Frontiers in Allergy

Editorial: Anaphylaxis challenges: idiopathic and rare causes

2026-03-27

Maryam Ali Al-Nesf, Hassan Mobayed, Michael Makris, Iman Nasr, Ivan Cherrez-Ojeda, Luisa Ricciardi

Immunonutritional effects elicited by a novel multicomponent food supplement in children with cow's milk allergy: results from a randomized, placebo-controlled trial

2026-03-16

Laura Carucci, Erika Caldaria, Franca Oglio, Raffaele Federico Iorio, Vittoria Mauriello, Antonio Masino, Serena Coppola

IntroductionCow's milk allergy (CMA) is one of the most common food allergies in childhood frequently associated with body growth impairment and micronutrient deficiencies. Immunonutrition approach with selected bioactive compounds may have beneficial effects on nutritional status and immune tolerance mechanisms. We evaluated the effects of an immunonutrition approach, based on the use of a novel multicomponent food supplement containing prebiotics, postbiotics, vitamin D3, docosahexaenoic acid (DHA), Perilla frutescens extracts, and Quercetin in children with CMA.MethodsRandomized, double-blind, placebo-controlled pilot trial, involving 30 pediatric CMA patients (both sexes, age 36–60 months) randomly assigned to receive the study product or placebo (maltodextrins) for 6 months. The active study product and placebo were provided as powder sachets with identical features. Primary outcomes were changes in body growth. Co-primary exploratory outcomes were serum 25-hydroxyvitamin D (25(OH)D) and DHA levels. Secondary endpoints included the evaluation of Th2 interleukins (ILs) and IL-10, regulatory T cells (Tregs), and growth factors and cytokines modulating ILs production (Tgfb1, Ifna2, Ptgs2, Csf2) in peripheral blood mononuclear cells (PBMCs) collected from CMA pediatric patients.ResultsAll participants completed the study without adverse events and with >90% adherence to the allocated treatment. At 6-month follow-up, children in the study product group showed greater improvement in body weight, and height, compared with the patients in the placebo group. Serum 25(OH)D and DHA concentrations significantly improved only in the active study group. In PBMCs collected from the patients, the active study product, but not the placebo exposure, resulted in an inhibition of Th2 cytokines (IL- 4, IL-5, IL-13) response to the stimulation with antigenic peptide β-lactoglobulin and in an increase in IL-10 production and Treg activation rate. The expression of Tgfb1, Ifna2, Ptgs2, Csf2 resulted also upregulated, suggesting an overall modulation toward immune tolerance in these patients.ConclusionsThis novel multicomponent food supplement improved growth parameters and nutritional status while modulating immune tolerance mechanisms in children with CMA. These findings support the potential of an immunonutrition-based approach using this innovative supplement in managing pediatric food allergy.Clinical Trial Registrationclinicaltrial.gov, identifier NCT06751810.

Depemokimab demonstrates efficacy in patients with type 2 asthma with comorbid CRSwNP: Phase III SWIFT-1/-2 analysis

2026-03-06

Enrico Heffler, Diana Jarreta, Chang-Qing Zhu, Anna Vichiendilokkul, Peter Howarth, Anju Peters, Santiago Quirce, David J. Jackson

IntroductionThe efficacy of twice-yearly depemokimab was demonstrated in the Phase III SWIFT-1/-2 trials for type 2 asthma characterized by blood eosinophils, and ANCHOR-1/-2 trials for chronic rhinosinusitis with nasal polyps (CRSwNP). Up to 40% of patients with severe asthma are estimated to have comorbid CRSwNP, an overlap associated with increased disease burden. Depemokimab may therefore offer meaningful clinical benefit in this subpopulation. This analysis evaluated the efficacy of depemokimab in patients with type 2 asthma and comorbid CRSwNP using pooled data from SWIFT-1/-2.MethodsPatients with type 2 asthma were randomized 2:1 to receive depemokimab 100 mg subcutaneously or placebo, plus standard of care, every 26 weeks for 52 weeks. Pre-specified outcomes included annualized exacerbation rates over 52 weeks, and St George's Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores over 52 weeks, analyzed by baseline comorbid CRSwNP subgroup.ResultsIn the asthma with CRSwNP subgroup, the annualized rate of exacerbations over 52 weeks was lower in patients who received depemokimab [0.51 (95% CI: 0.34, 0.75); n = 80] vs. placebo [1.61 (95% CI: 0.99, 2.60); n = 33], with a rate ratio (95% CI) of 0.31 (0.17, 0.58). Additionally, an improvement in least squares (LS) mean SGRQ total score in the depemokimab group vs. placebo was noted after 4 weeks of treatment [−7.12-point difference (95% CI: −13.41, −0.83)] which was sustained up to 52 weeks [−8.32-point difference (95% CI: −15.77, −0.88)] in the asthma with CRSwNP subgroup. Similarly, an improvement from baseline in LS mean ACQ-5 score was noted with depemokimab vs. placebo after 2 weeks of treatment [−0.40-point difference (95% CI: −0.79, −0.01)], which was maintained up to 52 weeks [−0.76-point difference at (95% CI: −1.23, −0.28)] in the asthma with CRSwNP subgroup.DiscussionTwice-yearly depemokimab reduced annualized exacerbation rates and demonstrated greater improvements in SGRQ and ACQ-5 scores vs. placebo in patients with type 2 asthma and comorbid CRSwNP. These improvements were greater than those reported in the overall SWIFT-1/-2 population. These findings identify that type 2 asthma with CRSwNP is a clinically recognizable phenotype that is likely to have enhanced benefit with depemokimab therapy.Clinical trial identifiersNCT04719832/NCT04718103.

EUFOREA summit in Brussels 2025: inspiring the future of allergy and respiratory care

2026-03-06

S. Lau, V. Backer, G. K. Scadding, P. J. Barnes, M. Bernal Sprekelsen, X. Bertels, M. Blaiss, E. Borzova, M. C. Brüggen, L. O. Cardell, D. M. Conti, M. Cornet, E. De Corso, R. Djukanovic, W. J. Fokkens, A. T. Fox, M. Gaga, P. Gevaert, P. Gibson, C. L. Gray, L. G. Heaney, E. Heffler, H. J. Hoffmann, C. Hopkins, D. Jackson, M. Jesenak, P. Johansen, E. Khaleva, S. Lee, M. J. Mäkelä, E. Melén, J. Mullol, A. Nieto, I. Pavord, A. Peters, D. Price, S. Quirce, D. Ryan, S. Schneider, B. Senior, C. M. E. Shire, P. Smith, T. Teeling, J. C. Virchow, V. Lund, U. Wahn, P. W. Hellings

EUFOREA, the European Forum for Research and Education in Allergy and Airways diseases, is an international non-for-profit organisation of physicians, patients, and other stakeholders committed to the improvement of outcomes for patients suffering from chronic inflammatory respiratory conditions through collaborative research, education, and targeted advocacy. In February 2025, EUFOREA hosted its biennial summit in Brussels, convening expert panels, its Patient Advisory Board, and a range of leadership representatives. This event was pivotal in establishing the research, educational, and advocacy priorities for the subsequent 2-year period, coinciding with the organisation's 10th anniversary in April 2025. Building on its core competencies, EUFOREA advances evidence-based clinical tools and educational initiatives designed to narrow the gap between emerging science and routine care. In alignment with the objective of enhancing global healthcare standards, the specialists' panels of chronic rhinosinusitis and European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergic rhinitis, asthma, allergen immunotherapy, and paediatrics have devised and detailed a comprehensive range of initiatives that address significant unmet needs within the domains of allergy and respiratory care. This document presents a summary of EUFOREA's future objectives, aspirations, and strategy, providing a clear direction for the coming years. It serves as a valuable resource for individuals and organisations involved in both the allergy and the respiratory sectors, offering a comprehensive overview of the association's plans and initiatives.

The FOXA transcription factors in allergic airway disease and asthma

2026-03-05

Diana C. Yánez, Ching-In Lau, Jasmine Rowell, Eden Zhang, Tessa Crompton

The Forkhead box A (FOXA) transcription factors are pioneer factors that orchestrate diverse cellular and developmental processes. Within the respiratory system, FOXA1, FOXA2, and FOXA3 have emerged as modulators of pulmonary inflammation, with important implications for the pathogenesis of allergic asthma. In healthy lung and airways, FOXA1 and FOXA2 maintain epithelial integrity and promote ciliated cell development, thereby preserving homeostasis. FOXA2 additionally suppresses Th2 differentiation and goblet cell metaplasia and mucus overproduction. During allergic airway inflammation, FOXA2 expression is decreased and FOXA3 expression is induced by Th2 cytokines. Dysregulation of the FOXA regulatory network disrupts epithelial cell homeostasis and amplifies allergic inflammation, contributing to airway remodelling. Here we will review the potential mechanisms through which the FOXA family modulates airway inflammation, while also addressing gaps in current understanding, such as the context specific regulation of FOXA isoforms, their interplay with cytokine signalling pathways, and the translational relevance of these findings to therapeutic strategies in asthma.

Comparison of rapid and same-day desensitization protocols in hypersensitivity reactions to platinum and taxanes: a retrospective cohort study

2026-03-03

María Cruz Torres Górriz, Julián Borrás Cuartero, Paula Viedma Ayllón, Alfredo Sánchez Hernández, Carlos Vergara Hernández, Isabel Gil Viciano, Ernesto Enrique

BackgroundRapid drug desensitization (RDD) allows first-line treatment to continue after a hypersensitivity reaction to the antineoplastic agent. There are different desensitization procedures, and none of them are free from breakthrough reactions (BTR).ObjectivesThe objective of the study is to evaluate and compare the efficacy of different desensitization procedures, considering the effect of a series of confounding variables, and to describe the characteristics of BTRs in different procedures.MethodsA retrospective, comparative review of medical records from patients who experienced hypersensitivity reactions to platinum- or taxane-based chemotherapy was conducted. Patients were categorized into two groups; rapid drug desensitization (RDD) and same-day desensitization (SDD), according to the intervention performed on the day of the initial reaction. Demographic data, drug, retreatment, cancer type, phenotype and severity of the initial reaction, allergy testing, number of desensitizations performed, outcome of desensitizations, and number, phenotype and severity of BTRs were recorded according to group.ResultsIn the RDD group, 406 desensitizations were analyzed in 76 subjects with a BTR rate of 24%. In the SDD group, 164 desensitizations were analyzed in 44 subjects with a BTR rate of 15%. A marginaleffects analysis using a Bayesian hierarchical model showed a 14.6-point reduction in the probability of BTR in the SDD group.ConclusionThis study confirms that desensitization procedures are safe and effective and allows us to conclude, based on the data and the model, that the SDD group has a lower probability of BTR than the RDD group.

Histopathological alterations in airways associated with physiological changes in airway allergy phenotypes

2026-02-26

Marisol Alvarez-González, Angélica Flores-Flores, Ivonne Pacheco-Alba, Blanca Bazán-Perkins

IntroductionOvalbumin sensitization in guinea pigs induces diverse allergic responses. The asthma model exhibits airway obstruction, hyperresponsiveness, fibrosis, and reduced airway caliber, associated with elevated β1 integrin subunit expression. In contrast, the non-responder (NR) phenotype shows no obstruction or hyperresponsiveness under chronic antigen exposure. It is likely that NR guinea pigs lack increased β1 integrin subunit expression due to the absence of a typical asthma response. This study aimed to compare the histopathological and pathophysiological characteristics between the asthma model and NR phenotype in ovalbumin-sensitized guinea pigs to understand the differences in airway β1 integrin subunit expression.MethodsGuinea pigs were sensitized and challenged with ovalbumin nine times at 10-day intervals. The animals were then categorized into either the asthma model or the NR group. After the ninth antigen challenge, baseline obstruction, antigen-induced airway hyperresponsiveness, and immunohistopathological changes were evaluated.ResultsAirway hyperresponsiveness to histamine was only observed in the asthma model. Both asthma and NR groups had increased basal obstruction and accumulation of the integrin β1 subunit in the subepithelial region compared to controls, with a greater increase in NR. Integrin β1 subunit expression in airway smooth muscle was higher in the asthma model than in NR. The subepithelial area was enlarged in both asthma and NR groups compared to controls. Basal caliber reduction was correlated with fibrosis and integrin β1 subunit in the subepithelial region.DiscussionFibrosis and deposition of the β1 integrin subunit in the subepithelial region are associated with baseline obstruction but not with the magnitude of airway obstruction or hyperresponsiveness. In the asthma model, the airway smooth muscle phenotype, characterized by high β1 integrin subunit, could influence contraction and hyperreactivity.