Food hypersensitivity: an examination of factors influencing symptoms and temporal changes in the prevalence of sensitization in an adult sample

Food hypersensitivity (FHS), encompassing food allergy and intolerance, is prevalent (2-37% in Europe, 19% in the US). Symptoms vary, with oral and skin manifestations being most common, but respiratory or cardiovascular symptoms are also reported in a significant portion of adults. Predicting severe reactions is difficult, as severity depends on both food and host factors. Previous studies have explored risk factors but with limitations, including single outcome measures or focusing only on severe cases. The temporal changes in sensitization to food in adults are poorly understood, with limited studies and conflicting findings. This study aimed to identify factors associated with severe food reactions, determine the age of onset of FHS, and assess changes in sensitization prevalence over time in a large, diverse adult population across Europe and Australia, utilizing data from the ECRHS III (2010-2014). The study linked ECRHS III data with data collected ten years prior (ECRHS II) to track changes in sensitization.

The prevalence of FHS has been reported as high as 19% in the US and 2-37% across Europe, with studies reporting a variety of symptoms ranging from oral and skin symptoms to respiratory and cardiovascular problems. The difficulty in predicting severe food reactions is highlighted, as severity is influenced by multiple food and host factors. While prior food reactions might suggest future severe reactions, many cases of fatal food allergies have been preceded by only mild symptoms. Research on risk factors for severe reactions has shown conflicting results regarding the role of specific IgE levels in predicting symptom severity. The importance of pre-existing respiratory conditions like asthma in food-induced anaphylaxis and fatal food allergy has been noted. Studies on children suggest changes in sensitization to food with age or over time, but data on adult-onset FHS and changes in sensitization in adults is scarce, with existing studies limited in sample size or the range of foods examined. One US study revealed that about half of adults with self-reported food reactions highly suggestive of allergies developed symptoms after age 17. A study using data from Sweden and Iceland showed that sensitization to certain foods decreased in adults over 9 years, but this was based only on six foods.

This study used data from adults (n=4865) participating in the European Community Respiratory Health Survey (ECRHS) III (2010-2014). Participants provided information on food hypersensitivity, including symptoms, suspected culprit foods, and onset age. A subsample from six countries (n=1612) had serum food-specific IgE tested for 25 core foods, and data were also available from ECRHS II (10 years prior). FHS was defined as a positive response to questions regarding food-related illness. Severe food reactions were defined based on symptoms consistent with anaphylaxis guidelines, including breathlessness, fainting or dizziness, emergency injection, or combination of skin-mucosal and gastrointestinal symptoms. Statistical analyses included logistic regression and McNemar's test to identify associations between factors and severe reactions, and to examine the temporal changes in sensitization. Univariate analyses (chi-square test, Wilcoxon rank sum test, or t-test) were also performed. Sensitization to food was defined as specific IgE greater than 0.35 kU/l. Asthma/nasal and skin allergies were defined based on self-reported history. The significance level was set at p<0.05.

The prevalence of self-reported FHS was 13.5% (655/4865). Of those reporting symptoms (n=611), 26.4% reported severe reactions. Approximately 80% of food-specific reactions (1033 reported by 596 participants) began after age 15. A history of asthma (OR 2.12, 95% CI 1.13-3.44) and younger age of FHS onset (OR 1.02, 95% CI 1.01-1.03 per year) were significantly associated with a higher risk of severe reactions. In the subsample with IgE tested in both surveys (n=1612), the overall prevalence of food sensitization did not change significantly over 10 years. However, subgroup analysis revealed a significant increase in sensitization for the 1954-1963 birth cohort (from 13.3% to 16.0%, p=0.019). Sensitization to the food mix group epcx3 (banana, kiwi fruit, apple, peach, melon) also increased significantly (from 9.3% to 12.0%, p<0.0005). Cow's milk, hazelnut, apple, kiwi fruit, and shrimp/lobster were the most commonly reported foods associated with FHS. Among those with measured food-specific IgE, sensitization to the relevant food was lower in those with severe reactions compared to those with mild reactions; however, this difference was not statistically significant (p=0.138). The median age of onset varied by food; for example, fish had the lowest median onset age (20 years), while peanut had the highest (40 years).

This large multicenter study confirms the high prevalence of self-reported FHS in adults. The finding that most FHS reactions begin after age 15 aligns with previous research. The association between asthma and severe food reactions corroborates earlier findings emphasizing the role of respiratory compromise in life-threatening food anaphylaxis. The relationship between younger onset age and severe reactions may be explained by the inclusion of food intolerance in the FHS definition. The high median onset age for peanut and kiwi FHS suggests potential cross-reactivity with pollen. The lack of significant change in overall sensitization over 10 years contrasts with some earlier reports and requires further investigation, considering possible variations in baseline prevalence and methodologies across studies. Although increases in some individual food items and in specific birth cohorts were observed, the overall prevalence of sensitization remains unchanged.

This study demonstrates that a substantial proportion of adults reporting FHS experience severe reactions, with asthma history and younger age of onset as potential risk factors. The majority of reported FHS in adults develops after age 15. Longitudinal data suggest little overall change in food sensitization prevalence over 10 years. Further research is needed to fully understand the complex interplay of factors influencing FHS severity and the dynamic nature of food sensitization in adults.

The study relies on self-reported symptoms, introducing potential recall bias. The use of proxies for respiratory and cardiovascular symptoms might affect the accuracy of outcome measurement. Biomarkers measured at survey time points may not fully reflect the biological condition during food reactions. The self-reported FHS likely over-diagnoses IgE-dependent food allergy. Cohort effects should be interpreted cautiously due to multiple testing. The power of food-specific analysis was limited by sample size.