Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial.

Context: While oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans. Methods: In this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges. Discussion: This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.

Simulation-based education to improve management of refractory anaphylaxis in an allergy clinic.

BACKGROUND: High-fidelity simulations based on real-life clinical scenarios have frequently been used to improve patient care, knowledge and teamwork in the acute care setting. Still, they are seldom included in the allergy-immunology curriculum or continuous medical education. Our main goal was to assess if critical care simulations in allergy improved performance in the clinical setting. METHODS: Advanced anaphylaxis scenarios were designed by a panel of emergency, intensive care unit, anesthesiology and allergy-immunology specialists and then adapted for the adult allergy clinic setting. This simulation activity included a first part in the high-fidelity simulation-training laboratory and a second at the adult allergy clinic involving actors and a high-fidelity mannequin. Participants filled out a questionnaire, and qualitative interviews were performed with staff after they had managed cases of refractory anaphylaxis. RESULTS: Four nurses, seven allergy-immunology fellows and six allergy/immunologists underwent the simulation. Questionnaires showed a perceived improvement in aspects of crisis and anaphylaxis management. The in-situ simulation revealed gaps in the process, which were subsequently resolved. Qualitative interviews with participants revealed a more rapid and orderly response and improved confidence in their abilities and that of their colleagues to manage anaphylaxis. CONCLUSION: High-fidelity simulations can improve the management of anaphylaxis in the allergy clinic and team confidence. This activity was instrumental in reducing staff reluctance to perform high-risk challenges in the ambulatory setting, thus lifting a critical barrier for implementing oral immunotherapy at our adult center.

Specific IgE to Total IgE Ratio Does Not Improve Peanut Diagnostic Accuracy in Adults.

BACKGROUND: Peanut specific IgE (sIgE) can lead to false-positive results. OBJECTIVE: We aimed to assess whether peanut sIgE to total IgE (tIgE) ratio improves accuracy in predicting clinical reactivity to peanut compared to peanut sIgE alone, which has not been explored in the adult population so far. METHOD: A retrospective chart review was performed for adults who underwent peanut oral food challenge (OFC) and/or oral immunotherapy (OIT) at the Centre Hospitalier de l'Université de Montréal's allergy clinic between January 2017 and July 2021. Patients with positive peanut OFC and/or undergoing OIT were considered peanut-allergic. Patients with negative OFC were considered peanut-tolerant. Peanut sIgE to tIgE ratios were calculated and performance characteristics of the sIgE to tIgE ratio were compared to sIgE alone by using receiver operator characteristics curves. RESULTS: Forty-two patients were included (52% male) with a median age of 26 years (range 14-54). Forty-five percent had atopic dermatitis. Median sIgE levels were 2.64 kUA/L (range 0.1-100), median tIgE levels were 154 kUA/L (range 19-3,400), and median sIgE to tIgE ratio was 0.66% (range 0.04-38.3). Twenty-four patients (57%) were classified as peanut-allergic and 18 (43%) as peanut tolerant. The area under the curve for peanut sIgE was 0.921 compared to 0.926 for peanut sIgE/tIgE (p not statistically significant). CONCLUSIONS: We found that there was no significant benefit in using peanut sIgE to tIgE ratio over sIgE alone to predict peanut reactivity in an adult population. Larger prospective studies are needed to further confirm these findings.

Recent advances in the diagnosis and management of tree nut and seed allergy.

PURPOSE OF REVIEW: Tree nut (TN) and seed allergies are frequent, and their prevalence appears to be on the rise. Allergic reactions associated with these foods are more frequently severe, and these allergies tend to persist into adulthood, consequently affecting quality of life. In this review, we summarize recent advances in diagnostic modalities and management strategies for TN/seed-allergic patients. RECENT FINDINGS: Clinical manifestations of TN and seed allergy range from asymptomatic sensitization to severe anaphylactic reactions. The use of emerging diagnostic tools such as component resolved diagnostics (CRD) and the basophil activation test (BAT) can help better predict clinical reactivity, the latter being currently reserved for research settings. Strict avoidance of all TN is generally not required, as most patients can tolerate select TN despite co-sensitization. Oral immunotherapy (OIT) is a promising alternative treatment instead of complete avoidance of culprit allergens, as it can safely increase the allergy threshold. SUMMARY: Our recent understanding of co-reactivity between various TN and seeds has shaped management opportunities, including select TN introduction and optimization of OIT, two strategies which may improve quality of life. There is a need for better minimally invasive diagnostic methods for TN and seed allergy, with CRD and BAT being promising tools.

Mapping the Food Allergy Quality of Life Questionnaire Parent Form onto the Short-Form Six-Dimensions version 2.

BACKGROUND: The Food Allergy Quality of Life Questionnaire Parent Form (FAQLQ-PF) is the most widely used quality of life questionnaire in food allergy. The objective of this study was to develop a mapping algorithm to convert FAQLQ-PF scores into health state utilities. METHODS: The Short-Form Six-Dimensions version 2 (SF-6Dv2) and FAQLQ-PF questionnaires were collected from an academic center oral immunotherapy referral cohort. Utility estimates were derived from the SF-6Dv2 using the food allergy preference set. Candidate mapping algorithm models were developed using seven regression methods starting from either the total average score, the average scores of each of the three domains or the individual item scores of FAQLQ-PF. The process was repeated twice, including only section A, common to all age groups, or including all age-applicable sections of the FAQLQ-PF. The mean absolute error (MAE) and root mean squared error (RMSE) were used to select the best fitting model. An independent cohort from a previous national online survey was used for external validation. RESULTS: In the index cohort, 1000 of 1257 respondents had completed both questionnaires. The lowest MAE (0.0791) and RMSE (0.1020) were recorded when entering individual item scores in a categorical regression model. The model including only FAQLQ-PF section A was found to be most consistent when tested in the external validation cohort (n = 248) (MAE of 0.0898). CONCLUSION: The FAQLQ-PF was mapped onto SF-6Dv2 utilities with good predictive accuracy in two independent cohorts. This will enable calculation of health utility for cost-effectiveness analyses in food allergy.

Evaluation of Adverse Reactions to Vaccines.

The development and widespread use of vaccination over the past centuries has been the single most impactful intervention in public health, by effectively preventing morbidity and mortality from infectious diseases. Vaccination is generally well tolerated in the vast majority of the population, and the benefits of vaccination largely outweigh the risk of severe adverse events in the majority of patients. Vaccine hesitancy can be a significant concern and lead to infectious disease outbreaks. All health care providers play an important role in maintaining public confidence in vaccines because their attitude and knowledge is often critical in facilitating acceptance of a vaccine. The purpose of this review is to first, provide an understanding of the basic concepts that are relevant to vaccine pharmacovigilance, and secondly, to provide an overview and discuss management of both immune and nonimmune adverse events after vaccination.

Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge.

BACKGROUND: Abdominal pain is a frequent symptom of IgE-mediated food allergy with limited therapeutic options. Visceral smooth muscle cell relaxation can be induced through beta-adrenergic stimulation. OBJECTIVE: To evaluate the efficacy of inhaled salbutamol empirically used to relieve abdominal pain caused by IgE-mediated allergic reactions at 1 center. METHODS: All double-blind placebo-controlled food challenges to peanut performed at 1 center between 2016 and 2021 were reviewed to identify patients who presented abdominal pain as part of their reaction. The primary outcome measure was the delay between the initiation of therapy and improvement of abdominal pain. It was compared between patients who had received inhaled salbutamol as part of their treatment and those who did not. Cox regression was performed to control for potential confounders. RESULTS: During the study period, 186 positive double-blind placebo-controlled food challenges were performed, including 126 for peanut allergy. Of these, 77 were treated for abdominal pain and 57 met the criteria for inclusion in the study. Patients who received salbutamol improved significantly faster (median, 12.5 minutes) than those who did not (median, 65 minutes) (χ2 = 45; P < .0001). In Cox regression, the administration of salbutamol and emesis were found to increase the rate of improvement by a hazard ratio of 11.35 (95% CI, 5.40-23.9; P < .0005) and 4.00-fold (95% CI, 1.90-8.42; P < .0005), respectively. CONCLUSIONS: This retrospective study provides hypothesis-generating evidence for the use of salbutamol in the treatment of IgE-mediated abdominal pain. Further investigation in a double-blind randomized controlled trial is warranted.

Practical challenges in oral immunotherapy resolved through patient-centered care.

Oral immunotherapy (OIT) is now widely recognized as a valid option for the management of IgE-mediated food allergies. However, in real-life practice, OIT can lead to a variety of unique situations where the best course of action is undetermined. In patient-centered care, individual patient preferences, needs and values, should guide all clinical decisions. This can be achieved by using shared-decision making and treatment customization to navigate areas of uncertainty in a way that is responsive to patient's needs and preferences. However, in the context of OIT, lack of awareness of potential protocol adaptability or alternatives can become a barrier to treatment personalization. The purpose of this article is to review the theoretical bases of patient-centered care and shared decision-making and their practical implication for the patient-centered delivery of OIT. Clinical cases highlighting common challenges in real-life OIT practice are presented along with a discussion of potential personalized management options to be considered. While the practice of OIT is bound to evolve as additional scientific and experiential knowledge is gained, it should always remain rooted in the general principles of patient-centered care.

Beta-2 Agonists May be Superior to Epinephrine to Relieve Severe Anaphylactic Uterine Contractions.

BACKGROUND: Uterine contractions are recognized as a potential manifestation of anaphylaxis, but literature on their proper management is limited. It is widely recognized that anaphylactic reactions can cause uterine contractions, but little is known about their optimal management. OBJECTIVE: Review potential treatments for painful uterine contractions associated with anaphylaxis or mast cell activation. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed, Embase, and Cochrane were searched in English, French, and Spanish for reports of uterine anaphylaxis published up until July 2020. The search strategy used a combination of Boolean operators and included the following Medical Subject Heading terms and keywords: hypersensitivity; anaphylaxis; mastocytosis; uterus; uterine contraction; pelvic pain; labor, obstetric; labor, premature; and endometriosis. RESULTS: This systematic review identified 19 studies reporting on 31 cases of painful uterine contractions occurring during anaphylaxis or other events associated with mast cell activation. Nine patients were pregnant. We present 2 additional cases in nonpregnant women, one associated with an oral food challenge and the other associated with oral food desensitization. The most frequent triggers were subcutaneous immunotherapy (14 cases), food (6 cases), and drugs (4 cases). Uterine cramps were associated with systemic symptoms in 24 cases and lasted on average for 2.4 hours. Pretreatment with antihistamines and montelukast generally failed to prevent recurrence, but nonsteroidal anti-inflammatory drugs were used successfully in some reports. Response to intramuscular epinephrine was inconsistent. Data from ex vivo models indicate that epinephrine may paradoxically contribute to uterine contractions through alpha-receptor activity. A small number of cases showed good response to beta-2 agonists. CONCLUSIONS: There is a lack of quality data on painful uterine contractions occurring in the context of anaphylactic reactions and on their optimal management. In the absence of counterindication, use of a beta-2 agonist and premedication with nonsteroidal anti-inflammatory drugs could be the preferred options.