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.

Risk factors associated with safety of preschool peanut oral immunotherapy.

Background: An understanding of how patient characteristics such as age, baseline peanut-specific IgE, and atopic comorbidities may influence potential safety outcomes during peanut oral immunotherapy (P-OIT) could aid in shared decision making between clinicians and patient families. Objective: This study explored the relationship between baseline patient characteristics and reactions during P-OIT using a large sample size to better understand potential risk factors influencing P-OIT safety. Methods: Data were obtained from the Food Allergy Immunotherapy (FAIT) registry, which collects real-world OIT data from community and academic allergy clinics across Canada. Multivariable logistic regression modeling was performed to examine the relationship between baseline patient characteristics and reactions during P-OIT. Multiple imputation was applied to reduce potential bias caused by missingness and to maximize the use of available information to preserve statistical power. Results: Between April 2017 and June 2021, a total of 653 eligible patients initiated P-OIT. Multivariable regression analysis showed pre-OIT grade 2+ initial reaction (odds ratio [OR] = 1.33, 95% confidence interval [CI] 1.10, 1.61), allergic rhinitis (OR = 1.60, 95% CI 1.08, 2.38), older age (OR = 1.01, 95% CI 1.00, 1.02), and higher baseline peanut-specific IgE (OR = 1.02, 95% CI 1.02, 1.03) were associated with grade 2+ reaction during P-OIT after adjusting for potential risk factors. Conclusion: Our study identified several clinically important risk factors for grade 2+ reactions during P-OIT: pre-OIT grade 2+ initial reaction, allergic rhinitis, older age, and higher baseline peanut-specific IgE. These results highlight the need for individualized risk stratification for OIT.

Using the canadian egg ladder in children with food protein-induced enterocolitis syndrome: a case series.

BACKGROUND: Current management of food protein-induced enterocolitis syndrome (FPIES) involves strict avoidance of the offending food for 12-18 months, followed by oral food challenge (OFC) under physician supervision. OFCs are resource-intensive and there is a lack of a universal standardized protocol for FPIES. Prolonged avoidance may increase the risk of IgE-mediated allergy, particularly in atopic patients. Food ladders have shown success in promoting accelerated tolerance in patients with IgE-mediated allergy. Our case series evaluated the safety of use of the Canadian Egg Ladder in patients with mild-to-moderate FPIES to egg. METHODS: From May 2020 to November 2021, patients with mild-to-moderate FPIES to egg, defined as no history of lethargy or intravenous fluid administration, were started on the Canadian Egg Ladder. Instructions for advancing up the ladder were identical to using the Canadian Egg Ladder in patients with IgE-mediated allergy. Patients were followed every 3-6 months, at which time information was collected regarding progression up the ladder, symptoms while on treatment and interventions required. Treating allergists completed a survey to capture baseline demographic characteristics and prior tolerance to egg. Descriptive statistics were analyzed using MS Excel. RESULTS: Twenty-one patients with mild-to-moderate FPIES were started on the Canadian Egg Ladder. Median age at initiation of the ladder was 10 months (IQR, 9-11). Nineteen (90.5%) patients completed the ladder, tolerating a serving size amount of cooked egg, over a median duration of 7 month (IQR, 4-9 months). Four patients (19.0%) had mild symptoms including vomiting (9.5%), pallor (9.5%), belching (4.8%), irritability (4.8%) and small spit up (4.8%). In three of the four patients, symptoms were the result of accidental exposure to a higher step of the ladder. There were no reports of lethargy. No patients required health care presentation or intravenous fluid administration. No patients discontinued the ladder. CONCLUSIONS: The Canadian Egg Ladder can safely guide the dietary advancement of egg-containing foods in patients with mild-to-moderate FPIES to egg, without the need for prolonged avoidance and resource-intensive OFCs.

Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy.

BACKGROUND: Our group previously described preschool peanut oral immunotherapy (OIT) in a real-world, multicenter setting, suggesting that this therapy is safe for most preschoolers. OBJECTIVE: To examine the safety and tolerability of tree nut (TN) OIT in preschoolers in the real world. METHODS: As part of a Canada-wide quality improvement project, TN-OIT (cashew/pistachio, walnut/pecan, hazelnut, almond, and macadamia nut) was performed in preschoolers who had (1) a skin prick test wheal diameter greater than or equal to 3 mm or a specific IgE level greater than or equal to 0.35 kU/L and a convincing objective IgE-mediated reaction or (2) no ingestion history and a specific IgE level greater than or equal to 5 kU/L. Dose escalations were performed every 2 to 4 weeks till a maintenance dose of 300 mg of TN protein was reached. Symptoms were recorded and classified using the modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System (1, mildest; 5, fatal). RESULTS: Of the 92 patients who started TN-OIT from 2018 to 2021, 79 (85.9%) underwent single-food TN-OIT and 13 (14.1%) underwent multifood TN-OIT to 2 (10.8%) or 3 (3.3%) TNs. Eighty-nine (96.7%) patients reached maintenance, and 4 (4.3%) dropped out. Sixty-five (70.7%) patients experienced reactions during buildup: 35 (38.0%) grade 1 reactions, 30 (32.6%) grade 2 reactions, no grade 3 or 4 reactions, and 2 (2.17%) received epinephrine. CONCLUSIONS: Preschool TN-OIT in a real-world, multicenter setting appears safe and tolerable, with results comparable with our previously reported peanut OIT findings.

How We Manage Gastrointestinal Symptoms During Oral Immunotherapy Through a Shared Decision-Making Process-A Practical Guide for the Community Practitioner.

Allergists addressing gastrointestinal (GI) symptoms during oral immunotherapy (OIT) may be biased toward diagnoses related to OIT; however, non-OIT causes may occur. Although there is currently a lack of robust data for evidence-based treatment recommendations, we provide 3 real-world illustrative cases along with a proposed management algorithm for GI symptoms encountered during OIT. This algorithm was developed because of a significant clinical need, given the number of new-to-OIT providers that include practicing allergists, trainees transitioning into practice, and allied health care providers who manage GI symptoms in OIT patients. We developed the algorithm based on the opinions of community and academic allergy clinics across Canada with significant clinical experience offering infant, preschool, and school-aged OIT patients, with gastroenterologist input. Further research is needed to fill the knowledge gaps in the management of GI symptoms during OIT before formal recommendations can be suggested.

The Case for Prompt Salvage Infant Peanut Oral Immunotherapy Following Failed Primary Prevention.

Recent guideline recommendations have shifted from recommending prolonged avoidance of allergenic foods in the first 3 years of life to a primary prevention approach involving the deliberate early introduction to infants at risk of developing food allergy. Despite this, some infants, especially those with severe eczema who are at highest risk for developing peanut allergy, fail to receive the preventative benefits of early peanut introduction due to hesitancy and other factors. Difficulty adhering to regular ingestion after introduction further reduces the effectiveness of primary prevention. As emerging real-world evidence has demonstrated that performing peanut oral immunotherapy (OIT) among infants is effective and safe, peanut OIT could be a treatment option for infants with peanut allergy. This review discusses the benefits, risks, and barriers to offering peanut OIT to infants who fail primary prevention strategies. We propose the novel concept that infants with peanut allergy be offered peanut OIT as soon as possible after failed peanut introduction through a shared decision-making process with the family, where there is a preference for active management rather than avoidance.

Allergic reactions to emerging food allergens in Canadian children.

Most Canadian food allergy data has focused on Health Canada's priority food allergens. This study describes which non-priority (emerging) food allergens were most commonly reported by Canadian parents and categorized/confirmed by allergists. A secondary aim was to describe severity of allergic reactions to emerging allergens. Parents reported allergic reactions to emerging food allergens experienced by their child (< 18 years) which occurred in the past 12 months, and allergists categorized/confirmed them according to likelihood of IgE-mediated food allergy. Of 68 eligible patients completing the survey, the most commonly reported emerging allergens were fruits/vegetables (58.8%), seeds (22.1%), legumes (19.1%) and other (11.8%). Median allergist ranking for legumes was 'probable' IgE-mediated food allergy, 'possible' for seeds and fruits/vegetables, and 'unlikely' for other. Median reaction severity was mild for legumes, and moderate for seeds, fruits/vegetables, and other. Our study highlights that non-priority food allergens, namely legumes and seeds, can lead to probable/likely allergic reactions in Canadian children. These food allergens are increasing in popularity in the Canadian diet, which could lead to increasing reports of allergic reactions. More research is needed to confirm reports of reactions to emerging allergens, and to document their inclusion as ingredients in packaged foods.

Home-Based Peanut Oral Immunotherapy for Low-Risk Peanut-Allergic Preschoolers During the COVID-19 Pandemic and Beyond.

The coronavirus disease 2019 (COVID-19) pandemic has led to the deprioritization of non-emergency services, such as oral food challenges and the initiation of oral immunotherapy (OIT) for food-allergic children. Recent studies have suggested that home-based peanut OIT could be a safe and effective option for low-risk peanut-allergic children. In the period between September 1, 2020, and January 31, 2021, nine preschoolers with a history of mild allergic reactions to peanut underwent home-based peanut OIT. Eight of them (88.9%) completed the build-up phase at home in 11-28 weeks, tolerating a daily maintenance dose of 320 mg peanut protein. During the build-up, six patients (75.0%) reported urticaria, three (33.3%) reported gastrointestinal tract symptoms, and one (14.3%) reported oral pruritis. None of the patients developed anaphylaxis, required epinephrine, or attended emergency services related to OIT. One or two virtual follow-up visits were completed per patient during the build-up phase. Our case series shows that home-based OIT could be offered to the low-risk preschoolers during the COVID-19 pandemic when non-emergency services are limited and could be considered beyond the pandemic, especially for the families living in the rural or remote areas that may otherwise be unable to access OIT.

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy.

BACKGROUND: We previously described safety of preschool peanut oral immunotherapy (P-OIT) in a real-world setting; 0.4% of patients experienced a severe reaction, and 4.1% received epinephrine, during build-up. OBJECTIVE: To determine the effectiveness of preschool P-OIT after 1 year of maintenance. METHODS: Preschoolers (9-70 months) with at least 1 objective reaction to peanut (during baseline oral food challenge (OFC) or P-OIT build-up) received a follow-up OFC to cumulative 4000 mg protein after 1 year on 300 mg peanut daily maintenance. Effectiveness of desensitization was defined as proportion of patients with a negative follow-up OFC. Symptoms and treatment at follow-up OFC were recorded. RESULTS: Of the 117 patients who successfully completed 1 year of P-OIT and subsequently underwent a cumulative 4000-mg follow-up OFC, 92 (78.6%) had a negative OFC and 115 (98.3%) tolerated a cumulative dose of greater than or equal to 1000 mg. For the 25 (21.4%) who reacted, their threshold increased by 3376 mg (95% CI, 2884-3868) from baseline to follow-up; 17 (14.5%) patients experienced grade 1 reactions, 7 (6.00%) grade 2, and 1 (0.85%) grade 3. Two patients (1.71%) received epinephrine associated with P-OIT, and 1 (0.85%) went to the emergency department. CONCLUSIONS: Our data demonstrate that real-world preschool P-OIT is effective after 1 year of maintenance for those who received a follow-up OFC. For those who reacted, their threshold increased sufficiently to protect against accidental exposures. P-OIT should be considered for preschoolers as an alternative to current recommendations to avoid peanut.

First Real-World Safety Analysis of Preschool Peanut Oral Immunotherapy.

BACKGROUND: In 2017, a clinical trial of 37 subjects demonstrated that preschool peanut oral immunotherapy (P-OIT) was safe, with predominantly mild symptoms reported and only 1 moderate reaction requiring epinephrine. OBJECTIVES: We sought to examine whether these findings would be applicable in a real-world setting. METHODS: As part of a Canada-wide quality improvement project, community and academic allergists administered P-OIT to preschool-age children who had (1) skin prick test wheal diameter greater than or equal to 3 mm or specific IgE level greater than or equal to 0.35 kU/L and history of reaction and/or positive baseline oral food challenge, or (2) no ingestion history and specific IgE level greater than or equal to 5 kU/L. Over 16 to 22 weeks, patients had biweekly clinic visits for updosing, and consumed the dose daily at home between visits. Target maintenance dose was 300 mg peanut protein. Symptoms were classified using a modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System (1 mildest, 5 fatal). RESULTS: Of 270 patients who started P-OIT in the period 2017 to 2018, 243 reached maintenance, and 27 dropped out (10.0%); 67.8% of patients experienced reactions during buildup: 36.3% grade 1, 31.1% grade 2, and 0.40% grade 4. Eleven patients (4.10%) received epinephrine (10 patients received 1 dose, 1 patient received epinephrine on 2 separate days), representing 2.23% of reactions (12 of 538) and 0.029% of doses (12 of 41,020). CONCLUSIONS: We are the first group to describe preschool P-OIT in a real-world multicenter setting. The treatment appears to be safe for the vast majority of patients because symptoms were generally mild and very few reactions received epinephrine; however, life-threatening reactions in a minority of patients (0.4%) can still occur.

Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

KEY POINTS: Smn+/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. ABSTRACT: Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn+/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn+/- transgenic mouse increases their susceptibility to cell death demonstrated that all the motoneurons survived and they sustained their capacity to regenerate their nerve fibres. It is concluded the systematic die-back of motoneurons that innervate both fast- and slow-twitch muscle fibres is not related to immaturity of the neuromuscular system in SMA.

Respiratory Presentation of Pediatric Patients in the 2014 Enterovirus D68 Outbreak.

Background. In the fall of 2014, a North American outbreak of enterovirus D68 resulted in a significant number of pediatric hospital admissions for respiratory illness throughout North America. This study characterized the clinical presentation and risk factors for a severe clinical course in children admitted to British Columbia Children's Hospital during the 2014 outbreak. Methods. Retrospective chart review of patients with confirmed EV-D68 infection admitted to BCCH with respiratory symptoms in the fall of 2014. Past medical history, clinical presentation, management, and course in hospital was collected and analyzed using descriptive statistics. Comparison was made between those that did and did not require ICU admission to identify risk factors. Results. Thirty-four patients were included (median age 7.5 years). Fifty-three percent of children had a prior history of wheeze, 32% had other preexisting medical comorbidities, and 15% were previously healthy. Ten children (29%) were admitted to the pediatric intensive care unit. The presence of complex medical conditions (excluding wheezing) (P = 0.03) and copathogens was associated with PICU admission (P = 0.02). Conclusions. EV-D68 infection resulted in severe, prolonged presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of wheeze and preexisting medical comorbidities appear to be most severely affected, but the virus can also cause wheezing in previously well children.