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In Finland, a systematic public health programme was implemented from 2008 to 2018 to mitigate the burden of allergic disorders by revisiting the prevention strategy. Allergy health and contacts with natural environment were emphasized to promote immunological and psychological resilience instead of poorly justified avoidance. Allergy management practices were improved and low-valued recommendations for care, for example for food allergy, were revised. Patients and families were empowered to use guided self-management to proactively stop symptom exacerbations. A professional non-governmental organization implemented the nationwide education for healthcare and patient NGOs for patients, families and lay public. In healthcare, the work supporting allergic patients and families was organized towards common goals and integrated into everyday work without extra costs. Reaching the predefined goals was followed by employing the national healthcare registers and questionnaire surveys. Governmental bodies contributed with kick-off funding, which was supplemented by private funding. International collaboration, for example with the European patient organization (EFA), increased awareness of the Finnish action and predisposed it for peer review. The 10-year results are favourable, patients are less disabled, practices and attitudes in healthcare have changed, and major cost savings have been obtained. Views of the lay public and patients are slow to move, however. Local multidisciplinary allergy teams were set up to continue the activities also after the Programme. Changes in environment and lifestyle in the last 50 years are the main reasons for the allergy rise. The Finnish experience may help to manage allergic diseases, improve nature relatedness in the fast-urbanizing world, combat nature loss and reduce the disease burden.

© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet’s health in the context of the ‘epithelial barrier hypothesis,’ including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life.Methods: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of similar to 1.5 (Group A, n = 110) or similar to 2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores.Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life.Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

Allergic diseases like asthma, allergic rhinitis, food allergy, hymenoptera allergy, or atopic dermatitis are highly prevalent in women of childbearing age and may affect up to 30% of this age group. This review focuses on the management of allergic diseases during pregnancy. Furthermore, we discuss the challenges of counseling women with allergic diseases in the reproductive age, including considerations relevant to the ongoing SARS-CoV-2 pandemic. To create the optimal milieu for the unborn child, a multitude of immunological changes occur during pregnancy which may favor type 2 responses and aggravate disease phenotypes. In co-occurrence with suboptimal preconception disease control, this elevated Th2 responses may aggravate allergic disease manifestations during pregnancy and pose a risk for mother and child. Due to limitations in conducting clinical trials in pregnant women, safety data on anti-allergic drugs during pregnancy are limited. The lack of information and concerns among pregnant patients demands counseling on the benefits of anti-allergic drugs and the potential and known risks. This includes information on the risk for mother and child of disease aggravation in the absence of treatment. By doing so, informed decisions and shared decision-making can take place.

Background Alteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood. Methods We generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid-activated retinoic acid response was evaluated by flow cytometry, real-time RT-PCR and Illumina transcriptome sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC-MS analysis. Results In this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen-specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA-activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA-activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice. Conclusion Our research unveils a mechanism of food sensitization modulated by BA-RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.

The WHO/IUIS Allergen Nomenclature Database (http://allergen.org) provides up-to-date expert-reviewed data on newly discovered allergens and their unambiguous nomenclature to allergen researchers worldwide. This review discusses the 106 allergens that were accepted by the Allergen Nomenclature Sub-Committee between 01/2019 and 03/2021. Information about protein family membership, patient cohorts, and assays used for allergen characterization is summarized. A first allergenic fungal triosephosphate isomerase, Asp t 36, was discovered in Aspergillus terreus. Plant allergens contained 1 contact, 38 respiratory, and 16 food allergens. Can s 4 from Indian hemp was identified as the first allergenic oxygen-evolving enhancer protein 2 and Cic a 1 from chickpeas as the first allergenic group 4 late embryogenesis abundant protein. Among the animal allergens were 19 respiratory, 28 food, and 3 venom allergens. Important discoveries include Rap v 2, an allergenic paramyosin in molluscs, and Sal s 4 and Pan h 4, allergenic fish tropomyosins. Paramyosins and tropomyosins were previously known mainly as arthropod allergens. Collagens from barramundi, Lat c 6, and salmon, Sal s 6, were the first members from the collagen superfamily added to the database. In summary, the addition of 106 new allergens to the previously listed 930 allergens reflects the continuous linear growth of the allergen database. In addition, 17 newly described allergen sources were included.

Background Food allergen immunotherapy (FA-AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA-AIT. Methods An EAACI task force conducted an online survey to gather relevant information regarding FA-AIT practice and setting-specific resources after reviewing the published literature and congress abstracts throughout Europe. Results We identified 102 FA-AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital-based (77.5%), publicly funded (80.4%) and delivered FA-AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA-AIT for a median of 9 years [1-24] to a median of 105 [5-2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4-6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%-63%), eosinophilic esophagitis (56%-48%) and age below 5 years (47%-41%). Conclusions In Europe, FA-AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization.

Background: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods: From the Scandinavian antenatally recruited PreventADALL mother–child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA/L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA/L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Results: Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16–0.81 kUA/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53–8.68). Conclusion: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and

The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing oral food challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) is 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children.We retrospectively assessed consecutive OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children.Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 was 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 was 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are, respectively, 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds.The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared with milk in the determinism of fatal anaphylactic reactions in children.

Oral tolerance induction through early introduction of allergenic food has proven effective in randomized controlled trials. This new approach to weaning has been incorporated into many national and international infants' feeding guidelines. However, there are questions that require further discussion, such as, which foods should be introduced early, should the intervention be targeted to infants at high-risk or to the general population, and what is the ideal timing for early food introduction. This review examines the extent to which recent trials address these critical questions and highlights areas where further research is required.

Food allergy is an increasingly prevalent disease driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5, and IL-13 with infiltration of mast cells, eosinophils, and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. Unlike lymphocytes, ILCs lack They represent a group of lymphocytes that lack specific antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut, and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs toward inflammatory processes and regulatory mechanisms.

BACKGROUND Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy causing severe acute gastrointestinal symptoms and lethargy, mainly affecting infants and young children. There are geographic variations in its clinical features. This study aimed to describe the clinical characteristics and management of FPIES in Swedish children. METHODS The study included children who presented with acute FPIES during 2008-2017. All Swedish pediatric departments (n = 32) were invited to report their known patients. Data were collected through chart reviews and interviews with parents. RESULTS Eighteen pediatric departments contributed, and 113 patients were included. Most had a family history of atopy (74%), and 51% had an atopic disease. Common trigger foods were cow's milk (26%), fish (25%), oat (22%), and rice (8%). Most patients (85%) reacted to a single food. The median age at first reaction was 3.9 months for cow's milk and 6.0 months for other foods (p

The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry. It correlates directly with histamine release. From the dose-response curve resulting from BAT in allergic patients, basophil reactivity (%CD63(+) basophils) and basophil sensitivity (EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients' phenotype in most cases, it may be used to support the diagnosis of food, venom and drug allergies and chronic urticaria, to monitor the natural resolution of food allergies and to predict and monitor clinical the response to immunomodulatory treatments, such as allergen-specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for quality assurance and certification.

An increasing number of people suffer from IgE-mediated food allergies. The immunological mechanisms that cause IgE-mediated food allergy have been extensively studied. B cells play a key role in the development of IgE-mediated food allergies through the production of allergen-specific antibodies. While this particular function of B cells has been known for many years, we still do not fully understand the mechanisms that regulate the induction and maintenance of allergen-specific IgE production. It is still not fully understood where in the body IgE class switch recombination of food allergen-specific B cells occurs, and what processes are involved in the immunological memory of allergen-specific IgE responses. B cells can also contribute to the regulation of allergen-specific immune responses through other mechanisms such as antigen presentation and cytokine production. Recent technological advances have enabled highly detailed analysis of small subsets of B cells down to the single-cell level. In this review, we provide an overview of the current knowledge on the biology of B cells in relation to IgE-mediated food allergies.

BACKGROUND In up to 70%-80% of patients with a suspected non-steroidal anti-inflammatory drug hypersensitivity (NSAIDH), challenge tests with the culprit drug yield negative results. On the other hand, there could be a NSAIDH overdiagnosis when anaphylaxis is the clinical manifestation. We hypothesize that some negative NSAID challenge tests and an overdiagnosis of NSAIDH occur in patients with food-dependent NSAID-induced hypersensitivity (FDNIH). METHODS We studied 328 patients with a suspected acute NSAIDH. FDNIH was diagnosed in patients meeting all the following: (1) tolerance to the food ingested more temporally closed before the reaction, later the episode, (2) respiratory or cutaneous symptoms or anaphylaxis related to NSAID, (3) positive skin prick test to foods and/or specific IgE to food allergens (Pru p 3, Tri a 19, Pen a 1) involved in the reaction, and (4) negative oral provocation test to the culprit NSAID. RESULTS 199 patients (60%) were diagnosed with NSAIDH and 52 (16%) with FDNIH. Pru p 3 was involved in 44 cases (84.6%) and Tri a 19 in 6 cases (11%). FDNIH subjects were younger (p

Background Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota‐derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and to see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance. Methods HM butyrate concentration from 109 healthy women was assessed by GS‐MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in in vivo and in vitro models. Results The median butyrate concentration in mature HM was 0.75 mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up‐regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin‐3, mucus components and tight junctions expression in human enterocytes, and IL‐10, IFN‐γ and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells. Conclusion The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA., Human milk contains a significant level of the short‐chain fatty acid butyrate. At concentration detectable in human milk, butyrate effectively modulates several tolerogenic mechanisms involved in the protection against food allergy. The protective role of human milk against food allergy could be related, at least in part, to the presence of an effective concentration of butyrate

In the past decade, research in the molecular and cellular underpinnings of basic and clinical immunology has significantly advanced our understanding of allergic disorders, allowing scientists and clinicians to diagnose and treat disorders such as asthma, allergic and nonallergic rhinitis, and food allergy. In this review, we discuss several significant recent developments in basic and clinical research as well as important future research directions in allergic inflammation. Certain key regulatory cytokines, genes, and molecules have recently been shown to play key roles in allergic disorders. For example,interleukin-33 (IL-33)plays an important role in refractory disorders such as asthma, allergic rhinitis, and food allergy, mainly by inducing T helper (Th) 2 immune responses. Further, the cytokine TSLP has been shown to be a key factor in maintaining immune homeostasis and regulating inflammatory responses at mucosal barriers and targeting TSLP-mediated signaling is considered an attractive therapeutic strategy. We discuss interleukin 4 receptor pathways, which recently has shown to play a critical role among the allergic inflammatory pathways that drive allergic disorders and pathogenesis. The alarmin IL-33 has found to play a major role in type-2 immune responses in allergic diseases and clinical trials with IL33 inhibitors are underway in food allergy. Further, the cytokine Thymic Stromal Lymphopoietin (TSLP)has recently been shown a factor in maintaining immune homeostasis and regulating type-2 inflammatory responses at mucosal barriers in allergic inflammation. Also, new immune and genetic studies found that IL-4R pathways play a critical role among the allergic inflammatory pathways that drive allergic disorders and pathogenesis. In addition, new findings establish an important T cell-intrinsic role of Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) proteolytic activity in the suppression of autoimmune responses. We have seen how mutations in the filaggrin gene are significant risk factor for allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, food allergy (FA), and contact allergy and hand eczema. We are only beginning to understand the mechanisms by which the human microbiota may be regulating the immune system, and how sudden changes in the composition of the microbiota may have profound effects, linked with an increased risk of developing chronic inflammatory disorders, including allergies. New research has shown the important but complex role monocytes play in such disorders as food allergies. Finally, we discuss some of the new directions of research in this area, particularly the important use of biologicals in oral immunotherapy, advances in gene therapy, multi-food therapy, novel diagnostics in diagnosing allergic disorders, and the central role that OMICS plays in creating molecular signatures and biomarkers of allergic disorders such as food allergy. Such exciting new developments and advances has significantly moved forth our ability to understand the mechanisms underlying allergic diseases for improved patient care.

Background Oral food challenges have demonstrated that diagnosis of almond allergy based on extract‐sIgE tests displays low specificity. Molecular allergy diagnosis is expected to improve accuracy, but its value in diagnosing almond allergy remains unknown. The aim of this study was to identify relevant almond allergens and examine their ability to improve almond allergy diagnosis. Methods IgE‐reactive proteins were purified from almond kernels. IgE binding to almond extract and the allergens was analyzed by quantitative ELISA using sera from 18 subjects with a proven almond allergy. The control group consisted of sera from 18 subjects allergic to peanut and/or tree nuts but tolerant to almond. Results Three IgE‐binding proteins were identified: legumin (Pru du 6), alpha‐hairpinin (Pru du 8), and mandelonitrile lyase (Pru du 10). Positive IgE (≥0.35 kU/L) to almond extract showed 94% sensitivity but only 33% specificity. IgE to Pru du 6 maintained high sensitivity (83%) and provided superior specificity (78%). Sera from almond‐allergic subjects had significantly higher IgE levels to almond extract (P, Three allergens were identified in almond kernels: Pru du 6, Pru du 8, and a new allergen, Pru du 10, belonging to a novel family of allergenic proteins. Sensitization profiles of almond‐allergic individuals were dominated by almond‐specific allergens, particularly Pru du 6. The use of almond allergens for IgE tests markedly increased the diagnostic specificity compared to the extract. Abbreviations: FPLC, fast protein liquid chromatography; LC‐MS/MS: liquid chromatography tandem mass spectrometry; sIgE: specific IgE

International audience; BACKGROUND: As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort. METHODS: Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. RESULTS: Five clusters were identified among 3,446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitisation at 8 years. CONCLUSION: Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.

The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a commonly used patient-reported outcome measure in food allergy (FA) research. It was developed before FA treatment clinical trials were commonplace and is used as a secondary outcome measure in pivotal FA treatment trials. We examined the psychometric properties of the FAQLQ-PF and its relevance to children with peanut allergy engaged in an epicutaneous immunotherapy (EPIT) clinical trial.Analysis was performed on 26 universally answered items of the FAQLQ-PF, from assessments undertaken during the phase 3 PEPITES study (baseline, Month 12), which examined the safety and efficacy of EPIT for children with peanut allergy aged 4-11 years. Item response theory (IRT) was used to assess psychometric parameters of the FAQLQ-PF (i.e., discrimination, difficulty, and information). Confirmatory factor analysis was also employed; reliability was assessed using McDonald's omega (ω) and Cronbach's alpha (α).A total of 23 of 26 items presented very high discrimination levels (1.7), and all 26 fell within the recommended difficulty threshold (between -1.5 and 1.5). The items contributed a reasonable information level for their respective factors/subdomains. The measure also presented a marginally acceptable model fit for the 3-factor structure (e.g., comparative fit index = 0.88, Tucker-Lewis index = 0.87) and good reliability levels across time points (ω and α 0.90).Herein, we present a novel reanalysis of the FAQLQ-PF items using IRT. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in FA treatment trials.

Background EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy‐focused questionnaires. Objective To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food‐related adverse reactions. Methods Adult and school‐age participants in the standardized EuroPrevall population surveys, with self‐reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with “probable” FA, defined as a food‐specific case history supported by relevant IgE sensitization. Results In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29‐1.41]), oral allergy symptoms (OAS) (4.46 [4.19‐4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68‐2.95]), asthma comorbidity (1.38 [1.30‐1.46]) and male sex (1.50 [1.41‐1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85‐0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross‐validation. In children (N = 670), OAS (2.26 [2.09‐2.44]) and AR comorbidity (1.47 [CI 1.39‐1.55]) contributed most to prediction of probable FA, with a combined cross‐validation‐based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. Conclusions In both adults and school‐age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA., In support of expert opinion, data collected in a standardized manner all across Europe reveal that information available from patient history can accurately predict IgE sensitization corresponding to a food‐specific case history (probable FA). OAS and AR comorbidity are strongly associated with presence of FA and GI symptoms with absence of FA (particularly plant FA) in adults and children. Abbreviations: AA, allergic asthma; AR, allergic rhinitis; FA, food allergy; GI, gastrointestinal; OAS, oral allergy symptoms

Background The lack of a value set allowing the calculation of QALY is an important limitation when establishing the value of emerging therapies to treat food allergy. The aim of this study was to develop a Short-Form Six-Dimension version 2 (SF-6Dv2) preference value set for the calculation of health utility from the Canadian food-allergic population. Methods Two hundred ninety-five parents of patients aged 0-17 years old and 154 patients aged 12 years old and above with food allergy were recruited in clinic and online. Participants were asked to complete a self-administered online questionnaire including generic health-related quality of life questionnaires. Various health states described by the SF-6Dv2 were valued with time-trade-off and discrete choice experiments. Data from elicitation techniques were combined using the hybrid regression model. Results A total of 241 parents and 125 patients performed 3904 time-trade-off and 5112 discrete choice experiments. Utility decrements were estimated for each level of each SF-6Dv2 dimension. Utility values calculated based on the validated preference set were in average 0.15 lower (95%CI: 0.12-0.18) and were poorly correlated (R2 = 0.46) with those derived from the EQ-5D-5L generic questionnaire in the same cohort. Conclusion A representative preference value set for patients with food allergy was determined using the SF-6Dv2 generic questionnaire. This adapted preference set will contribute to improve the validity of future utility estimates in this population for the appraisal of upcoming potentially impactful but sometimes costly therapies.

BACKGROUND Oral immunotherapy (OIT) for food allergy improves the quality of life (QOL) of children from parental perspective but little is known about the child perception. METHODS The Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF) was administered to children aged 8-12 years, and the FAQLQ-Parent Form (FAQLQ-PF) was administered to their parents at the start of OIT for milk, egg, peanut, sesame, or tree nuts, at the end of up-dosing, and after 6 months of follow-up. Food-allergic children not undergoing OIT served as controls. Children QOL scores were compared to their parents. RESULTS The total FAQLQ-CF score of 103 children undergoing OIT improved significantly from start of OIT (median (IQR); 4.8, 3.8-5.7) to end of up-dosing (3.9, 3-5.2) (P

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.