Therapies For Food Allergy Research Articles

Harmonization of Terminology for Tolerated and Reactive Dose in Food Allergy Immunotherapy

Currently, there is no Food and Drug Administration-approved therapy for food allergy. Several new potential treatments are under investigation, including food allergen immunotherapy via various routes of administration, such as oral immunotherapy, epicutaneous immunotherapy, subcutaneous immunotherapy, and sublingual immunotherapy. The double-blind, placebo-controlled food challenge (DBPCFC) has traditionally been used for diagnostic purposes, but extrapolation of the specific terminology used in food allergy diagnosis to interpretation of efficacy in clinical trials is incongruent and difficult to apply. There is a need for standardization of the terminology used in food allergy clinical trials, because inconsistencies can lead to potential misinterpretation of end points. The reactive dose, previously referred to as the eliciting dose, is defined as the dose given that induces the onset of unequivocal allergic symptoms, or the dose that stops the challenge based on physician discretion. Conversely, the single highest tolerated dose is defined as the highest dose given during a food challenge that elicits either no symptoms or symptoms that do not meet stopping criteria per the study protocol. The evolving field of food allergy provides a novel opportunity to define those end points that are most meaningful for patients, which is fundamental for successful implementation, education, and safety.

APPLICATION OF ORAL IMMUNOTHERAPY (OIT) CLINICAL TRIAL ENDPOINTS TO A REAL-WORLD SETTING

Introduction Double-blind, placebo-controlled food challenges (DBPCFCs) are the gold standard for the diagnosis of food allergy and are being used as clinical trial endpoints for new food allergy therapies. We sought to determine how these endpoints translate into meaningful data that the practicing allergist can use. Methods In the phase 3 study of AR101 for treatment of peanut allergy, DBPCFCs (based on PRACTALL) of 3, 10, 30, 100, 300, 600, and 1000mg of peanut protein at 20-30 minute intervals were used to determine the single-highest dose that a patient could tolerate. Cumulative doses over the entire challenge period were also recorded. Exposure levels to peanut protein were compared to real-world accidental exposure levels and times. Results Of the AR101 patients who completed the study, 85.3% tolerated 600mg as the single-highest tolerated dose and 63% tolerated 1000mg. Using cumulative exposure levels, the mean (sd) time to reach this 1043mg-dose was 122.4 (25.3) mins vs 153.1 (35.1) for the 2043mg group. In comparison, the median dose of peanut consumed upon accidental exposure in a real-world setting was 125mg (IQR 34-177) with symptoms presenting 5-30 minutes post ingestion, suggesting that ability to tolerate at least 600mg of peanut protein in a single exposure is more clinically relevant than the ability to tolerate 1043mg cumulatively over 122.4 mins. Conclusions Symptomatic accidental exposures to peanut often occur at levels greater than 100mg suggesting that the ability to tolerate a single dose of at least 600mg (∼2 peanuts) in a clinical trial may offer clinically relevant protection.

Molecular diagnostics improves diagnosis and treatment of respiratory allergy and food allergy with economic optimization and cost saving

BackgroundComponent resolved diagnosis (CRD) allows to precisely identify the sensitization to specific molecules of a given allergenic source, resulting in an important improvement in clinical management, particularly of polysensitized subjects. This will end in the correct prescription of allergen immunotherapy (AIT) for respiratory allergy and in adequate avoidance diets or prescription of self-injectable adrenaline in food allergy. ObjectiveThe aim of this multicenter, real life study is to evaluate the percentage change of the diagnostic-therapeutic choice in polysensitized patients with respiratory allergy and in patients with food allergy, after using CRD compared to a first level diagnosis, along with an economic analysis of the patient's overall management according to the two different approaches. MethodsAn overall number of 462 polysensitized patients, as suggested by skin prick tests (SPT), and with clinical symptoms related to a respiratory (275 pts) or food (187 pts) allergy, were recruited. All patients underwent CRD for specific IgE against food or inhalant recombinant molecules, which were chosen according to medical history and positivity to SPT. The first diagnostic-therapeutic hypothesis, based only on medical history and SPT, was recorded for each patient while the final diagnostic-therapeutic choice was based on the results from CRD. The rate of change of the diagnostic-therapeutic choice from the first hypothesis to the final choice was statistically evaluated. The economic impact of CRD on the overall management of the allergic patients was analyzed to evaluate whether the increase in the diagnostic costs would be compensated and eventually exceeded by savings coming from the improved diagnostic-therapeutic appropriateness. ResultsAn approximate 50% change (k index 0.54) in the prescription of AIT for respiratory allergy as well as a change in the prescription of self-injectable adrenaline (k index 0.56) was measured; an overall saving of financial resources along with a higher diagnostic-therapeutic appropriateness was also detected. ConclusionThere is moderate agreement concerning prescription of AIT and self-injectable adrenaline before and after performing CRD: this highlights the usefulness of CRD, at least in polysensitized patients, in indicating the risk assessment and therefore the correct therapy of respiratory and food allergy, which results in a cost-saving approach.

Human umbilical cord-derived mesenchymal stem cells ameliorate the enteropathy of food allergies in mice.

Food allergy prevalence has steadily increased worldwide over the past decades and immunotherapeutic treatment strategies are gaining attention. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) exhibit similar immune regulatory properties to bone marrow-derived MSCs. hUC-MCSs can be prepared with fewer ethical constraints and are potential candidates for allergic disorder therapies. The current study aimed to investigate potential antiallergic properties of hUC-MSCs in mice with ovalbumin (OVA)-induced food allergy. Administration of hUC-MSCs cells intraperitoneally combined with oral gavage of the culture medium significantly alleviated OVA-induced diarrhea symptoms. Additionally, this treatment significantly decreased IgE levels and the percentage of T helper 2 cells in the blood, which were increased in mice with OVA-induced food allergy. The mRNA levels of the inflammatory cytokines interleukin-4 and tumor necrosis factor-α, and inflammatory cell infiltration in mouse colons were significantly decreased in hUC-MSCs-treated animals compared with mice with OVA-induced food allergy. Goblet cells were detected in colons of allergy-induced mice and their numbers were reduced following treatment with hUC-MSCs. In addition, treatment with hUC-MSCs reestablished the gut flora. The results revealed that hUC-MSCs may have a potential application in food allergy therapy.

Understanding caregiver goals, benefits, and acceptable risks of peanut allergy therapies

BackgroundBoth oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) are emerging potential treatments for peanut allergy. Caregiver goals and expectations of these therapies are poorly defined. ObjectiveTo determine caregiver goals and expectations of food allergy therapy. MethodsTwenty-two detailed, semistructured interviews of OIT and EPIT caregivers were conducted, allowing caregivers to describe their motivations for and experiences with food allergy therapy and life with a peanut allergic child. ResultsIn this sample, caregivers of peanut allergic children enrolled in OIT or EPIT phase 3 trials expressed a primary goal for their child to develop a buffer against an unintentional peanut exposure. The perception of the buffer varied, representing a decreased reaction severity on exposure, increased time to react to allow for assessment, or increased threshold of peanut exposure tolerated. Although caregivers expressed that a buffer may increase their confidence in travel and dining outside the home, they do not anticipate this buffer would lessen their overall level of pretherapy anxiety, allergen-associated vigilance, or avoidance practices. Most of the caregivers hope the buffer will increase their and their child's perceived sense of freedom for the child's actions and social interactions, translating to quality of life improvement, while still respecting the limitations of having a severe allergy that has been partially treated. No caregiver viewed these therapies as a cure, and most viewed treatment as a supplement to their current avoidance practices. ConclusionCaregivers of peanut allergic children strongly desire that OIT and EPIT result in a buffer against an unintentional reaction, although most admitted that this would not significantly change their anxiety and family's current lifestyle.

Food Allergy - Theory and Praxis

Allergies manifest differently in every patient: Even when the same allergen source is the causing agent, means of sensitization and complexity of symptoms can vary strongly across patients. This often complicates the prevention, diagnostics and therapy of food allergies - or even makes them impossible. This article gives an overview of the underlying immunological principles of food-allergies, as well as of the current therapeutic and diagnostic approaches.

Oral and Sublingual Immunotherapy for Treatment of IgE-Mediated Food Allergy.

Development of active therapies for IgE-mediated food allergy is a critical action step toward alleviating the adverse medical, psychosocial, and economic burdens on affected patients and families. Significant progress has been observed specifically in the application of single-allergen oral and sublingual immunotherapy for treatment of IgE-mediated food allergy, with emphasis on milk, egg, and peanut as the primary allergens. Oral immunotherapy (OIT) has demonstrated efficacy in promoting immunomodulatory effects that lead to the clinical outcome of desensitization, defined as reduced reactivity while on active OIT, in the majority of treated individuals; however, achievement of sustained unresponsiveness following cessation of therapy has been observed in a smaller subset of treated subjects. The potential therapeutic benefits of OIT must be carefully considered in light of the significant potential for adverse events ranging from self-limited or easily treated oropharyngeal, respiratory or gastrointestinal symptoms, to persistent abdominal complaints that lead to cessation of therapy in an estimated 10-15% of treated individuals. To date, the majority of studies have focused on single-allergen OIT approaches; however, multi-allergen OIT has shown promise in initial trials and is the subject of ongoing investigation to address the complex needs of multi-food allergic individuals. Sublingual immunotherapy (SLIT) has been utilized for the treatment of food allergy and pollen-food allergy syndrome, demonstrating moderate efficacy, a favorable safety profile and variable tolerability, with oropharyngeal symptoms most commonly observed. Although studies directly comparing OIT and SLIT are limited, in general, the favorable safety profile associated with SLIT comes at the expense of reduced efficacy, while the more robust clinical effects observed with OIT come at the risk of potentially intolerable, treatment-limiting side effects. Future investigation to address specific knowledge gaps including optimal dose, duration, age of initiation, maintenance schedule, mechanisms, predictors of risk and therapeutic response will be important to maximize efficacy, minimize risk and develop personalized, effective approaches to targeting food allergy.

The Nuts and Bolts of Food Immunotherapy: The Future of Food Allergy.

Food allergies are on the rise and have a major impact on the quality of life of the food allergic child and their family. Currently, the mainstream treatment for food allergies is strict avoidance and elimination of the allergenic food(s) from the patient’s diet in order to prevent an allergic reaction. However, recent advances in research have presented new therapeutic options for food allergic patients that are potentially becoming promising alternatives to traditional treatment. Food immunotherapy is the most popular of these new emerging interventions and has been studied intensively over the last decade for various foods. In this review, we discuss this exciting new development that is aspiring to become part of the mainstream therapy for food allergy.

Current Status of Potential Therapies for IgE-Mediated Food Allergy.

The goal of this review is to provide the reader with an updated summary of published trial data regarding the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for treatment of IgE-mediated food allergies. Data from phase 2 trials for treatment of peanut allergy with OIT and EPIT reveal an increase in the threshold of reactivity for peanut-allergic children. Compared to EPIT, OIT promotes a greater increase in the threshold of reactivity; however, adverse events are more common with OIT. OIT, EPIT, and SLIT appear to modulate the immune response for some food-allergic individuals. Data regarding utility for treatment of food allergies regardless of modality is limited to few foods, as is investigation into treatment of food-allergic infants, young children, and adults. Future trials are likely to focus on young children, food allergies other than peanut, and treatment of multifood-allergic individuals.

Current Status and Unanswered Questions for Food Allergy Treatments

Although there is no FDA approved therapy for food allergy, over the past decades, several routes of immunotherapy have been investigated for food allergy. Thus far, these therapies have shown variable levels of efficacy at desensitizing to foods, with oral immunotherapy (OIT) far more successful than sublingual immunotherapy (SLIT) or epicutaneous immunotherapy (EPIT). However, desensitization tends to be temporary, and safety remains a major concern with OIT. Moreover, although it seems logical that desensitization will result in fewer reactions, it is not clear whether OIT or other immunotherapies are associated with an overall lower or higher risk of reactions over the long term. Eosinophilic esophagitis is a known complication of OIT, and may also be a risk with SLIT and possibly EPIT, although it has not been reported in the relatively few patients treated thus far. Adjuvants such as omalizumab or probiotics may improve the safety and/or efficacy of immunotherapy for food allergy, but more research is needed. In the future, biomarkers may identify subsets of patients who are better candidates for specific treatments. As therapies become commercially available, patients and providers will need to consider whether the benefits justify the risks and burdens of these treatments.

Omalizumab gives tolerance in patients with severe food allergy

Background: Therapies for food allergy include elimination diets, Oral ImmunoTherapy (OIT), and the administration of biologics. Omalizumab has been licensed for use in severe allergic asthma and chronic urticaria.

Oral Immunotherapy, Sublingual Immunotherapy, or Epicutaneous Immunotherapy: Which Is the Right Solution?

The current standard of care treatment for food allergy relies on avoidance. However, as outlined in this review, over the past decade, the literature has grown significantly showing promising results for interventional therapies for IgE-mediated food allergies utilizing oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT). Within the near future, we expect to have multiple FDA-approved products on the market for treatment of life-threatening food allergies and will have options to present to our patients. As we move into this next phase of our practice, we will need to consider meaningful endpoints for our patients (e.g., likelihood of inducing desensitization versus sustained unresponsiveness, the relevance of various threshold changes induced by therapy, effects on quality of life, etc.). This review provides a comprehensive overview of the currently published literature and will prepare the practicing allergist for a thoughtful discussion with their patients and colleagues on the most recent developments in the field.

Oral administration of Clostridium butyricum CGMCC0313-1 inhibits \u03b2-lactoglobulin-induced intestinal anaphylaxis in a mouse model of food allergy

BackgroundProbiotic bacteria can induce immune regulation or immune tolerance in patients with allergic diseases, but the underlying mechanisms are still unclear. There has been a growing interest in the use of beneficial bacteria for allergic diseases recently. This study aimed at exploring whether Clostridium butyricum CGMCC0313-1 (C. butyricum) can reduce β-lactoglobulin(BLG)-induced intestinal anaphylaxis in a murine model of food allergy.MethodsThe preventive and therapeutic effects of oral C. butyricum on anaphylactic symptoms induced via BLG in food allergy mice were investigated. Intestinal anaphylaxis, T helper (Th)-specific cytokines and transcription factors, secretory IgA (sIgA), CD4+ CD25+ Foxp3Treg cell and histopathological alterations were examined.ResultsClostridium butyricum significantly ameliorated intestinal anaphylaxis symptoms in the food allergy mice. sIgA and CD4+ CD25+ Foxp3Treg cell were increased by oral C. butyricum. It also reversed the imbalance of Th1/Th2 andTh17/Treg.ConclusionsClostridium butyricum reduces BLG-induced intestinal anaphylaxis in mice and might be an additional or supplementary therapy for food allergy.

Update on Potential Therapies for IgE-Mediated Food Allergy

Food allergy is common, affecting up to 8% of children in the USA. Currently, therapy is limited to avoidance of the implicated allergen and availability of self-injectable epinephrine. However, several new approaches to food allergy are under investigation. This article reviews the published data on these new approaches. Oral immunotherapy, in which allergic subjects are exposed to increasing amounts of antigen, can be accomplished in the majority of allergic individuals. However, this approach is not a cure as most patients will react after cessation of regular intake. In addition, there is a high rate of side effects. Other approaches include epicutaneous immunotherapy, therapy with anti-IgE medications, and use of Chinese herbs. Several novel approaches on food allergy are under study. At the current time, these approaches show promise for preventing severe reactions to accidental exposures. However, there is little evidence that current approaches will represent a true cure for food allergy.

The role of the gut microbiota in food allergy.

The rise in the prevalence of food allergy over the past decades has focused attention of factors that may impact disease development, most notably the gut microbiota. The gut microbial communities play a crucial role in promoting oral tolerance. Their alteration by such factors as Cesarean section delivery, diet and antibiotics may influence disease development. This review highlights recent progress in our understanding of the role of the gut microbiota in the development of food allergy. Food allergy is associated with alterations in the gut microbiota or dysbiosis early in life that may be predictive of disease persistence versus tolerance acquisition. Evidence for the benefits of adjunct therapy with probiotics for the prevention of food allergies and for potentiating oral immunotherapy remains circumstantial, with further studies needed to validate its use. Studies in murine models of food allergy suggest that microbial therapy with protolerogenic bacteria such as certain Clostridial species holds promise in future applications for prevention or therapy of food allergy. Progress in understanding the role of dysbiosis in food allergy and the factors that promote its development, such as antibiotic therapy, diet, modes of infant delivery, and environmental exposures, offer windows of opportunity for both preventive and therapeutic interventions to stem the rising tide of the food allergy epidemic.

Induction of Regulatory T Cells as a Novel Mechanism Underlying the Therapeutic Action of Kakkonto, a Traditional Japanese Herbal Medicine, in a Murine Food Allergy Model

Background: The number of patients with food allergy (FA) has dramatically increased. Although satisfactory drug therapies for FA are not available, we have found that kakkonto, a traditional Japanese herbal medicine, suppressed the occurrence of allergic symptoms in an FA mouse model. Thus, we investigated whether kakkonto could regulate the activation and differentiation of T cells in the colon. Methods: BALB/c mice were systemically sensitized and then orally challenged with ovalbumin. FA mice were orally treated with kakkonto. Lamina propria (LP) cells from their colons were isolated and analyzed. Results: Kakkonto significantly reduced the proportion of CD69⁺ cells and the elevated helper T cell type 2-specific transcription factor GATA-3 mRNA expression in the LP CD4⁺ T cells, showing that kakkonto has a suppressive effect on the activation and Th2 differentiation of LP effector CD4⁺ T cells of the FA mouse colon. Furthermore, kakkonto significantly increased the proportion of Foxp3⁺CD4⁺ regulatory T cells in the LP CD4⁺ T cells of the FA mouse colon. Similarly, the number of Foxp3-positive cells was dramatically increased in the colonic mucosa of kakkonto-administered FA mice. However, the pharmacological effect and Foxp3⁺CD4⁺ regulatory T cell-inducing ability of kakkonto were not attenuated by the administration of an anti-CD25 monoclonal antibody in the FA model. Conclusions: The induction of Foxp3⁺CD4⁺CD25^- regulatory T cells in the colon as a novel mechanism underlying the therapeutic action of kakkonto could be utilized for the development of a novel anti-FA drug.

Current and Emerging Therapies for IgE-Mediated Food Allergy.

Food allergies are a growing clinical problem leading to increased health care utilization and decreases in patient quality of life. Current treatment recommendations include strict dietary avoidance of the offending food as well as use of self-injectable epinephrine in case of accidental exposure with allergic reaction. Although many individuals will eventually outgrow their food allergies, a substantial number will not. Significant effort has been made to find novel treatments that protect patients from food-triggered reactions as well as to develop immune-modulating therapies that could lead to tolerance. In this review, three therapies that have shown the most promise for the treatment of food allergies are highlighted: oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy.

The Natural History of Food Allergy

On a population level, it is well recognized that some IgE-mediated childhood food allergies, such as milk and egg allergies, are more likely to resolve than others, such as peanut and tree nuts allergies. Unfortunately, some studies suggest that resolution rates may have slowed compared with impressions from past decades. The clinician can apply the knowledge of the epidemiology of these allergies to describe likely patient outcomes, and direct management in a general manner. However, the ability to evaluate and predict the natural course of specific food allergies for individual patients is essential to inform personalized patient care. Data are accumulating to assist in identifying whether a child's allergy has likely resolved, informing the timing of oral food challenges or subsequent testing. Exciting recent studies are increasingly identifying early prognostic markers as well. Emerging food allergy therapies carry risks and costs. Identifying which egg-allergic patient has likely persistent allergy, and which patient with peanut allergy may experience natural resolution, is becoming an important goal to identify the best candidates for these therapies. Although more work needs to be done to identify reliable predictive markers and validate them, there is already much known about the natural course of food allergies that can be applied by the clinician to improve patient care.

Food Allergies: Novel Mechanisms and Therapeutic Perspectives.

Childhood food allergy (FA) rates have rapidly increased with significant direct medical costs for the health care system and even larger costs for the families with a food-allergic child. The possible causes of food allergy become the target of intense scrutiny in recent years. Increasing evidence underline the importance in early life of gut microbiome in the development of allergic diseases. There are a range of factors in the modern environment that may be associated with changes to both the gut microbiome and risk of FA, such as mode of delivery, antibiotic exposure, infant feeding practices, farming environment, and country of origin. Knowledge of the relationship between early life gut microbiome and allergic diseases may facilitate development of novel preventive and treatment strategies. Based on our current knowledge, there are no currently available approved therapies for food allergy. More studies are needed to evaluate the safety and efficacy of allergen-specific and allergen-nonspecific approaches, as well as combination approaches.

Oral Desensitization in Nursling with Cow’s Milk Allergy

Abstract Food allergy is a major public health problem affecting nearly 10 % of children in most industrialized countries. Unfortunately, there are no effective therapies for food allergy, relegating patients to simply avoid the offending foods and treating the reactions which occur on accidental exposure. Recently however, studies suggest that food immunotherapy may provide a promising new approach to food allergy, particularly using the oral form of immunotherapy (OIT). Enthusiasm for this approach though must be tempered because of the significant allergic reactions that often occur with OIT that tends to limit its use to patients with less severe disease. Actually this technique of desensitization is applied in child with ages over 5 years old, because many investigators think that this is the frontier from which the allergy is persistent all the life, and before this age the possibilities of natural tolerance to milk is very much probability. In contrast to this, are few investigational groups dedicated to try to desensitize children under 1 years old, and less in the first 6 months of the life, due to the high possibilities of secondary reactions, especially anaphylaxis