Precautionary Allergen Labeling: What Advice Is Available for Health Care Professionals, Allergists, and Allergic Consumers?

In most countries, the use of precautionary allergen labeling (PAL) is not governed by regulation. PAL was initially identified as a judicious risk management measure to address instances of "unavoidable" cross-contact with priority food allergens during food processing. However, PAL has gradually been devalued in part due to overuse and inconsistent application by the food industry. Currently, most food products do not contain detectable allergen residue or contain only low concentrations of residue of the allergens declared using PAL; however, occasionally, high concentrations of allergen residue are reported, rendering it an ineffective risk communication tool for allergic consumers. In this context, several reasons exist that make the consumption of products bearing a PAL statement not advisable for people with food allergies. The main reason is that the risk is generally not correlated with the statement used by manufacturers. Because of the increased use of PAL on prepackaged food products, and to maximize food choices for allergic individuals, health care professionals increasingly advise some patients considered to be "not highly allergic" to consume products bearing a PAL statement. This article explains why the consumption of products with PAL is not advisable without having a full clinical evaluation and knowledge that an allergen risk assessment has been conducted. It also discusses the perspectives for a better use of PAL on the basis of the recent Food and Agricultural Organization/World Health Organization recommendations on food allergens.

Economic burden of food allergy in Canada: Estimating costs and identifying determinants.

BACKGROUND: Limited data exist on the economic burden of food allergy (FA). OBJECTIVE: To assess FA-related direct (healthcare and out-of-pocket) and indirect (lost productivity) costs and their determinants in Canadian children and adults self-reporting FA. METHODS: FA-individuals self-reporting a convincing history or physician diagnosis were recruited through FA registries, an anaphylaxis registry, and advocacy associations, and electronically surveyed regarding FA-related healthcare use, out-of-pocket expenditures, and time lost from paid and unpaid labor. Direct and indirect costs (2020 Canadian dollars [CAD]) were stratified on severe reaction vs mild, moderate or no reaction, and children vs adults; multivariate regressions assessed the association between costs and sociodemographic and disease characteristics. RESULTS: Between May 2018 and July 2019, 2692 eligible individuals responded (2189 convincing history and 503 physician diagnosis only); 1020 experienced a severe reaction; 1752 were children. Per FA-individual, annual healthcare, out-of-pocket, and indirect costs were $1267, $2136, and $7950. Those with a severe reaction had higher healthcare and out-of-pocket costs than those with mild, moderate or no reaction. FA-children vs FA-adults had higher healthcare and out-of-pocket costs, and lower indirect costs. Multivariate results showed that lower age, a severe reaction ever, multiple FAs, and fair or poor general health were associated with higher healthcare and out-of-pocket costs. Higher age, lower household education and income, and fair or poor general health were associated with higher indirect costs. CONCLUSION: The economic burden of FA in Canada is substantial, particularly for those with a severe reaction ever, multiple FAs, and fair or poor general health. It is crucial that those most adversely affected are allocated appropriate resources to support disease management.

Effects of caffeinated energy drinks on cardiovascular responses during exercise in healthy adults: a systematic review and meta-analysis of randomized controlled trials.

The impact of caffeinated energy drinks (CEDs) on the cardiovascular (CV) response to exercise has not been well described. A systematic review and meta-analysis was conducted on the acute effects of CEDs on CV responses during dynamic, aerobic exercise in 296 healthy adult males (224) and females (72) in 21 randomized controlled trials. During exercise, there was an increase in heart rate (HR) (mean difference (MD), 2.86 bpm, 95% CI, 2.39-3.34 bpm, I2 = 0%, p < 0.00001), and systolic blood pressure (SBP) (MD, 9.02 mm Hg, 95% CI, 4.25-13.79 mm Hg, I2 = 0%, p = 0.0002) with consumption of CEDs, compared with controls, but diastolic blood pressure was similar. Insufficient data were available to evaluate rate pressure product (HR × SBP) and exercise-induced arrhythmia. Though changes to HR during exercise were modest, the significant increase in exercise SBP highlights the importance of directly assessing CV effects of CEDs with exercise, especially in individuals prone to hypertension. Novelty: Exercise SBP in healthy adults is significantly increased during exercise with the consumption of CEDs compared with controls, despite limited data. The direct assessment of CV effects of CEDs with exercise highlights the particular relevance to individuals prone to hypertension.

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis.

Regional and national legislation mandates the disclosure of "priority" allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen ("may contain") labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed "reference doses," below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure.

Sesame as an allergen in Lebanese food products: Occurrence, consumption and quantitative risk assessment.

Despite the intensive use of sesame in the Middle Eastern diet, studies on this allergen in this region are lacking. A survey on the occurrence of sesame in Lebanese food products that did not contain this allergen as an ingredient, a food consumption survey conducted in Beirut schools, and the most recent sesame eliciting dose estimates were used to build a probabilistic risk assessment model providing estimates of sesame-induced allergic reactions per eating occasion and per week in Lebanese children and adolescents. Of 1270 food samples analysed, 34% contained sesame proteins (0.44-3392 mg kg-1). Sesame was detected in 47% of unlabeled bulk samples, 43% of samples with PAL, and 27% of samples without PAL. "Sfouf" had the highest concentration of sesame proteins (mean 549 mg kg-1), highest mean exposure per eating occasion (78 mg sesame proteins for children and 103 mg sesame proteins for adolescents), and posed the highest predicted risk per eating occasion (>20%) and per week (>13% individuals predicted in simulation experience at least 1 reaction). Bakery products (notably "sfouf") may pose a serious risk to sesame-allergic children and adolescents in Lebanon. Enhanced guidance on the use of PAL is needed to better protect allergic consumers.

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.

Demographic characteristics associated with food allergy in a Nationwide Canadian Study.

INTRODUCTION: We conducted a nationwide Canadian telephone survey on food allergy prevalence between February 2016 and January 2017, targeting vulnerable populations (New, Indigenous, and lower-income Canadians). OBJECTIVE: To examine the independent effect of demographic characteristics on food allergy. METHODS: Canadian households with vulnerable populations were targeted using Canadian Census data and the household respondent reported whether each household member had a perceived (self-reported) or probable (self-report of a convincing history or physician diagnosis) food allergy. The association between perceived and probable food allergy and demographic characteristics was assessed through weighted multivariable random effects logistic regressions. RESULTS: Children, females, Canadian-born participants, adults with post-secondary education, and those residing in smaller households were more likely to report perceived or probable food allergy. Although immigrant parents self-reported less food allergy, Canadian-born children of Southeast/East Asian immigrant versus other immigrant or Canadian-born parents reported more food allergy. CONCLUSION: We have demonstrated clear associations between demographic characteristics and food allergy, which may provide important clues to the environmental determinants of food allergy.

Peanut and hazelnut occurrence as allergens in foodstuffs with precautionary allergen labeling in Canada.

Precautionary allergen labeling (PAL) is widely used by food industries. Occurrence studies revealed that few analyzed products contained the allergen(s) present in the statement, but little is known in Canada. To improve manufacturing practices and better manage allergen cross-contamination, occurrence data is needed to determine the exposure of allergic individuals eating those products. Samples were analyzed for peanuts (n = 871) and hazelnuts (n = 863) using ELISA methods. Within samples analyzed for peanuts, 72% had a PAL (n = 628), 1% had peanuts as a minor ingredient (n = 9) and 27% were claimed "peanut-free" (n = 234). Most hazelnut samples had a PAL for tree nuts/hazelnuts (94%; n = 807) with 6% claimed "nut-free" (n = 56). Peanuts and hazelnuts were found in 4% (0.6-28.1 ppm) and 9% (0.4-2167 ppm) of all samples, respectively. Chocolates were mostly impacted; they should be treated apart from other foods and used in risk assessments scenarios to improve manufacturing practices, reducing unnecessary PAL use.

Caffeinated energy drinks in the Canadian context: health risk assessment with a focus on cardiovascular effects.

In Canada, caffeinated energy drinks (CEDs) currently sold under Temporary Marketing Authorizations must meet strict eligibility criteria. These criteria, which include compositional and labelling requirements, were developed based on the outcome of a health risk assessment conducted by Health Canada (HC) in 2013. HC updated its assessment by reviewing new information with the focus on potential cardiovascular effects associated with the consumption of CEDs available for sale in Canada. Due to limited data on CED consumption among Canadians to derive accurate exposure information, the composition of a typical CED was characterized to assess the potential effects of single ingredients and synergistic interactions between ingredients on the cardiovascular system. Surveillance data on potential adverse effects related to CED consumption was also analyzed. After extensive review, HC's updated assessment confirms the current risk management approach for CEDs is health protective for Canadian consumers, including the potential for cardiovascular effects. The available evidence supports that moderate consumption (up to 500 mL per day) of a typical CED authorized for sale in Canada is safe for the general population of healthy adults and adolescents. It also re-confirms that vulnerable sub-populations (i.e., children, pregnant and/or breastfeeding women, and caffeine-sensitive individuals) should not consume CEDs. Novelty: Consumption up to 500 mL per day of a typical CED is not associated with an increased risk of cardiovascular effects. Children, pregnant and/or breastfeeding women, and caffeine-sensitive individuals should not consume CEDs.

Probabilistic risk assessment for milk in dark chocolate, cookies and other baked goods with PAL sold in Canada.

The risk of having an allergic reaction in milk-allergic individuals consuming products with precautionary allergen labelling (PAL) for milk has been rarely studied in products such as dark chocolate, cookies, and other baked goods. A probabilistic risk assessment model was developed to estimate potential risks. Milk occurrence and contamination levels were reported in a previous article from our group. Dose-response curves for milk were constructed using values (n = 1078) from published double-blind placebo-controlled food challenges. Canadian consumption data was extracted from a national survey, and a homemade survey involving food-allergic Canadians. Milk eliciting doses (ED) were 0.23 (ED01), 1.34 (ED05), 3.42 (ED10), and 16.3 (ED25) mg of milk protein (Log-Normal distribution). Average exposures, per eating occasion, were 24 mg (dark chocolate), 3.9 mg (baked goods), and 0.20 mg (cookies) of milk proteins. The estimated risk of having a milk-induced allergic reaction by consuming foods with PAL for milk was higher for dark chocolate (16%; 15,881/100,000) than baked goods (3.8%; 3802/100,000) or cookies (0.6%; 646/100,000) in milk-allergic Canadians. Dark chocolate, cookies, and baked goods with PAL for milk, should be avoided by milk-allergic Canadians (consuming or not products with PAL) to prevent allergic reactions.

Occurrence and risk assessment of sesame as an allergen in selected Middle Eastern foods available in Montreal, Canada.

Sesame allergy is a public health problem in many countries around the world. The purpose of this study is to determine the occurrence of sesame allergen in unlabelled or labelled free-sesame Middle Eastern foods with or without Precautionary Allergen Labelling (PAL) 'may contain' and estimate the risk incurred by the Canadian population allergic to sesame with a focus on products purchased in Middle Eastern grocery stores and bakeries in Montreal, Canada. A total of 571 samples were analysed to determine the level of sesame protein. Of the 571 samples analysed, 19% (109/571) contained sesame (results >LOQ) with concentrations of sesame proteins varying between 0.5 and 1,875 mg kg-1 and 35% (199/571) contained traces (a value between LOD and LOQ). Unpackaged products were found to present the highest proportion of sesame containing samples (36%). For packaged products, 16% (27/173) of samples with PAL and 3% (5/173) without PAL were found to contain sesame. A probabilistic approach was used to estimate the risk incurred by the Canadian consumers allergic to sesame. Our evaluation estimated that 33 to 308 allergic reactions may occur out of 10 000 individuals ingesting one type of bakery product contaminated at a level of 0.6-74 mg kg-1 sesame proteins. The incidence and level of sesame cross-contact reported in this study demonstrate that sesame allergic consumers could react if they ignore the precautionary allergen statements on product labels. Attention to sesame as a potential cross-contact agent and as a priority allergen calls for better management, given the growing interest in this ingredient to be included in food formulations. Enhanced risk management efforts must be coupled with targeted risk communication covering both producers and consumers as to the need to adopt and an approach for the application of precautionary allergen labelling based on risk.

Occurrence of milk and egg allergens in foodstuffs in Canada.

Food allergies are life-threatening conditions that allergic individuals can avoid by consulting the food labels before consuming. Precautionary allergen labelling (or PAL), to warn against possible allergen cross-contamination, is widely used by food industries, reducing the food choices for allergic individuals. In Canada, there is limited information on the actual occurrence of allergens in products with a PAL related to the given allergen. This study attempted to fill the data gap by evaluating the occurrence of milk and egg allergens in Canadian products with PAL. A total of 1125 samples were analysed for milk and 840 for eggs, with 23% and 7% of these samples showing positive detection of ≥2.5 mg kg-1 for milk and ≥0.245 mg kg-1 for eggs. Chocolate products gave the largest number of positive results. Although the proportion of positive results was low, the levels detected reached 6471 mg kg-1 in a chocolate sample and were indicative of possible health consequences, if PAL was ignored by allergic consumers. The occurrence data generated is destinated to be used in exposure and risk assessments, to support allergen management linked to cross-contamination, with the possible development of allergen action levels that would be used by food industries, thus improving a risk-based approach for the application of PAL.

Evaluation of Prehospital Management in a Canadian Emergency Department Anaphylaxis Cohort.

BACKGROUND: Studies assessing the use of antihistamines and corticosteroids for the treatment of anaphylaxis have not supported a conclusive effect. OBJECTIVE: To assess prehospital management of anaphylaxis by measuring the effect of epinephrine use compared with antihistamines and corticosteroids on negative outcomes of anaphylaxis (intensive care unit/hospital ward admission, multiple doses of epinephrine in the emergency department [ED], and intravenous fluids given in the ED). METHODS: The Cross-Canada Anaphylaxis Registry is a cohort study that enrolls anaphylaxis cases presenting to EDs in 5 Canadian provinces over a 6-year period. Participants were recruited prospectively and retrospectively and were excluded if the case did not meet the definition of anaphylaxis. RESULTS: A total of 3498 cases of anaphylaxis, of which 80.3% were children, presented to 9 EDs across Canada. Prehospital treatment with epinephrine was administered in 31% of cases, whereas antihistamines and corticosteroids were used in 46% and 2% of cases, respectively. Admission to the intensive care unit/hospital ward was associated with prehospital treatment with corticosteroids (adjusted odds ratio, 2.84; 95% confidence interval [CI], 1.55, 6.97) while adjusting for severity, treatment with epinephrine and antihistamines, asthma, sex, and age. Prehospital treatment with epinephrine (adjusted odds ratio, 0.23; 95% CI, 0.14, 0.38) and antihistamines (adjusted odds ratio, 0.61; 95% CI, 0.44, 0.85) decreased the likelihood of receiving multiple doses of epinephrine in the ED, while adjusting for severity, treatment with corticosteroids, asthma, sex, and age. CONCLUSIONS: Prompt epinephrine treatment is crucial. Use of antihistamines in conjunction with epinephrine may reduce the risk of uncontrolled reactions (administration of 2 or more doses of epinephrine in the ED), although our findings do not support the use of corticosteroids.

Dietary restrictions for people with glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world and renders those affected susceptible to potentially severe oxidative hemolysis. Although the resulting hemolysis is most often associated with drug exposure, it has also been reported after consumption of certain foods. With the exception of review articles that reiterated the historical knowledge that fava beans can provoke severe oxidative hemolysis in individuals with G6PD deficiency, very few articles have examined the safety of other food ingredients and food additives for people with G6PD deficiency. Some articles that associated specific foods with hemolysis appeared to be speculative and based on limited information. The objective of this review was to examine the association between foods, including food additives, and the triggering factors of acute hemolysis. The literature was searched for studies and case reports on food consumption and G6PD deficiency. In this review, fava beans were found to be the only food for which there is conclusive clinical evidence linking the risk of hemolytic anemia to individuals with G6PD deficiency. Food additives, at their permitted level of use in North America, can be consumed safely by most patients with G6PD deficiency.

First reported case in Canada of anaphylaxis to lupine in a child with peanut allergy.

BACKGROUND: Lupine is a member of the legume family and is often used in many food products in Europe (e.g. pasta, pizza, sauces, etc.) as a wheat or soy substitute. Lupine cross-reacts with peanut, and cases of allergic reactions to lupine in peanut-allergic patients have been reported in Europe mainly. In contrast, lupine as an ingredient in food products is relatively new to the Canadian market. CASE PRESENTATION: We describe a 10-year old boy with diagnosed peanut and tree-nut allergy, who developed anaphylaxis to lupine flour in May 2017. A few minutes after eating a pre-made pancake mix that didn't contain any of his known allergens (peanuts, tree nuts), he developed oral pruritis followed by throat tightness, severe stomach ache, lightheadedness, cough, hoarse throat, nasal congestion, sneezing, and fatigue. He refused epinephrine, but was given cetirizine. The symptoms resolved after 3 h, but he was still unwell the following day. In a conversation between the mother and the allergist, it was determined that lupine was likely the cause of the reaction. To confirm, he was brought into clinic for skin testing to lupine. Results were consistent with lupine allergy (pancake mix: 10 × 7 mm, lupine bean: 12 × 6 mm). The family has since reported this to the Canadian Food Inspection Agency, resulting in a product recall and a consumer advisory bulletin published by Health Canada. CONCLUSIONS: This is the first reported case of allergic reaction to lupine in Canada, and highlights the need for education of Canadian families with peanut allergy as well as allergists, regarding the possibility of cross-reactivity between peanut and lupine and its new presence in the Canadian food supply. In addition, a precautionary label for those with peanut allergy who purchase products containing lupine should be considered. This case illustrates also the need for a clear mechanism for consumers and allergists to report emerging food allergens to regulatory bodies such as Health Canada.

Disparities in rate, triggers, and management in pediatric and adult cases of suspected drug-induced anaphylaxis in Canada.

INTRODUCTION: Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children. OBJECTIVE: We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada. METHODS: Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction and management was completed and patients were followed annually to determine assessment by allergist and use of confirmatory tests. RESULTS: From June 2012 to May 2016, 51 children were recruited from the pediatric centers and 64 adults from the adult center with drug-induced anaphyalxis. More than half the cases were prospectively recruited. The percentage of DIA among all cases of anaphylaxis was similar in all three pediatric centers but higher in the adult center in Montreal. Most reactions in children were triggered by non-antibiotic drugs, and in adults, by antibiotics. The majority of adults and a third of children did not see an allergist after the initial reaction. In those that did see an allergist, diagnosis was established by either a skin test or an oral challenge in less than 20% of cases. CONCLUSIONS: Our results reveal disparities in rate, culprit, and management of DIA in children versus adults. Further, most cases of suspected drug allergy are not appropriately diagnosed. Guidelines to improve assessment and diagnosis of DIA are required.