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Background: Mixed and non‐IgE‐mediated food allergy is a subset of immune‐mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied. Objective: As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non‐IgE‐mediated food allergy. Design: In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein‐induced enterocolitis syndrome, food protein‐induced allergic proctocolitis, food protein‐induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022. Results: Twenty‐six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient‐reported dysphagia, usually using a non‐validated questionnaire. Twenty‐two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non‐validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient‐reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient‐reported outcomes. Conclusions: Outcomes measured in clinical trials of EoE and non‐IgE‐mediated food allergy are heterogeneous and largely non‐validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non‐IgE‐mediated food allergies, core outcome development is needed to support the development of effective treatments. Systematic review registration: OSF public registry DOI:10.17605/OSF.IO/AZX8S [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have suggested an association between maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy in the offspring. However, prospective clinical studies on vitamin D measured in cord blood and development of clinical end-points are sparse. Objective: To investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin D) level and investigator-diagnosed asthma- and allergy-related conditions during preschool-age. Methods: Cord blood 25(OH)-Vitamin D level was measured in 257 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS), asthma, respiratory infections, allergic rhinitis, and eczema, at age 0–7 yrs were diagnosed exclusively by the COPSAC pediatricians strictly adhering to predefined algorithms. Objective assessments of lung function and sensitization were performed repeatedly from birth. Results: After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (<50 nmol/L) was associated with a 2.7-fold increased risk of recurrent TROLS (HR = 2.65; 95% CI = 1.02–6.86), but showed no association with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors. Conclusion: Cord blood 25(OH)-Vitamin D deficiency associated with increased risk of recurrent TROLS till age 7 years. Randomized controlled trials of vitamin D supplementation during pregnancy are needed to prove causality. [ABSTRACT FROM AUTHOR]

The article "Longitudinal Sensitization Patterns in Childhood and Adolescence" explores the development of allergen-specific immunoglobulin E (sIgE) production in children and adolescents, highlighting the complex nature of sensitization patterns over time. The study, conducted in a birth cohort, identified seven distinct sensitization patterns associated with asthma, rhinitis, and atopic dermatitis. The findings emphasize the importance of understanding these sensitization patterns for early identification of individuals at risk of developing allergic diseases and implementing timely interventions. The research provides valuable insights into the dynamic nature of childhood sensitization and its impact on long-term health outcomes, aiding clinicians in making informed decisions for managing and preventing allergic diseases in children. [Extracted from the article]

Background: It remains unclear whether phenotyping of type 2-high (T2-high) asthma can distinguish clinical characteristics and lung function trajectories in childhood., Objective: To explore differences between T2-high and T2-low asthma from birth to age 18 years., Methods: We included 47 children with asthma and 165 as a control group from the Copenhagen Prospective Studies on Asthma in Childhood 2000 mother-child cohort. T2-high and T2-low asthma was defined at age 7 by sensitization to aeroallergens, elevated eosinophilic blood count, and/or elevated fractional nitric oxide. Lung function measurements included whole-body plethysmography, spirometry, exercise test, cold air provocation, and methacholine challenge. Differences in lung function trajectories and traits were analyzed using linear mixed models, Wilcoxon rank-sum test, Fisher's exact test, and Quasi-Poisson regression., Results: At age 7 years, 47 had asthma (26 T2-high, 21 T2-low). By age 18, 12 (46.2%) with T2-high had persistent asthma whereas 2 (9.2%) with T2-low; OR 8.14 [1.57-42.34]. Specific airway resistance (sRaw) was 12.5% higher through childhood in children with T2-high asthma (estimate 0.53 [0.06; 1.01]); lung function was more reversible (OR 3.37 [1.03-11.00] for spirometry and OR 2.60 [1.17; 5.75] for sRaw), and they had increased airway hyperresponsiveness (AHR) to methacholine (as shown by 41% lower dose required to cause a 20% drop in lung function (estimate -0.70 [-1.18; -0.23])). There was no significant difference in exacerbation rate and other lung function measurements., Conclusion: Childhood T2-high asthma differs from T2-low asthma in terms of onset, duration, airway resistance, and airway responsiveness., (© 2025 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies., Methods: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria., Results: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV 1 ) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately)., Conclusions: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma., Competing Interests: Conflict of interest: E. Khaleva and A. Rattu declare funding from 3TR European Union Innovative Medicines Initiative 2 to their institution for the present manuscript. C. Brightling declares grants from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic and 4DPharma; consulting fees from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic, 4DPharma and Teva; and support from the 3TR project. G.W. Clarke declares that he is an employee of AstraZeneca; and that he holds stock or stock options in AstraZeneca. M. van den Berge declares grants from GlaxoSmithKline, AstraZeneca, Roche, Genentech and Novartis paid to the university. A. Bossios declares honoraria for lectures from GlaxoSmithKline, AstraZeneca, Teva and Novartis; support for attending meetings from AstraZeneca and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Novartis and Sanofi; being a member of the Steering Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) of the European Respiratory Society; Vice-chair of the Nordic Severe Asthma Network (NSAN). V. Ramiconi and S. Romagosa Vilarnau declare unrestricted educational grants paid to the organisation from Novartis, Pfizer, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, AbbVie, LeoPharma, Boehringer Ingelheim, Sanofi, Regeneron, OM Pharma, MSD, Roche and DBV Technologies; support for attending meetings from Novartis. S-E. Dahlén declares a 3TR Innovative Medicines Initiative grant; consulting fees for AstraZeneca, Cayman Co., GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva; payment for lectures from AstraZeneca and Sanofi. S. Principe declares support for provision of study materials and medical writing. G. Hedlin declares participation in advisory boards of AstraZeneca and Sanofi. F. Singer reports grants from Lung League Bern, grants from the Swiss Cystic Fibrosis Society (CFCH), personal fees from Vertex Pharmaceuticals, personal fees from Novartis, outside the submitted work. A. Deschildre reports personal consulting fees from Sanofi-Regeneron, ALK, Novartis and GlaxoSmithKline; honoraria for lectures from ALK, Boehringer Ingelheim and Novartis; support for attending meetings from AstraZeneca, Stallergènes-Greer, MEDA, Nutricia, Sanofi and Novartis, outside the submitted work; and being on the scientific committee of SFA (Société Française d'Allergologie). L.J. Fleming declares participation in advisory boards and honoraria for lectures from Sanofi, Respiri UK, AstraZeneca, Novartis and Teva, outside of the scope of this publication; all payments were made to her institution. H. Staudinger reports that he is a salaried employee of Sanofi Genzyme and owns company stock of Sanofi and Merck & Co. K.C. Pike declares consultancy fees from Novartis, Adherium and Respiri, and honoraria for a lecture from Novartis. J. Grigg declares payments from GlaxoSmithKline, OM Pharma, Omron and Novartis (advisory boards), Sanofi (for lectures) and AstraZeneca (CI clinical trial). N. Rutjes reports personal fees for advisory board work from Sanofi. G.H. Koppelman reports receiving research grants from the Lung Foundation of the Netherlands, Ubbo Emmius Foundation, H2020 European Union, Teva, GlaxoSmithKline and Vertex, outside this work (money to institution); he reports memberships of advisory boards to GlaxoSmithKline and PURE-IMS, outside this work (money to institution). D. Cunoosamy holds shares in AstraZeneca and Sanofi. A.H. Maitland-van der Zee has received research grants outside the submitted work from GlaxoSmithKline, Boehringer Ingelheim and Vertex, she is the PI of a P4O2 (Precision Medicine for more Oxygen) public private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Roche, Smartfish, SODAQ, Thirona, TopMD and Novartis), and she has served in advisory boards for AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim with money paid to her institution. K.F. Chung has received honoraria for participating in advisory board meetings of GlaxoSmithKline, AstraZeneca, Roche, Novartis, Merck and Shionogi, regarding treatments for asthma, COPD and chronic cough, and has also been remunerated for speaking engagements for Novartis and AstraZeneca; received a MRC grant on Precision Medicine for severe asthma, EPSRC grant on air pollution and asthma, and a GlaxoSmithKline grant on mepolizumab and eosinophils in asthma. P. Nagakumar received speaker fees for talks on severe asthma from GlaxoSmithKline and Novartis. G. Brusselle declares payments from AstraZeneca, Novartis, Boehringer Ingelheim, Chiesi, Sanofi, GlaxoSmithKline and MSD, outside the submitted work. E. Hamelmann declares support from the German Ministry of Education and Research (BMBF) and German Asthma Net (GAN) eV; funding for research in severe asthma in children (CHAMP-01GL1742D) and for Severe Asthma Register. S. Vijverberg is PI of the PERMEABLE consortium. The PERMEABLE consortium is a research consortium focused on severe asthma and allergy and supported by ZonMW (456008004), the Swedish Research Council (2018-05619), the Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012), and the German Ministry of Education and Research (BMBF) FKZ01KU1909A), under the frame of the ERA PerMed JTC 2018 Call. In addition, S. Vijverberg has received research funding for a project on severe paediatric asthma from the Lung Foundation Netherlands (6.2.18.244JO). A-M.M. Schoos has participated on an advisory board for ALK. B. Dahlén reports personal fees for lectures from AstraZeneca, Novartis and Sanofi; and grants from Novartis and GlaxoSmithKline, outside the submitted work; participation on an advisory board for AstraZeneca and Sanofi. A. Exley declares being a minority shareholder in GlaxoSmithKline Plc. E.A. Gaillard reports consultancy work for Boehringer Ingelheim with money paid to the institution (University of Leicester); investigator-led research grants from Circassia Group, Gilead Sciences, Chiesi Limited and Propeller Health; and has a research collaboration with Medimmune. M. Pijnenburg declares payments to her institution from Sanofi Genzyme (advisory work) and Novartis (speakers fee). E. Melén declares consulting fees from AstraZeneca, Chiesi, Novartis and Sanofi, outside the submitted work. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis; sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi and GlaxoSmithKline, and a research grant to her institute from AstraZeneca for a UK multi-centre study. C. Pilette declares grants, consulting fees and honoraria for lectures (paid to institution) from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Mundipharma, Teva, Sanofi and ALK. C. Porsbjerg declares grants (paid to institution), consulting fees (paid to institution and personal honoraria) and honoraria for lectures (paid to institution and personal honoraria) from AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK; participation on an advisory board (paid to institution and personal honoraria) for AstraZeneca, Novartis, Teva, Sanofi and ALK. C. Coleman and C. Williams declare funding received to support this work by the European Lung Foundation (ELF) from the European Commission's Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 831434 (3TR), and are employees of the ELF. B. Ahrens, S. Kaul, D. Hartenstein and V. Mahler declare no conflict of interest for this article and state that the views expressed in this review are the personal views of the author and may not be understood or quoted as being made on behalf of or reflecting the position of the respective national competent authorities, the European Medicines Agency or one of its committees or working parties. L.G. Heaney declares support from the 3TR; grants from industrial pharma partners Amgen, AstraZeneca, Medimmune, Janssen, Novartis, Roche/Genentech, GlaxoSmithKline and Boehringer Ingelheim; project grant funding from Medimmune, Novartis UK, Roche/Genentech and GlaxoSmithKline, outside the submitted work; payments for lectures by AstraZeneca, Novartis, Roche/Genentech, GlaxoSmithKline, Chiesi and Teva, outside the submitted work; travel funding support to international respiratory meetings by AstraZeneca, Chiesi, Novartis, Boehringer Ingelheim, Teva and GlaxoSmithKline, outside the submitted work; advisory boards for AstraZeneca, Novartis, GlaxoSmithKline, Chiesi, Teva, Theravance and Vectura, outside the submitted work. R. Djukanovic declares funding from the European Respiratory Society, Teva, GlaxoSmithKline, Novartis, Sanofi and Chiesi for the SHARP Clinical Research Collaboration; consulting fees for Synairgen; honorarium for a lecture from GlaxoSmithKline; participation on a data safety monitoring board or advisory board for Kymab (Cambridge) and shares in Synairgen outside of the submitted work. A. Bourdin declares grants from Boehringer and AstraZeneca; consulting fees and payments from Boehringer, AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, Regeneron, Sanofi and Amgen outside of the submitted work. B. Karadag declares participation in a trial conducted by Sanofi (payment to institution) and attending advisory board meetings for GlaxoSmithKline (personal fees). K. Blumchen declares grants from Aimmune Therapeutics, DBV Technologies and Hipp GmbH; consulting fees from Aimmune Therapeutics, DBV Technologies and Allergy Therapeutics; payments for lectures from Aimmune Therapeutics, DBV Technologies, Novartis, Allergy Therapeutics, HAL, ALK, Allergopharma, Nutricia, Thermo Fisher Scientific, and Bausch and Lomb; personal fees for expert discussions from Novartis and Nestle; fees for attending meetings from Aimmune Therapeutics and DBV Technologies; being on data safety monitoring board of Charité, IIT. A. Gupta received speaker/advisory board fees from GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim; received research grants from GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim, paid to institution. L. Giovannini-Chami declares consulting fees from ALK, AstraZeneca and Novartis; honoraria for lectures, presentations from Novartis, ALK, Stallergènes, Sanofi and AstraZeneca; support for attending meetings from Stallergènes; participation on a data safety monitoring board or advisory board for Sanofi; being head of the Scientific Committee of the French Pediatric Pulmonology and Allergology Society. C.S. Murray has received lecture fees from GlaxoSmithKline and Novartis; received grants from Asthma UK and National Institute for Health Research; and has participated on an advisory board for Boehringer Ingelheim. G. Roberts declares European Union Innovative Medicines Initiative funding and AstraZeneca paid to the institution. Other co-authors declare no conflicts of interest for this article., (Copyright ©The authors 2023.)