neither measure predicted the reaction threshold or severity during the challenge. Anaphylaxis occurred in 8.3% of infants undergoing TOFC. Among infants with a positive challenge, 12.7% experienced anaphylaxis. Two infants required adrenaline infusion for persistent hypotension, with both recovering without lasting effects. Researchers noted that serious reactions were managed safely in appropriately equipped hospitals. At the time of presentation, 376 infants had started OIT, with 97.1% successfully starting treatment at a dose below their individual reaction threshold identified during TOFC. The researchers concluded that oral food challenges should be routinely considered when evaluating infant peanut allergy, regardless of whether management plans involve immunotherapy or avoidance. Future studies could help clarify the longer-term implications of challenge-based assessment for peanut allergy diagnosis and treatment pathways.

Among infants with positive challenges, the median eliciting dose was 240 mg of peanut protein. Skin prick test (SPT) results and Ara h 2-specific IgE levels were higher in infants with positive challenges (median SPT: CC BY-NC 4.0 Licence

More than one-third of infants who underwent TOFC could be delabelled as having peanut allergy

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Clinical Algorithm Reduces Unnecessary Nut Elimination Diets TREE NUT and peanut allergies are among the most common food allergies in young children and can be difficult to diagnose and manage because spontaneous resolution is uncommon and concerns about severe allergic reactions often lead to prolonged dietary avoidance. Although oral food challenge (OFC) remains the diagnostic gold standard, clinicians may be reluctant to perform challenges because of the perceived risk of anaphylaxis. Consequently, many children continue unnecessary elimination diets that may adversely affect nutrition and quality of life.7 A study presented at EAACI 2026 aimed to develop a practical clinical algorithm incorporating clinical history, skin prick testing (SPT), specific IgE (sIgE) levels, recognised cross-reactivity patterns, and predictive thresholds to guide safer dietary reintroduction. Using this approach, unnecessary elimination was discontinued in 54.9% of avoided nut exposures.

according to the algorithm, only six (3.1%) were positive, comprising two episodes of anaphylaxis and four cases of generalised urticaria. Estimated 50% probability sIgE thresholds ranged from 1.44–10.90 kU/L and corresponding SPT thresholds from 4–6 mm, while 95% probability thresholds ranged from 15.1–63.0 kU/L for sIgE and 7–17 mm for SPT, depending on the specific nut.

This prospective, cross-sectional study enrolled children attending a paediatric allergy and immunology clinic between November 2024–December 2025. Participants were classified according to 2023 EAACI guidance as having allergy, or likely, probable, or possible allergy. All patients underwent fresh food SPT and sIgE testing. OFCs were undertaken when indicated using a four-step incremental protocol. Receiver operating characteristic analyses were performed using confirmed allergic reactions, based on clinical history or OFC, to establish clinically useful cutoff values. Logistic regression modelling was used to estimate probability curves for clinical reactivity.

These findings suggest that integrating clinical history, SPT, sIgE thresholds and selective OFC into a structured clinical algorithm can safely reduce unnecessary elimination diets while maintaining a low OFC positivity rate. This pragmatic approach could support more confident decision-making in routine paediatric allergy practice, reduce unnecessary dietary restrictions, and improve patient quality of life. However, the findings are limited by the single-centre design, relatively small sample size, and the need for external validation before widespread implementation.

Overall, 786 potential tree nut and peanut exposures from 131 children were assessed, with 466 foods initially eliminated from the diet. Elimination was safely discontinued in 256 of 466 cases (54.9%), including 187 following a negative OFC and 69 after negative allergy testing. Complete dietary liberalisation was achieved in 40 children, while 91 continued avoiding at least one nut. Median age at presentation was 34 months, symptom onset occurred at a median of 13 months, and 35.2% presented with anaphylaxis. Among 193 OFCs performed 20

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Unnecessary elimination was discontinued in 54.9% of avoided nut exposures

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Congress Review

Socioeconomic Deprivation Linked to Missed Paediatric Food Allergy Challenges A RETROSPECTIVE audit presented at EAACI 2026 has highlighted a significant socioeconomic disparity in attendance at paediatric oral food challenge appointments, with children from more deprived areas showing higher rates of non-attendance. The study examined whether deprivation and ethnicity influence engagement with specialist food allergy services.8 Oral food challenges are a key component of paediatric food allergy diagnosis and management, allowing clinicians to confirm or exclude allergy and guide dietary decisions. However, missed appointments, including parent cancellations and “Was Not Brought” (WNB) outcomes, reduce clinic efficiency, delay diagnosis, and may contribute to inequalities in care. The Midland Metropolitan University Hospital (MMUH), Smethwick, UK, serves communities including Sandwell and Birmingham, two of the most deprived local authority areas in England, making the evaluation of healthcare access particularly relevant. The audit reviewed 189 scheduled paediatric food challenge appointments between September 2024–September 2025, with 184 cases included after exclusions. Patients were categorised according to deprivation index, with scores grouped into lower (1–3), middle (4–5), and higher (6–10) socioeconomic categories. Attendance outcomes were recorded as completed challenges, parent cancellations, medical cancellations, or WNB episodes.

A clear socioeconomic gradient was observed. Children from the most deprived group accounted for 19 of the 34 WNB cases (55.9%). Within deprivation indices 1–3, WNB occurred in 26% of appointments and parent cancellations in 14%. In contrast, WNB rates were lower among children from higher socioeconomic groups, occurring in 18.5% of cases. Ethnic patterns reflected the deprivation distribution. Among children in the most deprived group, 78% were from ethnic minority backgrounds, compared with around half of those in the least deprived group being White British or from a Mixed ethnic background. Asthma and eczema were the most frequently reported atopic comorbidities across the cohort.

Asthma and eczema were the most frequently reported atopic comorbidities across the cohort The authors concluded that socioeconomic deprivation is strongly associated with reduced engagement with paediatric food challenge services. The findings suggest that standard appointment systems may not adequately address barriers faced by families experiencing deprivation, and that targeted approaches, including improved communication, additional support, and deprivation-sensitive service design, may help reduce missed appointments and improve equity in allergy care.

Overall, 34 children (18.5%) did not attend their appointment, and 24 (13.0%) had appointments cancelled by parents, resulting in a combined parent-driven non-attendance rate of 31.5%.

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References 1.

Bek TM et al. CD4 T cells disrupt the esophageal epithelial barrier and induce eosinophilic esophagitis-like epithelial transcriptional changes. Abstract 000600. EAACI Congress, 12-15 June, 2026.

immediate hypersensitivity reactions to chemotherapy (pleasing both the allergologist and oncologist). Abstract 001693. EAACI Congress, 12-15 June, 2026.

allergy using a threshold oral food challenge in the ADAPT peanut oral immunotherapy program. Abstract 100480. EAACI Congress, 12-15 June, 2026.

García-Escribano C et al. Synergetic stimulation of alarmins and antigenindependent signals induce a potent IFNgamma secretory phenotype on human MAIT cells with immunomodulatory properties. Abstract 000190. EAACI Congress, 12-15 June, 2026.

Yarin Y, Kalaitzidis I. New method for evaluation of sum symptom score for conjunctival provocation test. Abstract 002033. EAACI Congress, 12-15 June, 2026.

Sheehan W et al. Impact of asthma biologic therapies on regulatory B cell levels in children and adolescents with persistent asthma. Abstract 000824. EAACI Congress, 12-15 June, 2026.

Perlato M. Early skin testing as a reliable tool for the management of

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Brettig T et al. OFC before OIT: accurate diagnosis of peanut

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Akın TY et al. A clinical history-, skin prick test- and specific IgE-based algorithm to safely reduce unnecessary elimination in pediatric tree nut and peanut allergy. Abstract 100083. EAACI Congress, 12-15 June, 2026.

Kaur S et al. Food challenges in a district general hospital: ethnic and deprivation index variations. Abstract 100451. EAACI Congress, 12-15 June, 2026.

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Congress Feature

Omics and Allergic Diseases: Fact or Fiction Authors:

*Alma Villaseñor,1,2 Cristobalina Mayorga,3,4 María José Torres3-5 1.

Institute of Advanced Molecular Medicine “Nemesio Díez” (IMMA-ND), Department of Basic Medical Sciences, Faculty of Medicine, San Pablo-CEU University, CEU Universities, Boadilla del Monte, Spain 2. Center of Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, San Pablo-CEU University, CEU Universities, Boadilla del Monte, Spain 3. Allergy Clinical Unit, Hospital Regional Universitario de Málaga, Spain 4. Allergy Research Group, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), Spain 5. Medicine Department, Universidad de Málaga (UMA), Spain *Correspondence to alma.villasenor@ceu.es Disclosure:

The authors have declared no conflicts of interest.

Keywords:

Food allergy (FA), lipid transfer protein (LTP) allergy, microbiome, omics, pectin.

Citation:

EMJ Allergy Immunol. 2026;11[1]:23-26. https://doi.org/10.33590/emjallergyimmunol/US4534RO

OMICS technologies are focused on the massive analysis of systems biology levels. This means analysis of the different steps in the biological process and metabolism, which, in the end, are responsible for the clinical phenotype.1,2 This process starts with the genome, which encompasses the complete set of DNA, including the coding and noncoding genes. Coding genes produce all transcribed RNAs, which are expressed and transcribed into proteins. These, due to their biological activities, determine the metabolites. This mechanism is complex and full of interconnections among levels; thus, information from all levels is necessary to fully understand systems biology.2 Although there are more, genomics, transcriptomics, proteomics, and metabolomics are the main technologies that represent each broad level.

INTRODUCTION A single omics technology can characterise a biological organism at its level, but it is multi-omics integration that will help obtain the overall biological meaning. Clinical decisions should continue based on clinical history but combined with biomarkers coming from the characterisation of molecular phenotypes, such as a set of genes, transcripts, proteins, and/or metabolites, as well as cellular characteristics, to reach personalised medicine.3 CC BY-NC 4.0 Licence

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In the context of allergy, we have an umbrella of different diseases, including allergic rhinitis, asthma, drug allergy or hypersensitivity drug reactions, food allergy, and atopic dermatitis. These have a significant impact on the global population.2 Most of them have a common feature to be elicited by effector cells (including mast cells, eosinophils, basophils) and the release of pro-inflammatory cytokines and metabolic mediators upon exposure to an allergen.2 However, important questions, such as the molecular mechanisms underlying different endotypes to make

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a precise diagnosis, or how the patient evolves from a mild allergic phenotype into a severe one, or biomarkers for monitoring the response to allergen-immunotherapy, are still unsolved; here, omics technologies can be applied.

A single omics technology can characterise a biological organism at its level, but it is multi-omics integration that will help obtain the overall biological meaning

In a recent publication, the results of the DIFAMEM clinical trial, funded through the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL) European Research Area Network (ERANET), a European programme supporting transnational research on nutrition and health, were reported. The study adopted a multi-omics approach to investigate food allergy (FA).4 Lipid transfer protein (LTP) allergy is a prevalent FA in adults and is very heterogenous, as symptoms can range from mild manifestations such as oral allergy 24

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syndrome, to life-threatening reactions, including anaphylaxis. This means that allergen immunotherapy is not beneficial for some patients with LTP allergy. FA has been associated with microbial dysbiosis; the use of prebiotics has emerged as a promising option to restore the microbiome.5,6 Thus, the aim of DIFAMEM was to evaluate the use of prebiotics to treat LTP allergy. The prebiotics employed were pectins, which are natural polysaccharides usually found in the peel and pulp of fruits. Based on their esterification degree, pectins can be classified as low- or high- methoxyl pectins (LMP or HMP, respectively). Although both pectins have shown potential to be immune regulators, LMP is more fermentable by the microbiota than HMP.5,6 In DIFAMEM, 37 patients with a clinical history of FA, who were sensitised to the LTP allergen from peaches, Pru p 3, were recruited.4 Patients were randomly allocated into three groups to receive placebo or one of two pectin varieties with different degrees of esterification: citrus-derived pectin (CP), a LMP pectin derived from citrus fruits; and AP, an HMP pectin derived from apples.4 Serum and faecal samples were obtained before and after 2 months

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of intervention.4 Serum samples were used to perform targeted proteomics, whereas faeces were used for metagenomics and targeted metabolomics. Finally, the generated data were integrated using bioinformatic tools.4 Additionally, to assess the clinical efficacy of the pectin treatment, patients were on a double-blind placebocontrolled food challenge (DBPCFC) to Pru p 3, before and after the pectin intervention.4 Clinical characteristics of the enrolled patients with LTP allergy indicated that the majority of the participants were female and presented with rhinitis. Participants were positive to inhalant allergens, being mainly sensitised to olive and plane tree pollens. Regarding other LTP sensitisations, peanuts, walnuts, and hazelnuts were the main plant foods that participants were sensitised to. Results from the DBPCFC confirmed that none of the participants reached the maximum dose of the challenge, and only mild and moderate reactions were observed.4 These findings suggested that the groups were very homogenous before starting the treatment with pectin. After the 2-month intervention, no significant differences were found for specific IgE (sIgE) or skin-prick test, except

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for an increase in the wheal area for the CP after the treatment. Regarding the amount of Pru p 3 tolerated after the treatment, the authors found a significant increase in tolerated allergen in around 50% of the patients from both pectin groups, but not in the placebo group.4 Interestingly, following pectin treatment, four patients in the CP group and five patients in the AP group tolerated the maximum cumulative dose of Pru p 3, equivalent to the amount of allergen present in one medium-sized peach. Regarding the systemic proteins, the authors found that several of the significantly altered proteins highly related to the Th2 response. Common to both pectins, they found a decrease in IL-13 and IL-24 compared to placebo. However, specific changes were found for each pectin. For the AP treatment, IL-4 and TSLP were found to be reduced compared to placebo, suggesting a higher impact on the Th2 response. In the CP group, IL-33 and IL-17C were observed to be decreased compared to placebo, suggesting the downregulation of the Th17 response.4 Although these findings suggest a systemic decrease of the allergic response, they point out that each pectin follows a different path.

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Regarding the faecal metagenomics analysis, contrary to what was expected, the α-diversity of the gut microbiota of both pectin-treated groups was reduced after the intervention. Bacterial diversity reduction was associated with an increase in the abundance of pectin-degrading taxa. Some of these alterations were common to both pectins, whereas others were specific to each treatment. Among these, the authors highlighted the increase in the Bacteroides genus in the case of the CP, and Bifidobacterium in the case of AP.4 The metagenome prediction with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed five pathways that were common to both pectins. Among them, the production of microbial-derived metabolites, such as primary and secondary bile acids biosynthesis, was highlighted.4 Driven by these findings, bile acids and short-chain fatty acids (SCFA) were analysed in faecal samples. The faecal metabolome was also observed to be modified by both pectins. Surprisingly, no significant differences were observed in the canonical SCFA (i.e., acetic, propionic, and butyric acids). Instead, reduced concentrations of branchedSCFA in both pectins, namely isobutyric, isovaleric, and 2-methylbutyric acids, were found in the pectin-treated groups. These are the bacterial products of the fermentation of the branched-chain amino acids.4 Additionally, the authors confirmed alterations in the levels of primary and secondary bile acids modified by both pectins when compared to placebo.4

References 1.

Radzikowska U et al. Omics technologies in allergy and asthma research: an EAACI position paper. Allergy. 2022;77(10):2888-908. Tontini C et al. The use of omics sciences in allergic diseases from bench to bedside: an EAACI position paper. Allergy. 2025;80(9):2442-83.

Due to the potential interaction between the faecal metabolites and proteins and bacterial taxa, correlation analyses were carried out. Branched-SCFA were significant and positively correlated with Th2-type inflammatory cytokines such as IL13, IL4, and IL33, and with the Th17-response by the cytokine IL17C.4 These associations were not observed for the canonical SCFA. These findings highlighted their yet unexplored importance. Multi-omics integration revealed a possible stronger immune modulation by AP treatment, as the analysis showed one model that clustered the AP group separately from the others.4 Discussing the title of this presentation, are the omics findings a fact or fiction? The interest in omics findings in allergy has been captured in different and important reviews.2,3,7 A position paper published last year points out that in the near future, the analysis of some omics markers could be of help to detect patients at asthma risk, defining asthma endotypes, or the severity of the patients.2

CONCLUSION In summary, omics are rapidly expanding our knowledge of allergic diseases. We are still in the process of extracting critical information that can be effectively used in clinical practice. As shown by the DIFAMEM clinical trial, discovered molecular targets should be explored in follow-up studies to better understand their role in the allergic process.

of allergen immunotherapy. J Allergy Clin Immunol. 2025;156(3):523-34. 4.

Shamji MH et al. Multiomics approach to evaluating personalized biomarkers

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Gómez F et al. Multi-omics analysis of a prebiotic intervention with pectin in lipid transfer proteins (LTPs) allergic patients. Carbohydr Polym. 2025;369:124236. Blanco-Pérez F et al. The dietary fiber pectin: health benefits and potential for the treatment of allergies by modulation of gut microbiota. Curr Allergy Asthma Rep. 2021;21(10):43.

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Steigerwald H et al. Effects of pectin methyl-esterification on intestinal microbiota and its immunomodulatory properties in naive mice. Carbohydr Polym. 2024;334:122007.

Saito H et al. Omics in allergy and asthma. J Allergy Clin Immunol. 2024;154(6):1378-90.

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Abstract Reviews Drawing on new insights from the European Association of Allergy and Clinical Immunology (EAACI) Congress 2026, these abstract reviews highlight notable new research in the field of allergy and immunology.

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Clustering of Tree Allergen Components and Phylogenetic Analysis of Patient Profiles Reveal Key Combinations for Allergen Immunotherapy Authors: Maryna Yasniuk,1 *Victoria Rodinkova,1 Serhii Yuriev,2 Vitalii Mokin,3 Georgii Goriachev,3 Nataliia Vasylieva4 1. National Pirogov Memorial Medical University, Vinnytsya, Ukraine 2. DIVERO Medical Centre, Kyiv, Ukraine 3. Vinnytsia National Technical University, Vinnytsia, Ukraine 4. Odesa I.I. Mechnikov National University, Odesa, Ukraine *Correspondence to rodinkova@vnmu.edu.ua Disclosure: Rodinkova has received support for attending the European Academy of Allergy and Clinical Immunology (EAACI) 2026 Congress. The other authors have declared no conflicts of interest. Keywords: Allergen immunotherapy, component-resolved diagnostics, non-specific lipid transfer proteins, polysensitisation, pathogenesis-related protein 10 (PR-10), pectate lyases, tree pollen, Ukraine. Citation: EMJ Allergy Immunol. 2026;11[1]:28-29. https://doi.org/10.33590/emjallergyimmnol/74GZ3004

BACKGROUND AND AIMS Polysensitisation to tree pollen allergens is a central challenge in the diagnosis and management of respiratory allergy, particularly in regions spanning multiple bioclimatic zones. Identifying the molecular architecture of sensitisation profiles rather than relying solely on whole-allergen extracts is increasingly recognised as essential for effective allergen immunotherapy (AIT). This study applied component-resolved diagnostics and bioinformatic clustering to characterise real-world sensitisation patterns across Ukraine.1

MATERIALS AND METHODS Data were drawn from 7,518 individuals from 17 Ukrainian regions who were sensitised to tree pollen components and tested between 2020–2022, using the 28

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ALEX multiplex microarray platform (Macro Array Diagnostics, Vienna, Austria; 295 allergen components). Agglomerative clustering with Ward’s method was applied to all 295 molecular components to identify co-sensitisation patterns. The most frequent allergen combinations (pairs, triplets, and four- or five-molecule sets) within patient profiles were enumerated computationally. Phylogenetic analysis of allergen amino acid sequences, using the Multiple Alignment using Fast Fourier Transform (MAFFT), Multiple Sequence Comparison by Log-Expectation (MUSCLE), and ClustalW alignment algorithms with the Iterative Quick Tree (IQ-TREE) maximum-likelihood framework, was performed to compare biologically driven groupings against clinical clustering.

RESULTS Clustering analysis revealed that most allergen groupings aligned with established biochemical classes: pathogenesis-related protein 10 (PR-10) proteins (Bet v 1, Aln g 1, Cor a 1.0103, Fag s 1, Mal d 1), nonspecific lipid transfer proteins (Pla a 3, Cor a 8, Mal d 3), profilins (Bet v 2, Hev b 8), and pectate lyases (Cry j 1, Amb a 1), each formed coherent, phylogenetically supported clusters. The most frequent binary sensitisation combination was co-reactivity to the pectate lyases Amb a 1 (ragweed) and Cry j 1 (Japanese cedar/ Cupressaceae), reflecting cross-reactivity to ragweed with ornamental conifers widely planted in Ukrainian cities. Co-sensitisation to Bet v 1 and the food homologue Mal d 1 (apple) was found in 23.1% of tested individuals, a prevalence equal to that of the Bet v 1 – Amb a 1 combination and a clinically recognised predictor of pollen-food allergy syndrome. The major cat allergen Fel d 1, despite lacking structural homology to any tree allergen, recurred prominently in triplet and higher-order profiles alongside pollen molecules; a pattern attributed

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to its adjuvant-like ubiquity in indoor environments rather than cross-reactivity. Grass components (Phl p 1, Lol p 1, and notably the subtropical Cyn d 1) appeared in approximately one-fifth of complex profiles, suggesting climate-driven northward migration of southern species and an extension of the effective allergy season.

CONCLUSION The integration of clinical clustering with phylogenetic analysis demonstrates that co-sensitisation in this population is driven by a combination of protein homology, regional ecology, and indoor allergen exposure rather than by random accumulation. The dominant molecular nodes identified (PR-10 proteins and pectate lyases, each affecting over 40% of sensitised individuals) provide a rational

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basis for designing precision allergen immunotherapy formulations. The authors propose that Cry j 1 positivity in cedar-free zones should be interpreted as a marker for local Cupressaceae cross-reactivity, that early detection of Bet v 1 and Phl p 1 sensitisation in children should prompt prophylactic intervention, and that urban landscaping policy should consider the allergenic burden of ornamental tree selection. Further investigation into cross-kingdom sensitisation pathways and the immunological basis of phylogenetically non-obvious allergen clusters is warranted.

Reference 1.

Yasniuk M et al. Clustering of tree allergen components and phylogenetic analysis of patient profiles reveal key combinations for allergen immunotherapy. Abstract 001848. EAACI Congress, 12-15 June, 2026.

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Characterising Endovascular Profiles in ACE Inhibitor-Induced Angioedema in a South African Cohort Authors: *Sarah Pedretti,1,2 Rachael Gachogo,2 Nomawethu Masina,1 Cascia Day,2 Jonny Peter1,2 1. Allergy and Immunology Unit, University of Cape Town Lung Institute, South Africa 2. Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, South Africa *Correspondence to sarah.pedretti@uct.ac.za Disclosure: Pedretti has received travel support for attendance at the EAACI Congress from the University of Cape Town. Day has received honoraria from the Allergy Foundation of South Africa; and holds a leadership role in the Allergy Society of South Africa Executive Committee, Education Division. Peter has received grants from NIHR Global Professorship, the South African Medical Research Council, the Wellcome Trust, and the National Institutes of Health; has participated on advisory boards for Argo Biopharma, Novartis, and ITM Belgium; and holds leadership roles in the Allergy of South Africa Executive Committee, National Immunisation Safety Executive Committee, IUIS Clinical Immunology Committee, WAO Drug Allergy Committee, and AAAAI Drug and Latex Committee. The other authors have declared no conflicts of interest. The present manuscript received research funding from the South African Medical Research Council. Acknowledgements: The authors would like to thank the patients, without whom this work would not be possible. They also thank Wisahl Wallace, Thandokazi Bezana, and Nomafu Jayiya for all administrative assistance. Appreciation is extended by the authors to the Provincial Health Data Centre (PHDC) team for their valuable contributions. Situated within the Western Cape Government: Department of Health and Wellness, the Provincial Health Data Centre functions as a Health Information Exchange, established to positively impact patient care and health outcomes by leveraging data and technology. Keywords: Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI), bradykinin (BK), endothelial activation, inflammation, Olink® proteomics (Thermo Fisher Scientific, Waltham, Massachusetts, USA), vascular inflammation, vascular permeability. Citation: EMJ Allergy Immunol. 2026;11[1]:30-31. https://doi.org/10.33590/emjallergyimmunol/C0Z0005N

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BACKGROUND AND AIMS Angiotensin-converting enzyme inhibitorinduced angioedema (AE-ACEI) is more frequent in Black African populations.1,2 Although bradykinin (BK) is central to current models, incomplete response to B2 receptor antagonism3 suggests additional inflammatory and endothelial activation mechanisms during acute attacks. The authors’ aim was to characterise inflammatory and endothelial markers in AEACEI cases by measuring plasma and serum profiles during acute episodes and recovery, compared with ACEI-tolerant controls.4

MATERIALS AND METHODS Over 4 years, 54 patients with AE-ACEI were sampled during acute episodes (AE) and at follow-up (FU; 3–6 months postAE), alongside 91 ACEI-tolerant matched controls (MC; median [interquartile range]: 10.4 [7.9] years on ACEI). Plasma BK, secreted phospholipase 2 (sPLA2), and vascular endothelial growth factor (VEGF) were quantified by ELISA. Serum tryptase and total IgE were measured using UniCAP fluoroimmunoassay. C-reactive protein (CRP), D-dimer, and fibrinogen were processed at the local National Reference Laboratory. A total of 92 inflammationrelated proteins were profiled using proximity extension assay (Olink®, Thermo Fisher Scientific, Waltham, Massachusetts, USA). Wilcoxon testing with correction for multiple comparisons was applied.

RESULTS Plasma BK levels were significantly higher in AE-ACEI cases, at both AE and FU, compared to MC. During AE, VEGF and sPLA2 levels were increased relative to FU and MC for VEGF only. Total IgE (measured only AE) was higher in AE-ACEI cases compared to MC. Acute CRP, D-dimer, and fibrinogen levels were elevated

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relative to FU and MC. Proteomic analysis demonstrated a distinct acute endovascular signature. Pairwise comparison between AE and FU revealed increased EN-RAGE and OSM in AE samples, accompanied by vascular permeability and repair mediators (VEGFA, HGF), and endothelial–immune interaction markers (TNFSF14/LIGHT, CD40, TGF-α). Importantly, FU samples did not differ from MC after multiple-testing correction, indicating resolution of the acute proteomic signature.

CONCLUSION AE-ACEI is characterised by a transient, attack-specific endovascular inflammatory programme involving RAGE-axis activation, endothelial permeability mediators, and immune–endothelial crosstalk, rather than isolated BK excess. The absence of proteomic differences at FU supports

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a reversible, event-locked vascular inflammatory process. Further work is required to understand distinct endotypes and compare with other acute angioedemas.

References 1.

Brown NJ et al. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996;60(1):8-13.

Burkhart DG et al. Angiotensin converting enzyme inhibitor-associated angioedema: higher risk in blacks than whites. Pharmacoepidemiol Drug Saf. 1996;5(3):149-54.

Jeon J et al. Effect of icatibant on angiotensinconverting enzyme inhibitor-induced angioedema: a meta-analysis of randomized controlled trials. J Clin Pharm Ther. 2019;44(5):685-92.

Pedretti S et al. Characterising endovascular profiles in ACE inhibitor–induced angioedema in a South African cohort. Abstract 100370. EAACI Congress, 12-15 June, 2026.

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Testing a Predictive Diagnostic Scale for NSAID Hypersensitivity in Paediatric Patients Authors: P. Falabella,1 *A. Machinena-Spera,1,2 M. Piquer-Gibert,1,2 M.M. Folqué,1,2 O. Domínguez,1,2 R. Jiménez-Feijoo,1,2 J. Lozano-Blasco,1,2 M. Alvaro-Lozano1,2

cohort of paediatric patients referred to the authors’ tertiary paediatric allergy department for suspected NSAID-HSR between 2022–2025.

1. Hospital Sant Joan de Déu, Barcelona, Spain 2. Institut de Recerca Sant Joan de Déu, Barcelona, Spain *Correspondence to adrianna.machinena@sjd.es

MATERIALS AND METHODS

Disclosure: The authors have declared no conflicts of interest. Keywords: Drug provocation test (DPT), hypersensitivity reactions (HSR), non-steroidal anti-inflammatory drugs (NSAID), paediatric allergy, predictive diagnostic scale, risk stratification, urticaria/angioedema. Citation: EMJ Allergy Immunol. 2026;11[1]:32-33. https://doi.org/10.33590/emjallergyimmunol/I83A5R59

BACKGROUND AND AIMS Non-steroidal anti-inflammatory drugs (NSAID) are among the most common triggers of drug hypersensitivity reactions (HSR) in paediatric patients. Diagnosing NSAID-HSR in children remains challenging, as clinical history alone is often insufficient to distinguish HSRs from non-allergic reactions. A drug provocation test (DPT) is the gold standard, but it is timeand resource-consuming and carries potential risks to patients undergoing the procedure.1-3 Identifying tools to stratify NSAID-HSR risk before DPT remains challenging.4 The authors previously developed a clinical prediction scale to facilitate diagnostic evaluation of suspected NSAID-HSR in children.5 It included five variables: age >12 years, presence of angioedema, absence of exanthema, ≥2 NSAID-related reactions, and pain as an indication for NSAID administration. Each variable was scored 0–1 (total 0–5); a cutoff ≥3 yielded 82.4% sensitivity and 62.4% specificity (Table 1). The present prospective, tertiary, singlecentre study aimed to validate the performance of this scale in a real-world 32

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All patients included underwent standardised NSAID-DPT according to institutional protocols. Hypersensitivity phenotypes were classified following the European Academy of Allergy and Clinical Immunology (EAACI) 2018 position paper. A total of 72 paediatric patients were evaluated, with an equal distribution by sex. Median age at onset was 9 years, while the median age at DPT was 11 years (interquartile range: 5–12 years). Nearly half the patients had a personal history of atopy, predominantly respiratory allergy. Ibuprofen was the most frequently implicated drug, representing more than three-quarters of suspected HSR. Pain was the primary indication for NSAID use, followed by fever.

RESULTS Angioedema (78%) was the most common symptom at onset, and in 39% of patients it occurred in an isolated form. Exanthema was presented in 53% of patients, either alone or associated with other symptoms. Respiratory symptoms were less common (five patients). More than 40% of children reported at least two previous suspected NSAID-HSRs. At baseline, 16 patients presented with isolated exanthema; of these, 14 (87.5%) tolerated the drug upon evaluation. NSAID-HSR was confirmed in only two of these cases (2/16), with paracetamol identified as the culprit drug in both. A total of 105 DPTs were performed, confirming NSAID-HSRs in 30.6% (n=22) of patients. Cross-intolerance phenotypes predominated (17/22), particularly NSAID-induced urticaria/angioedema/ anaphylaxis (NSAID-induced urticaria/

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Table 1: Clinical predictive score for NSAID hypersensitivity (0–5 points).

HSR: hypersensitivity reaction; NSAID: nonsteroidal anti-inflammatory drugs.

angioedema, NSAID-induced urticaria/ angioedema/anaphylaxis), while selective-HSRs (5/22) were less frequent. After applying the predictive scale, the authors observed that: among patients with a score of less than 3 points, 94.3% had negative DPT results (p<0.001), while among those with a positive DPT (n=22), 90.9% had a score of ≥3 (p<0.001). Analysis of the receiver operating characteristic (ROC) curve yielded an area under the curve of 0.815 (95% CI: 0.700–0.919), indicating a good discriminatory power. A cut-off value of ≥3 points was used, with a sensitivity of 90% and a specificity of 66%.

prospective multicentre studies are needed to validate these findings and facilitate their implementation in clinical practice.

References 1.

Kidon M et al. EAACI/ENDA position paper: diagnosis and management of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in children and adolescents. Pediatr Allergy Immunol. 2018;29(5):469-80.

Barbaud A et al. EAACI/ENDA position paper on drug provocation testing. Allergy. 2024;79(3):565-79.

Topal OY et al. Results of NSAID provocation tests and difficulties in the classification of children with nonsteroidal anti-inflammatory drug hypersensitivity. Ann Allergy Asthma Immunol. 2020;125(2):202-7.

Stehlin F et al. Guiding drug provocation testing for ibuprofen hypersensitivity in a pediatric population: development of the I3A risk-stratification tool. J Allergy Clin Immunol Pract. 2205;13(3):583-93.e3.

Falabella P et al. Testing a predictive diagnostic scale for NSAID hypersensitivity in pediatric patients. EAACI Congress, 12-15 June, 2026.

CONCLUSION The scale applied to the prospective cohort demonstrated improved diagnostic performance, particularly in terms of sensitivity, when compared to the original model. Its use could improve patient selection for DPT, helping to prioritise testing and reduce procedures in low-risk patients. In this cohort, the presence of isolated exanthema indicated a low risk of developing an NSAID-HSR. Further CC BY-NC 4.0 Licence

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Congress Interviews EMJ is delighted to present exclusive interviews with three leading figures from the European Academy of Allergy and Clinical Immunology (EAACI): María Torres, the EAACI President, who discusses the Congress theme of ‘Vision Zero in Allergy’ and the latest advances in precision medicine and allergen immunotherapy; Ian Adcock, Vice President of Science, who explores the future of asthma care, biomarkers, and AI-driven personalised treatment; and Aspasia Karavelia, Chair of the Junior Members Assembly, who shares her perspective on empowering the next generation of allergy specialists and advancing integrated airway care. Featuring: María Torres, Aspasia Karavelia, and Ian Adcock

EMJ Allergy Immunol. 2026;11[1]:34-40. https://doi.org/10.33590/emjallergyimmunol/Q2W2APL2

Citation:

Q1 María Torres President of the European Academy of Allergy and Clinical Immunology (EAACI); Head of the Allergy Department, Malaga Regional University Hospital, Spain

Our goal is to move towards a future with zero preventable deaths, zero avoidable severe exacerbations, and minimal disease burden for patients living with allergic conditions 34

As President of EAACI and of the 2026 Congress, how would you describe the scientific and clinical priorities shaping this year’s programme? How does the 2026 Congress build on last year’s focus, whilst still adapting to any changes occurring in the field over the past year? As President of EAACI and of the 2026 Congress, I would describe this year’s scientific and clinical priorities under a clear and ambitious theme: ‘Vision Zero in Allergy’. Our goal is to move towards a future with zero preventable deaths, zero avoidable severe exacerbations, and minimal disease burden for patients living with allergic conditions. This vision is grounded in robust science and a strong commitment to clinical implementation. The central focus of the programme is allergen

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immunotherapy (AIT), not only as a disease-modifying treatment, but as a strategic tool capable of altering the natural course of allergy. We will highlight the latest advances in subcutaneous and sublingual AIT, emerging indications, predictive biomarkers of response, patient selection strategies, real-world evidence, and its role in early intervention and prevention. The 2026 Congress builds on the progress presented in 2025 by moving from innovation to practical integration, incorporating new clinical trial data, updated therapeutic algorithms, and the increasing role of precision medicine and digital tools in everyday care. At the same time, we continue to address severe and complex diseases, the impact of climate change, and the need for more integrated and sustainable models of care. In essence, this year’s programme reflects both continuity and

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evolution, maintaining the scientific momentum of last year while adapting decisively to the rapid advances shaping the field, always with the patient at the centre of our efforts.

Your work has consistently focused on improving diagnostic precision in allergy. How does the 2026 Congress reflect this shift from simply identifying sensitisation to defining clinically meaningful disease and treatment eligibility? My work has long centred on improving diagnostic precision in allergy, and the 2026 Congress clearly reflects this evolution: from merely identifying sensitisation to defining clinically meaningful disease and treatment eligibility. In line with our ‘Vision Zero in Allergy’ theme and strong focus on AIT, we emphasise diagnostics that directly inform safer and more effective clinical decisions. One important example is the progress in in vitro testing for drug allergy, including validated cellular and immunoassays

that help confirm or exclude hypersensitivity reactions. These tools significantly reduce the need for high-risk drug provocation tests, improving patient safety while streamlining care. At the same time, more accurate laboratory diagnostics facilitate better risk stratification, allowing us to identify patients who can safely undergo desensitisation protocols when treatment with first-line drugs is essential. In respiratory allergy, the Congress also highlights the growing role of nasal provocation testing to diagnose local allergic rhinitis. By distinguishing true local allergic disease from nonallergic rhinitis or asymptomatic sensitisation, we can more accurately select patients who are likely to benefit from AIT. This shift, from detecting IgE sensitisation to confirming clinically relevant, organ-specific disease, represents a fundamental step toward precision allergy care and ensures that advanced therapies are offered to the right patients at the right time.

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Food allergy has traditionally been managed through strict avoidance, but this paradigm is clearly evolving. How is the 2026 Congress addressing the growing role of active treatment strategies, such as low-dose oral and sublingual immunotherapy, particularly regarding safety and patient selection? Food allergy management is undergoing a profound transformation, and the 2026 Congress fully reflects this shift from strict avoidance toward active, disease-modifying treatment strategies. While avoidance and emergency preparedness remain essential, we are now entering an era in which oral immunotherapy (OIT) and adjunctive biologics are redefining standards of care. A major focus of the programme is the evolution of low-dose OIT protocols, which aim to improve safety while maintaining efficacy. Over recent years, we have gained important insights into optimal dosing

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regimens, build-up schedules, and maintenance strategies that reduce the frequency and severity of adverse reactions. Real-world data and long-term follow-up studies presented at the Congress address sustained unresponsiveness, quality of life improvements, and the balance between desensitisation and true tolerance induction. Particular attention is given to patient selection, identifying those most likely to benefit from OIT based on clinical history, biomarker profiles, and comorbidities such as asthma. Equally transformative is the advent of biologics in food allergy. Anti-IgE therapy and emerging biologics targeting Type 2 inflammation are reshaping how we approach high-risk patients. These agents can be used as monotherapy in selected cases or as adjuncts to OIT to enhance safety, reduce reaction rates, and facilitate more rapid up-dosing. The integration of biologics opens new possibilities for patients previously considered unsuitable for immunotherapy due to severe reactions or multiple food allergies.

At the 2026 Congress, we emphasise structured protocols, shared decision-making, and clear criteria for treatment eligibility. The goal is not simply to expand access to active therapies, but to implement them responsibly, safely, and based on robust evidence, moving food allergy care toward a more proactive and personalised future.

Which biomarkers or functional assays do you believe hold the greatest promise for guiding clinical decision-making?

In my view, the most promising biomarkers and functional assays are those that move us beyond simple sensitisation and help us quantify clinical risk, predict severity, and guide therapeutic decisions. First, we must not underestimate the importance of clinical risk stratification. A detailed history, including reaction phenotype, timing, co-factors, comorbid asthma, and previous anaphylaxis, remains the foundation of precision allergy

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care. Clinical context is still the most powerful ‘biomarker’ when integrated systematically into structured algorithms. Among functional assays, the basophil activation test (BAT) holds significant promise. By measuring basophil responsiveness upon allergen exposure, BAT provides a functional readout of IgE-mediated reactivity and correlates with reaction severity in food, venom, and drug allergy. It can reduce the need for high-risk provocation tests and may help monitor response to immunotherapy. Similarly, emerging mast cell activation tests, including ex vivo models assessing mediator release, may further refine risk prediction, particularly in complex or severe phenotypes. Beyond cellular assays, omics sciences, including transcriptomics, proteomics, and metabolomics, are opening new avenues for identifying molecular endotypes, predicting treatment response, and stratifying patients for biologics or immunotherapy. While not yet fully integrated into routine practice,

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they are rapidly moving from discovery to clinical applicability. Finally, well-standardised in vivo provocation protocols remain indispensable. Oral food challenges, drug provocation tests, and nasal or bronchial challenges, when performed in controlled settings, continue to serve as reference standards. The future lies in integrating clinical risk factors, functional assays, molecular biomarkers, and carefully designed provocation protocols into cohesive decision-making pathways that maximise safety while enabling personalised therapy.

What steps is EAACI taking to integrate delabelling pathways into routine care, and how will this improve antimicrobial stewardship and health system efficiency? EAACI is taking concrete steps to integrate structured drug allergy de-labelling pathways into routine clinical care, recognising that inaccurate antibiotic allergy labels (particularly to beta-lactams) have major consequences for both individual patients and public health. A key pillar is risk stratification based on clinical history, allowing clinicians to distinguish low-risk patients who can safely undergo direct oral challenge from those who require skin testing or more complex evaluation. Standardised algorithms and educational initiatives are being disseminated across member countries to harmonise practice and ensure safety. In parallel, EAACI is supporting the development and implementation of AI-based decision-support tools built on validated clinical risk factors. A recent example is the beta-lactam allergy predictor, which helps quantify the likelihood

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of true hypersensitivity and guide appropriate testing pathways. These digital tools aim to simplify triage, reduce unnecessary referrals, and facilitate de-labelling directly within hospital and primary care settings. By safely removing incorrect allergy labels, patients can receive first-line, narrowspectrum antibiotics instead of broader alternatives. This directly improves antimicrobial stewardship, reduces healthcare costs, shortens hospital stays, and lowers the risk of adverse drug reactions associated with second-line agents. Importantly, appropriate antibiotic use is a critical strategy in reducing antimicrobial resistance. Through its ongoing campaign on antibiotic resistance, EAACI is actively raising awareness of the link between mislabelled drug allergy and antimicrobial resistance, promoting multidisciplinary collaboration between allergists, infectious disease specialists, pharmacists, and policymakers. De-labelling is therefore not only a clinical priority, but also a systemic intervention to improve health system efficiency and safeguard future antibiotic effectiveness.

Biologic therapies are now central to the management of multiple allergic and eosinophilic diseases. How is the Congress addressing the challenge of matching biologic treatments to inflammatory endotypes rather than traditional disease labels? Biologic therapies have fundamentally changed the management of allergic and eosinophilic diseases, but the key challenge today is no longer access; it is precision. The 2026

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Congress directly addresses the need to move beyond traditional disease labels such as asthma, atopic dermatitis, or chronic rhinosinusitis, and instead match biologics to the underlying inflammatory endotype driving disease in each individual patient. A major focus of the programme is the development and validation of biomarkers derived from omics sciences, including transcriptomics, proteomics, and molecular profiling, to better characterise Type 2 and non–Type 2 inflammation. These tools allow us to identify dominant pathways, such as IgE-mediated mechanisms, IL-4/IL-13 signalling, or IL-5-driven eosinophilia, and to understand how these pathways overlap in complex cases. Many patients present with multimorbidity and multiple inflammatory mechanisms; therefore, the challenge is to determine which pathway is clinically most relevant and therapeutically actionable at a given time. The Congress also highlights strategies for prioritising targets in patients with overlapping phenotypes and partial responses, including switching and sequencing

approaches. Importantly, we are presenting growing realworld evidence demonstrating the effectiveness of biologics in broader or evolving indications, beyond those initially studied in pivotal trials. These data help refine patient selection, identify predictors of response, and inform cost-effectiveness discussions. Ultimately, our goal is to integrate molecular biomarkers, clinical features, and real-world outcomes into a coherent decision-making framework, ensuring that each patient receives the biologic most aligned with their individual inflammatory signature rather than a one-size-fits-all approach based solely on diagnostic category.

central driver linking skin, gut, and airway disease. This concept is profoundly influencing current research directions by shifting attention toward epithelial biology, barrier integrity, and the mechanisms regulating host–environment interactions. Rather than viewing atopic dermatitis, food allergy, and asthma as isolated conditions, we now understand them as interconnected manifestations of impaired epithelial homeostasis across different organs.

There is growing recognition that epithelial barrier dysfunction links skin, gut, and airway disease. How is this concept influencing current research directions, and do you see it reshaping prevention or early-intervention strategies in allergy?

Current research is exploring how genetic susceptibility, environmental exposures, microbiome alterations, and pollutants disrupt epithelial tight junctions and immune signalling. The goal is to identify molecular pathways that can be targeted to restore barrier function and resilience. This includes investigating barrier-enhancing topical strategies, microbiome modulation, and biologics or small molecules that reduce epithelial inflammation and promote repair.

There is increasing recognition that epithelial barrier dysfunction is not simply a consequence of allergic inflammation, but a

Importantly, this paradigm has major implications for prevention. Restoration and maintenance of epithelial health in early life may

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help prevent allergen sensitisation and the onset of respiratory, skin, and food allergies, representing a true primary prevention strategy. If we can preserve barrier integrity before immune dysregulation becomes established, we may interrupt the atopic march at its earliest stages. Even once allergic disease is established, improving epithelial homeostasis may reduce disease severity, prevent exacerbations, and limit the development of comorbidities. In this sense, barrierdirected approaches may also serve as secondary or even tertiary prevention strategies, preventing progression and multimorbidity. Overall, the epithelial barrier concept is reshaping how we think about allergy, not only as immune dysregulation, but as a failure of tissue resilience, and opening new avenues for earlier, more preventive, and more integrated therapeutic interventions.

You have previously highlighted the potential of AI and digital health in allergy care. Where do you see digital tools making the most immediate difference and how is this reflected in the Congress programme? I see digital tools and AI making their most immediate impact in areas where pattern recognition and data integration are critical. At the 2026 Congress, AI and digital health are fully embedded in the programme, not only within dedicated Innovation Hub sessions, but also integrated into plenary discussions, reflecting their transition from experimental concepts to practical clinical tools. In the short term, AI is already proving highly valuable in image-based diagnostics. Algorithms trained to analyse

skin lesions, radiological images of the sinuses or lungs, and even histopathology slides can support more accurate and standardised interpretation. In allergology, where differential diagnosis may include inflammatory, infectious, or immune-mediated conditions, these tools can enhance diagnostic precision and reduce variability between observers. They also facilitate multidisciplinary collaboration, particularly in complex cases requiring dermatologic, pulmonary, or pathological input. Beyond imaging, digital platforms for structured symptom monitoring, remote follow-up, and adherence tracking are improving longitudinal disease management. These tools generate high-quality real-world data that can inform clinical decisions and optimise treatment adjustments.

Which under-recognised diseases or mechanisms do you feel deserve greater attention from the allergy community in the coming years, and why? While Type 2-driven diseases have seen extraordinary therapeutic progress, I believe several nonType 2 conditions deserve far Copyright © 2026 EMJ

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greater attention from the allergy community in the coming years, precisely because major unmet needs remain. First, non-Type 2 asthma represents a significant clinical challenge. These patients often lack eosinophilia or classical biomarkers and respond poorly to currently available biologics. The underlying mechanisms, whether neutrophilic inflammation, epithelial dysfunction, metabolic factors, or mixed endotypes, are still insufficiently defined. Without a clearer mechanistic understanding, we cannot develop targeted diagnostics or effective therapies.

Food protein-induced enterocolitis syndrome is another underrecognised condition. Although awareness has increased, its pathophysiology is not fully elucidated, reliable biomarkers are lacking, and diagnosis often depends on oral food challenges. This creates anxiety for families and variability in care.

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Similarly, most non-immediate drug hypersensitivity reactions remain poorly characterised. Unlike IgE-mediated reactions, delayed T cell-mediated responses involve complex immunopathology that is not yet fully understood. Diagnostic tools are limited, in vitro assays are not standardised, and we still rely heavily on clinical history and, in selected cases, cautious re-exposure. This uncertainty directly impacts patient safety and antimicrobial stewardship.

Looking ahead, the real transformative potential lies in AIdriven symptom-based diagnostic algorithms and prediction models for therapy response. By integrating clinical data, biomarkers, and patient-reported outcomes, digital systems may help identify the most appropriate biologic or immunotherapy strategy for each individual. Ultimately, the Congress reflects a clear message: digital health is no longer peripheral; it is becoming an essential pillar of precision allergy care.

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Finally, allergic contact dermatitis continues to pose diagnostic and mechanistic challenges. Despite being common, it involves complex cellular immune pathways, and predictive testing and prevention strategies remain limited.

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Across all these conditions, the core issue is the same: an incomplete understanding of mechanisms leads to suboptimal diagnostics and limited therapeutic innovation. Investing in mechanistic research, biomarker discovery, and translational studies in non-Type 2 diseases is essential if we are to deliver truly comprehensive and equitable allergy care in the future.

Q10

Finally, for earlycareer clinicians and researchers entering the field, what skills do you believe will be most critical for shaping the future of allergy and clinical immunology? For early-career clinicians and researchers entering the field, the future of allergy and clinical immunology will be shaped not only by scientific knowledge but by mindset and skill set. Scientific excellence remains fundamental: a solid understanding of immunology,

rigorous methodology, and a commitment to high-quality research and clinical standards are non-negotiable. However, excellence must be paired with critical thinking: the ability to question assumptions, interpret data cautiously, and distinguish true innovation from incremental change. Equally important is networking and meaningful interaction. Allergy is an increasingly interdisciplinary specialty, and progress depends on collaboration between clinicians, basic scientists, epidemiologists, data scientists, and industry partners. Engaging actively in congress discussions, research consortia, and international task forces not only broadens perspective but accelerates impact. The ability to communicate clearly, across disciplines and cultures, is becoming a core professional competency.

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Young professionals should also cultivate a strong sense of self-demand and continuous improvement. Seeking feedback, pursuing advanced training, and aiming for measurable quality in both research output and patient care are essential for long-term credibility and leadership. Professional progress should not be driven solely by career advancement, but by a commitment to raising standards and improving patient outcomes. Finally, adaptability will be crucial. With the rise of biologics, omics sciences, and digital health, the next generation must feel comfortable integrating innovation into practice. Those who combine scientific rigour, collaboration, intellectual curiosity, and personal accountability will be best positioned to shape the future of our specialty.

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ENT Consultant, General Hospital of Kalamata, Greece

The JMA serves as a bridge between early-career professionals and the wider EAACI community

As Chair of the Junior Members Assembly (JMA), how are you helping ensure that early-career clinicians and researchers can play a meaningful role in shaping the future of allergy and clinical immunology within the European Academy of Allergy and Clinical Immunology (EAACI)?

They are entering the field at a time of unprecedented advances in precision medicine, biologic therapies, digital health, and AI, all of which have the potential to improve patient outcomes and disease prevention.

The JMA serves as a bridge between early-career professionals and the wider EAACI community. Our goal is not only to provide educational opportunities but also to ensure that junior members actively contribute to scientific discussions, guideline development, research initiatives, and leadership activities within the Academy. We are strengthening junior representation across EAACI task forces, working groups, and scientific committees, while creating mentorship opportunities that connect emerging talent with established experts. Through dedicated educational programmes, research collaborations, and networking initiatives, we aim to empower young clinicians and researchers to become future leaders who will shape the direction of allergy and clinical immunology in Europe and beyond.

This year’s Congress theme is ‘Vision Zero: A Future Free from Allergy and Asthma Burden’. What role do you believe the next generation of allergy specialists will play in achieving this ambitious goal? The next generation of allergy specialists will be instrumental in transforming this vision into reality.

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EMJ Allergy Immunol. 2026;11[1]:41-43. https://doi.org/10.33590/emjallergyimmunol/M4PVH8JO

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Beyond adopting new technologies, young specialists will play a key role in generating high-quality research, promoting evidence-based practice, reducing healthcare inequalities, and strengthening multidisciplinary collaboration. Achieving a future with a significantly reduced allergy and asthma burden will require innovation, advocacy, and international cooperation, and junior members are uniquely positioned to drive these changes over the coming decades.

The JMA has become an increasingly visible part of EAACI. What opportunities at this year’s Congress would you particularly encourage junior delegates to take advantage of? The EAACI Congress offers an exceptional range of opportunities for junior delegates. I would strongly encourage them to participate in JMA sessions, educational tracks, hands-on workshops, and networking events designed specifically for early-career professionals. Presenting research, engaging with experts during scientific sessions, and connecting with peers from different countries are invaluable experiences that often lead to future collaborations. I would also encourage delegates to explore mentorship opportunities and become involved in EAACI

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activities beyond the Congress itself. Building professional relationships and becoming an active member of the EAACI community can have a lasting impact on career development.

a central role in appropriately selected patients. While the core recommendations are broadly applicable across Europe, local adaptations may be necessary depending on allergen exposure patterns, healthcare systems, treatment availability, and reimbursement policies. Nevertheless, the underlying principles of diagnosis, symptom control, and integrated airway management are universally relevant.

You have contributed to several recent EAACI and Allergic Rhinitis and its Impact on Asthma (ARIA) guideline initiatives. What are the most important updates in allergic rhinitis management that clinicians should be aware of? Are these applicable across Europe, or are they more region-specific?

There is growing recognition of the close relationship between upper and lower airway diseases. How is the concept of united airway disease influencing both clinical practice and research priorities?

Recent EAACI and ARIA initiatives continue to emphasise a patientcentred and evidence-based approach to allergic rhinitis management. One of the key developments is the increasing use of integrated care pathways and precision medicine principles to tailor treatment according to disease severity, symptom control, and patient preferences.

The concept of united airway disease has fundamentally changed how we understand and manage respiratory disorders. We now recognise that conditions such as allergic rhinitis, chronic rhinosinusitis, and asthma are closely interconnected through shared inflammatory mechanisms.

Another important aspect is the growing emphasis on real-world evidence, digital health tools, and patient-reported outcomes to support treatment decisions. Allergen immunotherapy remains the only disease-modifying treatment and continues to play

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In clinical practice, this means adopting a more holistic approach, assessing both upper and lower airway involvement

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rather than treating each condition in isolation. Effective management of upper airway disease can positively influence asthma control and overall patient outcomes. From a research perspective, there is increasing focus on identifying common disease pathways, biomarkers, and therapeutic targets that address airway inflammation as a whole. This integrated approach is helping to advance precision medicine and improve care for patients with complex airway diseases.

Your recent work has focused on conditions such as chronic rhinosinusitis, olfactory dysfunction, and other upper airway disorders. Which areas do you feel remain under-recognised despite their significant impact on patients’ quality of life? Olfactory dysfunction remains one of the most underrecognised conditions in upper airway medicine. Loss or impairment of smell can profoundly affect nutrition, safety, emotional wellbeing, social interactions, and overall quality of life, yet it is often underestimated in routine clinical practice.

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Similarly, chronic rhinosinusitis is frequently perceived as a minor condition despite its substantial impact on sleep, productivity, mental health, and daily functioning. The burden experienced by patients can be comparable to that of many other chronic diseases. There is also a growing need to recognise the psychological and social consequences of chronic upper airway disorders. Greater awareness, earlier diagnosis, and more comprehensive patientcentred management strategies are essential to address these unmet needs.

For junior clinicians and researchers attending EAACI 2026, what advice would you give for building a successful career in allergy and clinical immunology while making the most of the educational and networking opportunities available at Congress?

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questions, and introduce yourself to colleagues from different disciplines and countries. Present your work whenever possible and seek feedback as an opportunity for growth.

My advice is to remain curious, proactive, and open to collaboration. Scientific knowledge and clinical expertise are fundamental, but building meaningful professional relationships is equally important for long-term career development. Attend sessions outside your immediate area of interest, engage with experts, ask

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Most importantly, become actively involved in the EAACI community. The Congress is not only a place to learn about the latest scientific advances: it is also a platform to build networks, discover mentors, develop collaborations, and contribute to the future of our specialty. The connections and experiences gained at EAACI often become defining moments in a young professional’s career.

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EMJ Allergy Immunol. 2026;11[1]:44-49. https://doi.org/10.33590/emjallergyimmunol/33ALG787

Citation:

Q1 Ian Adcock Professor of Respiratory Cell & Molecular Biology and Head of the Molecular Cell Biology Group, National Heart & Lung Institute, Imperial College London, UK; VP Science, European Academy of Allergy and Clinical Immunology (EAACI)

We have some amazing tools now, whether we're using large language models to collect data, view data, or pull everything together

The theme of this year's European Academy of Allergy and Clinical Immunology (EAACI) Congress is built around a future free from asthma and allergy burden. From an asthma point of view, what would meaningful progress look like in this field in the next decade? We have brilliant drugs and biomarkers that allow us to stratify patients for therapeutic response, but they're not perfect. They don't precisely match the patient’s molecular phenotype, which is why, even after optimising the response population, we still only see complete remission in around 20–40% of patients. So, in relation to that, we need to find a signature or set of biomarkers that help improve that percentage. We know from previous works that if you take sputum and analyse it in depth (inflammometry), and direct therapy towards what's going on in sputum as a marker of airway inflammation, you can get up to 60% remission, which is much better than with current biomarkers.

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But that's still not practical. So, we need something much more accessible, whether that's a blood test, a breath test, or a nasal sample, that's going to help us. And I think that this type of analysis is ongoing. Studies across Europe, including those I'm involved in, as well as collaborative studies between Korea and the UK, are performing multi-analysis on responder and non-responder populations for specific biologics. The question is, is there a biologic or molecular biomarker that can tell us whether a patient is more likely to respond to a specific biologic, rather than indicating they're likely to respond to biologic therapy in general, which is essentially what blood eosinophils and fractional exhaled nitric oxide tell us today. I think that would be the real transformation. We will eventually be using deep metadata and AI to help define what combination of biomarkers and clinical signs is optimal for predicting the best biologic for each patient. Ultimately, we'll have algorithms that collect data as you

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come into the clinic and quickly determine the treatment you need.

AI approach requires a large amount of data for training and validation. Most of the data that's out there so far includes small numbers of patients, and we're self-validating. We need to validate results in large independent cohorts.

I'd like to see biomarker testing become almost as quick as COVID tests were, fast, easy, and simple. If we could test for four particular biomarkers, that would be really valuable. Blood would be the easiest, but you can readily take nasal swabs, as we did for COVID-19.

We've done some interesting studies. For example, we measured lung function and pollution exposure in preschoolers and kindergarten kids, as well as teachers, parents, and grandparents. The question is, can we predict their lung functional changes according to the environmental pollution exposure? You get good predictive data using AI, but the numbers are low, and it doesn't reproduce when you go to another cohort. So, it's a good indication of what we could achieve, but the real limitation is the initial sample size for predictive modelling. Numbers are everything.

We can perform flow tests against most analytes, so if we knew what we were looking for, then I think that's something that would come forward because it's quick and practical. I also think we will get there by applying machine learning and AI to the data that we're collecting from these reasonably large responder and non-responder cohorts to biologics. We're not doing it in paediatrics to the same degree, so that's going to be a huge issue that we need to resolve.

We've talked about AI so far, and AI is expanding at such a rate that, from what I've seen, especially looking at the UK, often theoretical technologies outstrip the capacity in hospitals. They don't have the technology to actually implement these tools. Is the current landscape across Europe equipped to deal with these changes, looking towards biomarkers and testing these kinds of things?

What are the limitations to rolling these practices out across Europe? You've already touched on data, but I wanted to ask specifically about access to it. Given that patient data is highly personal and subject to GDPR and other privacy regulations, how do you access the data required to train these AI models? We, as a community, are getting away from what used to be ‘This is my little data set, I'm keeping it for myself’, because it's not our data; it's the patient's data. And the patients are quite happy to give ethics approval so that we can share it.

I think it's exactly the same. We have some amazing tools now, whether we're using large language models to collect data, view data, or pull everything together. We're using graphical neural networks or encoders to look at data and identify hidden patterns. There are approaches being taken across Europe, as well as globally, which is essential, because this CC BY-NC 4.0 Licence

The large EU studies and some of the individual countries are saying that we must share data, make it available, and make it findable.

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You don't have to give it away, but you can make the types of data you have visible to anybody else and say, "Well, I'd like to validate my data set. You've got this data, can we collaborate?" So, it's going to be two levels. First, the data is findable, and then we have the personal interaction. Data sharing can create issues with GDPR. But I think we've got some good ways to perform analyses through cloud-based analysis, so we don't have to worry. The only major problem currently is access to the huge data sets being generated in China. They have access to Western databases, but currently we can't use theirs. One option is greater collaboration, where we go to China and get them to do the validation or primary analysis. It used to be impossible to do this type of analysis, but it is a lot easier now.

We’ve touched on biomarkers and AI, but as the asthma section chair, looking ahead at the rest of the Congress, what other kind of developments do you think people should keep an eye on, either at the Congress or in the general landscape? I have been thinking about the environment and how it impacts the incidence and severity of asthma. We know it has an effect, but what can you do about it? We understand that we can use it in prevention, but we can also try to lobby governments. One of the really great things that Japan has done, for example, is address the huge allergy wave that comes every year. Around 40% of Japanese people are allergic to Japanese cedar. Most of Japan was reforested after the Second World War with Japanese cedar because it grows

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quickly. However, this tree is hyperallergenic and drives the seasonal allergy wave. So, they are now reforesting with non-allergenic trees. To me, this is amazing. This is an example of what you can do. Thus, allergists are working with the government to change the whole landscape of the country. We have similar problems throughout Europe, although the allergen-driving trees, bushes, or grasses are different depending on which part of Europe we come from. That's something that I feel is within the remit of EAACI, and that we should be pushing for these types of societal changes. We'll need to get numbers by improving collaboration between registries. Working together with the national registries across Europe is one way to obtain data to highlight the importance of allergies in population health at local, national, and regional levels.

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People say, "an apple a day keeps the doctor away," and there is real truth in that. I feel that there are social aspects that are really important to try and overcome to help us with the severity and incidence of asthma as well as other allergic diseases.

In the session I chaired today, we discussed how the gut microbiome affects allergic response. People are doing faecal transplants and taking ‘poo’ tablets, but that’s not really the answer. There is a strong link between the gut and health, and if you understand that link, you will be able to find out what it is that the gut bacteria are secreting (e.g., butyrate or itaconate) and the effect on the immune cell community trafficking into the lung.

I know people are talking within the UK government regarding allergy prevention, although not to the extent seen in Japan. The UK government does have a new National Allergy Strategy with stricter safety laws such as Benedict's Law, which mandates that all schools in England conform to comprehensive allergy and anaphylaxis training and keep ‘spare’ adrenaline injectors onsite. Furthermore, Natasha's Law requires all directly sold pre-packed foods to have a full allergen listing. In relation to asthma, there's the Committee on the Medical Effects of Air Pollutants (COMEAP), but they're only one of many voices talking to the government. They don't have a direct line to number 10

It's really interesting to hear about the intersection between public health and allergy. How important do you think that overlap is?

We have registries for allergies across Europe, but they don’t work together as much as possible. We should join up these registries, and then we can say to governments that, for example, 40% of your voters have allergies. It doesn't matter what age they are; they have

allergies, their children have allergies, and you need to do something about it. If you don't, there's an electoral issue. I think that's something we should be advocating for. I am very keen on getting registries coordinated so that we can really demonstrate the scale of the problem.

For undergraduate teaching, I use things like ‘you are what you eat’, and I get specialist dietitians to come in and talk to medical students, as it shows how much of an impact diet can have.

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Are there any other examples of similar schemes or good examples of allergy prevention, similar to the example you provided from Japan?

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to change the policy, so they can only advise. We've made advances in some areas of allergic diseases and asthma in relation to the environment and related issues, but we need greater success. You do get some local authorities that buy into this. It takes a lot of money to regreen some of the parks, plant trees or bushes where there weren’t any beforehand, and try to change traffic flows near schools. So, on the local level, I think we're getting a little bit more traction in relation to low emission zones. However, nationally, we could do better.

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Pivoting slightly to look at other aspects, there's been a lot of advances in treatments. Why doessteroid resistance remain such a challenge?

symptoms will not improve, but they will get side effects, including their bones crumbling away, or potential steroidinduced psychosis or paranoia.

I think it's because the new drugs, biologics, are expensive, and they're not available to everybody. So, the default is ‘we will increase the amount of inhaled steroids’ as they are mostly cheap. If patients do not respond to these, oral steroids are another easy option. They are very cheap and are effective, but they have devastating side effects. If we don’t know whether a patient will respond to inhaled and/or oral steroids, we risk giving increasing doses of the drugs to patients whose disease

For certain areas across the globe, this is a huge issue, because steroids are the only option available. If we cannot identify who will not respond well to these drugs, we may end up increasing the dose tremendously without any clinical effect. Alternative options could be bronchodilators in combination with other less powerful antiinflammatory drugs. If patients are going to get side effects without responding to the steroids, we're doing the patient a disservice. Although the initial drug cost is

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low, the societal cost is high due to the side-effects. If you’re in a low-middle income country and are indicated as needing to take steroids for the rest of your life, you are at risk of having a shorter and less productive life. I think, therefore, that understanding why steroid resistance exists, and how this may be overcome, remains really important. There are some great studies from the Severe Asthma Research Programme (SARP), in the USA as well as in Europe, showing that Type 2 (T2) high asthma, reflected in elevated levels of eosinophils, is not the only kind of asthma. Patients with other types of asthma, including high levels of both activated eosinophils (T2 high) and neutrophils (Type 1 high) in the airway, have more severe disease that doesn’t respond to steroids. So, could you, by targeting one aspect of that T2 or Type 1 inflammation, enable patients to respond to low levels of steroids? I think we still have an issue, and it's gone off the radar a bit because we have really good biologic drugs. This has now changed our perspective on asthma therapy from control to remission. However, despite the use of T2 biomarkers, a large number of patients do not attain full remission with anti-T2 biologics, and we use the same biomarkers for these biologics. Future work is needed in this area.

Looking outside of steroids and biomarkers, what are the pathways you think are going to be significant in future treatment? I think we will start using nasal biomarkers more prominently as they’re easy to collect. You can do it in kids: it’s easy and it doesn't hurt. You can do RNA studies as

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well as protein studies. We're also starting to use machine learning algorithms to predict what's going on in the nose and compare that with, and even predict, what's happening in the airways. That's one way of helping stratify an asthma type, just by looking at the nose. I think that's going to be an area that will be advanced. Of course, that's using standard biomarkers. We don't really work closely enough with biomarker companies, which is why we don't have that many biomarkers, which goes back to what I said earlier about lateral flow tests. If we identify specific targets that reflect asthma severity and/or response to therapy with specific cut-off points, we should be able to work with companies to generate simple assays. We probably don’t need to do a screen on 20 biomarkers; you may just need three. You can just use a traffic light system to indicate that further assessment is required if your sample is more ‘red’. The other area that we will see improve will be imaging. That's going to give us a non-invasive insight into the lung. At the moment, most people are focused on mucus plugs. Can we see those? Can we detect them? Can biologics target this? Imaging will tell us more about airways and disease, and, in combination with impulse oscillometry or other non-invasive markers of airway physiology, will help us to better phenotype patients and detect responder populations. We've been doing studies using multi-omics analysis in relation to some airway diseases and imaging to see if there is activation of particular pathways that reflect CT features or changes in the R5–R20 ratio. These types of analysis may give us an indication as to novel drug therapies for patients with

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specific imaging criteria. We have performed similar multi-omics analysis in combination with patient-reported outcomes and quality-of-life measures. This is interesting because, when you add patient-reported outcomes to remission criteria, the remission rate goes down quite dramatically. Roy Meys, University of Maastricht, the Netherlands, published a paper last year, which showed that patient-reported outcomes weren't strongly linked to lung function or the other measures we usually look at. Instead, they were associated with specific systemic pathways that made biological sense and could potentially be targeted with a dual-warhead antibody. What kind of systemic pathways and antibodies? TNF pathways and TNFassociated pathways are coming up, which makes sense if you think of symptoms like fatigue, which is one of the major issues that people with asthma have, even when they're treated well with biologics.

In terms of moving forwards, what do you think is the biggest unmet need in asthma management? The biggest unmet need involves those who don't have classic T2-

high biology. We have no drugs that have passed clinical trials because the mechanisms are more diverse and we don't have a biomarker to identify those mechanisms, so we just lump everyone in together. Since we have no biomarkers at present, we can't differentiate between a patient who might respond to a drug and a patient who might not. Take anti-IL-17 therapies, for example. I think Th17 biology is important in certain subgroups of people with asthma, but because we don't have a biomarker, we just combine all patients together and the trial fails. Similarly, issues arise across many chronic inflammatory diseases where more personalised drug therapy is needed but biomarkers cannot, as yet, identify who to give a specific drug or biologic to. As such, we have to get away from the mindset that a single disease will provide our blockbuster drug. The drugs may have blockbuster potential when considered across several allergic or inflammatory diseases.

Q10

What is the take-home message you'd like to leave allergy and immunology specialists with?

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here at EAACI. This is not seen in respiratory meetings. I've just come back from the American Thoracic Society International Conference, where the science is good but lacks the hardcore immunology, and that's where we're going to make advances. Bringing together great clinicians and great scientists will help make both better, but it will also help us make those changes in disease diagnosis and treatment. If you could bring engineers in, that would be fantastic, because they can help with biomarkers and a whole range of wearables. Another thing is mobiles phones and watches, which can track and record our data. We're not good at keeping the data to ourselves or using it for academic research. We readily give it to companies via purchase agreements, who then sell this onto insurance agencies, for example. And I think this is something we, as a community, should be thinking about. Let's utilise that data by linking it to our electronic healthcare records and our personal databases.

The key message for allergy and immunology specialists is that we have really good state of the art immunology presented

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Interviews In this interview series, EMJ speaks with leading voices across allergy, immunology, and environmental health, including pioneers in immune tolerance, exposome research, childhood food allergy prevention, viral immunology, and health equity. Together, they explore how advances in barrier biology, epidemiology, precision medicine, AI, and public health policy are reshaping our understanding of allergic disease and driving the field towards prevention-focused, personalised care. Featuring: Cezmi Akdis, Isabella Annesi-Maesano, Jennifer Koplin, Mitchell H. Grayson, and Ruchi Gupta

EMJ Allergy Immunol. 2026;11[1]:50-53. https://doi.org/10.33590/ emjallergyimmunol/ME9457Y3

Citation:

Q1 Cezmi Akdis Director, Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland

It’s not just about attacking pathogens, but about teaching the immune system when to pause, when to tolerate, and when to escalate

You originally trained in infectious diseases and clinical microbiology before specialising in allergy and immunology. What drew you into the field of allergy and immune regulation, and at what point did you realise this would become your life’s work? Something that often crystallises this passion for me is watching clinical phenomena (seasonal allergies, asthma, autoimmunity) unfold through the lens of immune regulation. You see how small miscommunications among cells and signals can lead to big, tangible experiences in patients’ lives. My thesis was on immune tolerance and immune activation in miliary tuberculosis. It was based on the identification of lymphocyte subsets (CD4, CD8, CD16, and CD25 monoclonal antibodies) in my experiments via confocal microscopy, which was before the introduction of flow cytometry into laboratories.

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We had demonstrated how the immune system shuts down and goes into a silent phase in miliary tuberculosis, which is in parallel with diminished tuberculin skin test reactivity (cellular immunity). It also demonstrated the development of regulatory T cells (Treg) for tuberculosis tolerance in this last stage of the disease. It was a great motivation to realise that immune regulation is a symphony of checks and balances in allergies, autoimmunity, chronic infections, tumours, and pregnancy, partially from our own experiments. It’s not just about attacking pathogens, but about teaching the immune system when to pause, when to tolerate, and when to escalate. That orchestration is exquisitely elegant and endlessly complex. Better understanding is a practical superpower. Each discovery about Tregs, cytokine networks, innate sensing, or epithelial barrier function translates into

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new therapies, diagnostics, and strategies to prevent, mitigate, and treat diseases.

Over the past 3 decades, you’ve witnessed and helped shape major conceptual shifts in allergy and clinical immunology. What do you consider the most transformative change in our understanding of allergic disease since the 1990s? If I were to distil it to a single thread: the shift from viewing allergy as a predominantly effector-driven, IgE-centric problem to seeing it as a dysregulation of immune tolerance, shaped by barrier integrity and epithelial-immune crosstalk, has been the most transformative. This perspective unifies pathophysiology across tissues, explains why exposures matter differently across individuals, and directly informs therapies that aim to restore regulatory balance and tolerance. Early models emphasised Th2skewed responses as the drivers of allergy. The last 2 decades revealed that regulatory networks, especially Tregs, regulatory B cells (Breg), and tolerogenic dendritic cells, actively shape, restrain, or fail to restrain

allergic inflammation. This reframes allergy as a failure (or insufficiency) of regulatory control rather than a pure overactive effector response. The use of checkpoint blockers for cancer treatment based on these ideas was extremely important.

other regulatory checkpoints have transformed severe allergic diseases from chronic, life-impacting conditions into manageable ones for many patients.

Discoveries highlighting the epithelium’s active role (airway and skin barriers) and its sensing of environmental cues positioned barrier integrity and innate sensing as central to atopy. Epithelialderived cytokines (e.g., thymic stromal lymphopoietin [TSLP], IL25, IL-33) became key initiators of downstream adaptive responses, linking environmental exposures with immune regulation. The understanding that there is an immense capacity of the innate immune response in almost every cell of the body to fight pathogens and tolerate non-pathogens that evolved together has increased, with a better understanding of adaptive immune responses of T and B cells. Understanding regulatory pathways and epithelial-immune crosstalk paved the way for therapies that actually modify the disease course, not just treat symptoms. Biologics targeting IgE, IL-4/IL-13 axes, TSLP, and

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The field moved beyond one-sizefits-all phenotypes to endotypes defined by underlying mechanisms (e.g., non-IgE-mediated triggers, barrier defects, regulatory dysfunction). This reframing supports more precise diagnostics and targeted therapies.

Your early work was pivotal in defining human Tregs and Bregs and mechanisms of immune tolerance. Looking back, how did those discoveries influence your later thinking about chronic inflammatory diseases more broadly? Our early work showed that immune responses can be checked and redirected rather than simply suppressed. The studies mentioned in my thesis and performed in the Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland, in 1995 were quite important to show the plasticity of human Th1 and Th2 cells. This sets the stage for viewing chronic inflammatory diseases not just as hyperactive effector reactions, but

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as problems of regulatory balance, where tolerance mechanisms fail or become dysregulated. The discovery of human Tregs, Bregs, and allergen tolerance provided a scaffolding that reframed chronic inflammatory diseases as disorders of regulatory balance and barrier-immune dialogue. This has driven a shift from symptom control towards restoration of immune homeostasis across a spectrum of conditions. This perspective naturally extends beyond classic allergy to autoimmunity, chronic infections, and inflammatory conditions, where re-establishing tolerance can be therapeutic. In contrast, cancer and the treatment of chronic infections required the breaking of established antigen-specific immune tolerance. By characterising human Tregs and Bregs, we highlighted that multiple immune compartments collaborate to maintain homeostasis. In chronic inflammation, the breakdown often involves a cascade of regulatory derangements: Tregs, Bregs, dendritic cells, and barrierepithelial signalling all contribute. This holistic view encourages strategies that restore the entire regulatory ecosystem, rather than targeting a single cytokine or cell type in isolation.

You are widely associated with the development of the epithelial barrier theory. What were the key clinical or experimental observations that convinced you that barrier dysfunction could be a unifying mechanism across allergic, autoimmune, and even metabolic diseases? Our epithelial barrier-centric view posits that barrier dysfunction at the epithelial interfaces of skin, 52

airways, and the gut acts as a primary gateway to dysregulated immunity. Our paper on eczema mechanisms and skin barrier, and the following papers on asthma and chronic rhinosinusitis, showed that defects in the epithelial barrier allow greater environmental allergen and microbe penetration, transforming a local breach into broader immune activation via epithelial-derived cues that shape overall immune system responses. A paper from 2006 argued that maintaining barrier integrity (keep away), reducing ongoing stimuli and decreasing the inflammatory burden by draining the inflammation out of the tissues (wash away), and re-educating the immune system toward tolerance (suppress, based on our immune tolerance studies) together prevent or redirect chronic inflammation. Taken together, these works present barrier dysfunction and epithelial–immune crosstalk as a unifying mechanism underpinning allergic, autoimmune, and metabolic inflammatory diseases, shaping strategies that prioritise barrier health and regulatory restoration across tissues.

A central component of your work links environmental exposures, such as pollutants, detergents, and food additives, to epithelial damage. From a mechanistic standpoint, what do you see as the most critical pathways by which modern environmental factors disrupt barrier integrity and drive immune dysregulation? Environmental exposures, such as pollutants, detergents, micro and nanoplastics, and food additives, act as barrier disruptors at skin, airway, and gut interfaces. Mechanistically, they impair epithelial barrier

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components (barrier lipids and tight junctions), increasing permeability and allergen/microbial ingress. Damaged epithelia release alarmins (TSLP, IL-25, IL-33) that skew dendritic cells and promote Type 2-biased responses while activating innate lymphoid cells and pro-inflammatory circuits. This epithelial–immune crosstalk, augmented by oxidative stress and redox signalling, shapes downstream immune responses and inflammation. Chronic oxidative stress and loss of the capacity of mitochondria in the cells is one of the most important ageing and tissuedestructive factors in response to toxic substance exposure. Other mechanisms of toxicity have been identified as mitochondrial stress, endoplasmic reticulum stress, protein folding defects, DNA repair defects, cell death, and recovery mechanisms called autophagy and mitophagy. Barrier disruption also fosters dysbiosis, reducing tolerogenic microbial signals and enhancing pro-inflammatory cues. Opportunistic pathogen colonisation in the surface tissues and loss of commensals is another main event taking place. Diet and metabolites further modulate barrier resilience, epigenetic programmes, and developmental timing, imprinting a long-term inflammation and barrier leakiness. Therapeutic modalities that are currently developed include avoiding or decreasing the exposure dose of these toxic substances, barrier restoration (ceramides and lipid-rich emollients that occlude, hydrate and actively rebuild lamellar lipids), targeting epithelial alarmins (TSLP, IL-33), and microbiome-supportive strategies to sustain tolerance. In our understanding, these pathways

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unify allergic, autoimmune, and metabolic inflammation through a shared barrier–immune axis.

You have long advocated for disease ‘endotyping’ and precision medicine approaches in asthma and other allergic conditions. How do you envision integrating barrier biology, microbiome data, and immune profiling into a clinically usable framework for personalised care? A practical, clinically usable precision framework would integrate barrier biology, microbiome context, and immune profiling into a modular decisionsupport approach that guides diagnosis, prognosis, and therapy across airway and skin allergic diseases, with explicit inclusion of the epithelial barrier as a major factor in diseases in the European Academy of Allergy and Clinical Immunology (EAACI) nomenclature paper. Baseline barrier assessment would use standardised, noninvasive tests, such as electric impedance spectroscopy for skin barrier function tests or gut/ permeability markers for the gut and airways, to classify patients as defective/leaky, hyperreactive, or robust. Recognising the leaky endotype, characterised by increased permeability, enhanced alarmin release, and heightened sensitisation risk, would directly steer towards barrier repair and tolerogenic strategies. Parallel microbiome analysis (taxonomic, functional metagenomics, and metabolomics) would reveal dysbiosis patterns linked to barrier vulnerability, informing risk scores and guiding microbiome-modulating therapies.

Immune-endotype profiling (Treg/ Breg function, IL-4/IL-13/TSLP signatures, and innate lymphoid cell activity) would define mechanistic subtypes with distinct therapeutic implications.

reducing volatile organic compounds, particulates, mould, and fumigants; 3) safer consumer products through green chemistry, substituting hazardous ingredients with benign alternatives and improving labelling and consumer awareness; 4) safeguarding water and food supplies by monitoring additives, contaminants, reducing contamination events, and promoting safe agricultural practices; 5) urban planning that expands green spaces, reduces heat islands, and facilitates active transport, thereby lowering exposure to pollutants and promoting resilience; and 6) vulnerable-population protections (pregnant women, children, migrants, the elderly) via targeted advisories, surveillance, and access to protective resources.

Decision tools would synthesise these data into treatment recommendations, from barrier restoration and epithelial alarmin targeting to biologics and microbiome approaches, while dynamic monitoring reclasses endotypes over time, ensuring therapy remains aligned with the patient’s evolving biology.

Looking ahead 10–20 years, do you believe the greatest advances in allergy and immunology will come from biologic therapies, environmental prevention strategies, barrier repair approaches, or from an entirely new paradigm we have yet to define?

An exposome framework integrates real-time monitoring, biomarker data, and longitudinal health outcomes to tailor interventions and policy. Ultimately, prevention relies on cross-sector collaboration, transparent risk communication, and investment in safer environments that support lifelong health.

The most important of all is environmental prevention of the exposome, which focuses on reducing harmful exposures that shape long-term health across life stages. The approach spots toxic substances, such as air pollutants, pesticides, industrial chemicals, heavy metals, detergents, rinse aids, food additives, micro and nanoplastics, and endocrine disruptors, in everyday environments such as homes, schools, workplaces, and urban landscapes, aiming to minimise cumulative burden. Micro and nanoplastic pollution will be one of the biggest threats to nature and humanity in the coming decades. Key strategies include: 1) emission reductions and cleaner production to lower ambient pollution; 2) robust indoor air quality standards,

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EMJ Allergy Immunol. 2026;11[1]:54-56. https://doi.org/10.33590/emjallergyimmunol/QN5DK645

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Q1 Isabella Annesi-Maesano Research Director, Professor of Environmental Epidemiology, Department of Environmental and Prevention Sciences, University of Ferrara, Italy

The most exciting frontier in allergy and respiratory epidemiology lies in moving beyond the ‘one-size-fitsall’ model toward precision prevention

What initially drew you to respiratory epidemiology and environmental health, and how did your journey from medicine, physics, and epidemiology shape the way you approach allergy and immunology research today? Since my first readings (among the most important, Albert Schweitzer on leprosy in Lambaréné, Gabon), my idea was to protect human health. To reach it, my ‘journey’ was shaped by interdisciplinarity. Medicine (which for me is the human anchor needed to start) has provided the foundational understanding of the biological toll that health status (allergies and respiratory diseases in my research activity) takes on patients. It ensures that my research remains patient-centred as an entity of the general population, focusing not just on data, but on ‘pathological consequences’ and the realworld efficacy of prevention, primary when possible. Physics (which, for me, represents the structural lens) introduced the rigor of assessments, complex systems modelling, and validation of the methods. This background allows me to critically evaluate the limitations of current environmental models. It has encouraged looking at the ‘mechanics’ of exposure, for example, in the case of air pollution from particle emission to atmospheric behaviour and then penetration in the human body. Finally, epidemiology (for me, the population perspective) has served as the bridge, translating individual biological mechanisms, clinical outcomes, and external

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exposures into public health imperatives. It provides the methods and statistical toolkit to quantify without risk of bias, and the framework to advocate for large-scale interventions, such as environmental surveillance and the promotion of peace as a prerequisite for health.

The exposome concept has gained traction as a framework for understanding disease causation. In your view, what are the biggest methodological challenges in measuring the exposome, and how are advances in data science helping to overcome them? For a researcher with a background in physics and epidemiology like me, the exposome (the totality to which every individual is exposed in his/her life and that shapes his/ her health) is essentially a signalto-noise problem. Data science provides the ‘filter’ needed to extract meaningful biological signals and clinical outcomes from the noisy environmental data of modern, conflictaffected landscapes. Advances in assessments and computation are transforming the exposome from a theoretical concept into a quantifiable metric. I’m directly involved in individual assessment of air pollution exposure with personal sensors. Major methodological challenges include: •

The spatio-temporal resolution gap. Exposure is dynamic, but our measurement tools are often static. While we can measure pollutants at a specific station, ascribing that level to a person moving

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through a city is difficult. •

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High-dimensionality and ‘the cocktail effect’. Traditional epidemiology struggles with the sheer volume of variables. Individuals are not exposed to single risk factors, but to mixtures (heavy metals, particulate matter, biocontaminants, noise, heat, and psychosocial stress, among others for instance). Statistical models often suffer from multicollinearity (where exposures are correlated) and the ‘curse of dimensionality’, making it hard to isolate the specific driver of a health outcome. Latency and life-course tracking. The most critical exposure for an adult-onset respiratory disease may have occurred in utero or during early childhood (the developmental origins of health and disease concept).

respiratory diseases’ development, the so-called incidence. Robust data exist for asthma, COPD, idiopathic pulmonary fibrosis, and lung cancer. Moving beyond simple correlation toward causation, strengthening the evidence for both the development (incidence) and exacerbation of respiratory diseases as a consequence of the exposome requires: •

Closing the resolution gap: integrating hyper-local data to capture acute, point-source exposures.

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Understanding ‘the cocktail effect’: investigating how multipollutant mixtures synergise with heat and allergens.

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Life-course tracking: solidifying the links between early-life (in utero) environmental insults and adult-onset chronic disease through epigenetic and ‘multi-omic’ research.

Air pollution, climate change, and biodiversity loss are increasingly implicated in allergic and respiratory diseases. Which of these environmental drivers do you believe has the most immediate impact on patient outcomes, and what evidence still needs to be strengthened? All these factors are all very important as they constitute the triple planetary crisis impacting allergic and respiratory health through different mechanisms and timeframes. In my view, and supported by current clinical and epidemiologic data, air pollution remains the most immediate threat to patient outcomes, while biodiversity loss represents the most significant ‘blind spot’ in our long-term preventative strategy. Air pollution acts not only as an immediate trigger, but also as a contributing factor for several

This requires substantial data and resources, typically supported through dedicated projects and associated funding. Unfortunately, research funding is becoming increasingly limited.

Your work often focuses on early-life exposure and critical windows of vulnerability. What have we learned about interventions in pregnancy and early childhood that could meaningfully reduce lifelong allergy or respiratory disease risk? Research into the developmental origins of health and disease hypothesis has confirmed that the prenatal period and the first 1,000 days of life are the most critical windows for immune

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‘programming’ and later health. With other colleagues in the frame of the international Pregnancy and Childhood Epigenetics (PACE) consortium, we have published that environmental risk factors already act on newborns’ epigenome. More importantly, interventions during these stages are not just about preventing paediatric symptoms; they are about altering the structural and epigenetic trajectory of the immune system and the lungs for a lifetime. Interventions include nutritional and supplementation strategies (vitamin D, omega-3 fatty acids, early allergen introduction), and implementing the need for early biodiversity exposure or reducing air pollution exposure.

Twin cohorts and multiomics approaches are powerful tools in disentangling genetic and environmental influences. What unique insights have twin studies provided in your research, and where do you see their limitations? Twin studies act as a ‘natural experiment’ that allows us to bypass the noise of genetic variability, providing the unique insight that, while genetic predisposition sets the ‘ceiling’ for lung function, environmental hits, especially in early life, determine whether that ceiling is reached. By comparing monozygotic twins, my research in the EU Health and Environment-Wide Associations Based on Large Population Surveys (HEALS) project has highlighted how discordant environmental exposures, such as growing up in a high-pollution urban centre versus a rural area, lead to distinct epigenetic signatures and ‘multi-omic’ profiles despite identical DNA. However, a primary limitation of twins studies lies in representativeness; twins often have different prenatal

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growth patterns (e.g., lower birth weight) than singletons, which can confound respiratory outcomes. Furthermore, even monozygotic twins are not truly ‘identical’ at the molecular level due to somatic mutations and stochastic epigenetic drift, meaning that while they help disentangle the ‘nature versus nurture’ debate, they cannot fully account for the sheer complexity of the individual exposome.

During the COVID-19 pandemic you studied interactions between air pollution and viral infections. What surprised you most about these relationships, and how might this knowledge inform preparedness for future respiratory pandemics? The shift in understanding SARS-CoV-2 as a primarily airborne pathogen, to which I contributed by signing the first published paper on the topic, has fundamentally redefined the landscape of respiratory protection, moving the focus from surface hygiene to the ‘atmospheric commons’. This realisation underscored the urgent need for structural prevention, particularly through the implementation of pharmaceutical-grade ventilation and high-efficiency particulate air filtration in public spaces to mitigate the concentration of infectious aerosols. Furthermore, since air pollution can upregulate entry receptors like angiotensinconverting enzyme 2 (ACE2), the ‘clean air mandate’ must be viewed as a critical form of environmental

prophylaxis; by reducing the baseline of particulate matter and gaseous pollutants, we can effectively lower population-wide susceptibility to viral penetration. Ultimately, integrated environmental and clinical surveillance is essential to transform our indoor and outdoor air from a vector of transmission into a primary barrier against future respiratory pandemics.

Machine learning and big data are increasingly used in epidemiology. How do you balance the promise of these methods with concerns about interpretability and bias, especially when translating findings into public health policy? I’m presently working on AI application to air pollution (for instance, on the ‘cocktail effect’ of complex mixtures) and pollen assessment and interpretation of molecular allergy (the so-called ‘chips’). In the former case, to translate these findings safely into policy, we must prioritise interpretability, ensuring that the identified ‘risk clusters’ align with biological plausibility and clinical reality, while implementing strict algorithmic auditing to detect and correct for socioeconomic and geographic biases. Ultimately, machine learning should be viewed as a sophisticated tool for hypothesis generation, which must then be validated through traditional causal inference and clinical expertise before being codified into public health mandates.

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Looking ahead, what do you consider the most exciting unanswered questions in allergy and respiratory epidemiology, and where should the next generation of researchers focus their efforts to drive meaningful prevention strategies? The most exciting frontier in allergy and respiratory epidemiology lies in moving beyond the ‘one-sizefits-all’ model toward precision prevention that accounts for the dynamic plasticity of human beings. The next generation of researchers must focus on closing the ‘resolution gap’ by integrating hyper-local, real-time exposomics with multi-omic data to identify not just who is at risk, but during which critical windows environmental scarring, such as epigenetic changes from air pollution or biodiversity loss, can be reversed. By leveraging explainable AI to decode the ‘cocktail effect’ of complex mixtures and advocating for the peace–health nexus, young scientists can transform our understanding of the atmosphere from a passive backdrop into a manageable biological shield. The ultimate goal is to design urban environments and public health policies that proactively ‘programme’ immune tolerance rather than merely reacting to chronic inflammation.

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Citation:

EMJ Allergy Immunol. 2026;11[1]:57-60. https://doi.org/10.33590/emjallergyimmunol/052BF5S2

Q1 Jennifer Koplin Principal Research Fellow, Child Health Research Centre, Faculty of Health, Medicine and Behavioural Sciences, University of Queensland, Australia

One of the key challenges in connecting evidence with practice is the speed at which research findings can be translated into guidelines

What initially inspired you to pursue a career in allergy and immunology, and what led you to focus specifically on childhood food allergies and epidemiology? Back in 2006, I had a conversation with the late Professor Katie Allen, and that started the course of my career in this area. Allen was incredibly passionate about the need to better understand childhood food allergies through high-quality research. She encouraged me to undertake a PhD under her supervision to explore some of the big unanswered questions of the time. I was inspired by the potential to provide answers to questions that were being asked by new parents every day, including “Is it likely that my child will develop a food allergy?” and “How can I prevent them from becoming food allergic?” The potential for research to translate into meaningful, practical guidance for families was a powerful motivator. Allen was an exceptional mentor to me and to many others and played a huge role in advancing food allergy research in Australia. She passed away in December 2025 and is sorely missed.

From your perspective, how has the understanding and management of childhood allergic diseases evolved most dramatically over the past decade?

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In the 1990s and early 2000s, avoidance of foods like peanuts in infancy and early life was common, based on the belief that this might reduce the risk of developing food allergy. In Australia, children presenting with food reactions were sometimes ‘screened’ for a broad range of potential food allergies, and where there was evidence of sensitisation, avoidance was encouraged. Once a food allergy was diagnosed, strict avoidance was essentially the only management option available. This approach has now changed fundamentally. Parents are advised to introduce a range of common allergenic foods in infancy, soon after the introduction of solid foods, to reduce the risk of food allergy developing. These recommendations are based on robust evidence from large highquality RCTs and subsequent meta-analyses, most of which have been published within the past decade. In parallel, management options for children with established food allergy have also evolved. Treatments such as oral immunotherapy, as well as

From my perspective, the most dramatic change in childhood food CC BY-NC 4.0 Licence

allergy over the past decades has been the shift from a focus on allergen avoidance to a focus on preventing allergy through early exposure and tolerance induction. While this shift began more than a decade ago, the evidence base and resulting changes in clinical practice have accelerated most markedly in the past 10 years.

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structured egg and milk ‘ladders’, may now be considered for some children as alternatives to complete avoidance, reflecting a broader shift toward active management and promotion of immune tolerance rather than strict exclusion alone.

Your research emphasises populationbased studies to inform prevention. How do you see large cohort studies, like HealthNuts and EarlyNuts, shaping public health strategies for allergy prevention? Large population-based studies have the potential to answer questions that can’t be answered through clinical trials alone. They allow us to accurately estimate the population prevalence of food allergy, identify novel risk factors, and generate hypotheses about prevention strategies that can then be tested in RCTs.

One of the things that most excites me is the possibility that in the next 5–10 years, we might start to see large reductions in the number of children living with food allergy

In Australia, prior to the HealthNuts study, there was widespread concern about rising rates of food allergy, but little highquality population data to quantify the problem. HealthNuts provided some of the first evidence on how common food allergy really was in infants and young children, driving an increased research focus on prevention and improved management. 58

Population-based cohort data have also been instrumental in identifying potential modifiable risk factors. For example, research led by Allen using HealthNuts identified low vitamin D as a possible risk factor for food allergy. This directly led to the design of the VITALITY trial, a large RCT of vitamin D supplementation involving more than 2,700 infants, with results expected later this year. Another key strength of large cohort studies is their ability to capture the burden and impact of food allergy in groups that are often underrepresented in clinical trials. When participation is designed to be low burden for families, population-based studies can achieve high participation rates and generate samples that are more representative of the wider community. Importantly, establishing a robust baseline prevalence of food allergy allows us to evaluate the realworld impact of population-level prevention strategies as they are implemented through public health guidelines. By recruiting a population-based sample a decade after HealthNuts, the EarlyNuts study was able to assess the uptake and impact of guidelines recommending the timely introduction of allergenic foods in infancy, examine changes in feeding practices and allergy outcomes, and identify areas where further improvement is needed. These examples demonstrate how large cohorts can directly inform, refine, and evaluate public health strategies for allergy prevention.

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You’ve contributed to national and international guidelines on infant feeding to prevent food allergy. What do you see as the most important lessons from these guidelines, and how have they impacted real-world feeding practices? It has been very encouraging to see the dramatic shift in infant feeding practices in Australia following the introduction of guidelines recommending the timely introduction of peanut and other allergenic foods. After the guidelines were updated, more than 80% of infants were introduced to peanut before 12 months of age, compared with fewer than 30% previously. Introduction of other allergenic foods, such as egg and tree nuts, has also occurred earlier, although the changes have been less pronounced. We found that advice consistent with the new guidelines was widely received by families. Importantly, receiving accurate advice was associated with the timely introduction of allergenic foods. These experiences have shown that guidelines based on high-quality evidence from RCTs can lead to meaningful changes in real-world practice, provided they are effectively disseminated to healthcare professionals and the broader community. We are also starting to see these changes in infant feeding practices translate into reductions in food allergy prevalence in Australia. Similar trends have been reported in the USA, where a decline in peanut allergy diagnoses has been observed following the introduction of guidelines recommending peanut introduction during the first year of life. However, one important lesson has been the importance of culturally

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tailored advice and implementation strategies. Families in which one or both parents were born outside Australia were less likely to report receiving advice about timely allergen introduction and were less likely to follow the guidelines in practice. This is particularly significant, because infants of parents born in East Asia are known to be at higher risk of developing food allergy. These findings underscore the need for targeted, culturally appropriate approaches to ensure guideline benefits occur across all populations.

Through initiatives like the National Allergy Centre of Excellence (NACE) Living Evidence Collection, you aim to connect evidence and practice. What challenges do you encounter when translating complex research findings into actionable recommendations for clinicians and families? One of the key challenges in connecting evidence with practice is the speed at which research findings can be translated into guidelines and, ultimately, changes in clinical care. Traditional systematic reviews can take years to complete, potentially delaying

the incorporation of new evidence into recommendations. The NACE Living Evidence Collection aims to change this by enabling rapid incorporation of newly published studies into living systematic reviews and meta-analyses, making it easier for high-quality evidence to be rapidly incorporated into guidelines. Another ongoing challenge is how best to communicate uncertainty when translating complex research findings into actionable recommendations for clinicians and families. There are often questions that are highly relevant and important to families, but for which robust, high-quality evidence does not yet exist. In these situations, it can be tempting to issue interim recommendations; however, without a strong evidence base, there is a real risk that wellintentioned guidance could be ineffective or even cause harm. Striking the right balance between providing practical guidance and acknowledging uncertainty remains one of the most difficult aspects of evidence translation.

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Some of your research examines allergic disease among Aboriginal and Torres Strait Islander children. What have you learned about the social, environmental, or genetic factors that contribute to differences in allergy prevalence and outcomes? There is still a lot to learn about factors that contribute to differences in allergy prevalence and outcomes between populations. One of the most consistent findings across our population-based studies is that children born in Australia to parents born in East Asia have a substantially higher risk of eczema and food allergy compared to children whose parents were born in Australia. In contrast, children born and raised in East Asia, or those who migrate later in childhood, appear to have the lowest risk. Similar patterns have been observed in other Western countries among children born to East Asian-born parents. These findings suggest an interaction between genetic susceptibility and early-life environmental exposures. Children with East Asian ancestry may carry genetic variants that make them

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more likely to develop food allergy when they are exposed to certain environmental factors common in Western settings. The specific environmental factors involved are not yet fully understood, but may include different patterns of microbial exposure, changes in dietary patterns and infant feeding practices, changes in sunlight exposure and vitamin D status, humidity, or other aspects of the early-life environment. Much less is known about allergic disease among Aboriginal and Torres Strait Islander children. Although national data show that asthma is more commonly reported among First Nations Australians, other allergic diseases have not necessarily been recognised as an important concern among First Nations people, particularly in remote areas. National surveys also suggest a lower rate of reported allergies among First Nations people. However, it remains unclear whether this reflects genuinely lower prevalence, underrecognition, underreporting, or barriers to diagnosis and access to care. Despite lower rates of reported allergy in surveys, our research in Queensland found that First Nations Australians were more likely to present to emergency departments with allergy-related

illnesses compared with nonIndigenous Australians. This may reflect more severe disease at presentation, limited access to specialist services, or delays in diagnosis and management, particularly in regional and remote settings. These findings highlight the importance of improving access to culturally safe allergy services, strengthening data collection, and working in partnership with First Nations communities to better understand and address allergic disease across diverse populations.

Looking ahead, what areas of allergy and immunology research are you most excited about, whether in prevention, early intervention, or novel therapies, and where do you see the field heading in the next 5–10 years? One of the things that most excites me is the possibility that in the next 5–10 years, we might start to see large reductions in the number of children living with food allergy. We already have prevention strategies that we know can reduce the number of new cases of food allergy when implemented effectively, and other promising strategies are currently being tested in large RCTs. These include infant vitamin D supplementation as well as maternal consumption

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of allergenic foods during pregnancy and breastfeeding. Other areas of active research include skincare interventions aimed at preventing eczema and subsequent food allergy, as well as strategies targeting the infant microbiome. Hopefully, some of these approaches will prove effective and be incorporated into clinical guidelines in the coming years. Combined with emerging treatments that may help some children, and possibly adults, outgrow existing food allergies, there is genuine potential for meaningful, population-level reductions in food allergy prevalence. Another area where I am encouraged by recent progress is the increasing inclusion of the perspectives of families and people living with allergies across all stages of the research process. Continued improvement in this area should help ensure that research over the next 5 years and beyond addresses questions that matter most to those directly affected by allergic disease, ultimately leading to prevention and treatment strategies that are both effective and relevant.

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Citation:

EMJ Allergy Immunol. 2026;11[1]:61-63. https://doi.org/10.33590/emjallergyimmunol/Y71H5287

What initially drew you to medicine, and how did you ultimately gravitate towards allergy and immunology as your specialty?

Mitchell H. Grayson Grant Morrow, III, MD Endowed Chair in Pediatric Research; Professor of Pediatrics and Chief, Division of Allergy & Immunology, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, USA

I’m most excited about a hypothesis that we’ve been exploring, which is that atopic disease can provide protection from severe respiratory viral infections

My father trained as a dermatologist and then became board certified in allergy and immunology the first year that allergy and immunology became a board-certified specialty. It seems that from birth I knew I wanted to be a physician. When I was little, I went with my dad to see a patient in the emergency room, and my dad joked that I would give the patient a shot. Supposedly, I picked up a syringe and was going to inject the patient (I didn’t and they quickly took the syringe away from me). My dad would also come to my elementary classes and teach us about the immune system. He had cards with hand-drawn T cells, B cells, and macrophages, and would use them to demonstrate how the immune system worked. I think it was seeing my dad as a physician and allergist that led me to want to go into medicine, and by the time I was in high school, I knew I wanted to do research. In college, it was the peak of the AIDS epidemic, and the whole focus on the disease and what happens when cluster of differentiation (CD)4 T cells are depleted led me to want to study the immune system. In medical school, it seemed that either allergy and immunology or rheumatology were the two specialties that focused on immunology. My medical school, the University of Chicago, Illinois, USA, did not have an allergy and

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immunology division or clinic, so I rotated in the rheumatology clinic. At that time, most of the treatments were injecting steroids into patient’s joints, which I found unfulfilling, so I decided I would follow my dad into allergy and immunology. It was a specialty where you would have time to do research and have a clinical practice where patients weren’t that ill and really only required outpatient care.

Your research focuses on how viral infections can drive allergic disease. Why do you think respiratory viruses seem to have such a long-term impact on immune development, and what do we now understand that we didn’t a decade ago? I think the impact of a respiratory viral infection on the immune system is very much due to timing. Early in life, the immune system is still developing, and this seems to be the time at which a respiratory viral infection has the greatest impact (at least in terms of skewing the immune response). This may relate to immaturity of the immune response at the time (impaired interferon responses, for example) or even the relative naïveté of the immune system early in life. We have learned many things over the past decade, including the previously mentioned impaired immune response; the fact that different respiratory viruses drive risk for asthma in different ways (respiratory syncytial virus [RSV] drives a risk for recurrent wheeze/ asthma in those who aren’t atopic, while rhinovirus drives the risk in

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those who already have allergic disease); the potential impact of biologics (like anti-IgE or antiIL4/IL13) on immune response; and even the effect of atopy on the antiviral immune response (including protection from severe disease). And this is all ignoring the unique, real-life experiment of the COVID-19 pandemic.

Allergic diseases are increasing worldwide, particularly in westernised settings. Beyond genetics, what environmental or societal factors do you believe are most influential, and are there any emerging hypotheses that excite you? I’m most excited about a hypothesis that we’ve been exploring, which is that atopic disease can provide protection from severe respiratory viral infections. The thought here is that with increased urban communities, we are seeing more respiratory viral infections, and that an immune response skewed towards Type 2 immunity (atopy) can protect from severe disease. If this hypothesis is correct, it may lead to novel

interventions that could prevent death from future respiratory viral pandemics, and even from the seasonal influenza outbreaks.

In your laboratory work, what discovery has surprised you the most, either by confirming or challenging assumptions about how allergies develop? I was most surprised about our initial discovery 20 years ago that IgE, the antibody associated with allergic disease, was necessary to translate a respiratory viral infection into ‘asthma’ in a mouse model. This led to the idea that anti-viral IgE (that is, IgE directed against the virus itself) might be important in developing and exacerbating asthma. Indeed, studies have shown that use of anti-IgE prevents viral induced asthma exacerbations, as well as seasonal allergen (like pollen) exacerbations. However, whether this protection is through blockage of anti-viral IgE has never been studied. More recently, I’ve been surprised by the fact that making mice atopic can prevent them

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from dying from a normally lethal respiratory viral infection. This has led to my thoughts on the potential evolutionary advantage that atopy might impart on the host and is something we are actively studying at this time.

Asthma and food allergy remain major public health burdens. Where do you see the greatest opportunities for prevention rather than treatment, and what would a truly preventative strategy look like? Our current strategies for asthma and food allergies are primarily focused on treating the disease once it develops. However, in food allergy, there has been more interest in prevention through feeding children the food before they develop the allergy. I think we have a great opportunity with our biologics to potentially prevent the development of allergic disease, if only we were able to identify those most at risk before they had a disease. I also think the RSV vaccine has the potential to reduce the number of children that will go on to develop asthma, presuming

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that we are going to be able to convince pregnant mothers to get inoculated, which may be difficult in the current environment. Looking ahead, I think we will get to a point where infants are protected from RSV infection through vaccination (primarily of their mothers). Then, using a predictive algorithm (probably utilising AI), those most at risk of allergic disease will be treated with a biologic (likely antiIL4/IL13 or similar) for a short period of time (probably less than a year). After this, they will develop normally and not have any allergic diseases (eczema, allergic rhinosinusitis, food allergy, or asthma).

AI will provide the power to really bring personalised medicine to fruition

As a leader in multiple professional organisations and editor-in-chief of a journal, how do you balance advancing rigorous science with ensuring it translates into patient benefit? As an editor, I want to provide my journal readers with the most cutting-edge and up-to-date information in the field. This includes mechanistic and clinical science that will impact patient care. However, determining whether a given study will truly impact patient care is difficult. The best we can really do is make sure the study is rigorous and novel, and that the conclusions apply to the patient population (or disease, if mechanistic) that is seen by our readership (allergists and immunologists, in my case). Allergy and immunology is a field in which basic discoveries do translate fairly rapidly into clinical

care, and I think this is in part due to the dissemination efforts of the field. Not only do the fields’ journals provide a robust source of research across the entire research spectrum (basic science to population health), but our national organisations highlight these advances in their annual meetings. My responsibilities are to identify these findings and try and bring them to the specialty through both my activities as an editor and as a speaker and/or programme committee member of the various professional organisations.

Immunology is advancing rapidly with tools like single-cell sequencing and AI. How might new technologies reshape allergy research and patient care in the next 10–20 years? I think that the big change in allergy research and patient care will come through use of AI. In the research realm, I believe AI will provide the power to really bring personalised medicine to fruition. In the future, AI could produce algorithms to predict which patients are at risk of disease (such as recurrent wheeze/asthma after a respiratory viral infection), which could allow for preventative intervention. AI will also allow researchers to quickly consider multiple hypotheses and design appropriate studies to test these. For better or worse, I suspect that grant and paper writing will involve AI editing (if not writing much of the text), and there likely will be an AI version of ‘peer-review’ that occurs before human review of the proposals and manuscripts. From a clinical standpoint, AI will likely run in the background on electronic medical records, providing support and assistance to the physician as they see the patient. This could be suggesting diagnoses, as well as potential medications, in real time. Already, AI is reducing the burden of medical note writing through various

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ambient scribe programmes.

For young scientists or clinicians considering a career in allergy and immunology, what advice would you give, and what qualities do you think are most important for driving meaningful progress in the field? For those considering a career in allergy and immunology, I would say you have picked an outstanding field. This is an area of medicine that is strongly based in mechanistic science and allows you to take care of patients across all age groups. We have treatments that really make people’s lives better, and this can lead to an extremely rewarding career. In my opinion, successful clinicians are those who show empathy and a consistent thirst for knowledge. This is a field where playing detective is required to find out the triggers that are making a patient sick (is it the dog, dust mites, tree pollen, etc.). For those considering a research career, my advice is to stay focused and be persistent. Research does not usually bring rapid success; it is called ‘research’ for a reason. Persistence is what leads to those ‘aha’ moments and the discoveries that really move the field forwards. And for both clinicians and scientists, I think identifying mentors who can provide advice and a path forward is always critically important.

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EMJ Allergy Immunol. 2026;11[1]:64-67. https://doi.org/10.33590/emjallergyimmunol/D68B9E54

Citation:

Prevention, Precision, and Policy: Interview with Ruchi Gupta

Q1 Ruchi Gupta

Professor of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Director, Center for Food Allergy & Asthma Research (CFAAR)

Our mission is simple, but ambitious: use rigorous science to make a meaningful difference in the lives of children and adults living with food allergy and asthma

What initially drew you to allergy and immunology, and what motivated you to focus so deeply on food allergy research in particular? When I began my career in Chicago, USA, my research was centred on asthma, a condition that affects so many children every day, but one family shifted my entire path. They had two young sons with food allergies and invited me into their daily world of label reading, reaction vigilance, and constant uncertainty. Their courage was inspiring, but their challenges were eye opening. At the time, the field lacked the most basic data and guidance. Families were essentially told: “Avoid the food and carry epinephrine.” It was clear that it wasn’t enough, not for public health and certainly not for families living this reality. A few years later, the issue became personal. When my daughter was a year old, she had a severe reaction to peanut butter. In that moment, I wasn’t a researcher or a clinician; I was a mom terrified for her child. That experience changed my trajectory. It deepened my commitment to building the evidence base we desperately needed, improving diagnosis and prevention, and advocating for policies that would make daily life safer and more manageable for families everywhere. These experiences ultimately led me to establish the Center for Food Allergy & Asthma Research (CFAAR) at Northwestern

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University, Chicago, and Lurie Children’s Hospital of Chicago, Illinois, USA. Our mission is simple, but ambitious: use rigorous science to make a meaningful difference in the lives of children and adults living with food allergy and asthma. At CFAAR, we study how allergic conditions develop, who is most affected, and which interventions truly help. Our team brings together epidemiology, clinical research, and community partnerships to create solutions that work in the real world, whether that’s defining national prevalence, advancing early life prevention strategies, or improving preparedness in schools and communities. Above all, we want every child and adult living with food allergy or asthma to have the knowledge, support, and systems they need to stay safe and thrive.

What do you see as the most significant changes in how we conceptualise and manage food allergy and asthma today compared with when you began your career? One of the biggest shifts over the past two decades has been recognising these conditions as widespread public health issues that affect entire communities. Large, population based studies finally gave us the data we lacked, showing not only how common these conditions are, but how unevenly the burden falls across racial, ethnic, and socioeconomic groups. That knowledge changed the conversation. It

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pushed schools, workplaces, and healthcare systems to think more proactively about preparedness, equity, access to epinephrine and inhalers, and the day to day quality of life for families. Another major change is the movement toward prevention and precision care. In food allergy, we’ve gone from advising parents to avoid allergenic foods in infancy to learning that early and sustained introduction, combined with good skin barrier care in babies with eczema, may actually reduce risk. In asthma, we’ve strengthened guideline based care and integrated better risk assessment, environmental support, and school based partnerships. Across both conditions, we now have targeted therapies that are changing lives: biologics for moderate to severe asthma, and oral immunotherapy and other approaches that reduce both the likelihood and severity of reactions in food allergy. We’re also getting better at being flexible. Prevention isn’t a one size fits all protocol; it’s a toolkit we adapt to each infant, family, and community. Asthma management works the same way: some families benefit most from environmental remediation or school support, others from biologics, inhaled therapy adjustments, or a focus on symptom pattern monitoring. The goal isn’t to force families into rigid pathways, but to give them choices, clarity, and support, so they feel confident navigating what can be unpredictable conditions. Overall, the biggest shift is that we’re thinking more holistically about risk, resilience, equity, families, and the environments where people live and learn, and that shift is making a real difference.

Your work has been instrumental in defining the prevalence of paediatric and adult food allergy in the USA. How has having more precise epidemiological data changed the national conversation around food allergy, from clinical care to school policy and public awareness? Good data have reshaped the national conversation about food allergy. When our team published national, population based estimates showing that about one in 13 American children and one in 10 American adults are affected by food allergy, it gave the field a new, shared baseline for addressing this widespread public health issue. These numbers drove action. School districts strengthened emergency preparedness and epinephrine access, legislators advanced stock epinephrine and labelling policies, and healthcare systems began treating food allergy as a condition requiring structured pathways, better diagnosis, and attention to disparities. Data show that over 40% of food allergic children have experienced a severe reaction, and a similar share have required emergency care at some point (with about one in 5 in the past year), which underscored the urgency and helped set priorities. The prevalence work also reframed food allergy as a quality of life and equity issue. Understanding which allergens are most common, how many children have multiple allergies, and the financial and emotional toll on families shifted the conversation from individual burden to community responsibility. In short, precise epidemiology didn’t just inform science; it changed systems, policies, and public awareness in ways that tangibly support families.

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A major focus of your research has been understanding racial, ethnic, and socioeconomic disparities in food allergy development and care. What do you see as the most urgent gaps in equity today, and what practical interventions have shown the greatest promise in closing those gaps? The most urgent gaps in equity come down to diagnosis, access, and safety. Families in under resourced communities are less likely to receive a clinician confirmed food allergy diagnosis and more likely to rely on emergency departments for care. They also face higher costs and reduced access to safe foods, epinephrine, and allergist follow up. Together, these barriers increase the risk of severe reactions while placing disproportionate financial and emotional strain on families who already carry the heaviest burdens. The most effective solutions are those that meet families where they are. School based preparedness and stock epinephrine programmes consistently save lives by ensuring timely treatment. Community health workers, peer support, and culturally tailored education help families navigate diagnosis, label reading, and prevention strategies with confidence. In primary care, practical tools that help clinicians recognise food allergy, and clear pathways for referral, can significantly reduce under and misdiagnosis. Policy change is also critical: lowering out of pocket costs for epinephrine and medically necessary foods can make an immediate difference for families. In research, embedding equity considerations at the design stage helps ensure that new interventions are both effective and feasible in the communities most affected.

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Recent research, including work on eczema onset and food allergy risk, suggests that early-life factors play a critical role in allergic disease trajectories. How do you think emerging insights into atopic dermatitis, early feeding practices, and skin barrier health will reshape prevention strategies over the next decade? Infancy is a critical window for shaping the immune system. We now understand that severe eczema in the first year of life often reflects skin barrier disruption, which increases the likelihood of sensitisation through the skin. At the same time, early and consistent oral exposure to a variety of foods helps promote tolerance rather than allergy. Together, these insights point toward a prevention strategy that is both simple and powerful: protect the skin and feed the immune system early. Over the next decade, I expect prevention to become more integrated and practical. We’ll likely see pathways that combine proactive eczema management, timely introduction of allergens, and nutrition that supports a healthy microbiome, all delivered in ways that are easy for families and paediatricians to follow. Large, diverse early life cohorts are already giving us the evidence we need to design tools paediatricians can use during routine 4 and 6 month visits, with tailored guidance for infants at highest risk. Most importantly, these approaches must be flexible. Prevention should adapt to each family’s culture, resources, and comfort level. When we create space for shared decision making and honour the realities of family life, we make it possible for prevention strategies to work not just in theory, but in practice. 66

Your recent work estimating the societal economic burden of food allergy highlights the wide-reaching impact beyond the clinic. How should policymakers and healthcare systems respond to these findings, and what systemic changes are most needed to reduce this burden for families? When families are spending thousands of dollars each year on medical visits, emergency care, epinephrine, and the higher cost of safe foods, it’s a sign that our systems are asking too much of individuals and not enough of institutions. Policymakers can make a meaningful difference by reducing the financial burden, from lowering out of pocket costs for epinephrine and evidence based treatments to improving the clarity and consistency of food labelling. Strengthening preparedness in schools and workplaces, and ensuring that federal and state nutrition programmes accommodate allergen free needs, can also prevent families from having to choose between safety and affordability. Importantly, policy should protect choice, making it feasible for families to pursue the management pathway that fits their needs, whether that’s strict avoidance, immunotherapy, or a combination of approaches. On the health care side, we need systems that make accurate diagnosis accessible, including the ability to complete oral food challenges when appropriate, and regular re evaluation so families aren’t avoiding foods unnecessarily. Care models that integrate allergy, dermatology, gastroenterology, nutrition, and mental health can make a profound difference. For many families, quality of life, not just anaphylaxis risk, is a real driver of burden, and multidisciplinary support helps

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address the emotional, social, and nutritional dimensions that traditional models often overlook.

You’ve studied clinician adherence to peanut allergy prevention guidelines and developed school-based interventions for asthma management. What are the biggest challenges in translating evidencebased guidelines into real-world practice, particularly in primary care and community settings? Bringing evidence based guidelines into real world practice remains one of the most persistent challenges in primary care and community health. Many clinicians are aware of the early feeding and asthma management recommendations, but they often lack quick, practical tools to assess risk, counsel families, and arrange follow up within the constraints of a short visit. There’s also understandable hesitation, especially with high risk infants, when workflows aren’t clear or when support for follow through is limited. Even the strongest guidelines can fall short if they don’t account for daily realities, such as food insecurity, limited access to safe infant foods, cultural feeding practices, or caregiver anxiety. We’ve seen real progress when implementation is made easy and intuitive. Electronic health record prompts that fit naturally into the visit, short training modules, and parent friendly materials in multiple languages all help clinicians and families act on the evidence with confidence. In schools, the same model that has strengthened asthma care, bringing protocols, supplies, and staff training directly into the environment where children spend most of their day, works equally well for food allergy prevention and emergency response.

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Interview

Ultimately, translation takes time, because it’s not just about sharing new information; it’s about building systems that make evidence based care easy to understand and easy to carry out. When research is paired with practical tools, community partnerships, and culturally grounded support, evidence based guidelines become something families and frontline providers can truly use.

Looking forward, what developments, whether in prevention, precision medicine, policy, or community-based interventions, do you believe will most meaningfully reduce the burden of food allergy and asthma over the next 10–15 years, and where should the next generation of researchers focus their efforts? I’m excited for the next decade of research, when so many of the puzzle pieces in prevention, precision medicine, and equity will finally come together. With these

pieces aligning, we have a real opportunity to not only treat allergic disease more effectively, but to fundamentally change its trajectory. For infants, I expect integrated pathways that combine proactive eczema care with early, sustained multi allergen feeding, supported by clear tools in primary care and community based resources so every family, not only those with easy access to specialists, can participate. In diagnosis, smarter use of component testing and thoughtfully chosen oral food challenges will help reduce unnecessary avoidance and improve quality of life. Therapeutically, we’ll continue refining immunotherapy and biologics, guided by biomarkers and microbiome insights that make treatments safer, more precise, and more tolerable. At the systems level, evidence based policy (stronger food labelling,

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improved access to epinephrine and specialty care, and insurance coverage for prevention and diagnostic services) will help reduce the burden families face every day. For the next generation of researchers, I think some of the most meaningful progress will come from working at the intersections. The breakthroughs ahead lie where skin barrier biology meets infant feeding, where microbiome science connects to daily behaviour, and where precision biomarkers shape school and community health policies. We need scientists and clinicians who can move between population research, clinical care, and implementation.

Allergy & Immunology

Society Update

Spotlight from Europe German Society for Allergology and Clinical Immunology (DGAKI)

DGAKI’s mission is to advance research, education, guideline development, and evidence-based patient care across the spectrum of allergic and immunological disease. The German Society for Allergology and Clinical Immunology (Deutsche Gesellschaft für Allergologie und Klinische Immunologie [DGAKI]) is Germany’s leading scientific medical society in the field of allergy and clinical immunology, bringing together clinicians and researchers from paediatrics, pneumology, dermatology, otorhinolaryngology, immunology, and environmental medicine.

OVERVIEW A central pillar of DGAKI’s work is the development and updating of national guidelines. Current and ongoing activities focus particularly on anaphylaxis, allergen immunotherapy, food allergy, atopic dermatitis, and allergy prevention, areas that reflect the breadth of modern allergology, from emergency management and diseasemodifying therapies to long-term care of chronic inflammatory conditions and prevention from early life onwards. DGAKI is also committed to making future guideline work increasingly gender-sensitive, ensuring

that sex- and gender-related aspects of disease risk, presentation, and treatment response are more consistently reflected in evidence-based recommendations. Beyond guideline development, DGAKI is actively engaged in strategic and researchoriented initiatives that aim to strengthen allergy care in Germany. These include the Nationaler Aktionsplan Allergologie (NAP), which seeks to improve the visibility, coordination, and long-term delivery of allergology within the healthcare system, as well as the ‘Early Risk Assessment and Recognition of Allergies in Children’ Task Force, which focuses on structured early

©Sebastian Semmer, Berlin/AKM Allergiekongress und Marketing GmbH

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recognition and prevention of allergic disease in paediatric care. DGAKI also contributes to the Network for Online Registration of Anaphylaxis (NORA) anaphylaxis registry, which has generated important real-world data on triggers, cofactors, and management of severe allergic reactions. In chronic inflammatory disease, DGAKI members are involved in TREATgermany, for atopic dermatitis, and German Asthma Net (GAN), for severe asthma, initiatives including collaborative work on biologics and registry-based approaches in paediatric and adult care. Education remains another core priority. DGAKI’s annual and topic-focused meetings provide a platform for scientific exchange and continuing professional development across the field. Key activities include the Mainzer Allergie-Workshop, Allergologie Kompakt, and Allergie im Fokus, all of which translate current evidence into practical clinical learning. A major highlight is the 21st Deutscher Allergiekongress, taking place in Wiesbaden, Germany in October 2026, which will bring together clinicians, scientists, and early-career colleagues from across the German-speaking allergy community.

DGAKI’S PERSPECTIVE ON THE ALLERGY AND IMMUNOLOGY LANDSCAPE IN GERMANY From a German perspective, allergy and clinical immunology are currently shaped by two parallel developments: substantial scientific progress on the one hand, and persistent structural challenges in healthcare delivery on the other. Precision medicine, biologics, molecular diagnostics, and a better understanding of inflammatory endotypes are transforming the care of patients with severe asthma, atopic dermatitis, chronic urticaria, food allergy, and other immune-mediated diseases. These advances represent a major success for the field and have already improved outcomes for many patients with severe or difficult-to-control disease.

innovation into routine care is still uneven. Access to specialist allergy services varies across regions, and allergy expertise is not always sufficiently integrated into primary care, paediatric care, or emergency care pathways. This is particularly relevant in food allergy and anaphylaxis, where timely diagnosis, structured education, and emergency preparedness remain essential. Prevention is another key challenge. Germany has a strong tradition of allergy research and guideline-based care, but more effort is needed to implement preventive strategies consistently from early childhood onwards and to strengthen awareness of allergic disease across the wider healthcare system. Environmental change adds a further layer of complexity. Longer pollen seasons, changing allergen exposure, and the interaction between environmental factors and chronic airway disease are increasingly relevant in daily clinical practice and in public health planning. In this setting, DGAKI sees its role as both scientific and strategic: to support evidence-based care, to promote interdisciplinary collaboration, and to help ensure that advances in allergy and immunology translate into real benefit for patients. Strengthening prevention, improving access to specialist expertise, and integrating precision medicine into routine care will remain key priorities for the years ahead.

Eckard Hamelmann President of DGAKI

At the same time, the burden of allergic disease remains high, and the translation of CC BY-NC 4.0 Licence

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Society Update

Spotlight from Europe Serbian Association of Allergologists and Clinical Immunologists (SAACI)

SAACI brings together physicians from a range of primary specialties, including internal medicine, paediatrics, ENT, dermatovenereology, infectious diseases, and clinical immunology. The Serbian Association of Allergologists and Clinical Immunologists (SAACI), known in Serbian as the Udruženje alergologa i kliničkih imunologa Srbije (UAKIS), was founded in 1958 and serves as the national professional body representing specialists in allergology and clinical immunology across Serbia. SAACI has approximately 120 members, all of whom have completed an additional year of subspecialty training in allergology and clinical immunology, following 4–6 years of postgraduate training in total. The Association is currently led by its President, Snežana Aranđelović, and organises a National Congress every 4 years alongside a Scientific Meeting every 2 years.

OVERVIEW SAACI actively participates in European forums, including the European Academy of Allergy and Clinical Immunology (EAACI) National Allergy and Immunology Societies (NAIS) Network, where it holds formal member status, and is a member of the Central & Southern European Allergy and Asthma Alliance (CSEA3), a regional alliance fostering research, education, and collaboration across Central and Southern Europe. Through these memberships, SAACI advocates for the needs of Serbian specialists and patients at a continental level. SAACI operates dedicated working groups and actively contributes to EAACI projects, including those focused on anaphylaxis. In March 2026, the Association also hosted the EAACI Spring Meeting in Belgrade, bringing together the wider European allergy and immunology community in Serbia.

CHALLENGES AND OPPORTUNITIES IN SERBIAN ALLERGOLOGY AND CLINICAL IMMUNOLOGY Serbia, like many countries in the region, faces a distinctive set of challenges in delivering high-quality allergy and immunology care. Access to advanced diagnostics, including molecular allergology and specialised clinical immunology 70

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testing, remains concentrated in larger university centres, leaving patients in other parts of the country with significant barriers to timely and accurate diagnosis. On the treatment side, the availability and reimbursement of adrenaline autoinjectors, a life-saving intervention in anaphylaxis, remains limited within the national healthcare system, while allergen immunotherapy, the only disease-modifying treatment for allergic conditions, is not consistently available across all regions. Biological therapies have been introduced in major centres, yet wider availability across the country remains a significant unmet need. Outside major centres, there are too few specialists, and SAACI recognises this as a priority that requires investment in training and workforce development. Despite these challenges, major centres in Serbia have excellent academic institutions with growing experience in biologic therapies and an increasing number of multidisciplinary centres for the management of complex allergic and immunological conditions.

STRATEGIC PRIORITIES Looking ahead, SAACI has identified several key priorities. A major focus is the development of national clinical guidelines for anaphylaxis, one of the most urgent unmet needs in Serbian allergology. Despite

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anaphylaxis representing a potentially lifethreatening emergency, Serbia currently lacks a nationally adopted guideline, and SAACI is committed to addressing this gap by producing evidence-based recommendations tailored to the local healthcare context. Alongside this, SAACI is working to support the establishment of a national registry for allergic diseases and anaphylaxis, which would provide the data infrastructure needed to better understand disease burden and guide future policy decisions. SAACI is also committed to fostering multicentre research and deepening collaboration with Balkan neighbours, recognising that shared regional challenges are best addressed through coordinated action. Serbian specialists already actively contribute to international studies in the field, and SAACI aims to build further on this foundation. Looking to the future, SAACI plans to develop dedicated support mechanisms for young allergologists and clinical immunologists, including scholarships and mentorship opportunities, with the aim of attracting new generations of specialists to the field and securing the longterm development of the specialty in Serbia.

PUBLIC AWARENESS AND PATIENT ENGAGEMENT Public awareness of allergic and immunemediated conditions remains low in Serbia, and SAACI is working to improve education among both the general population and healthcare professionals in primary and secondary care. In this regard, SAACI has established collaboration with patient associations representing individuals living with allergic diseases, actively participating in their initiatives and advocating for their rights within the healthcare system. Strengthening the profile and recognition of allergology and clinical immunology within the Serbian healthcare system is a goal that underpins all of SAACI's current initiatives.

to be held from 4th–6th December 2026 in Sokobanja, Serbia. The programme will focus on eosinophilic disorders and Type 2 inflammation, covering conditions such as severe asthma, chronic rhinosinusitis with nasal polyps, atopic dermatitis, and food allergy, alongside biologic therapies and the multidisciplinary management of these conditions. The Meeting will bring together allergologists, clinical immunologists, and specialists from related fields across the region to discuss the latest advances in the understanding and management of Type 2-driven conditions, an area of rapidly evolving science and clinical practice. Looking further ahead, SAACI will host its National Congress in 2028, which will represent a major landmark for the specialty in Serbia. As allergic and immune-mediated diseases continue to rise in prevalence, SAACI remains committed to ensuring that patients in Serbia have access to timely diagnosis, modern treatments, and evidence-based care. With over 6 decades of activity behind it, SAACI enters its next chapter with a clear agenda: stronger regional collaboration, a growing evidence base, and a healthcare system better equipped to meet the needs of patients living with allergic and immunological conditions.

Snežana Aranđelović

President, SAACI/UKAIS; Clinic for Allergology and Immunology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia

Milica Terzić

Secretary, SAACI/UKAIS; Clinic for Allergology and Immunology, University Clinical Centre of Serbia, Belgrade, Serbia

UPCOMING EVENTS A key upcoming milestone is the 5th Scientific Meeting of SAACI, entitled ‘T2 Inflammation and Eosinophilic Diseases: From Pathogenesis to Clinical Outcomes’, CC BY-NC 4.0 Licence

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Biologics in High-Risk, Non-Severe Asthma: Current Evidence and Future Studies Editor's Pick

Severe asthma has been transformed by biologic therapies, but emerging evidence suggests their potential role may extend to patients with less severe disease who carry high-risk inflammatory features. This article explores the shift towards precision medicine in asthma management, highlighting the use of biomarkers such as eosinophil counts and fractional exhaled nitric oxide to identify patients who may benefit from earlier targeted intervention, while examining ongoing clinical trials that could redefine the future role of biologics beyond current treatment guidelines. Prof Jacques Bouchard La Malbaie Hospital, Quebec, Canada

Authors:

Alexa Rahem,1 Abderaouf Hamadouche,1 Liam Coyle,2 Jack Jeskey,3,4 P. Jane McDowell,2 *Simon Couillard1 1. Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Canada 2. Welcome Wolfson Institute for Experimental Medicine, Queen’s University, Belfast, UK 3. Division of Allergy and Immunology, Department of Medicine, University of South Florida Morasni College of Medicine, Tampa, USA 4. Division of Allergy and Immunology, Department of Medicine, James A. Haley Veterans’ Hospital, Tampa, Florida, USA *Correspondence to S.Couillard@usherbrooke.ca

Disclosure:

McDowell has reported speaker fees from GlaxoSmithKline; and speaker and advisory board fees from Astrazeneca. Couillard has received non-restricted research grants from the NIHR Oxford BRC, the Quebec Respiratory Health Research Network, the Association Pulmonaire du Québec, the Academy of Medical Sciences, AstraZeneca, bioMérieux, Circassia Niox Group, and Sanofi-Genyme-Regeneron; is the holder of the Association Pulmonaire du Québec’s Research Chair in Respiratory medicine; is a clinical research scholar of the Fonds de recherche du Québec; has received speaker honoraria from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, Circassia Niox Group, and Valeo Pharma; has received consultancy fees for FirstThought, Apogee Therapeutics, Upstream Bio, AstraZeneca, GlaxoSmithKline, SanofiRegeneron, Access Biotechnology, and Access Industries; has received sponsorship to attend/speak at international scientific meetings by/for AstraZeneca and Sanofi-Regeneron; is an advisory board member and detains stock options for Biometry Inc, a company which is developing a FeNO device (myBiometry); is co-inventor for the patent filed as ‘Method for alleviating dyspnea with neuromodulation’; advised the Institut national d'excellence en santé et services sociaux (INESSS) for an update of the asthma general practice information booklet for general practitioners as well as therapeutic indications for Enerzair; and is a member of the asthma steering committee of the Canadian Thoracic Society. The other authors have declared no conflicts of interest. The study was funded by Fonds de Recherche du Québec-Santé and the Association Pulmonaire du Québec.

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Acknowledgements:

Rahem, Hamadouche, and Coyle drafted the manuscript. Couillard and Mcdowell designed the figures. All authors approved and reviewed the final manuscript. Couillard is the guarantor of the study.

Received:

19.03.26

Accepted:

01.06.26

Keywords:

Asthma, biologic, corticosteroids, eosinophilia, risk.

Citation:

EMJ Allergy Immunol. 2026;11[1]:73-84. https://doi.org/10.33590/emjallergyimmunol/3P4347FT

Abstract Asthma is a heterogeneous chronic respiratory disease. Biologic therapies directed against IgE, IL-5, IL-4 receptor alpha, and thymic stromal lymphopoietin have transformed the management of severe asthma by reducing severe attacks (‘exacerbations’), improving lung function, and enhancing quality of life. Despite these advances, their use remains restricted to patients with severe, uncontrolled disease. The aim of this review is to synthesise the concepts and evidence supporting the use of biologics in non-severe, high-risk asthma not typically eligible for biologics in current treatment algorithms. Evidence from other chronic inflammatory diseases supports a shift toward earlier, targeted therapy to prevent irreversible damage. In asthma, robust evidence suggests that Type 2 inflammatory pathways are active in a substantial proportion of patients, placing them at increased risk of severe attacks and lung function decline. Biomarkers such as the blood eosinophil count and fractional exhaled nitric oxide may enable identification of these high-risk individuals and provide a rationale for earlier intervention in less severe asthma with high-risk features, including Type 2 biomarker elevation. This is a step away from the paradigm of asthma treated based on treatment received, towards a paradigm of precision medicine with earlier targeting driven by biomarkers of inflammation. Five recently announced and/or ongoing clinical trials are evaluating the efficacy of biologics in patients with less severe disease (defined as patients not on high-dose inhaled therapy): AIM4, BRISOTE, HOTHOT, MODIFY, and AIRLYMPUS. Innovative trial designs include composite biomarker-high patient selection, relaxed inclusion criteria permitting patients with less disease burden, on-treatment adjustment of background therapies, and targeting clinical remission. As trial designs adapt and evolve, biologics may play an expanding role beyond severe asthma. Current evidence supports the rationale for studying biologics earlier in high-risk asthma, but routine clinical use in non-severe asthma awaits trial results, cost-effectiveness analyses, and implementation frameworks.

Key Points 1. Biologics have transformed severe asthma care, but many high-risk patients with non-severe disease remain ineligible despite ongoing Type 2 inflammation. 2. This narrative review synthesised current evidence and ongoing clinical trials evaluating biologics in high-risk, non-severe asthma. 3. Earlier biomarker-guided use of biologics may improve long-term outcomes in high-risk asthma, but routine use awaits results from ongoing trials.

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INTRODUCTION Asthma is a chronic respiratory disease affecting more than 300 million people worldwide, characterised by variable symptoms and airflow limitation.1,2 The disease course may involve flare-ups (asthma attacks), loss in lung function, and decreased quality of life over time.3,4 Asthma-related deaths may occur secondarily to attacks or due to comorbidity associated with cumulative systemic corticosteroid therapy exposure.5,6 Asthma attacks and loss of lung function are closely related to Type 2 inflammation,4,7-22 but can be disconnected from chronic symptom burden or treatment intensity (‘asthma severity’), which often reflect damage because of previously active disease or co-existent comorbidity.23-25 Biologics targeting Type 2 inflammation have revolutionised management of severe asthma.4,26-28 Severe asthma represents a minority (approximately 10%) of patients who require high intensity treatment to maintain control, or remain uncontrolled despite high intensity treatment.29-30 These patients with severe asthma account for most of the morbidity, mortality and societal costs attributed to the disease.3 Substantial progress in our understanding of asthma immunology, specifically the crucial role of Type 2 inflammation in initiating, propagating, and aggravating asthma attacks,31-35 was arguably the most important development leading to the life-changing effects of biologics. The term ‘remission’ has been used to describe the best possible outcome with biologics as it signifies a state of enhanced disease control which does not require oral steroid use, stable end organ (lung) function, and a level of symptom control reported by patients.36 Across studies and molecules, remission was more likely to be achieved in people with shorter disease duration, lower morbidity, and higher Type 2 inflammatory biomarkers.36-39 These observations have increased interest in the earlier use of biologics in non-severe forms of asthma to try and maximise the effectiveness of these biological agents.18,23,36,40,41 The aim of this review is 74

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to synthesise the concepts and evidence supporting the use of biologics in mild-tomoderate asthma, herein liberally defined for the purpose of this narrative review as ‘asthma not on high-dose inhaled corticosteroids (ICS)’.29

METHODS This is a non-systematic narrative review of indirect evidence assessing the potential for biological therapies used in non-severe forms of asthma, as well as the ongoing trials on the matter.

ASTHMA IMMUNOLOGY Biologic targeting strategies used in asthma rely on our understanding of its immunology. Asthma is an inflammatory disease of the airways with polarisation towards a Type 2 immune response through innate immune signalling, adaptive antibody responses, and an autocrine Type 2 cytokine milieu contributing to asthma pathogenesis. Repeated exposure to external triggers (allergens, pathogens, toxins) disrupts the physical integrity of the airway epithelial barrier in asthma,42 causing activation of innate epithelial pattern recognition receptors, such as toll-like receptors and nod-like receptors, which recognise pathogen and damage associated molecular patterns.43,44 These trigger the release of the epithelial alarmins thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 with extensive downstream effects, including TSLP augmentation of dendritic cell (DC) activation of Type 2 immunity.45 In health, potential allergens are collected by epithelial DCs and not recognised as harmful; however, in allergic asthma DCs ingest and process allergens, migrate to lymph nodes, and present their antigen to immature T cells via major histocompatibility Class II (MHCII).46 This triggers differentiation of T cells to CD4+ T-helper-2 cells which secrete Type 2 inflammatory cytokines, IL-4, IL-5, and IL-13. The role of epithelial alarmins in mediating Type 2 inflammation via innate mechanisms

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is increasingly important. TSLP, IL-33, and IL-25 increase the proliferation of and activate Group 2 innate lymphoid cells, which also secrete Type 2 inflammatory cytokines. IL-33 acts directly on CD4+ T cells and mast cells via ST2 receptors to further augment Type 2 inflammatory cytokine release.47-48

and lung function decline.4 Therefore, it is intuitive that inhibition of effector cytokines, both directly through IL-4, IL-5, or IL-13, and indirectly through binding of IgE or inhibition of upstream mediators such as TSLP, have been effective in asthma management (Figure 1).4,28,54,55,57,58

The central effector cytokines of the Type 2 response are IL-5, IL-4, and IL13, which act synergistically to result in airway inflammation, giving the constellation of symptoms we recognise clinically as asthma. IL-5 stimulates bone marrow eosinophilopoiesis, chemotaxis of eosinophils to the airways, and prolongs eosinophil survival, together resulting in an increased pool of mature airway eosinophils.49 Activation of eosinophils results in degranulation and release of cytotoxins and proinflammatory mediators such as major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase in the airways, resulting in bronchial hyper-responsiveness and mucous hypersecretion. IL-5 activity leads to increases in blood eosinophil count (BEC), which can be measured as a biomarker of IL-5 activity. IL-4 and IL-13 act via a common receptor sub-chain, IL-4Rα, driving the Type 2 inflammatory cascade, including the promotion of eosinophil migration to the airway via chemotaxis.50 IL-4 promotes immunoglobulin class switching of B cells to release allergen specific IgE,51 thus increasing mast cell activation and release of inflammatory mediators such as histamine in the airways. IL-13 promotes goblet cell hyperplasia, mucous production,52 and acts as a chemotactic agent drawing fibroblasts to the airway submucosa and stimulating collagen deposition, resulting in subepithelial fibrosis, causing airway remodelling and fixed airflow obstruction.53 Whereas IL-5 correlates with blood eosinophil counts and represents the systemic reservoir of effector cells, IL-13 activity can be measured by its biomarker fractional exhaled Nitric Oxide (FeNO) which reflects Type 2 inflammatory activation in the airways.54-56 Elevation of these cytokines in asthma are known to be associated with risk of uncontrolled asthma, attacks,18

TARGETING STRATEGIES OF BIOLOGICS IN ASTHMA

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Targeting IgE (Omalizumab)

Omalizumab is a humanised monoclonal antibody directed against circulating IgE, approved for the treatment of moderateto-severe atopic asthma. Its use has been approved for patients aged ≥6 years with persistently inadequate asthma control despite optimised inhaled treatment. Prior to initiation, it is necessary to show total IgE levels ≥30 IU/mL and reactivity to at least one perennial allergen (positive specific IgE test or skin prick test). This treatment is administered subcutaneously every 2–4 weeks, depending on body weight and total IgE levels. Omalizumab is generally well tolerated, with adverse events primarily consisting of local cutaneous reactions at the injection site (3%). The risk of anaphylaxis is low (<0.2%), but warrants proper monitoring.59 The efficacy of omalizumab has been widely investigated, showing a modest reduction in severe attacks (about 30%) with concomitant improvement in asthma control and quality-of-life score.59 These effects were maintained for up to 9 years in real-life studies.60 The effect of omalizumab on forced expiratory volume in 1 second (FEV₁) is a 100–200 mL increase, which is a modest but significant improvement.61

Phase II-IV trials in mild-moderate asthma

Omalizumab has mostly been studied in moderate-to-severe forms of asthma.59 Nevertheless, the results of the headto-head trial between omalizumab and dupilumab (anti-IL-4/-13) in patients with physician-diagnosed asthma with comorbid nasal polyposis were clearly in favour of dupilumab.62 These data, which

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Figure 1: The Type 2 inflammatory cascade in severe asthma and the effects of anti-inflammatory therapies.55-59

Nitric oxide Airway epithelium

Allergen

Anti-IgE Anti-IL-5/IL-5 r-α Anti-IL-4 r-a Anti-TSLP Anti IL-13×TSLPa

IL-25 TSLP IL-33 TSLPR

iNOS

IL-13

IL-4 receptor 1

IL-4&13

TH2 cell

IL-5 IL-5 receptor

IL-13 IL-5

Eos Proteins Leukotrienes Cytokines

IL-13 IL-4

IL-25 TSLP IL-33

IL-13 IL-4

TH0 cell

Goblet cell

IL-13

APC (Dendritic cell)

Non-IL-5R induced eosinophil maturation

B Cell

IL-4 receptor 2 Free IgE

IL C2 ST2

Eosinophil

Mast cell

Bone marrow

Blood eosinophils

Other environmental triggers

Mucous plugs

Eotaxin

Subepithelial mucosa

Charcot-Leiden crystals and MUC-5A cross linking

IL-5

Airway smooth muscle hyperplasia

Blood vessel

Histamine Leukotrienes Prostaglandins Cytokines

Airway hyperresponsiveness

Investigational product not authorised for use.

The Type 2 immune response may be set off by a trigger (e.g., allergen, smoke/pollution, infection) in the airways, leading to epithelial alarmin signalling with downstream Type 2 cytokine (IL-5, IL-4, IL-13) activity and migration of circulating eosinophils to the airways in most cases, and non-Type 2 mechanisms in others (e.g., mastocyte activation). In Type 2 inflammatory severe asthma, blood eosinophils reflect circulating IL-5 and the systemic pool of available effector cells, whereas fractional exhaled nitric oxide reflects IL-13 activity in the airway compartment (mucus hypersecretion, bronchial motor tone, and chemotaxis of eosinophils).55-57,59 Targeting the end products of the Type 2 pathway, such as IgE, has had modest success in asthma. In the past decade, a strategy based on blocking progressively more proximal drivers of inflammation such as IL-5, IL-4, IL-13, and TSLP has proven successful. New bispecific therapies, such as one targeting IL-13 and TSLP (anti-IL-13×TSLP), have the potential to more fully abrogate the Type 2 inflammatory cascade, a strategy which is currently under investigation for use in mild-moderate asthma. Modified with permission from Couillard et al.55-59 APC: antigen-presenting cell; iNOS: inducible nitric oxide synthase; MUC5AC: mucin 5AC; ST2: suppression of tumorigenicity 2; TSLP: thymic stromal lymphopoietin; TSLPR: thymic stromal lymphopoietin receptor.

are discussed further under the dupilumab section, highlight the shortcoming of targeting IgE, which lies distal in the immune cascade and is thus not a proximal driver of inflammation.

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Targeting IL-5 (Mepolizumab, Reslizumab, Benralizumab, and Depemokimab)

IL-5 is a key mediator of the initiation and maintenance of Type 2 airway inflammation through expansion of eosinophil differentiation and chemotaxis to the airways. There are four approved monoclonal antibodies: mepolizumab, reslizumab, and depemokimab, which

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bind to circulating IL-5, and benralizumab, which binds to the alpha subunit of the IL-5 receptor (IL-5Rα). Clinical trials that led to the use of this therapeutic class included patients with moderate-to-severe asthma, substantial blood eosinophilia (e.g., ≥300 cells/µL in the past 12 months and/or ≥150 cells/µL at baseline), and frequent attacks (e.g., ≥2 in the past year). Mepolizumab was approved following the MENSA and SIRIUS trials, which led to impressive results. Both attacks and OCS doses were reduced by approximately 50%. Extension studies confirmed the persistence of benefits for up to 4–5 years.63 Benralizumab was studied in the SIROCCO and CALIMA trials,13 which showed a 45–55% reduction in severe asthma attack rates in the study population. Reslizumab is an IL-5 antagonist that is administered intravenously monthly at a dose of 3 mg/kg, which significantly hampers its use. Phase III trials showed a 50–60% reduction in attacks in an adult population with eosinophilia ≥400 cells/ µL.64 Depemokimab is a novel long-half-life biologic, which allows for subcutaneous administration every 6 months. The parallel, identical Phase III studies SWIFT-1 and SWIFT-2 showed a 54–56% reduction in the annualised rate of attacks, which is still comparable to other IL-5 inhibitors.65

Phase II–IV trials in mild-moderate asthma

Mepolizumab was initially evaluated in a Phase II trial involving patients with moderate asthma, a study now widely regarded as having underestimated the importance of selecting patients with an active underlying pathway targeted by the antibody and of assessing outcomes aligned with its mechanism of action.63,66 Indeed, in addition to not selecting patients with eosinophilic asthma, the trial was oriented toward improvements in lung function at 12 weeks rather than annualised asthma attacks. Benralizumab was trialled in patients with mild-to-moderate asthma in the 12-week Phase III BISE trial, showing statistically significant changes in lung function, which were predominantly observed in eosinophilic patients.67 More recently, the ABRA trial showing CC BY-NC 4.0 Licence

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efficacy of benralizumab used acutely during eosinophilic asthma and/or chronic obstructive pulmonary disease attacks included a group of patients with asthma of which 70% were not severe, representing less than 40 patients in total.68 Hence, IL-5 targeting strategies have scarcely been trialled in mild-moderate asthma, with short follow-up durations.

Targeting IL-4 Receptor (Dupilumab)

IL-4 and IL-13 signal through receptor complexes that share the IL-4Rα subunit. Dupilumab is a fully human monoclonal antibody that targets IL-4Rα, thereby inhibiting downstream signalling pathways mediated by both cytokines. This drug is used as add-on maintenance therapy in patients aged ≥6 years with moderateto-severe uncontrolled asthma and documented Type 2 inflammatory profile (blood eosinophils ≥150 cells/µL or FeNO ≥25 ppb). The Phase III LIBERTY ASTHMA QUEST trial69 showed a decrease in the annualised attack rate by up to 70%, with a more pronounced reduction in the subgroup with ≥300 eosinophils /µL. The study also demonstrated a mean improvement in prebronchodilator FEV₁ ranging from 200–320 mL, depending on baseline eosinophil count. Clinically meaningful improvements were also observed in asthma control and quality-of-life scores.

Phase II–IV trials in mild-moderate asthma

The EVEREST Phase IV trial62 assessed the efficacy of dupilumab versus omalizumab in patients with nasal polyposis and comorbid physician-diagnosed asthma, without any severity criterion. Accordingly, a third of patients had milder forms of asthma treated by low-dose ICS, and more than half had not required systemic corticosteroids in the previous 2 years for their airway disease. As nearly all patients had evidence of Type 2 airway inflammation (i.e., elevation of blood eosinophils and/or FeNO), it is unsurprising that dupilumab was decidedly superior to omalizumab both in terms of the primary endpoints (nasal polyp and smell test scores) and other asthma-specific

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endpoints (lung function, asthma symptoms, FeNO, and quality of life). Although the VESTIGE trial population may be viewed as less severe than the current dupilumab label, these were nonetheless patients with moderate-to-severe asthma with a recent history of a severe asthma attack.70

Targeting Thymic Stromal Lymphopoietin (Tezepelumab)

Tezepelumab targets the alarmin TSLP. Unlike most biologic therapies, its administration is not restricted to patients with a prior established allergic or eosinophilic phenotype. It is approved for use in patients ≥12 years of age with severe asthma that remains uncontrolled despite optimised inhaled therapy, regardless of inflammatory profile. The PATHWAY Phase IIb trial71 first demonstrated a dose-dependent decrease in attacks, reaching up to 71% in patients with high eosinophil counts. These findings were confirmed in the pivotal Phase III NAVIGATOR trial,72 showing a 56% reduction in the annualised attack rate compared to placebo. Interestingly, a substantial decrease in attacks was observed across all patients, independent of Type 2 inflammatory biomarkers. However, patients with blood eosinophils ≥300/µL and/or FeNO ≥25 ppb exhibited substantially greater benefits. The efficacy of tezepelumab in reducing attacks was sustained for at least 2 years.73 Patients treated with tezepelumab also showed significant improvements in pulmonary function tests, with a mean FEV₁ increase of 130–230 mL at 52 weeks, along with improvements in clinical control scores and quality of life.72

Phase II–IV trials in mild-moderate asthma

To the best of the authors’ knowledge, there are none.

OPPORTUNITIES FOR USE OF BIOLOGICS IN MILD-MODERATE ASTHMA As the list of available or investigational biologic options expand, new opportunities for intervention in non-severe, high-risk asthma are being explored (Table 1).

Why Move from Targeting ‘Severe’ to ‘High-Risk’ Asthma

Patients exhibiting Type 2 high phenotypes have been associated with ‘high-risk asthma’, meaning an increased risk of developing severe asthma, attacks, and steeper decline in lung function.4,15,16,21,22,75 As decline in lung function correlates to mortality and morbidity in asthma, identifying high-risk patients before irreversible lung function impairment becomes crucial.75 This underlines the importance of biomarkers as a risk stratification tool; a potential foothold to identify patients most susceptible to benefit from Type 2 inflammationtargeted therapy. This ‘predict and prevent’ approach23 is supported by the ORACLE studies, a comprehensive analysis of biomarker-stratified RCT data that demonstrated that the excess risk conferred by Type 2 inflammation could be removed by appropriate, targeted, specific treatment.23,40 The value of monitoring Type 2 biomarkers to identify opportunities for intervention is compounded by a series of populational and retrospective cohort studies that have shown an association between blood eosinophils, FeNO, and lung function decline in non-severe forms of disease.15,16,22 It is important to highlight that 50% of patients with mild asthma have evidence of Type 2 inflammation, although the proportion is 95% in severe asthma.55 In summary, people with mild-to-moderate asthma and evidence of Type 2 immune activation represent a high-risk group, especially when the Type 2 phenotype occurs in the context of other clinical risk factors such as a prior asthma attack history.22 The recent move to target clinical remission as an outcome further substantiates the

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Table 1: Overview of ongoing or planned trials of biologics in mild-moderate asthma.

Trial (registration) drug phase AIM4 (NCT06572228) Dupilumab Phase IV BRISOTE (NCT06750289) Benralizumab Phase IV HOTHOT (NCT07309614)74 Dupilumab Phase III

ICS dose

Medium

Mediuma

MODIFY (NCT07456033) Depemokimab Phase IIIb–IV

Low or Medium

AIRLYMPUS (NCT06676319) Lunsekimig Phase II

Low or Medium

Severe asthma ACQ attack history

FEV₁ (% predicted)

Biomarker requirement

≥1 in past year

≥1.5

Pre-BD FEV₁ 50–80%

BEC ≥300 cells/µL

Control arm escalated to high-dose ICS (1 year)

Annualised severe asthma attack rate

≥1.5

Pre-BD FEV₁ ≤90%

BEC ≥150 cells/µL

Control arm escalated to high-dose ICS (1 year)

Annualised severe asthma attack rate

BEC ≥300 cells/µL and FeNO ≥35 ppb

Background therapy clinically titrated while blinded to biomarkers (1 year)

Win ratio for clinical remission, assessed at 1 year

N/A

BEC ≥300 cells/µL + FeNO ≥35 ppb or comorbid current CRSwNP OR BEC ≥500 cells/µL

Controlled background therapy (2–3 years)

Annualised severe asthma attack rate

N/A

Pre-BD FEV1 ≥40%

N/A

Controlled background therapy (1 year)

Annualised severe asthma attack rate

≥2 in past year

≥1 in past 2 yearsᵃ

≥1 in past 1 year with ≥2 in past 3 years

≥1 in past year

Background therapy (duration)

Primary endpoint

Patients must have at least 1 additional risk factor such as high-dose ICS, prior attack in past 12 months, ACQ-5>=1,5, FEV1< 80%. a

ACQ: Asthma Control Questionnaire; BEC: blood eosinophil count; CRSwNP: chronic rhinosinusitis with nasal polyps; FeNO: fractional exhaled nitric oxide; FEV1: Forced Expiratory Volume in 1 second; ICS: inhaled corticosteroids; N/A: not applicable; Pre-BD: pre-bronchodilator.

case to focus on high-risk asthma, rather than only severe asthma, to obtain the best possible outcomes. A systematic review and meta-analysis published in 2025 by Shackleford et al.39 analysed 25 studies, with 28 analyses of clinical remission for which 68 definitions were identified.39 Pulmonary factors identified as barriers to clinical remission were interestingly longer asthma duration, worse symptom control and lung function, use of maintenance oral corticosteroids, and worse FEV1 at baseline. The authors also demonstrated that patients with less severe asthma had a CC BY-NC 4.0 Licence

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better chance of achieving clinical remission than their more severe counterparts (Figure 2).39 These results imply that intervention in severe asthma is a ‘too late’ strategy, whereby the abrogation of the Type 2 inflammatory response often happens after the occurrence of irreversible damage. Potentially the most compelling evidence to target high-risk disease before it qualifies as ‘severe’ comes from the field of rheumatoid arthritis. Initially reserved for severe form only, biologics demonstrated their ability

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Figure 2: Barriers and predictors of remission.40

Barriers to achieving clinical remission with targeted therapies

Clinical remission was more commonly associated with:

Long disease duration and irreversible damage

Higher Type 2 biomarkers

High symptom burden

mOCS

Shorter disease duration

Lower FEV1

Lower symptom burden

Based on data from Shackleford et al.40 FEV1: Forced Expiratory Volume in 1 second; mOCS: maintenance oral corticosteroid.

to prevent progression of the disease and reduce the use of corticosteroids, reaching clinical remission.76 Over decades of applying such proactive medicine and ‘treatto-target’ approach, signs of long-standing damage such as rheumatoid hands (Figure 3)74 have reduced in frequency and are unlikely to be seen in a patient diagnosed with the disease today; a feat which the asthma field is looking to replicate.41

Announced and Ongoing Phase II–IV Trials in Mild-to-Moderate Asthma

Several trials are planned or recruiting patients with mild-to-moderate asthma and high-risk features (Table 1). Dupilumab has fielded two trials in patients not on high-dose ICS which we may thus qualify as mild or moderate. First, the AIM4 trial (NCT06572228). This trial enrols eosinophilic patients on medium-dose ICS with uncontrolled symptoms, low lung function (FEV1 50–80%), and a previous severe asthma attack in the past 12 months. 80

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Patients are randomised to either escalating to high-dose ICS (current standard of care) or initiating dupilumab with continued use of the medium-dose ICS, with allocation blinded through placebo/matched inhalers. The primary endpoint is the severe annualised asthma attack rate. Second, the HOTHOT placebo-controlled trial (NCT07309614),77 which targets patients with moderate asthma with composite Type 2 high biomarker elevation (‘hothot’), a prior severe attack in the past 24 months, and at least one other risk factor (uncontrolled symptoms, low lung function, or highdose ICS). During the conduct of the trial, patients’ background therapy is titrated whilst research personnel are blinded to Type 2 biomarker values (and treatment allocation). The primary endpoint is the ‘remission win ratio’, representing the odds of attaining remission criteria. Using a trial design very similar to the AIM4 trial, benralizumab will be trialled against increasing the ICS dose to a high dose in the BRISOTE trial (NCT06750289). Two differences include the FEV1 requirement

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Figure 3: Potential role for use of biologics in non-severe pathology across chronic inflammatory diseases.74

Progress in rheumatoid arthritis and, to a lesser extent, in asthma has led to earlier targeted use of biologics in high-risk patients to avoid downstream irreversible damage (e.g., rheumatoid hands or airway remodelling). Question marks indicate areas where there is indirect supportive data, but no robust clinical trial assessing efficacy. Modified from Ross et al.74

(<90% in BRISOTE) and the prior severe asthma attack history to meet eligibility (≥2 in the prior year). The recently announced MODIFY trial (NCT07456033) targets a similar Type 2 inflammatory population as HOTHOT (dual biomarker elevation or 1 biomarker elevated in the context of nasal polyposis) but with depemokimab as the intervention. However, eligible patients are required to be on lowor medium-dose ICS, and have had at least two severe attacks in the past 3 years (with at least one in the prior year). There is no symptom or FEV1 criterion. Background therapy is controlled for the up-to-156week duration of the trial, and the primary endpoint is the severe annualised asthma attack rate. A key secondary endpoint is remission.

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The bispecific targeting IL-13 and TSLP (anti-IL-13×TSLP) lunsekimig is investigated in the AIRLYMPUS trial (NCT06676319). Registered as a placebo-controlled trial in high-risk asthmatics with mild-moderate asthma and a prior severe asthma attack in the last 12 months. There is no criterion for low lung function, and it is not publicly disclosed whether evidence of Type 2 inflammatory activation is necessary. The primary endpoint is the annualised severe asthma attack rate.

Comparative observations

When reviewing newly announced or ongoing trials in Table 1, it is evident that different strategies are being developed to tackle the important clinical question: how can biologics be best used in mild-moderate asthma? As the costs of the drugs are high,

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moving to non-severe forms of the disease means targeting a high-risk subgroup that is particularly treatment responsive, e.g., the Type 2 inflammatory high group for the purpose of maximally modifying the disease course to improve healthcare outcomes. In that context, dual biomarker stratification may be preferable to single-biomarker frameworks, insofar as blood eosinophils and FeNO hold synergistic prognostic and theragnostic value. In addition to carefully selected study populations, the reviewed trial designs challenge the current trial dogma, for example, by comparing bio-intervention with escalation to high-dose ICS, adjusting background therapy in both arms, or adopting longer follow-up durations. Three of the five surveyed trials had relaxed lung function criteria, potentially improving recruitment rates while decreasing the potential for regression to the mean on the FEV1 endpoints. The results of these pioneering trials are likely to inform the design of asthma trials for the next decade.

LIMITATIONS OF THE AVAILABLE EVIDENCE This non-systematic narrative review applied a liberal definition of ‘non-severe asthma’ and predominantly assessed indirect lines of evidence suggesting that biological therapy in milder forms of asthma may be worthwhile. It is important to emphasise that defining non-severe asthma solely based on the absence of prescribed high-dose ICS is clinically inaccurate and may, in fact, be difficult to quantify in the setting of maintenanceand-reliever therapy regimens (e.g., regular plus as-needed ICS-formoterol). This definition is pragmatic rather than universally accepted, as treatment intensity References 1.

To T et al. Global asthma prevalence in adults: findings from the crosssectional world health survey. BMC Public Health. 2012;12:204. Erratum in: BMC Public Health. 2021;21(1):1809.

may reflect prescribing practice, adherence, access, or physician preference rather than intrinsic disease biology. In clinical practice and in clinical trials, the definition of severe asthma should be based on scientific society documents rigorously defining severe asthma. Furthermore, the authors acknowledge that there is no available RCTbased evidence that biological therapies are effective in these forms of asthma; this review is thus mostly to be viewed as a survey of the ongoing trials on the matter. Finally, the authors acknowledge that there are limitations to the eventual use of biologics in non-severe asthma, such as the potential of overtreatment, costs, access inequity, and uncertainty regarding whether biologics should be introduced before full optimisation of standard pharmacological and non-pharmacological treatments.

CONCLUSION Biologics for treatment of asthma were approved for use in patients with severe, uncontrolled disease to help patients for whom high-dose ICS and bronchodilators were insufficient. Although consensus on the definition of clinical remission in asthma is yet to be reached, emerging data provide indirect evidence that earlier recognition of high‑risk phenotypes and especially earlier initiation of targeted therapies could help improve long‑term outcomes. Thus, the next critical step is to continue to investigate whether biologic therapies could provide meaningful benefit earlier in the disease course, before severe asthma develops. Current evidence supports the rationale for studying biologics earlier in high-risk asthma, but routine clinical use in mild-tomoderate asthma awaits trial results, cost-effectiveness analyses, and implementation frameworks.

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Pituitary Macroadenoma Mimicking Perennial Allergic Rhinitis: A Case Report Authors:

Alketa Bakiri,1-3 *Ervin Ç. Mingomataj4 1. Department of Stomatology, Faculty of Medical Sciences, Albanian University, Tirana, Albania 2. Department of Nursing and Physiotherapy, Faculty of Medical Sciences, Albanian University, Tirana, Albania 3. Service of Allergy and Clinical Immunology, American Hospital 3, Tirana, Albania 4. Department of Allergology and Clinical Immunology, “Mother Teresa” School of Medicine, Tirana, Albania *Correspondence to allergology@gmx.de

Disclosure:

The authors have declared no conflicts of interest.

Acknowledgements:

Bakiri managed the case and contributed to discussions; Mingomataj conceived and drafted the manuscript.

Received:

08.04.26

Accepted:

06.05.26

Keywords:

Allergic rhinitis, cerebrospinal fluid, MRI, pituitary macroadenoma, rhinorrhoea.

Citation:

EMJ Allergy Immunol. 2026;11[1]:85-90. https://doi.org/10.33590/emjallergyimmunol/Q67A1940

Abstract Rhinorrhoea is the excessive production of mucus commonly triggered by inflammatory or irritative conditions like bacterial infections and allergic rhinitis (AR). Factors such as hormonal changes and structural issues, including cerebrospinal fluid leakage, are also contributors. This report presents a case of seasonal AR successfully treated with allergen-specific immunotherapy for grasses and rye. During the past 5 years, the patient experienced intermittent perennial AR symptoms through a moderate sensitisation to house dust mites, managed by medication. Recently, progressive bilateral rhinorrhoea occurred, along with headache and muscle malaise. The complementary cranial MRI identified a pituitary macroadenoma with involvement of the optic chiasm. Surgical removal of the adenoma and nasopharynx reconstruction resolved the symptoms, confirming the cerebrospinal fluid rhinorrhoea. This case highlights that pituitary macroadenoma can masquerade as perennial AR, particularly when classic signs such as unilateral rhinorrhoea and visual disturbances, including diplopia and lateral vision loss, are absent. A cranial MRI can thus help prevent diagnostic delays and facilitate an appropriate treatment.

Key Points 1. Pituitary macroadenoma can be suspected in the absence of specific symptoms (unilateral rhinorrhoea, visual disturbances), although house dust mite sensitisation and bilateral rhinorrhoea can hide it.

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2. An appropriate radiological examination for chronic headache or persistent rhinorrhoea can avoid diagnostic delay, enabling an appropriate treatment. 3.The pituitary macroadenoma-related visual disturbances and unilateral cerebrospinal fluid rhinorrhoea can be absent even when the MRI reveals the corresponding structural alterations.

INTRODUCTION Allergic rhinitis (AR) is an IgE-mediated immune response to inhaled allergens, like pollen, house dust mites (HDM), or pet dander, causing inflammation of the nasal airways.1-4 Symptoms include sneezing, nasal congestion, and an itchy, watery, runny nose (rhinorrhoea).1-3 Besides trigger avoidance, its management cornerstones include antihistamines and nasal steroid

sprays, often lasting for seasons or yearround. Meanwhile, allergen-specific immunotherapy (AIT) is an aetiological treatment that suppresses symptoms, need for medication, and disease progression through immune modulation.1-3 Pituitary macroadenoma (PMA) is a benign tumour of the pituitary gland that causes clinical signs through the mass effect and increased intracranial pressure, including

Figure 1: Spirometry results.

POST bronchodilation

This examination revealed normal expiratory volumes and an obstructive pattern in the small airways, with insignificant response to salbutamol. Best refers to maximal result. BTPS: body temperature, pressure, saturated; Chg: change; FEF25-75%: forced expiratory flow between 25% and 75% of vital capacity; FEV1: forced expiratory volume within the first second; FIVC: forced inspiratory vital capacity; FVC: forced vital capacity; PEF: peak expiratory flow; Post: the maximal result after salbutamol spray; PRE: pre-bronchodilator; Pred: predicted; VC: vital capacity.

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headache and hormonal imbalances.5-8 It induces additional diplopia and lateral vision loss by compressing the optic chiasm. When symptoms occur, the primary treatment is the surgical removal.5-9 Common causes of rhinorrhoea include inflammatory or irritative pathologies and hormonal changes, while structural alterations can be associated with cerebrospinal fluid (CSF) leakage.1-3,5,7-11 The aetiology determines the treatment, which includes the aforementioned antiallergics, as well as antibiotics, anti-leukotrienes, alpha-blockers, etc.1,2 We present a case of seasonal AR successfully treated with AIT that later experienced progressive chronic rhinorrhoea, resolved after PMA removal.

CASE PRESENTATION A male patient born in the early 80s visited the clinic for specialised examination and treatment about 5 years ago. The patient had had seasonal AR since the age of 25 years, with sneezing, rhinorrhoea, itchy throat, and nasal congestion. Symptoms

were present from late February–June, peaking in April and May, outdoors. Recently, before the first visit, the subject also experienced intermittent, nonseasonal, and moderate cough, sneezing, and rhinorrhoea, indoors. The treatment included oral antihistamines, intranasal decongestants, and intranasal glucocorticoids. The personal history noted arterial hypertension, and the family history was negative for atopic pathologies. The respiratory functional examination revealed normal expiratory volumes and an obstructive pattern in the small airways, with a nonsignificant response to salbutamol (Figure 1). Skin prick test resulted highly positive for grasses’ pollens, including cultivated rye, as well as moderately positive for HDM, hazel, and wall pellitory pollen (Table 1). Following these findings, the treatment comprised topical glucocorticoids and antihistamines. The IgE test (inhalation 30-l quantitative multiparameter assay [Polycheck® (bioCheck Gesellschaft für biologischimmunologische Nachweisverfahren mbH, Münster, Germany)] for locally relevant Mediterranean allergens confirmed B2

Table 1: The most relevant SPT (Allergy Therapeutics, Worthing, UK/Lofarma, Milan, Italy) and specific IgE (inhalation 30-l quantitative multiparameter assay [Polycheck® (bioCheck Gesellschaft für biologisch-immunologische Nachweisverfahren mbH, Münster, Germany)]) results.

Allergen

SPT (papule, flare; mm)

Specific IgE level (kU/L)/ class

Control histamine/CCDs

5,16

1.5/2

Dermatophagoides pteronyssinus

0,0

1.6/2

Dermatophagoides farinae

2,4

9.6/3

Mix grass B2 pollens

7,25

>100/6

Cultivated rye pollen

10,30

42/4

Wall pellitory (Parietaria judaica)

3,10

0.47/1

Corylus pollen

5,22

1.4/2

CCD: cross-reactive carbohydrate determinant; SPT: skin prick tests.

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grasses (Allergy Therapeutics, Worthing, UK), including cultivated rye, appropriate for AIT, which lasted for 3 years. The successful treatment brought the seasonal symptoms under control, except during the season’s peak, when the patient needed regular topical antihistamine and glucocorticoid medication (while outside the season, this was occasional). Later, post-seasonally, a few months after AIT discontinuation, the patient experienced chronic moderate congestion and progressive but controllable watery rhinorrhoea, while other symptoms did not change. Justifiably, the nasal complaints corresponded to a moderate HDM sensitisation, as the nonseasonal symptoms

predominated indoors. Within some weeks, together with (equally bilateral, turned refractory and tasteless) rhinorrhoea progression, the subject also complained of chronic headache, additional need for antihypertensives, muscular malaise, and general discomfort. The recommended cranial MRI by respective specialists identified a PMA with a circumferential diameter of 14 mm (anteroposterior) and 21 mm (transversal), mild compression of the optic chiasm and right optic nerve, with infiltration of the middle area of the right cavernous sinus, and a normal left one. Hormonal testing has detected prominent hyperprolactinemia, increased adrenocorticotropic hormone (ACTH) and cortisol levels, and slightly decreased

Table 2: Hormonal and electrolyte levels from PMA diagnosis to a few weeks after intervention.

Compound

Primary examination (ng/mL)

Perioperative period (ng/mL)

Days >

-28

-27

-24

0/1

+24

+25

IGF1

220

209

70–229

ACTH

75.2a

83.6ª

69ᵃ

438ᵃ

10.2

22.4

71.7ᵃ

7.2–63.3

Cortisol (08–10 am)

486

691ª

26.3

338

166ᵃ

365

505

171–536

Cortisol (02–07 pm)

1,032ᵃ

246

64–327

TSH

1.31

1.12

1.14

0.27–4.2

FT3

3.07

2.89

2.72

3.08

2–4.4

FT4

1.33

1.45

1.37

1.12

1.48

0.93–1.7

1,356.9a 14.5ᵃ

203.4

73.6–412.8

Prolactin

Convalescence (ng/mL)

Normal ranges (ng/mL)

Free testosterone

4.04ᵃ

12.1

5.0–27.8

Testosterone

3.74

3.78

2.49–8.36

8.44ᵃ

8.6–10.2

142

136–148

3.7

3.7–5.5

Cl-

107

98–107

Mg2+

2.14

1.6–2.6

2+ +

ᵃAbnormal values (or alterations from normal ranges). Cabergoline decreased prolactin levels before intervention. ACTH: adrenocorticotropic hormone; Ca: calcium; Cl: chloride; FT: free triiodothyronine; IGF1: insulin-like growth factor 1; K: potassium; Mg: magnesium; Na: sodium; PMA: pituitary macroadenoma; TSH: thyrotropin-stimulating hormone.

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testosterone and calcium levels (Table 2). Still, the haematoxylin and eosin examination supported the presence of a plurihormonal prolactin and ACTH neuroendocrine tumour, exhibiting a mixture of monomorphic, mostly chromophobic, and sparse granulated cells, generally in trabecular and sinusoidal structures. The administration of dopamine-synergist cabergoline protected the subject from the PMA-related hyperprolactinemia until the upcoming transsphenoidal surgery that followed a few weeks later. After a couple of months, a subsequent MRI revealed successful intervention, showing grafting in the sphenoidal sinus, malacia, and postoperative changes on the right side of the adenohypophysis without residual lesion. The sellar fossa showed enlargement, and the left side of the pituitary was homogeneous. Also, other related structures, including the infundibulum, suprasellar cistern, optic chiasm, and bilateral cavernous sinuses, were normal. Three months after the intervention, the patient still denied the persistent rhinorrhoea and is under periodical monitoring.

DIFFERENTIAL DIAGNOSIS Common causes of rhinorrhoea, including inflammatory pathologies (AR, bacterial rhinitis), irritant factors (cold air, tobacco smoke, medications), and rare cases (hormonal imbalances, structural deviations resulting from cranial trauma or increased CSF pressure) have been progressively explored.5-7 Together with diagnostic results, nonseasonal intermittent sneezing, nasal congestion, and watery rhinorrhoea can correspond with moderate perennial AR. In fact, watery rhinorrhoea characterises allergic and non-inflammatory pathologies, while the presence of sneezing, congestion, cough, and (almost seasonal) itchy throat supports the AR diagnosis.5-7,12 The recent non-allergological disease history excluded almost all the mentioned causes (tobacco smoke, medication abuse, cranial trauma, odours). Among nasal symptoms, only rhinorrhoea progressed over the recent month until surgical intervention. This showed CC BY-NC 4.0 Licence

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positional variation, with gravitational aggravation at the lower side. There were no unusual taste alterations, even during the preoperative period. Unfortunately, the cholinergic or nasal allergic provocation tests were not in disposition. Probably, the moderate malaise was first considered an adverse effect of antiallergic medications. Finally, the rhinorrhoea turned refractory to the medications, and the progressive muscular malaise and headache required supplementary diagnostic procedures. The MRI determined the correct diagnosis, which further guided the authors to an appropriate treatment.7-11,13,14 In accordance with the hormonal findings, the histological examination confirmed a plurihormonal (prolactin and adrenocorticotropic hormone) adenoma sensitive to cabergoline.13,14

DISCUSSION PMA is the most common suprasellar lesion in adults.5-7 This case shows that such adenomas and perennial AR are generally distinct conditions, but they can intersect in ways that complicate diagnosis and management.5-8 The most significant, though rare, intersection is when PMArelated CSF rhinorrhoea mimics a chronic AR.5,8-10 The authors’ case lacked specific unilateral persistent (and salty-tasting) nasal leakage during all allergist visits. So, the patient took medication for perennial AR, and afterwards followed the removal of PMA.5,6 The AR also implicates the neuronal structures, as immuno-allergic and neurogenic inflammation (mediated by the ophthalmic and maxillary branches of the trigeminal nerve), among others, induce bilateral watery rhinorrhoea, as in the authors’ case.1,3,15 Also, the domination of seasonal symptoms by AIT confirmed the AR over the years. In contrast to AR, the PMA increases intracranial pressure, destroying the bony sella and dura, allowing CSF to escape through the altered nasopharyngeal side.6-10 The sellar compression and infiltration of the optic chiasm/nerve(s) can lead to diplopia or a narrowed visual field. The authors’ patient did not complain of such symptoms despite alterations detected on MRI, which

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predominated on the right, possibly because the compression and infiltration were clinically insignificant. The PMA removal was associated with sphenoidal sinus grafting to repair skull base defects and prevent CSF leakage.5-11 This successful intervention interrupted the persistent rhinorrhoea and any need for treatment. Muscular malaise is a nonspecific symptom, but in the authors’ case, it finally suggested a hormonal imbalance.5,6,8 Also, the headache, a nonspecific symptom, has later been regarded as PMA-related because the patient had already been diagnosed and treated for arterial hypertension.8

Hao Y et al. Multi-omics in allergic rhinitis: mechanism dissection and precision medicine. Clin Rev Allergy Immunol. 2025;68(1):19.

Bauman CA et al. Nonfunctioning pituitary macroadenoma: a case report from the patient perspective. Chiropr Man Therap. 2016;24:12.

14. Lyu L et al. Hyperprolactinemia in clinical non-functional pituitary macroadenomas: a STROBE-compliant study. Medicine. 2020;99(41):e22673.

Kang BM et al. Treatment of pituitary adenoma with spontaneous cerebrospinal rhinorrhea using nasoseptal flap, two case reports. Surg Neurol Int. 2022;13:262.

15. Mingomataj E et al. Trigeminal nasalspecific neurons respond to nerve growth factor with substance-P biosynthesis. Clin Exp Allergy. 2008;38(7):1203-11.

Small P et al. Allergic rhinitis. Allergy Asthma Clin Immunol. 2018; 14(Suppl 2):51.

Bernstein JA et al. Allergic rhinitis: a review. JAMA. 2024;331(10):866-77.

Mingomataj EÇ et al. Prevalence of a family history of atopic disease among 3 generations of atopic respiratory patients in Tirana, Albania. J Invest Aller Clin Immunol. 2008;18(3):190-3.

This work emphasises that objective evidence of sensitisation does not exclude the atypical concurrent structural causes of rhinorrhoea, reinforcing the need for heightened clinical suspicion in patients with refractory, progressive, or treatmentdiscordant symptoms, even when an allergic diagnosis appears established. So, persistent rhinorrhoea, apart from being treated as allergic or chronic rhinitis, especially when other symptoms persist or develop, such as a watery (even non-unilateral) rhinorrhoea refractory to medication, warrants careful evaluation, as it can suggest other comorbidities, such as CSF leakage.

References

CONCLUSION

Tritos NA, Miller KK. Diagnosis and management of pituitary adenomas: a review. JAMA. 2023;329(16):1386-98. 6. Sieg EP et al. Vanishing pituitary macroadenoma: a case report. Cureus. 2016;8(10):e838. Eisold JE et al. Spontaneous cerebrospinal fluid rhinorrhea in pre-operative pituitary adenoma: a report of two cases. Cureus. 2024;16(10):e71642.

10. Lara Rezende G et al. Morbidity in the postoperative follow-up of endoscopic anterior skull base surgery. Braz J Otorhinolaryngol. 2021;87(6):689-94. 11. McDonough M et al. Pituitary adenoma presenting with nasal obstruction: a case report. Otolaryngol Case Rep. 2021;18(3):100259. 12. Agnihotri NT, McGrath KG. Allergic and nonallergic rhinitis. Aller Asthma Proc. 2019;40(6):376-9. 13. Uraki S et al. Hypersecretion of ACTH and PRL from pituitary adenoma in MEN1, adequately managed by medical therapy. Endocrinol Diabetes Metab Case Rep. 2017;2017:17-0027.

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EMJ Allergy & Immunology 11.1 2026