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.

The Risk of Recurrent Anaphylaxis.

OBJECTIVES: To determine the recurrence rate of anaphylaxis in children medically attended in an emergency department (ED), we performed a prospective cohort study to evaluate prehospital and ED management of children with recurrent anaphylaxis and to assess factors associated with recurrent anaphylaxis. STUDY DESIGN: As part of the Cross-Canada Anaphylaxis Registry, parents of children with anaphylaxis identified prospectively in 3 EDs and through an emergency medical response service were contacted annually after presentation and queried on subsequent reactions. Cox regression analysis determined factors associated with recurrence. RESULTS: Among 292 children who were registered as having had medical attended anaphylaxis, 68.5% completed annual follow-up questionnaires. Forty-seven patients experienced 65 episodes of anaphylaxis during 369 patient-years of follow-up. Food was the trigger in 84.6% of cases, and epinephrine was used in 66.2%. In 50.8%, epinephrine was used outside the health care facility, and 81.7% were brought to a health care facility for treatment. Asthma, reaction triggered by food, and use of epinephrine during the index episode increased the odds of recurrent reaction. Patients whose initial reaction was triggered by peanut were less likely to have a recurrent reaction. CONCLUSIONS: We report a yearly anaphylaxis recurrence rate of 17.6% in children. There is substantial underuse of epinephrine in cases of anaphylaxis. Educational programs that promote effective avoidance strategies and prompt use of epinephrine are required.

Tryptase levels in children presenting with anaphylaxis: Temporal trends and associated factors.

BACKGROUND: The diagnosis of anaphylaxis currently relies on suggestive clinical history after exposure to a potential triggering factor because no reliable diagnostic marker is available to confirm the diagnosis. OBJECTIVES: We aimed to evaluate tryptase levels in children with anaphylaxis and to examine predictors of elevated tryptase level (defined as ≥11.4 µg/L during reaction and for those with a baseline level, defined as a reaction level of at least 2 ng/mL + 1.2 × [postreaction tryptase level]). METHODS: Children presenting with anaphylaxis to the Montreal Children's Hospital were recruited over a 4-year period. Symptoms, triggers, and management of anaphylaxis were documented. Levels during the reaction and approximately 9 months after the reaction were compared on the basis of paired means using the t distribution. Multivariate linear and logistic regressions were used to evaluate the association between tryptase levels and risk factors. RESULTS: Over a 4-year period, 203 children had serum tryptase levels measured. Among these, 39 children (19.2%; 95% CI, 14.1%-25.4%) had elevated levels. Only severe reactions were associated with reaction levels of 11.4 µg/L or more (odds ratio, 6.5; 95% CI, 2.2-19.0). Milk-induced anaphylaxis and severe reactions were more likely associated with increased tryptase levels (beta-adjusted, 4.0; 95% CI, 0.95-7.0, and 7.5; 95% CI, 4.8-10.3, respectively). Reaction levels exceeding the threshold level of 2 ng/mL + 1.2 × (postreaction tryptase level) detected most of the anaphylactic reactions, particularly if baseline levels were taken within 2 months of the reaction. CONCLUSIONS: Tryptase levels are particularly useful for the diagnosis of severe and/or milk-induced anaphylaxis. Assessing the difference between reaction and postreaction tryptase levels may improve diagnostic sensitivity.

Simulated use of thresholds for precautionary allergen labeling: Impact on prevalence and risk.

Heterogeneity and overuse of precautionary allergen labelling (PAL) in prepackaged foods have eroded its risk communication efficacy. Experts recommend applying PAL based on allergen concentration thresholds, but adoption remains limited. The aim of this study was to quantitatively assess the potential impact of this approach using Monte Carlo risk simulations. Four allergens and 9 food categories were considered in 2 scenarios: (1) consumption of products currently carrying PAL in Canada where individuals with food allergy (FA) are assumed to consume them, and (2) consumption of products without PAL, in a hypothetical context where PAL is applied based on thresholds that would protect 99 % (ED01) and 95 % (ED05) of individuals with FA, and individuals with FA systematically avoid products with PAL. In scenario (1), although several cases studied would cause <10 reactions/10 000 eating occasions (e.o.), there were also many that would cause >20 reactions/10 000 e.o. Cross-contact milk posed the highest risk (max. 1120 reactions/10 000 e.o.), and peanut, the least (max. 10 reactions/10 000 e.o.). In scenario (2), consumption of products without PAL, when using thresholds for PAL based on ED01, could lead to a maximum of 15 reactions/10 000 e. o. for all studied cases, and based on ED05, to 57 (if excluding dark chocolate with milk PAL). In most cases, the estimated number of reactions per 10 000 e.o. attributed to products with PAL currently on the market would be higher (p < 0.05) than that attributed to products without PAL, if PAL is applied based on the simulated thresholds. Thus, a threshold driven approach to adopt PAL on prepackaged foods, while advising consumers to avoid these products, could be beneficial for individuals with FA in Canada, as products without PAL would result in very few and generally mild adverse reactions.

Time to ACT-UP: Update on precautionary allergen labelling (PAL).

Background: Precautionary Allergen ("may contain") Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation - which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL). Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards. Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products. Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows. Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020-2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Quantitative risk assessment relating to adventitious presence of allergens in food: a probabilistic model applied to peanut in chocolate.

Peanut allergy is a public health concern, owing to the high prevalence in France and the severity of the reactions. Despite peanut-containing product avoidance diets, a risk may exist due to the adventitious presence of peanut allergens in a wide range of food products. Peanut is not mentioned in their ingredients list, but precautionary labeling is often present. A method of quantifying the risk of allergic reactions following the consumption of such products is developed, taking the example of peanut in chocolate tablets. The occurrence of adventitious peanut proteins in chocolate and the dose-response relationship are estimated with a Bayesian approach using available published data. The consumption pattern is described by the French individual consumption survey INCA2. Risk simulations are performed using second-order Monte Carlo simulations, which separately propagates variability and uncertainty of the model input variables. Peanut allergens occur in approximately 36% of the chocolates, leading to a mean exposure level of 0.2 mg of peanut proteins per eating occasion. The estimated risk of reaction averages 0.57% per eating occasion for peanut-allergic adults. The 95% values of the risk stand between 0 and 3.61%, which illustrates the risk variability. The uncertainty, represented by the 95% credible intervals, is concentrated around these risk estimates. Children have similar results. The conclusion is that adventitious peanut allergens induce a risk of reaction for a part of the French peanut-allergic population. The method developed can be generalized to assess the risk due to the consumption of every foodstuff potentially contaminated by allergens.