Project description:Food allergy is a common condition for which the only currently approved treatments are avoidance of the allergenic food and the administration of emergency medications upon accidental exposure. Over the past 10 years, significant advances have been made in the field of food immunotherapy, with efforts focusing on allergen exposure via the oral mucosa. Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are the two modalities that have been most extensively studied, and this article will review recent advances in our knowledge of the efficacy and safety of these treatments.
Project description:BackgroundFor egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.MethodsIn this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.ResultsAfter 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.ConclusionsThese results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.).
Project description:Food allergies are increasing in prevalence and present an emerging epidemic for westernized countries. Strict dietary avoidance is the only approved management for food allergy, but accidental exposures regularly occur, leading to significant patient anxiety and decreased quality of life. Over the past decade, oral and sublingual immunotherapies have emerged as potential treatments for food allergy. While several small clinical trials have demonstrated that immunotherapy can desensitize food-allergic individuals, strategies for further enhancing safety and definitively establishing long-term efficacy are needed. This review presents an overview of recent oral and sublingual immunotherapy trials, and provides a glimpse into what the next generation of food immunotherapy may entail.
Project description:BackgroundOral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.ObjectiveWe sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy.MethodsWe randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.ResultsThirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.ConclusionOIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.
Project description:Hypersensitivity or an allergy to chicken egg proteins is a predominant symptomatic condition affecting 1 in 20 children in Australia; however, an effective form of therapy has not yet been found. This occurs as the immune system of the allergic individual overreacts when in contact with egg allergens (egg proteins), triggering a complex immune response. The subsequent instantaneous inflammatory immune response is characterized by the excessive production of immunoglobulin E (IgE) antibody against the allergen, T-cell mediators and inflammation. Current allergen-specific approaches to egg allergy diagnosis and treatment lack consistency and therefore pose safety concerns among anaphylactic patients. Immunotherapy has thus far been found to be the most efficient way to treat and relieve symptoms, this includes oral immunotherapy (OIT) and sublingual immunotherapy (SLIT). A major limitation in immunotherapy, however, is the difficulty in preparing effective and safe extracts from natural allergen sources. Advances in molecular techniques allow for the production of safe and standardized recombinant and hypoallergenic egg variants by targeting the IgE-binding epitopes responsible for clinical allergic symptoms. Site-directed mutagenesis can be performed to create such safe hypoallergens for their potential use in future methods of immunotherapy, providing a feasible standardized therapeutic approach to target egg allergies safely.
Project description:BackgroundWhile desensitization and sustained unresponsiveness (SU) have been shown with egg oral immunotherapy (OIT), the benefits of baked egg (BE) therapy for egg allergy have not been well studied.ObjectivesThis study sought to evaluate the safety and efficacy of BE ingestion compared with egg OIT in participants allergic to unbaked egg but tolerant to BE.MethodsChildren who are BE-tolerant but unbaked egg reactive ages 3 to 16 years were randomized to 2 years of treatment with either BE or egg OIT. Double-blind, placebo-controlled food challenges were conducted after 1 and 2 years of treatment to assess for desensitization, and after 2 years of treatment followed by 8 to 10 weeks off of treatment to assess for SU. Mechanistic studies were conducted to assess for immune modulation. A cohort of participants who are BE-reactive underwent egg OIT and identical double-blind, placebo-controlled food challenges as a comparator group.ResultsFifty participants (median age 7.3 years) were randomized and initiated treatment. SU was achieved in 3 of 27 participants assigned to BE (11.1%) versus 10 of 23 participants assigned to egg OIT (43.5%) (P = .009). In the BE-reactive comparator group, 7 of 39 participants (17.9%) achieved SU. More participants who are BE-tolerant withdrew from BE versus from egg OIT (29.6% vs 13%). Dosing symptom frequency in participants who are BE-tolerant was similar with BE and egg OIT, but more frequent in participants who are BE-reactive. Egg white-specific IgE, skin testing, and basophil activation decreased similarly after BE and egg OIT.ConclusionsAmong children allergic to unbaked egg but tolerant to BE, those treated with egg OIT were significantly more likely to achieve SU than were children ingesting BE.
Project description:We have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2009", available at http://www.waojournal.org. Namely, these comprise: "Mechanisms of sublingual immunotherapy;" "Clinical efficacy of sublingual immunotherapy" - reporting all the data of all controlled trials published after 2009; "Safety of sublingual immunotherapy" - with the recently published Grading System for adverse reactions; "Impact of sublingual immunotherapy on the natural history of respiratory allergy" - with the relevant evidences published since 2009; "Efficacy of SLIT in children" - with detailed analysis of all the studies; "Definition of SLIT patient selection" - reporting the criteria for eligibility to sublingual immunotherapy; "The future of immunotherapy in the community care setting"; "Methodology of clinical trials according to the current scientific and regulatory standards"; and "Guideline development: from evidence-based medicine to patients' views" - including the evolution of the methods to make clinical recommendations.Additionally, we have added new chapters to cover a few emerging crucial topics: "Practical aspects of schedules and dosages and counseling for adherence" - which is crucial in clinical practice for all treatments; "Perspectives and new approaches" - including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, "Raising public awareness about sublingual immunotherapy", as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail.
Project description:BackgroundBronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control.MethodsMethacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT.ResultsMethacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome.ConclusionBHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.
Project description:BackgroundThere are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy.ObjectiveWe sought to investigate the safety, clinical effectiveness, and immunologic changes with SLIT in children with peanut allergy.MethodsIn this double-blind, placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge.ResultsEighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median, 1,710 vs 85 mg; P = .011). Mechanistic studies demonstrated a decrease in skin prick test wheal size (P = .020) and decreased basophil responsiveness after stimulation with 10(-2) μg/mL (P = .009) and 10(-3) μg/mL (P = .009) of peanut. Peanut-specific IgE levels increased over the initial 4 months (P = .002) and then steadily decreased over the remaining 8 months (P = .003), whereas peanut-specific IgG4 levels increased during the 12 months (P = .014). Lastly, IL-5 levels decreased after 12 months (P = .015). No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-γ production.ConclusionPeanut SLIT is able to safely induce clinical desensitization in children with peanut allergy, with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance.
Project description:IntroductionEgg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo.Methods and analysis80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms-probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group.Ethics and disseminationThis study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.Trial registration numberACTRN12619000480189.