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

Study participants

The ECRHS was established to examine the prevalence of asthma and identify its associated factors in European adult populations. The detailed study design was published elsewhere [16]. In brief, a community based random sample of 1500 men and 1500 women aged 20–44 years old were recruited from each participating center (55 centers from 19 countries) in 1991–1993 (ECRHS I). After the completion of a short postal questionnaire in the first stage, a “random“ sample of responders (300 men, 300 women randomly selected from the first stage sample) plus a sample about 150 of those reporting asthma symptoms in the postal questionnaire were invited for an interviewer-administered questionnaire and clinical assessment including venous sampling and skin prick test.

Two follow-ups were conducted for those who took part in the clinical assessment—ECRHS II (1998–2002) [17], and ECRHS III (2010–2014)—and these follow-ups included similar clinical assessments as ECRHS I. This analysis was restricted to the “random” sample of those who had took part in all follow-ups (ECRHS II to III, n = 5904, Supplementary Fig. 1) (see Appendix 1 in the Supplementary File for the number of participating centers and countries included for each analysis).

Informed consent was obtained from participants and ethics approval were granted from local ethics committees.

Information collected

Questions on FHS collected in ECRHS III were used in this analysis. Participants were asked specifically about reaction to each of the 25 core foods (Supplementary Table 1) and were then asked to identify three foods (not necessarily from the core foods) that caused the “main problem” (ordered by the food giving the most severe reaction), the type of self-reported symptoms (from a pre-defined list as shown in Supplementary Table 2), the time from ingestion to reaction and the age of the first episode.

Serum specific IgE to food was tested in most participants of ECRHS II (related to availability of residual serum) and participants in six countries in ECRHS III (related to available funds, see Appendix 1 in Supplementary File for list of countries included). Venous blood samples were taken with serum stored at −20 °C before being tested in the laboratory (Kings College London in 2002 for ECRHS II, and AMC Amsterdam in 2013/2014 for ECRHS III) using the Pharmacia CAP System (Phadia, Uppsala, Sweden). Samples were screened against five food mix groups (excp1, expc2, excp3, fx5 and fx6) consisting of the 25 core food items (Supplementary Table 1) and if positive (sIgE level ≥0.35 ku/l), tested for positivity for individual foods within the food mix group.

Serum sIgE level to house dust mite, cat and Timothy grass pollen were assessed using the Pharmacia CAP system in ECRHS II and III. Sensitization to birch was examined using skin prick test in ECRHS III (reagents and standard lancets from ALK-ABELLO. Refer to Appendix 2 in Supplementary File for details). A summary of ECRHS data used in this analysis is summarized in Supplementary Table 3.

Definitions used

FHS—a positive response to both questions “Have you ever had an illness or trouble caused by eating a particular food or foods?” AND “Have you nearly always had the same illness or trouble after eating this type of food?” (In Switzerland, the second question was omitted. FHS is defined as a positive answer to the first question AND the report of reaction to at least one individual food).

Severe food reaction—there is no single definition of severe food reaction. We defined severe reaction in this analysis with reference to the guidelines for diagnosing anaphylaxis. Symptoms that started within 4 h after ingestion of a particular food item and including at least one of the following:

(1)

The presence of skin-mucosal symptoms (rash or itchy skin OR itching, tingling or swelling in mouth OR difficulty in swallowing) PLUS evidence of EITHER respiratory compromise (breathlessness) AND/OR a drop in blood pressure (dizziness and fainting) AND/OR severe gastrointestinal symptoms (diarrhea or vomiting) [18].

(2)

In the absence of skin symptoms EITHER, a drop in blood pressure (dizziness and fainting), AND/OR respiratory compromise AND/OR laryngeal involvement (breathlessness) [18].

(3)

The need for an “emergency injection”.

Mild food reaction—any other symptoms reported after ingestion of food.

Sensitization to food and grass, cat, house dust mite—specific IgE greater than 0.35 kU/l to the allergens.

Positive skin prick test to birch—wheal size ≥3 mm for birch and positive control with no reaction to the negative control.

Asthma/nasal and skin allergies—a positive response to any of the questions “Have you ever had asthma?”, “Do you have any nasal allergies, including hay fever?” and “Have you ever had eczema or any kind of skin allergy?”.

AnalysisAssociated factors of severe reactions

Using information at ECRHS III, we applied univariate analysis (chi-square test, Wilcoxon rank sum test or t-test, where appropriate) and multiple logistic regression to identify associations of severe food reactions with sex, age, self-reported asthma/allergic (nasal and skin) history, total IgE level and sensitization to common inhalant allergens.

Age of onset of food reactions

Each participant reported details of up to three food-specific reactions. We firstly reported the proportion of participants with symptoms beginning (to any food) ≤15 years old, then described the median onset age of commonly reported foods.

Sensitization to food and severe symptoms

At ECRHS III, a subsample of 1673 participants had serum specific IgE measured for all 25 core foods. Among those reported FHS, we compared the proportion of positive IgE to the food between participants did and did not report severe symptoms using chi-square test.

Change of prevalence of sensitization to food

Sixteen hundred and twelve participants had food-specific serum IgE and specific IgE to inhalant allergens measured at both ECRHS II and ECRHS III. McNemar’s test was used to compare the changes of the overall prevalence of sensitization (then by year-of-birth cohort for food). Wilcoxon signed-rank test was applied to compare the median of IgE level to food mix groups between ECRHS III and ECRHS II.

All statistical analyses were conducted using R 3.6.3 [19]. A significance level of 0.05 was adopted in this analysis.

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