[Mast Cell-Neutrophil Communication Regulates Allergic Diseases].

Allergic diseases (e.g., food allergies) are a growing problem, with increasing numbers of individuals experiencing them worldwide. Congruently, the adverse reactions (e.g., anaphylaxis) associated with the administration of vaccines against emerging infectious diseases such as coronavirus disease 2019 (COVID-19) have become a familiar problem. Allergic diseases, which have a wide variety of symptoms, are difficult to prevent or cure; treatment is currently limited to therapeutic drugs or allergen immunotherapy. Therefore, elucidating new allergic regulatory factors that control the allergic (i.e., mast cell) responses is important. While investigating the regulatory mechanisms of the wide range of allergic responses of mast cells, we found that the affinity of allergens to immunoglobin E (IgE) regulates allergic inflammation through the differences in the secretory responses of mast cells and the types and interactions of the cells infiltrating the tissues. Here, we present our recent findings regarding the affinity of allergens to IgE in regulating allergic inflammation, heterogeneous secretory granules inducing diverse secretory responses, and mast cells interacting with neutrophils, thereby regulating the various allergic responses.

Differences in the Course, Diagnosis, and Treatment of Food Allergies Depending on Age-Comparison of Children and Adults.

Food allergy (FA) has become a common global public health issue, with a growing prevalence in the modern world and a significant impact on the lives of patients, their families, and caregivers. It affects every area of life and is associated with elevated costs. Food allergy is an adverse immune reaction that occurs in response to a given food. The symptoms vary from mild to severe and can lead to anaphylaxis. This is why it is important to focus on the factors influencing the occurrence of food allergies, specific diagnostic methods, effective therapies, and especially prevention. Recently, many guidelines have emphasized the impact of introducing specific foods into a child's diet at an early age in order to prevent food allergies. Childhood allergies vary with age. In infants, the most common allergy is to cow's milk. Later in life, peanut allergy is more frequently diagnosed. Numerous common childhood allergies can be outgrown by adulthood. Adults can also develop new IgE-mediated FA. The gold standard for diagnosis is the oral provocation test. Skin prick tests, specific IgE measurements, and component-resolved diagnostic techniques are helpful in the diagnosis. Multiple different approaches are being tried as possible treatments, such as immunotherapy or monoclonal antibodies. This article focuses on the prevention and quality of life of allergic patients. This article aims to systematize the latest knowledge and highlight the differences between food allergies in pediatric and adult populations.

Perspectives in the validation of DEFASE: a paradigm shift in food allergy management.

PURPOSE OF REVIEW: To explore the groundbreaking international consensus on the DEFASE (DEfinition of Food Allergy Severity) project as a revolutionary grading system for IgE-mediated food allergy severity. Against the backdrop of the growing public health challenge posed by food allergy, this article delves into the importance of validating and implementing DEFASE in real-world clinical settings. RECENT FINDINGS: With new therapeutic options available for food allergy, including biologics alongside immunotherapy, it is urgent to properly support clinical decision-making in the management of the disease. The DEFASE score is the first international consensus-based grading system of severity associated with food allergy as a whole disease embracing multidisciplinary perspectives from different stakeholders involved. In its current version, this comprehensive scoring system has been developed to be used in research settings. SUMMARY: The review emphasizes the potential impact of DEFASE on patient outcomes, healthcare management, and resource allocation, underscoring its significance for the allergy scientific community. Future research should focus on internal and external validation of the scoring system, targeting these models to various food allergenic sources, populations, and settings.

Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development.

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future.

Dietary Management of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated food allergy-driven disease characterized by eosinophilic inflammation of the esophagus leading to symptoms of esophageal dysfunction. Prior studies have supported the key role of food allergen exposure as the main driver behind the etiopathogenesis showing that removal of food antigens can result in disease remission in both children and adults. These landmark studies serve as the basis for the rising interest and evolution of dietary therapy in EoE. This article will focus on the rationale for dietary therapy in EoE and provide helpful tools for the implementation of dietary therapy in practice.

Dietary Management of Non-EoE Eosinophilic Gastrointestinal Diseases.

Patients with non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) are prone to nutritional deficiencies due to food-avoidant behaviors, malabsorption, and high nutrition impact symptoms. Nutrient deficiencies correspond to the segment, depth, and extent of the gastrointestinal tract involved and can impact organs distant from the gut. Patients with non-EoE EGIDs are often atopic, and some appear to respond to dietary avoidance of specific food allergens. Tests to identify food triggers other than response to elimination diets are lacking. Dietary restriction therapy should be considered in such patients and is best implemented through a multidisciplinary approach to avoid nutritional complications.

Initial updosing phase of oral immunotherapy improves quality of life and psychological burden in parents of children with food allergy.

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.

Psychological support needs for children with food allergy and their families: A systematic review.

This systematic review aimed to review the evidence for psychological support for children with food allergies and their families, identify effective psychological interventions, and highlight the support needs for this group. A systematic search was undertaken across six databases (up to October 2023). Articles were checked by three reviewers for inclusion. Study data were extracted, and quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was undertaken. A total of 11 papers were included (n = 838 participants). Intervention types were based on cognitive behavioral therapy (CBT; n = 7); psycho-education (n = 1); peer mentoring (n = 1); self-regulation theory (n = 1); and coping (n = 1). Two interventions were for children only, three were for children and parents and six for parents only. Cognitive behavioral therapy-based interventions with highly anxious parents or children or those facilitated by a psychologist showed significant improvements with moderate-to-large effect sizes. The one self-help CBT-based online program showed no effects. Other intervention types reported mainly trends in improvement due to small sample sizes. Most interventions were aimed at supporting children or parents in day-to-day management of food allergy, measuring outcomes such as quality of life, self-efficacy, anxiety, worry, and depression. One intervention was designed to assist with oral immunotherapy outcomes. The majority of the studies had small sample sizes and were feasibility or proof-of-concept studies. Available research evidence points to effectiveness of facilitated CBT-based interventions for those that have high food allergy-related anxiety, but as many studies have small sample sizes and few report effect sizes, no firm conclusions can yet be drawn. A stepped care approach is likely to be useful for this population. Research using large interventional designs, particularly for children and adolescents, are needed.

A Review of Shared Decision-Making, Published Protocols, and Post-desensitization Strategies in Oral Immunotherapy (OIT).

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

PURPOSE OF REVIEW: Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. RECENT FINDINGS: Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. SUMMARY: Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.

Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Management of food allergy based on oral food challenge.

PURPOSE OF REVIEW: Food allergy is a growing health problem that affects both patients and society in multiple ways. Despite the emergence of novel diagnostic tools, such as component-resolved diagnostics (CRD) and basophil activation tests (BAT), oral food challenge (OFC) still plays an indispensable role in the management of food allergies. This review aimed to highlight the indications and safety concerns of conducting an OFC and to provide insights into post-OFC management based on recent findings. RECENT FINDINGS: Standardized OFC protocols have regional diversification, especially in Japan and Western countries. Recent studies suggested that the interval between doses should be at least more than an hour. Furthermore, applying a stepwise method tailored to the patient's specific immunoglobulin E level and history of anaphylaxis seems to mitigate these risks. Recent surveys have shown that, following a positive OFC, options other than strict avoidance are also selected. SUMMARY: OFC serves diverse purposes, yet the risks it carries warrant caution. The stepwise protocol appears promising for its safety. Subthreshold consumption following OFC shows potential; however, further research on its efficacy and safety is required. Management following OFC should be tailored and well discussed between clinicians and patients.

Role of biologics in severe food allergy.

PURPOSE OF REVIEW: This review examine the dynamic landscape of food allergy treatment within the context of emerging biologics. Our purpose is to comprehensively evaluate the potential benefits, challenges, and transformative impact associated with the utilization of biologics in comparison to conventional therapeutic modalities. RECENT FINDINGS: This document synthesizes recent scientific investigations to various biologics, such as omalizumab, ligelizumab, dupilumab, and tezepelumab, providing a nuanced understanding of their roles in oral immunotherapy, rapid desensitization, and overall food allergy management. Recent studies and clinical trials highlight the impact of anti-IgE treatment on food allergies, revealing critical findings such as dose-related efficacy, facilitation of rapid desensitization in peanut allergies, and the sustained positive outcomes observed in individuals with multifood allergies. SUMMARY: The use of biologics presents a groundbreaking approach in the treatment of food allergies. The multifaceted action of these agents, along with their potential to overcome the challenges associated with traditional therapies, marks a significant advancement. Despite the persisting challenges of economic constraints and the need for further safety studies, biologics offer a promising avenue for improving the quality of life for individuals with food allergies. Ongoing research and collaborative efforts are imperative to fully realize the transformative potential inherent in these emerging therapeutic frontiers.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.

New biologics for food allergy.

PURPOSE OF REVIEW: This review aims to explore role of emerging biologics, including ligelizumab, UB-221, dupilumab, and antialarmins, in food allergy management. With a focus on recent developments, we evaluate their promise in mitigating adverse events during oral immunotherapy (OIT), reducing allergic reactions, and addressing the limitations of current therapeutic options. RECENT FINDINGS: Antiimmunoglobulin E mAbs, exemplified by omalizumab, demonstrate efficacy in desensitization and safety improvement during multiallergen OIT. Next-generation antibodies like ligelizumab and UB-221 exhibit enhanced potency and unique mechanisms, holding promise for food allergy treatment. Dupilumab, targeting IL-4 receptor alpha, presents potential benefits in decreasing allergen-specific IgE and modifying the atopic march. Exploration of antialarmins, specifically anti-IL-33 (etokimab) and anti-TSLP (tezepelumab), reveals encouraging results, with etokimab showing early success in peanut allergy trials. SUMMARY: Biologics hold promising potential for food allergy treatment. Tailoring therapeutic approaches based on shared decision-making becomes pivotal. While omalizumab remains a significant option, next-generation anti-IgE antibodies and agents targeting alarmins exhibit unique strengths. Dupilumab, despite limited success as monotherapy, shows promise as an adjunct for OIT. Careful consideration of treatment goals, patient preferences, and the evolving landscape of biologics will shape future clinical practice, offering allergists an expanded toolbox for personalized food allergy management.