Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Age-Related Food Aversion and Anxiety Represent Primary Patient Barriers to Food Oral Immunotherapy.

BACKGROUND: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective. OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians. METHODS: A survey in Canada and the United States involved families currently enrolled in food OIT programs. RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001). CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.

Validated anxiety assessments among pediatric patients with peanut allergy on oral immunotherapy.

BACKGROUND: Although efficacy, safety, and quality of life measures associated with peanut oral immunotherapy (OIT) have been studied, the relationship between peanut OIT and clinical anxiety has not yet been evaluated. The latter is important to help providers and families have an improved shared medical decision discussion around the benefits of initiating OIT. OBJECTIVE: To investigate the relationship between undergoing OIT and anxiety in patients with peanut allergy. METHODS: In this prospective cross-sectional cohort study, using validated and age-appropriate anxiety scales administered with electronic survey questionnaires, we used generalized linear regressions to compare anxiety between patients undergoing OIT and similar patients with peanut allergy but not on OIT (controls). RESULTS: In the younger cohort (<7 years, n = 80), there was generally a low prevalence of diagnosable anxiety across patients on OIT and controls. In the older cohort (>7 years, n = 125), there was a higher prevalence of anxiety but no clinically meaningful difference between anxiety scores of patients on OIT and controls. In the older cohort, patients with asthma were more likely to have higher mean anxiety scores (P = .04), as were female patients compared with male patients (P = .004). A subanalysis of separation anxiety scores in the older cohort revealed that younger age (7-12 years vs >12 years, P < .001), non-White race (P = .04), and eczema (P = .02) were found to be meaningful predictors of higher scores. A subanalysis of social anxiety on the older cohort pointed toward non-White race as a meaningful predictor of higher scores (P < .02). CONCLUSION: The clinical implications of these findings suggest that allergists should particularly consider screening children with food allergy for anxiety and anxiety subtypes among patients who are non-White, female, or have asthma.

Clinical experience with sesame oral immunotherapy and a quality-of-life assessment.

Background: Allergic reactions to sesame have increased in prevalence in the United States. Sesame oral immunotherapy (OIT) is an emerging management strategy. Few reports assessed the benefits and risks of sesame OIT in children with sesame allergy. Objective: To study the adverse events and quality of life (QoL) on sesame OIT in a U.S. population. Methods: Twenty-three patient charts were retrospectively reviewed from 2017 to 2020. The patients received a validated Food Allergy Quality of Life Questionnaire and a survey on adverse reactions during maintenance therapy. Patients who were 8.5 ± 4.7 years of age (30% girls and 70% boys) with a documented history of sesame allergy and who had undergone sesame OIT were reviewed. Results: The buildup phase was 293.7 ± 87.1 days. Twenty-one of the 23 patients (91.3%) reached maintenance therapy. Twenty-one patients (91.3%) had at least one gastrointestinal reaction; 18 (78.3%) had at least one cutaneous reaction; 6 (26%) had at least one respiratory reaction. Age raised the odds of gastrointestinal reactions more than fivefold (odds ratio [OR] 5.653 (95% confidence interval [CI], 2.409 - 13.269); p = 0.0009). Asthma boosted the odds of respiratory reactions of more than ninefold (OR 9.206 [95% CI, 1.535 - 55.211]; p = 0.0187). Female gender increased the odds of having a respiratory reaction by more than sevenfold (OR 7.545 [95% CI, 1.207 - 47.153]; p = 0.0330). Asthma amplified the odds of cutaneous reactions (OR 11.725 [95% CI, 2.390 - 57.517]; p = 0.0053). Three patients ultimately discontinued therapy. Food-related anxiety (-0.773) and social/dietary limitation (-0.687) improved significantly in QoL. Conclusion: Sesame OIT may be safe and easily adaptable to private practice and significantly improves QoL. Further prospective studies would be helpful to fully assess these relationships.

A practical focus on sesame allergy and a brief review of other seed allergies.

Although seed allergies are relatively rare, sesame allergy has been increasing worldwide and is typically persistent in most patients. Because allergen labeling laws, until just recently, have not required the declaration of sesame as a major allergen, there is a clear need to better understand and potentially treat this food allergy. Although blood and skin prick testing for sesame have limited predictive value, this improves with the use of component diagnostics and skin-prick test with fresh sesame. A thorough history and oral food challenge should be used to diagnose sesame allergy. Treatment of sesame allergy with oral immunotherapy has been demonstrated to be safe and effective in case reports, and in at least one controlled study with a published sesame oral immunotherapy protocol. There is minimum literature with regard to management of other seed allergies.

An Approach to the Office-Based Practice of Food Oral Immunotherapy.

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes.

Validation of inducible basophil biomarkers: Time, temperature and transportation.

BACKGROUND: The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician. METHODS: Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions. RESULTS: The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory. CONCLUSIONS: It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range.

Community Private Practice Clinical Experience with Peanut Oral Immunotherapy.

BACKGROUND: Peanut oral immunotherapy is an effective treatment for desensitizing peanut-allergic patients, but the frequency of adverse reactions has limited its widespread use. OBJECTIVE: To review the frequency of adverse reactions that patients on peanut oral immunotherapy experience during build-up and maintenance phases and explore factors that may contribute to adverse events. METHODS: A retrospective chart review of children and adults with peanut allergy undergoing peanut oral immunotherapy at the New England Food Allergy Treatment Center in West Hartford, Conn was performed. Data on patient demographics, allergic profile, peanut allergy testing, and details of reactions in build-up and maintenance phases were collected. A systemic reaction was defined as one of the following: (1) severe reaction involving 1 system, such as generalized hives and/or angioedema; (2) 2 or more of the following symptoms: cutaneous or oral, respiratory, or gastrointestinal symptoms; (3) drop in blood pressure; or (4) need for epinephrine. RESULTS: Data were available on 783 patients aged 3.5 to 48.3 years. During buildup, 78 patients (10%) experienced at least 1 systemic reaction, 660 (84%) at least 1 gastrointestinal adverse event, 369 (47%) at least 1 cutaneous adverse event, and 157 (20%) at least 1 respiratory adverse event. Thirty-four patients (4%) required epinephrine during buildup. Six hundred ninety-seven patients (89%) completed buildup and progressed to maintenance. During maintenance, 131 patients (19%) experienced at least 1 systemic reaction, 190 (27%) at least 1 gastrointestinal adverse event, 104 (15%) at least 1 cutaneous adverse event, and 50 (7%) at least 1 respiratory adverse event. Seventy-four patients (11%) required epinephrine during maintenance. None of the adverse events required hospitalizations, and there were no mortalities. Nine patients (1%) were diagnosed with eosinophilic esophagitis during buildup or maintenance. Increasing pretreatment peanut specific IgE levels were associated with increased odds of a systemic reaction during buildup. Increasing age, pretreatment peanut specific IgE level, and a systemic reaction in buildup were associated with increased odds of a systemic reaction during maintenance. CONCLUSIONS: Peanut oral immunotherapy may be an effective and safe treatment for carefully selected peanut-allergic patients under the guidance of experienced providers. Specific patient characteristics and immunologic factors may help predict adverse events.

Oral immunotherapy for peanut allergy: multipractice experience with epinephrine-treated reactions.

BACKGROUND: Peanut allergy creates the risk of life-threatening anaphylaxis that can disrupt psychosocial development and family life. The avoidance management strategy often fails to prevent anaphylaxis and may contribute to social dysfunction. Peanut oral immunotherapy may address these problems, but there are safety concerns regarding implementation in clinical practice. OBJECTIVE: The purpose of this report is to communicate observations about the frequency of epinephrine-treated reactions during peanut oral immunotherapy in 5 different allergy/immunology practices. METHODS: Retrospective chart review of peanut oral immunotherapy performed in 5 clinical allergy practices. RESULTS: A total of 352 treated patients received 240,351 doses of peanut, peanut butter, or peanut flour, and experienced 95 reactions that were treated with epinephrine. Only 3 patients received 2 doses of epinephrine, and no patient required more intensive treatment. A total of 298 patients achieved the target maintenance dose for a success rate of 85%. CONCLUSION: Peanut oral immunotherapy carries a risk of systemic reactions. In the context of oral immunotherapy, those reactions were recognized and treated promptly. Peanut oral immunotherapy may be a suitable therapy for patients managed by qualified allergists/immunologists.

Effect of oral immunotherapy to peanut on food-specific quality of life.

BACKGROUND: Peanut allergy is an increasingly common problem for which the only available treatment is avoidance. Oral immunotherapy has shown promise for increasing tolerance of peanut in allergic children. Food allergy has an effect on the quality of life of children and adolescents. OBJECTIVE: To measure the effect of oral immunotherapy to peanut on food-specific quality of life in children and adolescents. METHODS: One hundred patients (5-18 years of age) were enrolled in an open trial of peanut oral immunotherapy. Parents of children 5 to 12 years old, children 8 to 12 years old, and teenagers completed validated, age-specific, food-related quality-of-life surveys before and after peanut oral immunotherapy. RESULTS: Ninety patients (76 children 5-12 years old and 14 adolescents 13-18 years old) achieved the maintenance daily dose of 450 mg of peanut protein. A significant improvement in quality of life was found in all survey domains (allergen avoidance, dietary restriction, risk of accidental exposure, emotional impact, food-related anxiety, and social and dietary limitations) with the exception of the emotional impact domain on the adolescents' survey. Quality of life significantly improved (P < .02) on all 30 questions when parents assessed their children 5 to 12 years old. When children (8-12 years old) and teens assessed themselves, quality of life improved (P < .05) on 22 of 24 questions and 12 of 18 questions, respectively. CONCLUSION: Peanut oral immunotherapy significantly improves food-specific quality of life.