Allergen-specific IL-4+ and IL-13+ CD4+ cells (Type 2 cells) are essential for helping B cells class-switch to IgE and establishing an allergic milieu in the gastrointestinal tract. The role of T cells in established food allergy is less clear.

We examined the food allergen-specific T cell response in participants of two food allergen immunotherapy (IT) trials to assess the relationship of the T cell response to clinical phenotypes including response to IT.

Blood was obtained from 84 peanut-allergic and 142 egg-allergic participants who underwent double-blind placebo-controlled food challenges. Peanut and egg-responsive T cells were identified by CD154 upregulation after stimulation with the respective extract. Intracellular cytokines and chemokine receptors were also detected. The response to peanut epicutaneous immunotherapy (CoFAR6, 49 participants receiving EPIT) and egg oral immunotherapy or baked egg diet (CoFAR7, 92 participants) was monitored over time.

Peanut-specific Type 2 and CCR6+ T cells were negatively correlated with each other, and differently associated with immune parameters including specific IgE and basophil activation test. At baseline, Type 2 cells, but not CCR6+ cells, were predictive of clinical parameters including successfully consumed dose of peanut and baked egg tolerance. Exposure to peanut or egg immunotherapy was associated with a decrease in Type 2 cell frequency. At baseline, high egg-specific Type 2 cell frequency was the most predictive immune feature of oral immunotherapy failure.

Food-specific Type 2 T cells at baseline are informative of threshold of reactivity and response to immunotherapy.

Clinical trials of allergen immunotherapy (AIT) may require up to 5 years to complete. These lengthy trials may be complicated by high and potentially differential dropouts, especially among participants who perceive that they are receiving placebo. We propose a three-stage design in which the placebo group in Stage 1 crosses over to receive active treatment in Stage 2. In Stage 3, AIT is discontinued to determine whether benefit is maintained post treatment. We apply inferential statistics to support the three-stage design for clinical trials to determine clinical efficacy, treatment response over time, and sustained response to AIT.

The proposed framework constitutes a series of hypothesis tests for comparing treatment responses at the end of each stage. A simulation study was performed to illustrate the statistical properties under varying statistical missing mechanisms and effect sizes.

The statistical properties in terms of bias and statistical power were consistent with what are expected from conventional analyses. Specifically, the extent of bias depended on the missing mechanism and magnitude. The statistical powers were largely driven by effect and sample sizes as well as prespecified success margins. As an illustration, assuming relative treatment differences of 25% and stagewise dropout rate of 15%, a sample size of 200 per group may achieve 93% power to demonstrate a treatment effect and 60% power to demonstrate a maintained response post-treatment.

Inferential statistics support our proposed study design for evaluating benefits of AIT over time and inform clinical understanding and decisions.

Reducing the psychosocial impact of food allergy (FA) represents a top patient-centered research priority. This priority recognizes that psychosocial impact is an important outcome of current FA therapies (eg, oral immunotherapy), as well as interventions aimed at improving overall quality of life and illness adaptation. Reliable and valid measurement is a necessary prerequisite to developing and evaluating current and emerging FA therapies and potential changes in psychosocial impact.

In this systematic review, we applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate available parent report measures assessing the psychosocial impact of pediatric IgE mediated FA.

The systematic search yielded 64 articles involving 13 unique measures. Measures were evaluated through the lens of the Patient Reported Outcomes Measurement Information System (PROMIS) guidelines. Findings indicated that available measures show some evidence of reliability and validity; however, none completely adhere to PROMIS guidelines for measure development.

Results highlight a continued need to dedicate research to develop a measurement approach that assesses the full range of psychosocial impact that parents and families may experience as a result of FA, as well as serve as a research outcome as the field continues to develop effective treatments, including immunotherapy.

Compare the cost-effectiveness of subcutaneous immunotherapy (SCIT) and aqueous sublingual immunotherapy (SLIT) as treatment modalities for adult patients with allergic rhinitis and conjunctivitis who undergo testing and qualify for allergen immunotherapy (AIT).

A systematic review was performed to identify key statistics for analysis, including the compliance and efficacy rates for each treatment. The body of literature on this topic is highly heterogeneous, so ranges were obtained and assumptions stated clearly where they were made. Charges were derived from average commercial payor charges from a single hospital institution. A hypothetical 100 patients are examined for the study.

A cost-effectiveness sensitivity analysis was then performed using a decision tree model to compare the modalities. A sensitivity and threshold analysis was then performed to assess the strength of recommendations after identifying results at baseline.

Assuming an 80% compliance rate with allergen immunotherapy and an estimated efficacy (assumed to be clinically significant improvement in symptoms) of 70% for SLIT and 80% for SCIT, at the 12-month mark, the baseline total cost to the payor of SLIT per successful treatment outcome is $1196 while the charge of SCIT per successful treatment outcome is $2691. Our analysis favors SLIT as the more cost-effective modality per successful outcome.

When compared to SCIT, SLIT is economically favorable and should be considered the financially conscious option for patients with >40% adherence to therapy.

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders that induces immunological tolerance through administration of specific allergens. Studies on AIT for subcutaneous route are in abundance; however, the efficacy of AIT in tablet form through sublingual route has not been well elucidated. The present prospective, parallel-group, controlled study sought to compare the efficacy of sublingual immunotherapy (SLIT) tablets with pharmacotherapy (PT) in 332 house dust mite (HDM)-specific allergic asthma and/or rhinitis patients over a period of 3 years. Patients were followed up for a 6 month run-in period and then randomly stratified as those who would receive SLIT, SLIT in addition to PT (SLIT+PT), and PT alone. AIT was administered in the form of sublingual tablets. Symptom and medication scores were measured every 3 months. In vitro evaluation of serum total and HDM specific immunoglobulin E (HDM sIgE) levels was carried out every 3 months, whereas in vivo skin prick test was performed annually for 3 years. Our study demonstrated sustained clinical improvement, reduction in inhaled corticosteroid (ICS) dose and duration as well as prevention from development of neosensitization to other aero allergens in HDM-allergic asthmatics and/or rhinitis patients treated with 3 years SLIT. Despite a remarkable clinical improvement with AIT, we observed that SLIT did not significantly change the skin reactivity to HDM at 3 years and there was no significant change in the ratio of serum total and HDM sIgE. Given the immune and disease modifying effects of AIT in allergic diseases, the present study supports the notion of its sublingual mode being an effective long-term immunomodulator in HDM-sensitized nasobronchial allergies.

Subcutaneous immunotherapy (SCIT) has been used for treating local allergic rhinitis (LAR) patients. However, the clinical efficacy and safety were still questioned.

This study was designed to estimate the efficacy and safety of SCIT for treating LAR patients through meta-analysis.

We systemically searched MEDLINE, Cochrane Library, and Embase publications. Randomized, double-blind, clinical trials for the efficacy and safety of Allergen Immunotherapy (AIT) for LAR were included. A meta-analysis of 4 clinical endpoints (combined symptom and medication scores [CSMS], symptom scores [SS], medication scores [MS] and rhinoconjunctivitis quality of life questionnaire [RQLQ]) and adverse events (AEs)) was performed after bias and heterogeneity assessments. The immunologic response results were summarized.

Four RCTs with 134 patients were included. Four studies for analyzing primary outcomes (CSMS, SS, MS) and AEs, three for RQLQ results. The results indicated an important significant difference between SCIT and placebo groups, list as follows: CSMS (SMD = -2.42, 95% CI: -3.60 to -1.25, P < .0001), SS (SMD = -2.08, 95% CI -3.68 to -0.48, P = .01), MS (SMD = -1.43, 95% CI: -2.65 to -0.21, P = 0.02), RQLQ (SMD = -0.70, 95% CI -1.29 to -0.12, P = .02), Local AEs (RR = 4.13, 95% CI 1.08 to 15.77, P = .04). For immunologic response, significantly increased serum sIgG4 levels and improvements of allergen tolerance was observed after SCIT.

Our meta-analysis suggests that SCIT has a significant effect on improving symptoms and reducing medicine consumption for LAR patients. Larger and multicenter clinical trials are needed to clarify the safety and long-term efficacy.

Local allergic rhinitis (LAR) is a phenotype of chronic rhinitis exhibiting a local Th2-driven inflammation without positive clinical markers of atopy. Immunomodulatory effects of allergen-specific immunotherapy (AIT) induce allergen-specific tolerance. However, AIT is not well-recognized as a treatment for LAR.

Systematic search on six electronic databases and registries was performed. Experimental and observational studies of AIT for LAR patients were retrieved. The primary outcomes were symptom score, medication score, combined symptom medication score, and disease-specific quality of life. Secondary outcomes were serum specific(s) IgG4, sIgE, and adverse events.

Four double-blind randomized controlled trials (156 patients) from two research units assessed the effects of subcutaneous immunotherapy (SCIT). Compared with placebo, SCIT showed significant reductions in symptom score, medication score, combined symptom medication score, disease specific quality of life, and an increase in serum sIgG4. There was no significant change in serum sIgE. Likewise, two observational studies (one using SCIT and one using sublingual immunotherapy) improved post-therapeutic symptom score. No studies assessed the effects after discontinuation of treatment. AIT was safe without serious adverse events.

AIT has beneficial effects and safe for LAR. Its effects are restricted to studies with short-term follow-up. AIT may be considered in LAR patients.

The number of hospitalizations due to an anaphylactic reaction to food is continuously increasing. Therefore, there is an urgent need to seek effective therapy. Currently, the only way to treat food allergies is to avoid allergens and to administer intramuscular epinephrine if an accidental allergen intake occurs. The only causal therapeutic strategy is specific oral immunotherapy. An increasing amount of data confirms this therapy's effectiveness and safety, but the results remain inconclusive due to the lack of long-term follow-up. In this state-of-the art review, we briefly summarize the latest placebo-controlled randomized-controlled trials on oral immunotherapy to treat food allergy. During the paper's review, we asked the following questions: does the therapy permanently increase the amount of allergen consumed without symptoms? Does it significantly increase or decrease the occurrence of severe systemic reactions - requiring the administration of epinephrine or hospitalization? Many authors describe outcomes such as an increase in the amount of allergen that can be safely ingested; however, significant clinical benefits such as decreased hospitalizations or anaphylaxis incidence are rarely included in the results. To date, there is no unified protocol of therapy, which makes comparisons between studies difficult because of significant differences in types, doses, and routes of administration of the allergen, timeline for updosing and maintenance, duration of the therapy, and primary outcomes of OIT.

Cow's milk allergy (CMA) is one of the most common IgE-dependent food allergies in children. Some children develop severe and persistent CMA, with near-fatal reactions after exposure to trace amounts of cow's milk (CM). Because milk and dairy products are included in various processed food products, it is difficult to completely remove milk, which negatively affects the quality of life of children with CMA. Oral immunotherapy (OIT) can alleviate food allergen-induced anaphylaxis under continuous ingestion of a little of the causative food. Children with severe CMA may benefit from OIT, but the treatment requires a long time and poses a risk of anaphylaxis. Moreover, in recent years, new therapies, including omalizumab, sublingual immunotherapy, and epicutaneous immunotherapy, have played the role of optional OIT. In this review, we present the current methods of and other attempts at OIT, and discuss OIT for safely treating CMA.

Subcutaneous immunotherapy (SCIT) is a classic form of allergen specific immunotherapy that is used to treat birch pollen induced allergic asthma. To investigate the underlying molecular mechanisms of SCIT, we aimed to profile lung samples to explore changes in the differential proteome before and after SCIT in mice with allergic asthma. Fresh lungs were collected from three groups of female BALB/c mice: 1) control mice, 2) birch pollen-induced allergic mice, and 3) birch polleninduced allergic mice with SCIT. Tandem mass tag (TMT) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the lung proteome in the mice. Ingenuity pathway analysis (IPA) and Gene Ontology (GO) classification analysis were applied to identify differentially expressed proteins (DEPs) and crucial pathways. The screened DEPs were validated by immunohistochemistry analysis. A total of 317 proteins were upregulated and 184 proteins were downregulated in the asthma group compared to those of the control group. In contrast, 639 DEPs (163 upregulated and 456 downregulated proteins) were identified after SCIT in comparison with those of the asthma group. Among the 639 DEPs, 277 proteins returned to similar levels as those of the relative nonasthma condition. Bioinformatic analysis revealed that the 277 proteins played a significant role in the leukocyte extravasation signaling pathway. The leukocyte extravasation signaling pathway and related DEPs were of crucial importance in birch pollen SCIT.