• Frequency of food allergy in school-aged children in eight European countries-The EuroPrevall-iFAAM birth cohort.

      Grabenhenrich, Linus; Trendelenburg, Valérie; Bellach, Johanna; Yürek, Songül; Reich, Andreas; Fiandor, Ana; Rivero, Daniela; Sigurdardottir, Sigurveig; Clausen, Michael; Papadopoulos, Nikolaos G; et al. (Wiley, 2020-03-27)
      Background: The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods: A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). Results: A total of 6105 children participated in this school-age follow-up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow-up) and 3.8% (88 related to 2289 with completed eligibility assessment). Interpretation: In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons. Keywords: IgE; birth cohort study; epidemiology; food allergy; prevalence.
    • Predicting food allergy: The value of patient history reinforced.

      Lyons, Sarah A; Knulst, André C; Burney, Peter G J; Fernandez-Rivas, Montserrat; Ballmer-Weber, Barbara K; Barreales, Laura; Bieli, Christian; Clausen, Michael; Dubakiene, Ruta; Fernandez-Perez, Cristina; et al. (Wiley, 2020-09-07)
      Background: EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy-focused questionnaires. Objective: To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food-related adverse reactions. Methods: Adult and school-age participants in the standardized EuroPrevall population surveys, with self-reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with "probable" FA, defined as a food-specific case history supported by relevant IgE sensitization. Results: In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29-1.41]), oral allergy symptoms (OAS) (4.46 [4.19-4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68-2.95]), asthma comorbidity (1.38 [1.30-1.46]) and male sex (1.50 [1.41-1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85-0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross-validation. In children (N = 670), OAS (2.26 [2.09-2.44]) and AR comorbidity (1.47 [CI 1.39-1.55]) contributed most to prediction of probable FA, with a combined cross-validation-based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. Conclusions: In both adults and school-age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA. Keywords: Europe; food allergy; food sensitization; patient history; prediction.
    • Predictors of Food Sensitization in Children and Adults Across Europe.

      Lyons, Sarah A; Knulst, André C; Burney, Peter G J; Fernández-Rivas, Montserrat; Ballmer-Weber, Barbara K; Barreales, Laura; Bieli, Christian; Clausen, Michael; Dubakiene, Ruta; Fernández-Perez, Cristina; et al. (Elsevier, 2020-04-26)
      Background: The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. Objective: To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. Methods: Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS. Results: Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. Conclusions: Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed. Keywords: Dog; Early-life exposures; Environment; Europe; Food allergy; Food sensitization; Infant diet; Inhalant sensitization; Predictors; Risk factors.
    • Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

      Sigurdardottir, Sigurveig T; Jonasson, Kristjan; Clausen, Michael; Lilja Bjornsdottir, Kristin; Sigurdardottir, Sigridur Erla; Roberts, Graham; Grimshaw, Kate; Papadopoulos, Nikolaos G; Xepapadaki, Paraskevi; Fiandor, Ana; et al. (Wiley, 2021-06-08)
      Background: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children. Methods: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. Results: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors. Conclusion: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies. Keywords: allergic multimorbidity; allergic rhinitis; asthma; children; eczema.
    • Prevalence estimates and risk factors for early childhood wheeze across Europe: the EuroPrevall birth cohort.

      Selby, Anna; Munro, Alasdair; Grimshaw, Kate E; Cornelius, Victoria; Keil, Thomas; Grabenhenrich, Linus; Clausen, Michael; Dubakiene, Ruta; Fiocchi, Alessandro; Kowalski, Marek L; et al. (BMJ Publishing Group, 2018-11-01)
      Preschool wheeze is an important problem worldwide. No comparative population-based studies covering different countries have previously been undertaken. To assess the prevalence of early childhood wheeze across Europe and evaluate risk factors focusing on food allergy, breast feeding and smoke exposure. Infants from nine countries were recruited into the EuroPrevall birth cohort. At 12 and 24 months, data on wheeze, allergic signs/symptoms, feeding, smoke exposure, infections and day care attendance were collected using questionnaires. Poisson regression was used to assess risk factors for wheeze. 12 049 infants were recruited. Data from the second year of life were available in 8805 (73.1%). The prevalence of wheeze in the second year of life ranged from <2% in Lodz (Poland) and Vilnius (Lithuania) to 13.1% (95% CI 10.7% to 15.5%) in Southampton (UK) and 17.2% (95% CI 15.0% 19.5%) in Reykjavik (Iceland). In multivariable analysis, frequent lower respiratory tract infections in the first and second years of life (incidence rate ratio (IRR) 1.9 (95% CI 1.3 to 2.6) and 2.5 (95% CI 1.9 to3.4), respectively), postnatal maternal smoking (IRR 1.6, 95% CI 1.1 to 2.4), day care attendance (IRR 1.6, 95% CI 1.1 to 2.5) and male gender (IRR 1.3, 95% CI 1.0 to 1.7) were associated with wheeze. The strength of their association with wheeze differed between countries. Food allergy and breast feeding were not independently associated with wheeze.
    • Prevalence of Food Sensitization and Food Allergy in Children Across Europe.

      Lyons, Sarah A; Clausen, Michael; Knulst, André C; Ballmer-Weber, Barbara K; Fernandez-Rivas, Montserrat; Barreales, Laura; Bieli, Christian; Dubakiene, Ruta; Fernandez-Perez, Cristina; Jedrzejczak-Czechowicz, Monika; et al. (Elsevier, 2020-04-21)
      Background: For adults, prevalence estimates of food sensitization (FS) and food allergy (FA) have been obtained in a standardized manner across Europe. For children, such estimates are lacking. Objectives: To determine the prevalence of self-reported FA, FS, probable FA (symptoms plus IgE sensitization), and challenge-confirmed FA in European school-age children. Methods: Data on self-reported FA were collected through a screening questionnaire sent to a random sample of the general population of 7- to 10-year-old children in 8 European centers in phase I of the EuroPrevall study. Data on FS and probable FA were obtained in phase II, comprising an extensive questionnaire on reactions to 24 commonly implicated foods, and serology testing. Food challenge was performed in phase III. Results: Prevalence (95% CI) of self-reported FA ranged from 6.5% (5.4-7.6) in Athens to 24.6% (22.8-26.5) in Lodz; prevalence of FS ranged from 11.0% (9.7-12.3) in Reykjavik to 28.7% (26.9-30.6) in Zurich; and prevalence of probable FA ranged from 1.9% (0.8-3.5) in Reykjavik to 5.6% (3.6-8.1) in Lodz. In all centers, most food-sensitized subjects had primary (non-cross-reactive) FS. However, FS due to birch pollen related cross-reactivity was also common in Central-Northern Europe. Probable FA to milk and egg occurred frequently throughout Europe; to fish and shrimp mainly in the Mediterranean and Reykjavik. Peach, kiwi, and peanut were prominent sources of plant FA in most countries, along with notably hazelnut, apple, carrot, and celery in Central-Northern Europe and lentils and walnut in the Mediterranean. Conclusions: There are large geograhical differences in the prevalence of FS and FA in school-age children across Europe. Both primary and cross-reactive FS and FA occur frequently. Keywords: Causative foods; Children; Cross-reactivity; Europe; Food allergy; Food sensitization; Prevalence.
    • Risk Factors for Hen's Egg Allergy in Europe: EuroPrevall Birth Cohort.

      Grimshaw, Kate E C; Roberts, Graham; Selby, Anna; Reich, Andreas; Butiene, Indra; Clausen, Michael; Dubakiene, Ruta; Fiandor, Ana; Fiocchi, Alessandro; Grabenhenrich, Linus B; et al. (Elsevier, 2019-12-14)
      Background: Hen's egg is one of the commonest causes of food allergy, but there are little data on its risk factors. Objective: To assess the risk factors, particularly eczema, for hen's egg allergy in the EuroPrevall birth cohort. Methods: In the pan-European EuroPrevall birth cohort, questionnaires were undertaken at 12 and 24 months or when parents reported symptoms. Children with suspected egg allergy were invited for skin prick testing, specific IgE assessment, and double-blind, placebo-controlled food challenge (DBPCFC) as indicated. Each egg allergy case (positive DBPCFC or egg-induced anaphylaxis) was allocated up to 2 age- and country-matched controls. Results: A total of 12,049 infants were recruited into the EuroPrevall birth cohort, and 9,336 (77.5%) were followed until 2 years. A total of 86 infants had egg allergy (84 by DBPCFC) and were matched with 140 controls. Independently associated with egg allergy were past/current eczema (adjusted odds ratio, 9.21; 95% CI, 2.65-32.04), Scoring Atopic Dermatitis (1.54 per 5 units; 1.28-1.86), antibiotics in the first week of life (6.17; 1.42-26.89), and current rhinitis (3.02; 1.04-8.78). Increasing eczema severity was associated with an increasing likelihood of egg allergy. Eczema was reported to have started 3.6 (SE, 0.5) months before egg allergy. Age of introduction of egg into the diet was not associated with egg allergy. Conclusions: Similar to peanut allergy, eczema was strongly associated with egg allergy development and the association increased with increasing eczema severity. The age of introduction of dietary egg was not a risk factor. The potential role of antibiotics in early life as a risk factor for egg allergy needs further examination.