Search

Aim: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 di ...

BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P

Background: Published data about a relationship of atopic diseases to Bacillus Calmette-Guerin (BCG) vaccination and tuberculin responses are inconsistent. Our aim was to determine this association in a country with a low prevalence of allergies. Methods: A random sample of 10–11-year-old schoolchildren in Tallinn was studied by a parental questionnaire (n = 979) and skin-prick tests (n = 643), according to the International Study of Asthma and Allergies in Childhood. Data about BCG vaccinations and tuberculin tests were obtained from school records (n = 723). Results: The prevalence of allergic symptoms and atopy was similar in children vaccinated during the first month of life and later. Positive tuberculin responses (≥5 mm) were inversely related to symptoms of asthma [odds ratio (OR) 0.10 (95% confidence interval 0.00–0.68) for exercise-induced wheezing; OR 0.37 (0.12–0.99) for night cough], and eczema [OR 0.53 (0.28–0.98)] but not to atopy. However, among BCG-revaccinated children, atopy tended to be more common in tuberculin responders, and the atopic children were significantly more likely to have a positive tuberculin response after the revaccination than would be predicted by their first test. Conclusions: We found no protective effect of early BCG vaccination against atopy in school age, although tuberculin responses and allergic symptoms were inversely related.

Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis.Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P0.05), with per allele odds ratios generally1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies.Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

The authors are indebted to the collaborators in the participating centres and all parents, children, teachers and other school staff who participated in the surveys. There are many field workers and funding agencies who supported data collection and national, regional and international meetings, including the meetings of the ISAAC Steering Committee. Unfortunately, these are too numerous to mention (they are acknowledged elsewhere) but the authors particularly wish to thank the funders who supported the ISAAC International Data Centre including the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the National Child Health Research Foundation, the Hawke’s Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand and Astra New Zealand, as well as Glaxo Wellcome International Medical Affairs for finding the regional coordinating centres. The International Data Centre is now supported by a grant from the BUPA Foundation., The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit., peer-reviewed

To compare the prevalence of self-reported food allergy and IgE antibodies to food allergens in wheezing and non-wheezing Estonian and Swedish schoolchildren, in the light of the disparities in the standard of living, food consumption and prevalence of respiratory allergies that still exist between Estonia and the Scandinavian countries.As a part of the ISAAC Phase II study, children from a random sample of schools in Tallinn in Estonia and Linköping and Ostersund in Sweden participated in skin prick tests to inhalant allergens and the parents replied to questionnaires. IgE antibodies against a panel of food allergens (egg white, milk, soy bean, fish, wheat and peanut) were taken from children with questionnaire-reported wheezing and a random sample of nonwheezing children.Children aged 10-11 y.The prevalence of self-reported food allergy was similar in Estonia and Sweden and about twice as high in wheezing children than in nonwheezing children. In Estonia, however, 3% of the children with perceived food allergy reported reactions from at least four different foods, as compared to 31% in Sweden. The prevalence of sensitisation to food allergens was similar in wheezing and nonwheezing children in Estonia (8%) while, in Swedish children, IgE antibodies to food allergens were more likely among wheezing children (Linköping 38 vs 11%, crude OR 5.1, 95% CI 2.2-11.6, and Ostersund 24 vs 7%, crude OR 4.1, 95% CI 1.9-8.5).Our study suggests that IgE-mediated food reactions were less likely in Estonian schoolchildren. Moreover, the perception of food allergy and thereby the meaning of self-reported food allergy appears to be different in the two countries.

We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood.We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence.The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03).The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors.To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries.In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Linköping (n = 911) and Ostersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol.The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in Ostersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Linköping and 58% in Ostersund) bronchial hyper-responsiveness (BHR) (48% in Linköping and Ostersund) and anti-asthmatic treatment (63% in Linköping and 81% in Ostersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (Ostersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children.Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

There is a lack of established criteria to identify asthma and bronchial hyperreactivity (BHR) in epidemiological studies, although both conditions appear to bear some relationship to atopy, at least in children. Recent studies indicate a low prevalence of atopy in former Socialist countries in Europe, yet the prevalence of BHR has been reported to be high. We have analysed the relationship between the outcome of various lung function tests, atopy and clinical symptoms of bronchial asthma in an epidemiological survey of Estonian 10-12 year old schoolchildren. Metacholine provocation test (four steps with the cumulative doses 100, 300, 700 and 1100 micrograms), exercise challenge test and PEF-variability over two weeks were done in 806 children in Tallinn (coastal, industrialised city) and 774 children in Tartu (inland, university town). A positive response to the metacholine challenge test was recorded in 19% in Tallinn and in 32% in Tartu (p < 0.001). A similar tendency was observed for a more than 15% decrease of FEV1 in the exercise challenge test, i.e. 6% in Tallinn and 18% in Tartu. There was only a weak relationship between BHR, as defined by either a positive metacholine challenge and/or exercise test, diagnosed asthma and reported wheezing. Thus, 47% of the wheezing children and 30% of the children with asthma had negative test results. Only 17% of the children with a positive metacholine challenge were atopic, as defined by at least one positive skin prick test. In conclusion, none of the methods employed to assess bronchial hyperresponsiveness were very useful for the identification of wheezing and asthmatic children in this epidemiological study. In contrast to the results of studies in Western Europe, most children with bronchial hyperreactivity in Estonia are not atopic.

For establishing asthma prevalence among Estonian schoolchildren 753 10-12 years old children in Tallinn (Tln) and 766 in Tartu (Ta) were investigated in a cross-sectional study, including parental questionnaires, skin prick tests (SPT), serial PEF-measurements and provocation tests with metacholine and exercise tests. Allergic respiratory symptoms were less common among Estonian children than among children in West- and North-European countries. 5.1% of children in Tln and 4.1% in Ta had nocturnal cough without signs of cold; 9.4% of children in Tln and 5.8 in Ta had wheezing in the chest during cold, physical exertion or in contact with animals. The corresponding figure in Sundsvall in Central-Sweden was 13.1%. 13% of children in Tln and 8.3% in Ta had at least one positive SPT (in Urban Sundsvall – 35.3%). 10% had common cold > 6 times a year and coughing bouts for more than 2 weeks after a common cold - respectively 18.8% in Tln and 13.8% in Ta. Estonian schoolchildren have a low prevalence of atopic sensitization but symptoms of respiratory infections and hyperreactivity are frequent.

Four-step methacholine provocation test (cumulative doses of methacholine, respectively 100, 300, 700 and 1100 μg), exercise challenge test and assessment of peak expiratory flow variability (four times daily for two weeks) were used in the cross-sectional study in order to reveal the prevalence of bronchial hyperreactivity among the Estonian schoolchildren. The study included 458 children from Tallinn (industrialized capital, situated on the cost) and 653 children from Tartu (inland, university town) aged 10-12 years. The prevalence of positive skin prick test was 13% in Tallinn and 8.3% in Tartu. Surprisingly the number of positive responses in the methacholine challenge tests was significantly higher in Tartu than in Tallinn (31% and 19% respectively). Similarily, decrease of FEV1, value more than 15% was observed in exercise challenge tests (18% and 6% respectively). There was a good correlation between the data obtained in the methacholine and exercise challenge tests (p=0.006). The findings show that other factors than sensitization to allergens are important for bronchial hyperreactivity.