Food Allergy Research Articles

Addressing Disparities in Food Allergen Immunotherapy Trials

Addressing Disparities in Food Allergen Immunotherapy Trials

Subcutaneous Immunotherapy of Food Allergy.

While there are compelling arguments for developing subcutaneous allergen-specific immunotherapy for alleviation of food allergies, there is a limited number of studies in the public domain. The review seeks to present the approaches taken, to explain the paucity of studies, and to identify new roads for development. A literature search revealed clinical trials of immunotherapy of food allergies to fish and peanut, but studies had limited patient numbers, short treatment courses and follow-up periods. Indications, but no clearcut effects, were seen with both classical allergen extracts and hypo-allergenic preparations. A special case is the influence on cross-reactive food allergies, when subcutaneously administered birch-pollen extracts are used for treatment of birch pollen hayfever and/or asthma. Again indications, but no convincing efficacy has been registered. Newer developments include recombinant hypoallergens and DNA-technologies. Subcutaneous immunotherapy for food allergies has not matured to provide clinically relevant treatment opportunities.

Allergens weaning: what is missing from commercial baby food?

Background. Current recommendations for infant weaning suggest introducing common food allergens by the age of 12 months. While homemade meals are advisable, there is a notable demand for commercially available complementary foods (CACF). Furthermore, emerging evidence suggests a potential link between the consumption of ultra-processed products and the incidence of allergic diseases. This study aimed to examine the presence of the fourteen main food allergens in CACF ingredients through label analysis and evaluate their extent of processing. Methods. Between January and February 2024, labels of all CACF found in infant feeding sections of 10 Portuguese grocery retailers were analyzed. CACF were categorized based on the NOVA food classification system's processing levels. Milk formulas, products for children over 15 months, and those for children with food allergies or intolerances were excluded Results. Of the 492 products analysed, 132 contained wheat and 112 contained milk. 16 products included fish and 6 contained egg. Soy was listed as an ingredient in 11 products, mainly as soy lecithin. Only 2 product contained nuts, and 1 product contained peanuts. None of the products contained the remaining six allergens. The majority of milk- and wheat-containing products were classified as ultra-processed and contained added sugars and/or sweeteners. Conclusions. Despite the current guidelines, commercial baby foods often lack major allergens, namely nuts and peanuts, eggs, and shellfish. Our results underscore the need for healthy, age-appropriate, minimally processed products that incorporate rather than exclude major food allergens.

Progressive accumulation of hyperinflammatory NKG2Dlow NK cells in early childhood severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor-α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD.

Eczema in early childhood increases the risk of allergic multimorbidity.

Eczema in early childhood is associated with the development of subsequent allergic diseases, including food allergy (FA), asthma and hay fever. However, eczema has a heterogenous presentation regarding onset age and persistence, which may lead to different allergic outcomes during childhood/adolescence. Recently, sub-phenotypes of eczema have been suggested as predictors of allergic multimorbidity. Thus, we aimed to identify associations of eczema phenotypes with FA, asthma and hay fever during childhood/adolescence. Additionally, we described the trajectories of eczema, asthma and hay fever stratified by FA presence. TRACKER (Trajectories of Allergy in Children in Real Life Databases) is a population-based cohort study of 6852 children/adolescents from the Lifelines cohort. We investigated the associations of seven eczema phenotypes, based on onset age and persistence, with FA, asthma and hay fever using logistic regression, adjusted for appropriate covariates. Disease trajectories were determined by calculating prevalence at different ages. Participants who suffered from eczema throughout childhood showed higher risks of developing FA, hay fever and asthma. "Very early onset-persistent" eczema showed the strongest associations with FA, asthma and hay fever. The prevalence of eczema, asthma and hay fever at all ages was significantly higher in participants with FA, compared to those without. One of the largest cohort studies on this topic to date shows that (very) early onset and persistent eczema increases the risk of allergic multimorbidity. Identification of infants at risk for developing (very) early onset eczema is of utmost importance to prevent allergic multimorbidity.

The potential of orally exposed risk factors and constituents aggravating food allergy: Possible mechanism and target cells.

Food allergy is a significant concern for the health of humans worldwide. In addition to dietary exposure of food allergens, genetic and environmental factors also play an important role in the development of food allergy. However, only the tip of the iceberg of risk factors in food allergy has been identified. The importance of food allergy caused by orally exposed risk factors and constituents, including veterinary drugs, pesticides, processed foods/derivatives, nanoparticles, microplastics, pathogens, toxins, food additives, dietary intake of salt/sugar/total fat, vitamin D, and therapeutic drugs, are highlighted and discussed in this review. Moreover, the epithelial barrier hypothesis, which is closely associated with the occurrence of food allergy, is also introduced. Additionally, several orally exposed risk factors and constituents that have been reported to disrupt the epithelial barrier are elucidated. Finally, the possible mechanisms and key immune cells of orally exposed risk factors and constituents in aggravating food allergy are overviewed. Further work should be conducted to define the specific mechanism by which these risk factors and constituents are driving food allergy, which will be of central importance to the targeted therapy of food allergy.

IgE- and non-IgE-mediated food allergies - an overview

Food allergies are divided into 2 main categories: IgE-mediated and non-IgE-mediated food allergies. Both forms can have significant health effects but differ in mechanism, symptoms, and management. The manifestation of the 2 forms differs between children and adults. These differences can be observed in the prevalence and the type of most common allergens and clinical presentation. The prevalence of food allergies has increased worldwide in recent decades. IgE-mediated allergies are the best researched and documented. They are particularly common in children, while non-IgE-mediated allergies are less well understood and diagnosed, leading to uncertainty about their prevalence. They often manifest as gastrointestinal symptoms that can occur hours to days after ingestion and are often difficult to distinguish from other food intolerances. The occurrence of food allergies varies significantly geographically. Differences in dietary habits, food composition, and environmental factors can partly explain these differences. There are also indications that genetics may play a role. IgE-mediated and non-IgE-mediated food allergies represent a significant and growing challenge for the global healthcare system. This article provides an in-depth review of both types of food allergy, discussing their potential causes, diagnostic possibilities, and available therapeutic strategies. Some diseases represent a mixed form of IgE and non-IgE-mediated immunological adverse reactions. Eosinophilic oesophagitis is the most common eosinophilic disease, and the diagnosis and treatment options are explained in more detail below.

Understanding the needs of children and young people with food hypersensitivities: A qualitative study

BackgroundResearch has highlighted the psychosocial impact of living with food hypersensitivities (FHS) on children and young people (CYP). However, there is a paucity of qualitative data from CYP themselves in terms of the support they would like to receive to improve their psychological well-being. ObjectiveTo further understand firsthand the experiences of CYP with FHS including the challenges they face and to inform structural changes in how their psychological well-being is supported. MethodsCYP aged 8 to 17 years were recruited with self-reported food allergy or celiac disease and asked about their experiences of living with and the psychological impact of FHS, through online, semistructured interviews. Interviews were transcribed verbatim, and data were analyzed using reflexive thematic analysis. ResultsA total of 25 CYP participated in the interviews. Three themes were generated, which addressed an aspect of change that CYP felt would enable support and improve their well-being: desire to feel heard, need for control, and appreciation of the severity of their FHS. ConclusionThis is the first study to investigate what CYP with FHS would find beneficial for their psychological well-being with recommendations provided as to how these may be implemented across various systems. Recommendations include health professionals being more aware of the psychosocial impact from diagnosis, schools being more open and consistent with FHS management strategies, and friends being educated on the management of FHS.

Living with and Caring for People with Multiple Food Allergies: A Qualitative Study.

The quality of life (QoL) impact of food allergies extends beyond severe allergic reactions, as food avoidance can permeate the daily lives of individuals with food allergies and their caregivers. People with multiple food allergies may experience a greater impact on QoL than people with a single food allergy, but there is limited evidence available. The aim of the study was to provide insight into the lived experiences of adults, teenagers, children, and caregivers of children with multiple food allergies. Semi-structured interviews were conducted of people with multiple food allergies and their caregivers (n = 20) in the United States, including 10 adults, 5 teenagers, and 5 caregivers of children. Patterns in responses were explored using reflexive thematic analysis. Four themes were developed by the researchers to convey the experiences of people with food allergies and QoL impact: preparedness and allergen avoidance results in a loss of spontaneity; emotional impact varies by person and for each person; participating in society involves speaking up and trusting others; and food is more than nutrition. In addition, 3 themes were identified that convey the experiences of caregivers: looking out for your child's safety is an emotional balancing act; limitations on what you can do on your own and as a family; and creating a safe and fulfilling environment can be time-consuming and costly. These findings highlight that people with multiple food allergies experience social limitations, stress about food safety and allergen avoidance, and restrictions on freedom. Caregiver QoL is impacted by the need to navigate social, emotional, and practical implications of caring for a child with multiple food allergies.

Improving Adherence Through Collaboration and Care Coordination in the Management of Food Allergies and Asthma

Food allergies and asthma significantly impact individual health and global healthcare systems. Despite established management protocols for asthma and the emerging use of oral immunotherapy for food allergy, adherence to treatments remains a challenge for healthcare professionals and patients. This review explores the differences in adherence required of asthma and food allergy treatments and strategies to improve adherence. We highlight the role of collaborative care coordination among healthcare professionals in enhancing adherence in asthma and food allergy management and improving patient outcomes.

Contribution of T cell subsets to different food allergic diseases.

Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.

Sensory sentinels: Neuroimmune detection and food allergy.

Food allergy is classically characterized by an inappropriate type-2 immune response to allergenic food antigens. However, how allergens are detected and how that detection leads to the initiation of allergic immunity is poorly understood. In addition to the gastrointestinal tract, the barrier epithelium of the skin may also act as a site of food allergen sensitization. These barrier epithelia are densely innervated by sensory neurons, which respond to diverse physical environmental stimuli. Recent findings suggest that sensory neurons can directly detect a broad array of immunogens, including allergens, triggering sensory responses and the release of neuropeptides that influence immune cell function. Reciprocally, immune mediators modulate the activation or responsiveness of sensory neurons, forming neuroimmune feedback loops that may impact allergic immune responses. By utilizing cutaneous allergen exposure as a model, this review explores the pivotal role of sensory neurons in allergen detection and their dynamic bidirectional communication with the immune system, which ultimately orchestrates the type-2 immune response. Furthermore, it sheds light on how peripheral signals are integrated within the central nervous system to coordinate hallmark features of allergic reactions. Drawing from this emerging evidence, we propose that atopy arises from a dysregulated neuroimmune circuit.

Ultra-processed foods, allergy outcomes and underlying mechanisms in children: An EAACI task force report.

Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated. We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines. Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies. More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma.

Schistosoma excretory/secretory products: an untapped library of tolerogenic immunotherapeutics against food allergy.

Food allergy (FA) is considered the 'second wave' of the allergy epidemic in developed countries after asthma and allergic rhinitis with a steadily growing burden of 40%. The absence of early childhood pathogen stimulation embodied by the hygiene hypothesis is one explanation, and in particular, the eradication of parasitic helminths could be at play. Infections with parasites Schistosoma spp. have been found to have a negative correlation with allergic diseases. Schistosomes induce regulatory responses to evade immune detection and ensure their long-term survival. This is achieved via excretory/secretory (E/S) products, consisting of proteins, lipids, metabolites, nucleic acids and extracellular vesicles, representing an untapped therapeutic avenue for the treatment of FA without the unpleasant side-effects and risks associated with live infection. Schistosome-derived immunotherapeutic development is in its infancy and novel discoveries are heavily technology dependent; thus, it is essential to better understand how newly identified molecules interact with host immune systems to ensure safety and successful translation. This review will outline the identified Schistosoma-derived E/S products at all life cycle stages and discuss known mechanisms of action and their ability to suppress FA.

Characteristics of childhood anaphylaxis in different age groups.

Anaphylaxis is a severe systemic hypersensitivity reaction that usually has a rapid onset and can be fatal. Presentations of childhood anaphylaxis vary widely in accordance with the triggers and the patient's age, geographical region and dietary and lifestyle habits. The medical records of 177 paediatric patients diagnosed with anaphylaxis between January 2021 and January 2024, whose disease progression was monitored at a single tertiary care centre, were reviewed retrospectively. The study included 177 patients diagnosed with anaphylaxis (107 males and 70 females with a median age of 48 months). The most common allergen responsible was food (53.7%). Egg allergy was the most common source of anaphylaxis, afflicting 35 patients (19.3%), while beta-lactam provoked the most common drug allergy, affecting 24 patients (13.6%). The most common organ involved was the skin (92.7%). When the patients were analysed by age group, there were more males in the infancy, preschool and school age groups, while there were more females in the adolescent group (p = 0.44). Food-induced anaphylaxis became less common with increasing age, whereas the rate of drug-induced anaphylaxis increased (p = 0.01 and p = 0.01, respectively). Cardiovascular system findings were observed more frequently in adolescents compared to other age groups (p = 0.003). Most cases stemming from a food allergy were mild, whereas most drug-induced cases were moderate or severe (p < 0.05). When severity was analysed by age group, mild cases in infants were more common than moderate to severe cases. The aetiological and clinical manifestations of childhood anaphylaxis vary among different age groups.

Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting

Oral immunotherapy (OIT) for food allergy has been largely studied in older children within the context of clinical trials, and its availability has historically been limited for younger patients with food allergy. Data has shown that the most impact may actually be seen with the use of OIT in younger infants and toddlers. To evaluate the safety and feasibility of OIT in subjects younger than 24 months in a real-world setting using commercially available food products. This was a retrospective study of subjects 24 months and younger initiated on OIT for peanut, tree nut, or sesame allergy within the Scripps Clinic allergy department. Medical records were reviewed for data regarding initial oral food challenges (OFCs), OIT, and adverse outcomes. Fifty-two subjects under 24 months of age were initiated on OIT. Most subjects (84.6%) were on single food OIT, some (15.4%) were on multi-food OIT. No increased adverse outcomes were observed on multi-food OIT. Of the 59 initial OFCs, objective reactions occurred during 42 challenges, the majority being low grade reactions. During initial OFCs, 86.1% of peanut allergic children tolerated 1/8 of one Bamba stick with no reaction. The majority (73.1%) of subjects up-dosed at home and most (51.9%) had no reactions while up-dosing. Some had low grade cutaneous reactions, none requiring epinephrine or emergency evaluation. OIT in infants is safe and feasible to perform in a real-world setting using commercially available food products with at home up-dosing, thus increasing the availability of OIT for patients.

Higher maternal bread and thiamine intakes are associated with increased infant allergic disease.

A mother's diet during pregnancy may influence her infant's immune development. However, as potential interactions between components of our dietary intakes can make any nutritional analysis complex, here we took a multi-component dietary analysis approach. Nutritional intake data was collected from 639 pregnant women using a validated semi-quantitative food frequency questionnaire to reflect their dietary intakes during 32-36 weeks of gestation. To investigate their dietary intake pattern, we calculated Dietary Inflammatory Index scores. Maternal consumption of 12 food groups, 20 individual whole foods, and 18 specific nutrient intakes, along with any vitamin and mineral supplementation, were determined. Infant outcomes included eczema, allergen sensitization, and IgE-mediated food allergy. Regression-based analyses with covariates adjustment were applied. Women with higher white bread consumption were more likely to have an infant with doctor-diagnosed eczema (adjusted relative risk [aRR] 1.16; 95% CI 1.08, 1.24; p < .001) and IgE-mediated food allergy (aRR 1.14; 95% CI 1.02, 1.28; p = .02). Higher maternal intakes of fiber-rich bread (aRR 1.14; 95% CI 1.04, 1.25; p = .01) and legumes (aRR 1.11; 95% CI 1.02, 1.21; p = .02) were also associated with infant doctor-diagnosed eczema. Higher maternal thiamine intakes were associated with increased parent-reported infant eczema (aRR 1.08; 95% CI 1.03, 1.12; p < .001). In Australia, where bread flour is fortified with thiamine, we identified consistent links between higher maternal thiamine-rich diets and increased risk of infant eczema and food allergy. Our results highlight a need for further investigation of potential effects of high thiamine exposures on immune development, especially in-utero.

Food allergies: A diagnostic challenge of increasing importance

Food allergies: A diagnostic challenge of increasing importance

Omalizumab Implementation in Practice: Lessons Learned From the OUtMATCH Study

In February 2024, omalizumab was approved by the Food and Drug Administration for the treatment of food allergy, based on data from the landmark Phase 3 clinical trial “Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH).” In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary endpoints, demonstrating a large effect size in multi-allergen desensitization compared to placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. . Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or co-treatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes.

Evolving Trends in Pediatric Allergic Diseases: A Cross-Sectional Study Over 20 Years in the Central Black Sea Region of Turkey.

Background: In the past two decades, the prevalence of asthma, eczema, and allergic rhinitis has increased among school-aged children in the Central Black Sea region of Turkey. This increase is consistent with national and international data, reflecting the impact and temporal changes of allergic diseases on the community. A similar increasing trend is also observed worldwide. This study aims to contribute to the development of health policies related to allergic diseases among Turkish children in the Central Black Sea region. Materials and Methods: This study compares the results of two cross-sectional surveys conducted in schools in and around Samsun, Turkey, between the years 2006 and 2022, examining changes in the prevalence of specific allergic diseases such as asthma, allergic rhinitis, and atopic eczema. Utilizing the Turkish translation of the International Study of Asthma and Allergies in Childhood protocol, the research encompassed a total of 1,310 and 3,219 children, respectively. Results: In the recent study conducted in 2022, the prevalence of asthma and allergic bronchitis diagnosed by physicians was found to be 10.5% and 4.6%, respectively. In addition, the prevalence of allergic rhinitis was determined to be 3.1% and the prevalence of atopic dermatitis was 2.5%. Moreover, previously unidentified rates of food allergy were determined to be 2.5%, and drug allergy was found to be 2.4%. Furthermore, a comparison with a cross-sectional study conducted in the same region 20 years ago revealed a statistically significant increase in the prevalence of physician-diagnosed asthma and allergic bronchitis (with P-values of 0.0375 and 0.0107, respectively). Discussion: The findings of this study suggest a similar trend of increasing prevalence of allergic diseases when compared with similar studies at national and global levels. Consistent with trends identified in the international literature, Turkey is also affected by the rising prevalence of allergic diseases.