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Background: Day care centre attendance is much more common in East than in West Germany. Although there is evidence that early day care might be protective against atopic diseases, several studies have shown a higher prevalence of childhood eczema in East Germany compared to West Germany.Objectives: To compare prevalence and cumulative incidence of eczema in a birth cohort study in East and West Germany and to identify risk factors that are associated with eczema, which might explain regional differences.Methods: We used data from the ongoing population-based birth cohort study Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany Plus the influence of traffic emissions and genetics. In 1997, 3097 children from study areas in East and West Germany were recruited. Cumulative incidence and 1-year prevalences of eczema up to the age of 6 years were determined from yearly questionnaires. Cox regression and generalized estimating equations/logistic regression were used to quantify regional differences and to identify risk factors that might explain them.Results: Prevalence and incidence of eczema were higher in children living in East Germany than those living in West Germany. We identified 11 risk factors that showed significant regional differences. From these factors, only 'day care attendance during the first 2 years of life' was significantly associated with eczema (odds ratio 1.56, 95% confidence interval CI 1.31-1.86). The regional differences in eczema could be explained by differences in early day care utilization.Conclusion: Day care centre attendance is associated with an increased prevalence and incidence of eczema. Regional differences in eczema prevalence could be explained by regional differences in utilization of early day care.

The aim of this study was to analyse whether altered cytokine production by cord blood (CB) T cells is of relevance regarding the development of allergic diseases during the first 2 yr of life independent from known or suspected risk factors for allergy. Within an ongoing birth cohort study (Life style - Immune System - Allergy; LISA) the cytokine production of PMA/ionomycin-stimulated CB cells was measured by intracellular cytokine staining. Data of 98 children from Leipzig and Munich with complete information on cytokine production at birth and allergic outcomes during the first 2 yr were analysed. Statistical analysis was performed using a regression model adjusted for gender, month of birth, parental history of atopy, parental education, exposure to environmental tobacco smoke, maternal smoking during pregnancy, renovation activities during pregnancy, pet ownership and study centre. During the first 2 yr of life, 17.3% of the children developed a physician-diagnosed atopic dermatitis. Children with reduced frequencies of interferon-g (IFN-g)-producing CD4+ T cells in the CB (1st quartile) had a higher risk to develop atopic dermatitis (adjusted OR 5.16, 95% CI: 1.04-25.6). Furthermore, a high percentage of interleukin (IL)-4-producing T cells in CB in children from the Leipzig cohort were associated with an increased risk for atopic dermatitis (adjusted OR 8.92, 95% CI: 1.40-56.93 for the 90th percentile). CD8+ cytokine-producing CB T cells had no relation to increased risk for atopic dermatitis. Low amounts of IFN-g and high amounts of IL-4-producing T cells at birth may enhance the risk of subsequent development of atopic dermatitis.

Functional studies have provided evidence for the importance of IL-17A and IL-17E in the regulation of immune responses. IL-17A is involved in inflammation and IL-17E is able to induce Th2 cytokine production and eosinophilia. By now it is not clear whether these cytokines correlate with specific IgE levels. The aim of our investigation was to analyse the relationship of these two cytokines to allergic sensitization in context of an epidemiological study. Within the Life style Immune System Allergy study (LISA), we analysed phytohemagglutinin (PHA)-stimulated blood samples of 6 yr old children for the concentration of IL-17A and IL-17E and sera for levels of specific IgE. In total, data from 293 children were available for blood analysis and for the analysis of confounding factors for the allergic sensitization. Among the investigated children, 29% reacted against inhalant and 13.6% against food allergens, whereas 33.1% of children were sensitized to any allergen. IL-17E was associated with high levels of any specific IgE (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI) 1.11-1.90). Furthermore, children with high IL-17E responses (>208.8 pg/ml) were sensitized to food and inhalant allergens (OR 1.45, 95% CI 1.02-2.07 and OR 1.35, 95% CI 1.03-1.77, respectively) and to Der p 1 (OR 1.55, 95% CI 1.12-2.15). In contrast, IL-17A, in trend, was negatively associated to sensitization to timothy (p for trend=0.013) and rye (p for trend=0.026). Concluding IL-17E production is linked to the amount of specific IgE antibodies in blood samples of 6 yr old children.

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There is concern about indoor air quality as a possible cause for health impairment. Exposure to indoor renovation activities has been shown to be associated with airway symptoms and allergic manifestations in children. The aim of this study is to analyse immune markers responsible for disease development in relation to renovation activities. Within the LISAplus (Life style Immune System Allergy) birth cohort study, blood samples of 6-yr-old children were analysed for concentration of the inflammatory markers interleukin (IL)-8, IL-6, tumour necrosis factor-?, MCP-1 and IL-10. Data on indoor renovation activities (painting, flooring, new furniture) were assessed with a questionnaire filled in by the parents. Data on cytokine blood concentrations and exposure variables were available for 250 children. Increased levels of IL-8 and MCP-1 in children's blood were related to renovation activities. In particular, new floor covering was associated with increased inflammatory markers. Among floor covering materials only wall-to-wall carpets were associated with elevated IL-8 and Monocyte Chemoattractant Protein-1 (MCP-1) levels. No association between the single renovation activities painting and furnishing and blood concentration of inflammatory markers has been found. Our data shows that IL-8 and MCP-1 may be suitable markers for monitoring inflammatory reactions in relation with renovation activities. Among renovation activities floor covering seems to induce the strongest inflammatory reactions.

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Background: In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels.Objective: The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts.Method: Data from two German birth cohorts were analysed (n = 1043 for the LISA cohort and n = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes.Results: In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect (P < 0.02 for blood samples taken at each time point in both cohorts). No interaction between the two FCER1A encoding gene and environmental exposures including endotoxin, worm infestation and day care centre attendance during early childhood were observed.Conclusion: Common variants in FCER1A strongly influence basal IgE production independently from environmental stimuli. These effects can be observed already in cord blood pointing to altered gene expression in foetus.

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Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-? (IFN-?) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-? concentrations in children's blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.

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Aim: To describe day care attendance in Germany today (in former East and former West Germany). To investigate longitudinally whether children attending day care centres have an increased risk of acquiring common cold, bronchitis, pneumonia, otitis media or diarrhea.Methods: Questionnaire information was collected when the children in the cohort were 6, 12, 18, 24 months, and 4 and 6 years old. Day care within the first and first 2 years of life was investigated longitudinally with GEE (generalised estimating equations) methods in relation to common cold, bronchitis, pneumonia, otitis media and diarrhea within the first 6 years of life.Results: Day care centre attendance is more common in former East than in former West Germany; this difference is evident even 10-12 years after German reunification. Children attending a day care centre were more likely to have common cold, bronchitis, pneumonia, otitis media and diarrhea within the first 2-3 years of life. With the exception of common cold, from year 4 onwards these associations were not statistically significant anymore and even reversed for some of the infections.Conclusions: Children attending day care centres were at an increased risk of respiratory and gastrointestinal infections within the first years of life. However, around school age these differences disappeared or even partly reversed.

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Indoor environment has been associated with allergic disease. Further, it has been observed that the prevalences of allergic sensitization are different in different social groups. We therefore investigated the association between socioeconomic status (SES) and indoor bio-contaminants. House dust samples were collected from parents' and infants' mattress from 2166 families in Munich (62.2%) and Leipzig (37.8%), Germany. Major mite allergen Der p 1 and Der f 1, cat allergen Fel d 1, and endotoxin were extracted and quantified. Parental educational level and family equivalent income were used independently as socioeconomic indicators. Indoor endotoxin, mite allergen Der p 1, and the amount of sampled dust were not associated with the social factors. Mite allergen Der f 1 was slightly associated by family SES but without a consistent pattern. In families who are not cat owners, however, a negative association between the amount of cat allergen and family SES were observed. The observed negative association between cat allergen loads and concentrations in mattress and family SES in non-cat owners' homes indicated that community is an important source of cat allergen exposure.

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Background: Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children.Subjects and Methods: Parents of participants of the ongoing LISA birth cohort study were asked to give information on life events, such as severe disease or death of a family member, unemployment, or divorce of the parents. Lifetime prevalence of AE and incidence after the assessment period for life events were compared.Results: Prevalence of AE until the age of 4 years was 21.4%. Reported life events within the first 2 years were: severe disease (17.5%) or death (8.4%) of a family member, divorce/separation (3.4%), and unemployment (2.7%). Divorce/separation was associated with a significantly [odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69-7.66] increased and disease with a significantly (OR 0.29, 95% CI 0.13-0.68) decreased incidence of AE for the subsequent 2 years of life. No effect was seen for unemployment.Conclusions: Divorce/separation of the parents and severe disease of a family member influence the risk of developing AE.

Background: It remains controversial whether fatty acid (FA) composition of breast milk relates to development of atopy in the infant. This study evaluates FA in colostrum from mothers of children at high risk of atopy in association with atopy at the age of 1 year.Methods: The FA of colostrum were analyzed for 218 children (60 with low birth weight between 1500 and 2500 g, 84 with a history of maternal atopy, and 74 with an elevated cord blood immunoglobulin (Ig)E of >0.9 IU/ml). Total lipids were extracted, methylated and separated by gas-liquid chromatography. Laboratory screening for allergic sensitization and clinical examination took place within the Leipzig Allergy Risk Children's Study (LARS).Results: Low birth weight was correlated with low percentage levels of 20:2n-6, 22:2n-6, and 22:3n-3 (r = 0.14, P < 0.05; r = 0.14, P < 0.05 and r = 0.20, P < 0.01, respectively) and low gestational age at birth was correlated with low 22:3n-3 (r = 0.15, P < 0.05). There was no association between FA and atopic eczema at the age of 1 year. However, high linoleic acid (LA, 18:2n-6) was linked to high specific IgE against cow's milk protein (P < 0.05), and low docosapentaenoic acid (DPA, 22:5n-3) was associated with elevated total serum IgE (P < 0.05) at the age of 1 year, respectively.Conclusions: The polyunsaturated fatty acid composition of colostrum in a high risk newborn population shows associations with atopic sensitization at the age of 1 year and may be predictive for later atopic disease.

It has been hypothesized that cesarean delivery might have an impact on the development of atopic diseases because of its gut flora modulating properties. In the present study, we analysed the association between cesarean delivery and atopic diseases using data of 2500 infants enrolled in the LISA-Study, a German prospective multicenter birth cohort study. Data on symptoms and physician-diagnosed atopic diseases were gathered by questionnaires shortly after birth and at infant's age 6, 12, 18, and 24 months. In addition, sensitization to common food and inhalant allergens was assessed by measuring specific immunoglobulin E (IgE) using the CAP-RAST FEIA method at the age of 2 yr. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. We found a positive association between cesarean delivery and occurrence of at least one episode of wheezing [aOR 1.31 (95% CI 1.02-1.68)] and of recurrent wheezing [1.41 (1.02-1.96)] during the first 2 yr of life. Furthermore, effect estimates for allergic sensitization defined as at least one specific IgE =0.70 kU/l against any allergen [1.48 (0.98-2.24)], against food allergens [1.64 (1.03-2.63)], and against inhalant allergens [1.75 (0.98-3.12)] were increased. Symptoms of atopic dermatitis [1.21 (0.92-1.59)], physician-diagnosed atopic dermatitis [1.04 (0.79-1.39)], and symptoms of allergic rhinoconjunctivitis [1.40 (0.80-2.44)] were only marginally increased in children delivered by cesarean section. In conclusion, our results suggest that cesarean delivery may be an additional risk factor for wheezing and allergic sensitization at least to food allergens up to the age of 2 yr. This should be considered when cesarean section is done for other than medical reasons.

East–West differences in prevalence of asthma and allergies were suggested to be associated with lifestyle factors. To describe endotoxin levels in mattress dust samples from East and West German homes collected approximately 10 years after reunification. To identify factors that may account for an East–West difference. Dust was collected from mattresses of 2157 infants and 2108 mothers living in Leipzig (former East Germany) and Munich (West Germany). Endotoxin was measured using a chromogenic kinetic Limulus amoebocyte lysate test. Data on bedding, dwelling, and housing characteristics, and occupants’ behavior were collected using a self-administered questionnaire. Endotoxin levels were significantly higher in Leipzig compared with Munich for the infants’ mattresses but not for the mothers’ mattresses. Apart from this, predictors for the mothers’ and the infants’ mattresses were very similar. Pet-ownership and contact with animals outside the home were most influential. Endotoxin levels in mattress dust were highest in summer and increased with the number of persons living in the household. The overall percentage of variability in endotoxin levels explained by these factors was low. Endotoxin levels were associated with lifestyle factors discussed within the framework of the hygiene hypothesis. None of these factors explains the difference in infant's mattress dust endotoxin between Leipzig and Munich or could be used as a surrogate for endotoxin.

Indoor VOC (volatile organic compound) exposure has been shown to be correlated with airway symptoms and allergic manifestations in children. An investigation was conducted within an ongoing birth cohort study (LISA: Lifestyle-Immune System-Allergy) of the association between maternal exposure to VOCs and immune status at birth, in particular the cytokine secretion profile of cord-blood T cells. In a randomly selected group of 85 neonates, cytokine-producing cord-blood T cells were analyzed using intracellular cytokine detection. VOC exposure was measured in children's dwellings by passive sampling, while parents were asked to complete questionnaires about possible sources of VOC exposure. Adjusted odds ratios (ORs) were calculated by logistic regression based on categorized quartiles. A positive association was found between elevated percentages of interleukin-4-producing (IL-4) type 2 T cells and exposure to naphthalene (OR = 2.9) and methylcyclopentane (OR = 3.3). Exposure to tetrachloroethylene was associated with reduced percentages of interferon-gamma-producing (IFN-gamma) type I T cells (OR = 2.9). In addition, smoking during pregnancy was correlated with a higher indoor air concentration of naphthalene (OR = 3.8), new carpets in infants' bedrooms with elevated methylcyclopentane concentrations (OR = 4.1), and home renovation with a higher trichloroethylene burden (OR = 4.9). Our data suggest that maternal exposure to VOC may have an influence on the immune status of the newborn child. (C) 2002 Wiley Periodicals, Inc.

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Background: Within an ongoing birth cohort study (LISA) the cytokine production of cord blood T cells was compared between neonates from Leipzig (East Germany) and Munich (West Germany). The aim of this study was to analyse regional differences and influencing factors of the immune status.Methods: Cytokine production was measured in a randomly selected subgroup of 158 children from the LISA (Life style - Immune system - Allergy) cohort by intracellular cytokine staining. Information on family "atopy" history (FAH) and home characteristics was obtained from questionnaires.Results: Reduced numbers of interferon-? (IFN-?) and tumor necrosis factor-a (TNF-a) producing T cells were found in association with biparental FAH and housing renovation during pregnancy. In addition, cytokine production was influenced by season. In Munich, the frequency of biparental FAH and of renovation measures during pregnancy was significantly higher as compared to Leipzig. Neonates from Munich showed significantly decreased amounts of IFN-? and TNF-a and elevated levels of interleukin-4 (IL-4) producing T cells. Differences in cytokine production between Munich and Leipzig were influenced by season (IL-4) and housing renovation (IFN-?, TNF-a).Conclusions: Since differences in the T cell cytokine production of neonates in Munich and Leipzig are independent from FAH our findings may provide evidence for the impact of environmental factors upon the fetal immune system.

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