Impact of socioeconomic factors on allergic diseases.

Allergic and immunologic conditions, including asthma, food allergy, atopic dermatitis, and allergic rhinitis, are among the most common chronic conditions in children and adolescents that often last into adulthood. Although rare, inborn errors of immunity are life-altering and potentially fatal if unrecognized or untreated. Thus, allergic and immunologic conditions are both medical and public health issues that are profoundly affected by socioeconomic factors. Recently, studies have highlighted societal issues to evaluate factors at multiple levels that contribute to health inequities and the potential steps toward closing those gaps. Socioeconomic disparities can influence all aspects of care, including health care access and quality, diagnosis, management, education, and disease prevalence and outcomes. Ongoing research, engagement, and deliberate investment of resources by relevant stakeholders and advocacy approaches are needed to identify and address the impact of socioeconomics on health care disparities and outcomes among patients with allergic and immunologic diseases.

Treatment for food allergy: Current status and unmet needs.

The treatment of food allergy has traditionally relied on avoidance of the offending food(s) and use of emergency medications in the event of accidental exposures. However, this long-standing paradigm is beginning to shift, as a variety of treatment approaches have been and are being developed. This report provides an overview of the past, present, and future landscape of interventional clinical trials for the treatment of food allergy. It focuses on specific issues related to participant characteristics, protocol design, and study end points in the key clinical trials in the literature and examine how differences between studies may impact the clinical significance of the study results. Recommendations are provided for the optimization of future trial designs and focus on specific unmet needs in this rapidly evolving field.

Identification of cow milk epitopes to characterize and quantify disease-specific T cells in allergic children.

BACKGROUND: Cow milk (CM) allergy is the most prevalent food allergy in young children in the United States and Great Britain. Current diagnostic tests are either unreliable (IgE test and skin prick test) or resource-intensive with risks (food challenges). OBJECTIVE: We sought to determine whether allergen-specific T cells in CM-allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. METHODS: Using PBMCs from 147 food-allergic pediatric subjects, we mapped T-cell responses to a set of reactive epitopes in CM that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing subjects with CMA from subjects without CMA. We further used the pool to isolate and characterize antigen-specific CD4 memory T cells using flow cytometry and single-cell RNA/TCR sequencing assays. RESULTS: We detected significant changes in the transcriptional program and clonality of CM antigen-specific (CM+) T cells elicited by the pool in subjects with CMA versus subjects without CMA ex vivo. CM+ T cells from subjects with CMA had increased percentages of FOXP3+ cells over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells that have suppressive activity, but CM+ FOXP3+ cells from subjects with CMA showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared with subjects without CMA, suggesting that these are not conventional regulatory T cells. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to use surface markers (CD25, CD127, and CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow-cytometry assay. We show increased percentages of CM+ CD127-CD25+ cells from subjects with CMA in an independent cohort, which could be used for diagnostic purposes. Looking specifically for TH2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in subjects with CMA and that had high expression of TH2 cytokines and pathogenic TH2/T follicular helper markers. CONCLUSIONS: Overall, these findings suggest that there are several differences in the phenotypes of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.

Anti-immunoglobulin E for food allergy.

OBJECTIVE: To review the safety and efficacy of anti-immunoglobulin E (IgE) monotherapy or as an adjunct to oral immunotherapy (OIT) in the treatment of IgE-mediated food allergy. DATA SOURCES: Literature searches were performed using the Excerpta Medica dataBASE, Medline, Scopus, and PubMed Central to identify articles in English related to food allergy and anti-IgE therapies, including omalizumab and ligelizemab. STUDY SELECTIONS: Original research articles reviewed include interventional studies, retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews. Data were reviewed and summarized. RESULTS: Here, we discuss the current anti-IgE therapies being studied as a potential treatment option for food allergy. We also review trial design, safety, and efficacy data on the use of anti-IgE therapies as monotherapy or in combination with OIT for food allergies. Finally, we discuss clinical trials in progress using omalizumab and ligelizumab and highlight important clinical considerations. CONCLUSION: Over the past 20 years, substantial progress has been made in understanding the potential role of anti-IgE therapies for food allergy. Anti-IgE therapies seem to be a promising option that may increase reaction dose thresholds and decrease time to reach OIT maintenance and OIT dosing-related reactions. Two phase 3 trials are currently in progress studying anti-IgE potential monotherapy for the treatment of peanut and multifood allergies. It is important for clinicians to be aware of these emerging treatment options.

Next-Generation Approaches for the Treatment of Food Allergy.

PURPOSE OF REVIEW: IgE-mediated food allergies are an increasing health concern, and current management includes food avoidance and use of emergency medications. Effective treatment of food allergy is highly desirable. Next generation approaches for the treatment of food allergy aim to improve both safety and efficacy, potentially including long-term tolerance. RECENT FINDINGS: Oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) will likely be integrated into clinical practice as part of food allergy management in the near future. Newer approaches, such as sublingual immunotherapy (SLIT), modified proteins, lysosomal-associated membrane protein DNA (LAMP DNA) vaccines, and the use of immunomodulatory agents, are early in development and depending on results, could also become important treatment options. This is a review of novel approaches to the treatment of food allergy that are currently under investigation, including the use of SLIT, modified proteins, probiotics, Chinese herbal supplements, biologic therapies, and DNA vaccines, as well as a summary of the current status of OIT and EPIT.

New Approaches to Food Allergy Immunotherapy.

Food allergy is an increasing public health problem in children and adults. In addition to the risk of potentially severe reactions, food allergy can have a significant burden on quality of life, nutrition, cost of living, and social activities. Traditionally, treatment has primarily included strict food allergen avoidance and use of emergency medications to treat an allergic reaction. However, in recent years, there have been significant strides in the advancement of food allergy treatment, including the approval of the first and only approved therapy (peanut oral immunotherapy) for food allergy in 2020. Clinical trials have primarily focused on food allergen immunotherapy (oral, epicutaneous, sublingual). Building off of a foundation of promising data supporting the efficacy of food oral immunotherapy and our greater understanding of the underlying mechanism of immunotherapy, newer approaches, including alternative routes of delivery, adjuncts to therapy, modified allergens, and utilization in younger patients, aim to provide safer and more effective treatment approaches to the millions of patients burdened by food allergy.

Home Introduction of Baked Egg After Oral Food Challenge.

BACKGROUND: Baked egg (BE) introduction may accelerate resolution of egg allergy. Long-term data regarding the safety and success of BE introduction in the real world are limited. OBJECTIVE: To identify predictors of future egg consumption and barriers to advancement based on characteristics during and after BE oral food challenges (OFCs). METHODS: We performed a retrospective review of consecutive BE OFCs with a minimum 24-month follow-up. Goal doses ranged from 1/16 to 1/4 egg. Outcomes were categorized as pass (no reaction), fail (but allowed BE introduction), or fail (avoid). Status of egg introduction and reactions were recorded. RESULTS: A total of 243 patients were included; 134 passed and 109 failed (70 of whom were instructed to introduce BE). At follow-up (median, 47 months), 90 (37%) were consuming direct egg, 26 (11%) lightly cooked egg, 39 (16%) BE, and 88 (36%) avoiding; 58% who failed versus 81% who passed were consuming some form of egg. Median egg white IgE level was significantly higher among avoiders versus introducers (8.7 vs 5.8; P = .008). Lower egg white IgE level and younger age were predictors of egg consumption in some form at follow-up (median IgE, 5.8 vs 8.4; P = .03; median age, 4.0 vs 8.0 years; P < .001). A total of 94 patients had a total of 136 reactions (132 mild, 4 severe); 22 (16.2%) were accidental exposures, 42 (30.9%) planned escalations, and 72 (52.9%) with previously tolerated doses. CONCLUSIONS: Most patients who underwent a BE OFC continued to consume some form of egg, often advancing to direct egg. However, many reverted to avoidance and adverse reactions were common.

Update on omalizumab in allergen immunotherapy.

PURPOSE OF REVIEW: To review the most relevant studies in the advancing field of omalizumab in allergen immunotherapy. RECENT FINDINGS: Omalizumab has been used in combination with inhalant, venom, and food allergen immunotherapy. These studies suggest that omalizumab can decrease the time required to reach maintenance dosing and adverse events. However, severe adverse events do still occur. Limited long-term data suggests that there is a risk for increased reactivity after stopping omalizumab. SUMMARY: Omalizumab in conjunction with immunotherapy has shown promising results for the treatment of allergic rhinitis, venom hypersensitivity, and food allergy, especially in the reduction of adverse events. Larger randomized, placebo-controlled trials are needed to better understand optimal dosing and duration, cost--benefit analysis, ideal patients, and long-term benefits. This combination therapy has the potential to improve treatment, particularly for high-risk patients.

Omalizumab as an adjuvant in food allergen immunotherapy.

PURPOSE OF REVIEW: To review the most relevant studies in the rapidly advancing field of omalizumab as an adjunct to food allergen oral immunotherapy (OIT). RECENT FINDINGS: Clinical trials have primarily focused on milk, peanut, and multiallergen OIT combined with omalizumab. These studies suggest that omalizumab in addition to OIT can decrease the time required to reach maintenance OIT dosing and adverse events; however, serious adverse events did still occur. There is limited long-term data but available information suggests that individuals are at risk for increased reactivity after stopping omalizumab, and many discontinued treatment. There has been diversity in study designs, dosing, and populations. SUMMARY: The use of anti-IgE antibody as an adjunct to food allergen OIT has been an expanding area of research with several additional trials underway. Significant progress has been made in the past decades but further studies are needed to optimize protocols, improve safety and efficacy, and identify patients who will have the greatest benefit.

Improving Diagnostic Accuracy in Food Allergy.

The diagnosis of food allergy can have a major impact on the lives of patients and families, imposing dietary restrictions and limitations on social activities. On the other hand, misdiagnosis can place the patient at risk of a potentially severe allergic reaction. Therefore, an accurate diagnosis of food allergy is of utmost importance. The diagnosis of food allergy is often established by the combination of the clinical history and allergen-specific IgE; however, without a clear history of an allergic reaction, the interpretation of IgE sensitization tests can be difficult. There are also rare cases of clinical food allergy in the absence of IgE sensitization. For that reason, testing for suspected food allergy ideally requires access to oral food challenges (OFCs), which are currently the gold standard tests to diagnose food allergy. As OFCs are time consuming and involve the risk of acute allergic reactions of unpredictable severity, the question remains: how can we improve the accuracy of diagnosis before referring the patient for an OFC? Herein, we review the predictive value of different tests used to support the diagnosis of food allergy, discuss implications for therapy and prognosis, and propose a diagnostic approach to be applied in clinical practice.