Background: The occurrence of food allergy has been increasing in the perception of both parents and paediatricians. However, true incidence and tolerance development are unclear due to a lack of good quality population-based studies. Our aim was to determine the frequency and development of hen's egg allergy during early childhood with the best diagnostic standard. Methods: For the German study center of the EuroPrevall birth cohort we included consecutively 1,570 healthy newborns from 4 Berlin university and academic teaching hospitals. Using a standardized questionnaire we interviewed the parents face-to-face at birth and after 12, 24 and 30 months by telephone. Symptomatic children were examined in the study center including double-blind placebo-controlled food challenges if food allergy was suspected. Results: 1,321 of 1,570 children (84.1%) completed the 24-months follow-up. In 12 children (8 boys and 4 girls) hen's egg allergy was confirmed. We estimated the 2-year hen's egg allergy incidence at 1.89% (95%-CI 1.28% - 2.69%) after correcting for eligible children whose parents refused food challenge tests. One year after the confirmed diagnosis 5 of the 12 children tolerated hen's egg, whereas 3 children were still allergic. The parents of the 4 remaining children rejected a second challenge test. Conclusions: The incidence of confirmed hen's egg allergy during the first 2 years of life was almost 2% in Berlin children. Approximately half of these children tolerated hen's egg 1 year later. In order to again assess the allergy status of all children, follow-up examinations at school age are planned.

ProGERD ist eine multizentrische Studie mit dem Hauptziel der Beobachtung von Patienten mit GERD in einem Zeitraum von 5 Jahren nach einer initialen Therapie mit Esomeprazol. Eine Vielzahl von Patienten mit GERD leidet zusätzlich unter Schlafstörungen. In dieser Analyse sind wir der Frage nachgegangen, wie häufig Schlafstörungen vorhanden sind und welche Veränderungen durch eine suffiziente Therapie mit Esomeprazol erreicht werden.

To cite this article: Keil T, McBride D, Grimshaw K, Niggemann B, Xepapadaki P, Zannikos K, Sigurdardottir ST, Clausen M, Reche M, Pascual C, Stanczyk AP, Kowalski ML, Dubakiene R, Drasutiene G, Roberts G, Schoemaker A‐FA, Sprikkelman AB, Fiocchi A, Martelli A, Dufour S, Hourihane J, Kulig M, Wjst M, Yazdanbakhsh M, Szépfalusi Z, van Ree R, Willich SN, Wahn U, Mills ENC, Beyer K. The multinational birth cohort of EuroPrevall: background, aims and methods. Allergy 2010; 65 : 482–490. Abstract Background/aim: The true prevalence and risk factors of food allergies in children are not known because estimates were based predominantly on subjective assessments and skin or serum tests of allergic sensitization to food. The diagnostic gold standard, a double‐blind placebo‐controlled food provocation test, was not performed consistently to confirm suspected allergic reactions in previous population studies in children. This protocol describes the specific aims and diagnostic protocol of a birth cohort study examining prevalence patterns and influential factors of confirmed food allergies in European children from different regions. Methods: Within the collaborative translational research project EuroPrevall, we started a multi‐center birth cohort study, recruiting a total of over 12 000 newborns in nine countries across Europe in 2005–2009. In addition to three telephone interviews during the first 30 months, parents were asked to immediately inform the centers about possible allergic reactions to food at any time during the follow‐up period. Results: All children with suspected food allergy symptoms were clinically evaluated including double‐blind placebo‐controlled food challenge tests. We assessed sensitization to different food allergens by measurements of specific serum immunoglobulin E and skin prick tests, collect blood, saliva or buccal swabs for genetic tests, breast milk for measurement of food proteins/cytokines, and evaluate quality‐of‐life and economic burden of families with food allergic children. Conclusions: This birth cohort provides unique data on prevalence, risk factors, quality‐of‐life, and costs of food allergies in Europe, leading to the development of more informed and integrated preventative and treatment strategies for children with food allergies.

Background: The role of passive smoking for allergies and asthma in children above the age of 3 years remains unclear and possible interactive effects with parental allergies have not been formally evaluated in long‐term studies. To examine the interaction of passive smoking and an allergic predisposition regarding allergic sensitization, allergic airway symptoms and respiratory infections during the first 10 years of life.Methods: In a prospective multicenter birth cohort study with 1314 recruited children in Germany, we assessed serum immunoglobulin E against common allergens at seven time points, and parental smoking and respiratory symptoms annually by using questionnaires. Longitudinal analyses were performed using generalized estimating equation models (stratified by parental allergy status).Results: During the first 10 years, 18% of the children were exposed to regular maternal smoking since pregnancy, 43% to irregular maternal or only paternal smoking. Among children with two allergic parents, a mother who smoked regularly significantly increased the odds for allergic sensitization (adjusted OR 4.8, 95% CI 1.3–18.2) and wheezing (adjusted OR 5.7, 95% CI 1.7–19.0) in her child compared with children who were never exposed. For those with only one allergic parent, the odds were doubled and also statistically significant, whereas in children without allergic parents maternal smoking had no effects. There was no association of maternal smoking with allergic rhinitis or respiratory infections.Conclusions: Our results suggest that regular maternal smoking is a strong risk factor for allergic sensitization and asthma symptoms during the first 10 years of life, but only in children with allergic parents.

BACKGROUND:Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis.METHODS:Infants aged 3-12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15-40) without current antiinflammatory treatment were randomized to receive LGG (5 x 10(9) colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL).RESULTS:Fifty-four infants (LGG group, mean +/- SD SCORAD index 24.6 +/- 8.8) and 48 infants (placebo group, SCORAD index 23.6 +/- 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 +/- 12.4 vs 20.6 +/- 9.9), 8 weeks (22.5 +/- 14.6 vs 17.9 +/- 13.1), and 12 weeks (19.6 +/- 15.4 vs 15.1 +/- 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 +/- 45.0 g vs 3.5 +/- 29.8 g), increase in mean logarithmic total serum IgE (0.17 +/- 0.30 kU/l vs 0.26 +/- 0.45 kU/l), and newly developed allergic sensitization against hen's egg or cow's milk (18.8%vs 10.0%).CONCLUSION:This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy.

BACKGROUND:Proton pump inhibitor therapy has been reported to reduce proliferative changes of the oesophagus significantly in gastro-oesophageal reflux disease (GERD).AIM:To assess the histological effects of esomeprazole treatment on the oesophagus.METHODS:Data were derived from a subgroup of patients participating in the proGERD study, who had either erosive reflux disease (n = 720) or non-erosive reflux disease (n = 35) and who had biopsy data from two sites [(i) 2 cm above the z-line and (ii) at the z-line], obtained at baseline and following treatment with esomeprazole. Proliferative changes of the squamous epithelium were assessed histologically by measuring thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness.RESULTS:In erosive reflux disease patients, the thickness of the basal cell layer and length of the papillae pretreatment were associated with the severity of oesophagitis (P < 0.05), at both biopsy sites. After esomeprazole treatment, baseline thickness and length of papillae were significantly reduced (P < 0.05) at both biopsy sites in non-erosive reflux disease and erosive reflux disease patients (particularly those with Los Angeles grades C and D).CONCLUSION:This demonstrates a strong correlation between severity of GERD and histological parameters. Esomeprazole therapy resulted in clear reversal of proliferative changes observed prior to treatment in the squamous epithelium at both biopsy locations.

BACKGROUND AND AIMS:Gastro-oesophageal reflux disease (GERD) can be associated with a variety of extra-oesophageal disorders (EED) such as chronic cough, asthma, laryngeal disorder or chest pain. The aim of the study was to estimate and compare the prevalence of EED in a population with symptomatic GERD presenting as either erosive reflux disease (ERD) or non-erosive reflux disease (NERD).METHODS:Baseline data were collected from a prospective, multicentre, open cohort study (ProGERD) in which patients will be followed for 5 years after initial treatment with esomeprazole. Within the framework of this trial, all patients underwent gastroscopy and filled out a questionnaire designed to assess EED. The influence of potential prognostic factors on the prevalence of EED was analysed by multivariate (stepwise logistic regression) analysis.RESULTS:6215 patients (3303 male, 2912 female; mean age 54 years) presenting with heartburn were included. EED was detected in 32.8% of all patients. The proportion was significantly higher (P = 0.0002) in ERD patients (34.9%) than in NERD patients (30.5%). As judged from the multivariate analysis, female gender, age, oesophagitis of LA grade C/D, duration of GERD disease greater than 1 years and smoking were significantly associated with EED. ERD patients with oesophagitis of LA grade A or B did not have a significantly higher risk of EED than patients with NERD.CONCLUSIONS:Patients with GERD have a high probability of experiencing EED, which may be associated with a number of prognostic factors such as duration and severity of GERD. Extra-oesophageal disorders are slightly, but statistically, more prevalent in ERD than in NERD patients.

BACKGROUND:The reasons for the rise in asthma and allergies remain unclear. To identify risk or protective factors, it is essential to carry out longitudinal epidemiological studies, preferably birth cohort studies. In Europe, several birth cohort studies on asthma and atopic diseases have been initiated over the last two decades.AIM:One of the work packages within the Global Allergy and Asthma European Network (GA(2)LEN) project was designed to identify and compare European birth cohorts on asthma and atopic diseases. The present review (part I) describes their objectives, study settings, recruitment process and follow-up rates. A subsequent review (part II) will compare outcome and exposure parameters.METHODS:For each birth cohort, we collected detailed information regarding recruitment process, study setting, baseline data (pregnancy, birth, parents/siblings) as well as follow-up rates, outcome and exposure parameters at each time point.RESULTS:We identified and assessed 18 European birth cohorts on asthma, allergic rhinitis and eczema. Six of these studies also focused on food allergies. The birth cohorts were mostly initiated in the 1990s with predominantly urban/metropolitan settings. Many studies were able to maintain high follow-up rates, even after five or more years.CONCLUSIONS:Due to the unique cooperation within the GA(2)LEN project a common database was established containing study characteristics of European birth cohorts on asthma and atopic diseases. This can be used as a basis for evaluating the possibility to pool data and perform meta-analyses, as well as to recommend criteria for conducting future birth cohorts.

BACKGROUND:The Global Allergy and Asthma European Network (GA2LEN) is a consortium of 26 leading European research centres committed to establish a European research area of excellence in the field of allergy and asthma.AIM:One of the GA2LEN work packages was designed to identify and compare the existing European birth cohort studies on asthma and atopic diseases. The present review compares their subjective and objective outcomes as well as exposure variables.METHODS:A common database was established to assess study characteristics of observational birth cohort studies designed to examine asthma and atopic diseases. Data were collected by visiting most of the participating research teams and interviewing all relevant study personnel. For each study, the type of objective/subjective outcome parameters and potentially influential factors were recorded precisely for every time point during follow-up.RESULTS:Eighteen birth cohort studies on asthma and atopic diseases were identified in eight European countries. Thirteen studies collected data on specific immunoglobulin E (IgE) to various inhalant and food allergens, whereas 12 performed skin prick tests (many at several time points during follow up). Several studies measured lung function, but across the cohorts no comparable standard procedures were used. For subjective evaluation of asthma and allergic rhinitis most studies applied the ISAAC questionnaire (sometimes modified), whereas the assessment of eczema was rather heterogeneous across the studies.CONCLUSION:This GA2LEN initiative established a unique common database of 18 European birth cohorts on asthma and atopic diseases. For selected cohorts, it seems that pooling data and performing common analyses may be possible to examine associations between certain exposure variables (e.g. pet ownership, tobacco smoke exposure and day-care) and selected outcome measures for atopy, asthma or allergic rhinitis (e.g. sensitization assessed by IgE or skin prick tests, doctor's diagnosis of asthma, parental perception regarding asthma/wheezing or hay fever symptoms).

SummaryBackgroundGastro‐oesophageal reflux disease (GERD) is a common and frequently chronic condition that causes considerable costs.AimTo estimate the economic burden caused by patients with erosive and non‐erosive reflux disease, and Barrett's oesophagus.MethodsThe Progression of Gastro‐oesophageal Reflux Disease study includes a total of 6215 patients. At baseline, patients were categorized as non‐erosive reflux disease, erosive reflux disease, or Barrett's oesophagus according to endoscopic findings alone or as confirmed by histology. Direct and indirect disease‐related costs were calculated based on 5273 patients with complete information in the second year of the study.ResultsA total of 73% of the Progression of Gastro‐oesophageal Reflux Disease patients had taken GERD medication, 61% had visited a doctor, and 2% had been hospitalized because of GERD during the previous 12 months. Of all employed persons, 6% reported days off work because of GERD. This health resource utilization caused direct costs of €342 ± 864 (mean ± s.d.) and indirect costs of €40 ± 473 per patient and year. Total costs for patients with Barrett's oesophagus or erosive reflux disease were higher than those for patients with non‐erosive reflux disease.ConclusionPatients with GERD frequently need long‐term medication and doctor care. The disorder is associated with a considerable health economic burden to society.

Objective We describe the validation of a German-language version of the Reflux Disease Questionnaire in what is the first validation study of this patient questionnaire for a non-English speaking population. Gastro-oesophageal reflux disease is one of the most common diseases in primary care and has a significant negative impact on patients' quality of life. There is no gold standard for diagnosing gastro-oesophageal reflux disease, however, so the valid assessment of symptoms is especially important.Design and methods A total of 5689 patients (92%) completed the questionnaire both before treatment and after 2 weeks. The results were tested for validity and reliability. Predictive validity was tested in a pilot study of 100 patients. Convergent validity-was examined using the Quality of Life in Reflux and Dyspepsia Questionnaire for the assessment of disease-specific quality of life and the McMaster Overall Treatment Evaluation for the assessment of therapeutic success.Results Principal component analysis suggested a threefactor solution with the subscores heartburn, regurgitation, and dyspepsia. The internal consistencies of the subscores were between 0.84 and 0.86. Item difficulty ranged from 0.33 to 0.53, and corrected item-total correlation from 0.66 to 0.72. Effect sizes were between 0.8 and 1.0.Conclusion The German version of the questionnaire has good psychometric properties and is responsive to changes in health. Thus, we conclude that the German Reflux Disease Questionnaire is suitable for the assessment of heartburn, regurgitation, and treatment response, both in primary care settings and clinical studies. (c) 2005 Lippincott Williams & Wilkins.

RATIONALE: ETS exposure has been reported as risk factor for allergic airway disorders. We investigated patterns of ETS exposure in children in relation to family characteristics and allergic conditions. METHODS: In a prospective birth cohort study (MAS with n=1314 newborns), ETS exposure, family characteristics, wheezing and allergic rhinitis (AR) were assessed annually by questionnaire or interview. Longitudinal data on patterns of ETS exposure were analyzed using multivariate generalized estimating equation models. RESULTS: Until 10 years of age, 25% of children have been regularly exposed to maternal ETS. The proportion of irregular parental exposure increased from 23% in infancy to 35%. Never been exposed to ETS were 40% (35% with non-atopic parents, 42% with one atopic and 49% with two atopic parents). However, 30% of wheezing children (25% with AR) had been regularly exposed by their mothers compared to 23% in non-wheezing children (23% in children without rhinitis). Children were more likely to be regularly exposed to ETS in families hen their parents had attended school for <10years (OR=2.0[1.6-2.4]), living with single parent (OR=2.5[1.8-3.5]), with no siblings (OR=2.5[1.6-2.8]), with younger mothers (OR=1.05[1.03-1.07]/year), with an obese parent (OR=1.8[1.3-2.7]), or with a cat at home (OR=2.3[1.8-3.1]). Children with an atopic father were less likely to be exposed (OR=1.7[1.2-2.5]). CONCLUSIONS: Despite the knowledge of ETS as a risk factor, a high proportion of children were exposed to parental ETS, also among allergic children. Our findings demonstrate an urgent need for counteractive measures in families with high probability of exposure (e.g. low education, single parent, younger mothers, obese parent).

Background: Mortality rates from ischaemic heart disease have consistently been higher in East compared to West Germany both prior to and since reunification. Coronary care is inversely related to mortality from ischaemic heart disease. The objective of the present study was, therefore, to compare cardiovascular medication in East and West German patients following cardiac rehabilitation.Methods: East German (n=530) and West German (n=1638) patients were included at admission to one of 18 rehabilitation centres. Inclusion criteria were myocardial infarction, coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. The follow-up period was 12 months.Results: At admission, East and West German patients differed with regard to sociodemographic variables, risk factors and medical conditions. At 12 months, a higher percentage of West compared to East German patients were prescribed beta-blockers (71% vs. 65%, P=0.04) and lipid-lowering agents (64% vs. 55%, P=0.002). Angiotensin converting enzyme (ACE) inhibitors, on the other hand, were prescribed more frequently in the East compared to the West (60% vs. 48%, P < 0.001). In multivariable analyses, region of residence remained a significant predictor for the prescription of lipid-lowering agents (East vs. West: OR 0.61, 95% CI 0.46-0.81) and ACE inhibitors (East vs. West: OR 1.78, 95% CI 1.33-2.39).Conclusion: There is a considerable variation in the prescription of cardiovascular medication in secondary prevention within Germany. Some, but not all, of this variation can be explained by differences in patient characteristics. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:Double-blind, placebo-controlled food challenges are time-consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value.OBJECTIVE:To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy.METHODS:We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)-curves were performed; predicted probabilities and predictive decision points were calculated.RESULTS:A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat.CONCLUSION:In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice.

BACKGROUND:Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment.OBJECTIVE:A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use.METHODS:A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab.RESULTS:Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone.CONCLUSIONS:Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.

Conclusions Longterm passive pre- and postnatal tobacco smoke exposure increases the risk for allergic sensitization or wheezing during the first 10 years of life. This effect, however, was only seen in children with a genetic predisposition to allergy.