Christian Fritzsch

Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany.

BACKGROUND Several surveys in children and adults have shown significantly lower prevalences of asthma and allergic diseases in eastern Europe than in western countries. In the former East Germany tremendous changes towards western lifestyle have occurred since unification. The aim of this survey was to investigate time trends in the prevalence of asthma and allergic diseases among children living in the eastern part of Germany. METHODS In 1995-96, 2334 (87.5%) schoolchildren in Leipzig participated in a cross-sectional study that used the same methods as a previous survey done shortly after the fall of communism in 1991-92. A self-administered questionnaire was distributed to the parents. Children underwent cold-air challenge and allergy skinprick tests to six common aeroallergens. FINDINGS The prevalence of hay fever (2.3% [34/1454] vs 5.1% [115/2252], p<0.0001) and atopic sensitisation (19.3% [252/1303] vs 26.7% [434/1624], p<0.0001) increased significantly between 1991-92 and 1995-96. However, there was no significant change in the prevalence of asthma, asthma-related symptoms, or bronchial hyper-responsiveness. INTERPRETATION These findings suggest important differences in the development of atopic disorders. The children were born about 3 years before unification and were therefore exposed to western living conditions only after the third birthday. Thus, factors operating very early in life may be particularly important for the acquisition of childhood asthma, whereas the development of atopic sensitisation and hay fever may also be affected by environmental factors occurring beyond infancy.

Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison.

OBJECTIVES--To compare the prevalence of asthma and allergic disorders among children in Munich, western Germany, and Leipzig, eastern Germany, where environmental exposure, particularly air concentrations of sulphur dioxide and particulate matter, and living conditions have differed over the past 45 years. DESIGN--Prevalence surveys among school-children aged 9-11 years in Leipzig and Munich. Self completion of written questionnaire by the childrens parents and lung function measurements. SUBJECTS--1051 children in Leipzig and 5030 in Munich. SETTING--Primary schools. MAIN OUTCOME MEASURES--Reported lifetime prevalence of asthma and allergic disorders, and bronchial hyperresponsiveness assessed by cold air inhalation challenge. RESULTS--The lifetime prevalence of asthma diagnosed by a doctor was 7.3% (72) in Leipzig and 9.3% (435) in Munich; prevalence of wheezing were 20% (191) and 17% (786) respectively. The prevalence of diagnosed bronchitis was higher in Leipzig than Munich (30.9% (303) v 15.9% (739); p < 0.01). A significant drop in forced expiratory volume (> 9%) after cold air challenge was measured in 6.4% (57) of children in Leipzig and in 7.7% (345) of those in Munich. Hay fever (2.4% (24) v 8.6% (410); p < 0.01) and typical symptoms of rhinitis (16.6% (171) v 19.7% (961); p < 0.05) were reported less often in Leipzig than in Munich. CONCLUSIONS--No significant differences were seen in the lifetime prevalence of asthma, wheezing, and bronchial hyperresponsiveness between children in Leipzig and Munich. The lifetime prevalence of bronchitis was higher in Leipzig than in Munich. The lower prevalence rates of allergic disorders in Leipzig could point toward aetiological factors that are associated with Western lifestyle and living conditions.

A Comprehensive Analysis of Interleukin-4 Receptor Polymorphisms and Their Association with Atopy and IgE Regulation in Childhood

Background: The interleukin (IL) 4/IL13 pathway is involved in the regulation of IgE production associated with atopic diseases. Numerous polymorphisms have been identified in the coding region of the IL4 receptor α chain (IL4Ra) and previous association studies have shown conflicting results. Based on their putative functional role, polymorphisms A148G, T1432C and A1652G, located in the coding region of IL4Ra, were selected for association and haplotype studies in a large German population sample (n = 1,120). Methods: Genotyping was performed using allele-specific PCR and restriction-enzyme-based assays. Haplotypes were estimated, and population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE >115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome variables in a haplotype trend regression analysis. Results: In our population, only polymorphism T1432C showed a trend for a protective effect against atopic rhinitis (odds ratio, OR: 0.52, 95% confidence interval, CI: 0.26–1.02, p = 0.05). When haplotypes were calculated, one haplotype was significantly associated with elevated serum IgE levels at the 50th percentile (OR 1.60, 95% CI 1.08–2.37, p = 0.02). Conclusions: These data indicate that IL4Ra polymorphisms, although suggested to be functionally relevant by in vitro studies, have only a minor influence on IgE regulation in our large population sample.

The treadmill exhausting test is not suitable for screening of growth hormone deficiency

Background/Method: We compared the growth hormone response to a modified exercise test – the treadmill exhausting test – to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. Results: The mean ± SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 ± 1.3 in the pharmacological tests vs. 5.0 ± 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean ± SEM peak GH concentrations (ng/ml) of 5.5 ± 0.5 in the pharmacological tests and 4.1 ± 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. Conclusion: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.

Polymorphismen in der IL-4/IL-13-Signalkaskade beeinflussen die IgE-Regulation und Asthma bronchiale

Background: The IL-4/IL-13 pathway plays a critical role in the IgE regulation and the development of asthma. Previous studies have described an association between genetic alterations in single genes of the IL-4/IL-13 pathway and these two phenotypes. In this study, we analyzed the combined effect of different genetic alterations in the genes of the IL-4/IL-13 pathway (IL-4, IL-13, IL-4Ra and STAT6) on the regulation of IgE and the development of asthma. Methods: In a large cross-sectional study population (ISAAC II) of 1,120 children, aged 9-11 years, 18 polymorphisms in the respective genes of the IL-4/IL-13 pathway were genotyped. Based on linkage disequilibrium and functional relevance, one polymorphism of each gene (IL-4 C-589T, IL-13 C-1112T, IL-4Ra A148G und STAT6 C2892T) was selected to assess gene by gene interactions using a stepwise haplotype procedure following a Cordell model. Results: Certain combinations of polymorphisms in the IL-4/IL-13 pathway significantly influence IgE regulation. Furthermore, a significant protective effect towards the development of asthma was identified. Compared to single gene effects, the risk to develop elevated serum IgE (> 90th percentile) decreased by 80% while the risk to develop asthma dropped by 60%. Conclusion: These data indicate that only a combined analysis of various genetic alterations within the IL-4/IL-13 pathway reveals the development of atopy and asthma bronchiale.