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Background: Data on the long-term impact of hydrolyzed formulas on allergies are scarce., Objective: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence., Methods: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models., Results: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula., Conclusion: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence., (© 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.)

The increase of allergies in East Germany--reaching West German prevalence shortly after the reunification--is considered a model for the allergy epidemic in the western world. Whether such a pattern was observed in all comparison studies and for all allergic manifestations is not known because a complete overview is missing. Hints about possible causal factors for the allergy epidemic could be gained by identifying known risk factors, which explain the observed pattern of allergy development in Germany. Again, an overview about these efforts is missing. We identified 14 cross-sectional studies conducted after 1989 and calculated prevalence ratios (West/East) for asthma, hayfever, eczema and allergic sensitization. Additionally, a tabular overview about the explanatory power of risk factors hypothesized in the nineties and covering outdoor exposure, indoor factors, early childhood influences, nutrition as well as awareness is given. At the time of the German reunification, the prevalence ratio West/East was largest for hayfever and sensitization to birch pollen, less pronounced for the other phenotypes and even less than one for atopic eczema. Hayfever and sensitization to birch pollen also showed the steepest increase in East Germany afterwards. Single-room heating with fossil fuels and living as only child in a family were identified as explaining up to 23.5% of the excess trend in East compared to the trend in West. Hayfever as most typical atopic disease showed the difference in allergy pattern between East and West Germany clearest. Risk factors identified for these phenotypes are completely different (single child) or even act in the opposite direction (single-room heating) from classical risk factors for airway diseases. This might be the most important lesson from the West/East German experience. It already stimulated many other studies focussing on protective factors such as microbial stimulation., (© 2014 John Wiley & Sons Ltd.)

Background: Geographical variation in the prevalence of sensitization to aeroallergens may reflect differences in exposure to risk factors such as having older siblings, being raised on a farm or other unidentified exposures., Objective: We wanted to measure geographical variation in skin prick test positivity and assess whether it was explained by differences in family size and/or farm exposure. We also compared prevalence in younger and older subjects., Methods: Within the Global Allergy and Asthma European Network (GA(2) LEN) survey, we measured the prevalence of skin prick positivity to a panel of allergens, and geometric mean serum total immunoglobulin E (IgE), in 3451 participants aged 18-75 years in 13 areas of Europe. Estimated prevalence was standardized to account for study design. We compared prevalence estimates in younger and older subjects and further adjusted for age, gender, smoking history, farm exposure, number of older siblings and body mass index (BMI)., Results: Skin prick test positivity to any one of the measured allergens varied within Europe from 31.4% to 52.9%. Prevalence of sensitization to single allergens also varied. Variation in serum total IgE was less marked. Younger participants had higher skin prick sensitivity prevalence, but not total IgE, than older participants. Geographical variation remained even after adjustment for confounders., Conclusion: Geographical variation in the prevalence of skin prick test positivity in Europe is unlikely to be explained by geographical variation in gender, age, smoking history, farm exposure, family size and BMI. Higher prevalence in younger, compared to older, adults may reflect cohort-associated increases in sensitization or the influence of ageing on immune or tissue responses., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Evidence on the long-term effects of air pollution exposure on childhood allergy is limited., Objective: We investigated the association between air pollution exposure and allergic sensitization to common allergens in children followed prospectively during the first 10 years of life., Methods: Five European birth cohorts participating in the European Study of Cohorts for Air Pollution Effects project were included: BAMSE (Sweden), LISAplus and GINIplus (Germany), MAAS (Great Britain), and PIAMA (The Netherlands). Land-use regression models were applied to assess the individual residential outdoor levels of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5), the mass concentration of particles between 2.5 and 10 μm in size, and levels of particulate matter with an aerodynamic diameter of less than 10 μm (PM10), as well as measurement of the blackness of PM2.5 filters and nitrogen dioxide and nitrogen oxide levels. Blood samples drawn at 4 to 6 years of age, 8 to 10 years of age, or both from more than 6500 children were analyzed for allergen-specific serum IgE against common allergens. Associations were assessed by using multiple logistic regression and subsequent meta-analysis., Results: The prevalence of sensitization to any common allergen within the 5 cohorts ranged between 24.1% and 40.4% at the age of 4 to 6 years and between 34.8% and 47.9% at the age of 8 to 10 years. Overall, air pollution exposure was not associated with sensitization to any common allergen, with odds ratios ranging from 0.94 (95% CI, 0.63-1.40) for a 1 × 10(-5) ∙ m(-1) increase in measurement of the blackness of PM2.5 filters to 1.26 (95% CI, 0.90-1.77) for a 5 μg/m(3) increase in PM2.5 exposure at birth address. Further analyses did not provide consistent evidence for a modification of the air pollution effects by sex, family history of atopy, or moving status., Conclusion: No clear associations between air pollution exposure and development of allergic sensitization in children up to 10 years of age were revealed., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

It may be a coincidence, but it is a fact that the first clear characterization of hay fever began in England where modern industrialization started in Europe. Only at the end of the 20th century were associations of the increasing prevalence of allergy with outdoor air pollution discussed. The seminal study came from Japan from the group of T. Miyamoto linking the increase in Japanese cedar pollinosis to an increased prevalence of Diesel cars and probably exposure to Diesel exhaust in epidemiological, animal experimental and in vitro studies. In Germany first epidemiological studies were done in North Rhine-Westphalia and Bavaria in 1987 and 1988 showing a striking prevalence of allergic disease of up to 10-20% in preschool children. After German reunification the most surprising observation was a lower prevalence of hay fever in East German children compared to the West, although there was a much higher air pollution with SO2 and large particulate matter. Modern smog as found over West German cities most likely originating from traffic exhaust and consisting of fine and ultrafine particles was shown to be associated with higher incidence rates of allergy and allergic sensitization. In the 10 years after reunification there was a steep increase of allergy prevalence in East German children reaching almost the same level as in West Germany. Obviously, a multitude of lifestyle factors - beyond air pollution - may be involved in the explanation of this phenomenon. Surprisingly the skin manifestation of atopy, namely atopic eczema, was more frequent in East German children compared to the West, thus differing from airway allergy. Meanwhile in vitro studies and animal experiments have shown that a variety of air pollutants mostly from environmental tobacco smoke (indoors) and from traffic exhaust (outdoors) can stimulate immune cells inducing a Th2-dominated response besides their irritative effects. While 50 years ago in allergy textbooks a clear distinction was made between 'toxic' or 'allergic', the newly developed concept of allergotoxicology has stimulated research tremendously, meaning 'the investigation of effects of toxic substances upon the induction, elicitation and maintenance of allergic reactions'., (© 2014 S. Karger AG, Basel.)

Background: The long-term effect of nutritional intervention with hydrolysate infant formulas on allergic manifestations in high-risk children is uncertain., Objective: We sought to investigate the effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age., Methods: We analyzed data from participants of the prospective German Infant Nutritional Intervention study after 10 years of follow-up. At birth, children were randomly assigned to receive, for the first 4 months, one of 4 blinded formulas as breast milk substitute, if necessary: partially hydrolyzed whey formula (pHF-W), extensively hydrolyzed whey formula (eHF-W), extensively hydrolyzed casein formula (eHF-C), or standard cow's milk formula. Outcomes were parent-reported, physician-diagnosed allergic diseases. Log-binomial regression models were used for statistical analysis., Results: The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis (n = 2252) was 0.87 (95% CI, 0.77-0.99) for pHF-W, 0.94 (95% CI, 0.83-1.07) for eHF-W, and 0.83 (95% CI, 0.72-0.95) for eHF-C compared with standard cow's milk formula. The corresponding figures for atopic eczema/dermatits (AD) were 0.82 (95% CI, 0.68-1.00), 0.91 (95% CI, 0.76-1.10), and 0.72 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis (n = 988) effects were stronger. The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis, but there was no preventive effect on asthma or allergic rhinitis., Conclusion: The significant preventive effect on the cumulative incidence of allergic diseases, particularly AD, with pHF-W and eHF-C persisted until 10 years without rebound, whereas eHF-W showed no significant risk reduction. There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objective: To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6-10 years., Design: Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. EXPOSURE DEFINITION: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. OUTCOME DEFINITION: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years of age., Data Synthesis: Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models., Results: We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with "no pets" (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84) (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens., Conclusions: Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6-10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Background: The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter-individual genetic differences in fatty acid metabolism., Objective: The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10-year-old children., Methods: The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype., Results: No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n-3/total n-6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%-CI: 1.00-1.57) to 1.31 (95%-CI: 1.01-1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03-1.34) to 1.22 (1.06-1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing., Conclusions & Clinical Relevance: The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children., (© 2011 Blackwell Publishing Ltd.)

In a cross-sectional study performed in 2000, an unexpected positive association between nickel (Ni) in ambient air, urinary Ni content and the prevalence of Ni sensitization in a subgroup of 6-yr-old children living near a steel mill was observed. Between 2005 and 2006, in a different and larger study population, we examined if Ni from ambient air or urinary Ni concentration was related to Ni sensitization in children living next to Ni-emitting steel mills. We studied 749 school beginners living in four Ni-polluted industrial areas of North Rhine-Westphalia, Germany. We assessed Ni in ambient air, Ni in urine from children and mothers, and Ni in tap water, conducted patch tests in children (including the NiSO(4)-dilution test) and collected questionnaire data. Statistics were done by linear and logistic regression analyses, adjusted for covariates. At increased Ni concentration in ambient air (unit of increase: 10 ng/m(3)), urinary Ni concentrations rose in both mothers (9.1%; 95% CI: 6.8-11.4%) and children (2.4%; 95% CI: 0.4-4.4%). The prevalence of Ni sensitization in children was associated with increased Ni from ambient air (unit of increase: 18 ng/m(3); odds ratio 1.28; 95% CI: 1.25-1.32) and urinary Ni concentration (unit of increase: 7.1 μg/L; odds ratio 2.4; 95% CI: 1.20-4.48). Ni in ambient air of areas with Ni-emitting factories contributes to internal Ni exposure in residents via inhalation and, furthermore, is a risk factor for the development of Ni sensitization in children., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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., (© 2010 John Wiley & Sons A/S.)

Background: At the time of the German reunification in 1990, manifestations of most allergic diseases were less prevalent in East than in West Germany. It was hypothesized that these East-West differences would diminish with lifestyle and pollution changes in East Germany., Objective: To investigate whether changes in the prevalence of asthma, hayfever, eczema or allergic sensitization in East Germany approached the levels seen in West Germany and to identify possible lifestyle or environmental factors that may influence this., Methods: Between 1991 and 2000, 6-year-old children from four areas in East Germany participated in an annual survey. Every 3rd year, a parallel survey was performed in four areas of West Germany. In total, 31 903 children were included. Parents completed a questionnaire regarding lifestyle factors and diagnoses and symptoms of asthma, hayfever and eczema. In sub-areas, eczema was clinically assessed by a dermatologist. Specific IgE sensitization was determined for 6121 children. Logistic regression was used to analyse differences in time trends and the influence of lifestyle and pollution changes., Results: Lifestyle and pollution changed significantly differently between East and West Germany. The trends in hayfever and in strong (specific IgE >3.5) sensitization against pollen, and particularly birch pollen, were steeper in East than in West Germany. The trend towards marked pollen sensitization was four times stronger (95% confidence interval 1.2-13.9) in East than in West Germany. Increasing numbers of only children, less single-room heating with fossil fuels and increasing importance of traffic-related pollution in East Germany partly explained these differences in time trends., Conclusions: Hayfever and sensitization against pollen were the most sensitive allergic manifestations to changes experienced specifically in East Germany. Influences of lifestyle (single-room heating, living as a single child) were important in explaining different trend developments.

Background: Only a few studies have analyzed the value of early sensitization in predicting the development of atopic disease. The relevance of low immunoglobulin (Ig) E antibody levels in this respect also remains unclear., Objective: To investigate the relevance of sensitization in 12-month-old children in the development of atopic disease by the age of 6 years., Methods: We analyzed data for 1290 children with a positive family history of atopy from the prospective, multicenter German Infant Nutritional Intervention (GINIplus) study and investigated the relationship between the presence of detectable specific IgE antibodies at the age of 12 months and the development of atopic disease by the age of 6 years., Results: In all, 10.9% of children analyzed developed sensitization. At the age of 6 years, 20.6% of children with early sensitization had eczema compared to 9.4% of those without (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.42-3.74). The corresponding figures were 15.4% vs 7.3% for allergic rhinitis (OR, 2.22; CI, 1.31-3.78) and 10.2% vs 2.6% (OR, 3.93; 95% CI, 1.98-7.76) for asthma. Children with early sensitization to aeroallergens had the greatest risk of subsequent atopic disease. Early sensitization did not increase risk in children without eczema within the first year of life. Very low specific IgE levels (0.18-0.34 kU/L) were not significantly associated with any of the outcomes analyzed., Conclusion: Sensitization to common food allergens and to aeroallergens in particular during the first year of life was found to be a strong predictor for the development of atopic disease by the age of 6 years in children with a positive family history of atopy.

Background: Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors., Aim: The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies., Methods: Within the EU-funded network of excellence GA(2)LEN, we performed meta-analyses with data from 12 ongoing European birth cohort studies on asthma and allergy. Each of the birth cohort studies enrolled between 485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis, eczema) of parents and siblings, parental education, access to ground floor, and number of people living at home were assessed by questionnaires., Results: Among the 25 056 families from seven European countries cats (14.9%) were more common than dogs (12.0%). Allergic family history significantly reduced the odds to own a cat (adjusted combined random-effect OR 0.91; 95% CI 0.85-0.99), or dog (0.90; 0.86-0.94). A higher parental educational level had even more pronounced effects on cat (0.84; 0.71-0.98), and dog ownership (0.61; 0.54-0.70). Elder siblings reduced the odds to own cats, but not dogs. Convenient ground access significantly increased the odds, whereas crowding at home was not associated with cat or dog ownership., Conclusions: The chances to own a cat or dog were significantly reduced in allergic families, in parents with a higher educational level, and in homes without convenient ground access. In addition to parental allergies, social and housing factors should be considered as potential confounders in studies on pet exposure and allergic diseases.

Swimming pool attendance and exposure to chlorination by-products showed adverse health effects on children. We assessed whether early swimming pool attendance, especially baby swimming, is related to higher rates of early infections and to the development of allergic diseases. In 2003-2005, 2192 children were analysed for the 6-year follow-up of a prospective birth cohort study. Data on early swimming pool attendance, other lifestyle factors and medical history were collected by parental-administered questionnaire. Bivariate and multivariate logistic regression analyses were used to evaluate associations. Babies who did not participate in baby swimming had lower rates of infection in the 1st year of life (i) diarrhoea: OR 0.68 CI 95% 0.54-0.85; (ii) otitis media: OR 0.81 CI 95% 0.62-1.05; (iii) airway infections: OR 0.85 CI 95% 0.67-1.09. No clear association could be found between late or non-swimmers and atopic dermatitis or hay fever until the age of 6 years, while higher rates of asthma were found (OR 2.15 95% CI 1.16-3.99), however, potentially due to reverse causation. The study indicates that, in terms of infections, baby swimming might not be as harmless as commonly thought. Further evidence is needed to make conclusions if the current regulations on chlorine in Germany might not protect swimming pool attendees from an increased risk of gastrointestinal infections. In terms of developing atopic diseases there is no verifiable detrimental effect of early swimming.

Background: The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated., Objective: We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial., Methods: Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis., Results: In the intent-to-treat analysis the relative risk of a physician's diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found., Conclusion: The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.

The effect of dog ownership during childhood on the development of allergy has been investigated in few studies with conflicting results. The association between dog contact and indoor endotoxin exposure during infancy and the development of allergic sensitisation and atopic disease up to age 6 yrs was investigated. Two ongoing birth cohorts, the German Infant Nutrition Intervention Programme (GINI; n = 1,962) and the Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA; n = 1,193), were analysed. In both studies, information on children's contact with dogs and their allergic symptoms and doctor-diagnosed allergic disease were collected during follow-up using questionnaires. Specific immunoglobulin E to common aeroallergens was measured at age 6 yrs. House dust samples were collected at age 3 months and the amount of endotoxin was determined. Dog ownership in early childhood was associated with a significantly lower rate of mixed pollen and inhalant sensitisation but not with dog sensitisation or allergic symptoms and diseases up to age 6 yrs. Regular contact with dogs, without ownership, during childhood was not associated with those health outcomes. No associations were found between house dust endotoxin exposure during infancy and sensitisation outcomes. In conclusion, dog ownership in early childhood protects against the development of inhalant sensitisation and this effect cannot be attributed to the simultaneous exposure to endotoxin.

Background: Suppressors of cytokine signalling (SOCS) family members have been shown to play an important role in the balance of cytokines that determine the onset of T-helper type 1 (Th1)- and Th2-mediated immune responses. In particular, for cytokine-induced Src-homology 2 protein (CIS), SOCS1, SOCS3 and SOCS5, a role in the regulation of T cell differentiation has been discussed. However, only few data exist so far in the human system., Objectives: The aim of the present study was to analyse the relationship between these suppressors and Th1/Th2 regulation as well as allergic sensitizations within a population-based study., Methods: Within the Lifestyle-Immune system-Allergy plus cohort study, mRNA was prepared from blood samples of 6-year-old children for the analysis of cytokines, transcription factors for T cell regulation and SOCS molecule expression by quantitative real-time polymerase chain reaction. In addition, total and specific IgE concentrations have been measured by the Pharmacia CAP System. A complete data set from 248 children was available. Results Among the SOCS molecules investigated, only SOCS1 showed a strong positive correlation to allergic sensitizations. In addition, an up-regulated SOCS1 expression correlated with down-regulated T-box expressed in T cells (Tbet) and higher expression levels of GATA-binding protein 3 (GATA-3) and IL-4. No association between SOCS1 and forkhead box P3 (FOXP3) was observed. For SOCS3, SOCS5 and CIS, a contradictory picture was found. The expression of these SOCS molecules was positively correlated with Tbet and FOXP3 and (with the exception of CIS) negatively with IL-4., Conclusions: Our data suggest that SOCS3, SOCS5 and CIS, which correlate with an up-regulated Th1 and regulatory T cell activity, are without relevance for the allergic status. In contrast, SOCS1 might be involved in the development of a Th2-skewed immune response and subsequent allergic sensitizations.

Background: The influence of cat allergen exposure in early childhood on the development of sensitization and allergic diseases is complex. Little is known about the natural course of the sensitization development within individuals., Objective: We investigated the association between cat allergen exposure in infancy and cat ownership and cat contact during childhood and the development of cat sensitization and allergic diseases up to age 6 years using a longitudinal analysis approach., Methods: Overall, 2166 children from an ongoing birth cohort study were included in the analysis. House dust samples were collected 3 months after birth. Cat allergen levels were extracted. Blood samples were collected when the children were 2 and 6 years old. Information on the allergic symptoms of children and doctor-diagnosed allergic disease were collected at each follow-up using questionnaires., Results: Cat allergen exposure in infancy was positively associated with sensitization at age 2 years but not at age 6 years. No associations existed between cat allergen exposure in infancy and allergic symptoms and diseases up to age 6 years. Cumulative allergen exposure from cat ownership and regular cat contact increased the risk of cat sensitization up to age 6 years., Conclusion: Cat allergen exposure in infancy increases the risk of sensitization development in early childhood but not in school-age children. Cumulative allergen exposure from cat ownership and regular cat contact during childhood contribute to sensitization development up to school age., Clinical Implications: Cat allergen avoidance at home alone might be not effective to prevent the development of allergic sensitization in young children.

Background: Among neurogenic factors, the neuropeptides have an important regulatory influence on immune system activity and may lead to allergic sensitization., Objective: The aim of our study was to investigate the relationship of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM) and substance P (SP) on modulation of Th1/Th2 balance and allergic sensitization in children., Methods: Within the LISAplus (Life style-Immune system-Allergy) study, blood samples of 321 six-year-old children were analysed for concentration of neuropeptides, Th1 and Th2 cytokines, transcription factors for T cell regulation and suppressors of cytokine signalling. In addition, samples were screened for specific IgE against inhalant and food allergens., Results: Children with high SOM values showed a Th2 polarization and a reduced expression of FOXP3, the marker for regulatory T cells. High (VIP) levels correlated inversely with the expression of T cell transcription factors (Tbet and SOCS3). In contrast, elevated levels of SP were associated with reduced GATA3 and SOCS3 expression and with increased IFN-gamma concentrations. Allergic sensitization was more prevalent in children with higher SOM and VIP concentrations but not associated with SP levels., Conclusion: Our data reveal an association between neuropeptides and modulatory effects on immune cells in vivo, especially on Th1/Th2 balance with a correlation to allergic sensitization in children. We suggest that elevated SOM and VIP concentrations and the inducing factors should be considered as allergy risk factors.

Background: The role of atopy in the pathophysiology of eczema is still under debate. The concept and analyses of the nonatopic and atopic subtypes of eczema have gained increasing interest in recent studies. The course of these subtypes and differences between boys and girls have not been investigated so far., Objectives: To examine the course of nonatopic and atopic eczema in preschool children from Germany with regard to sex., Methods: Repeated cross-sectional studies were performed in 5-7-year-old preschool children from Germany between 1994 and 2000. Individuals with eczema were identified by a dermatological examination. In addition to a questionnaire, skin prick tests and analyses of serum IgE antibodies against seven and five environmental allergens, respectively, were performed. Atopy was defined by sensitization to at least one of five common aeroallergens (birch, grass and mugwort pollen, house dust mites, cat dander). In part of the study population investigations of spare time behaviour and skin function were carried out (including stratum corneum hydration and skin surface pH)., Results: A total of 2693 girls and 2783 boys underwent a full dermatological examination of the skin and determination of sensitization. Among the girls, 8.7% demonstrated eczema clinically at the day of investigation in contrast to 6.1% of the boys. In girls, early onset eczema (< 2 years of age) was strongly related to atopy at age 5-7 years [odds ratio (OR) 3.7; 95% confidence interval (CI) 2.7-5.1], whereas late-onset eczema (> or = 2 years of age) was not (OR 1.0; 95% CI 0.7-1.5). Boys were more often atopic at the age of 5-7 years than girls (28.3% vs. 20.6%), and early and late-onset eczema were related to atopy without such a difference (OR 2.8, 95% CI 2.0-4.0; OR 1.9, 95% CI 1.3-2.8, respectively). The excess of current eczema in 5-7-year-old girls compared with boys was related to the nonatopic type. The higher susceptibility of girls in that age group to develop eczema was reflected by the skin physiological examination: even girls without eczema had significantly higher skin surface pH and lower stratum corneum hydration than boys. Additionally, questionnaire data revealed that girls more often than boys predominantly played indoors, which was associated with more eczema., Conclusions: Atopy and eczema develop differently in boys and girls. Boys are more often atopic, whereas girls suffer significantly more often from eczema without relation to atopy. The nonatopic type of eczema in preschool girls is noticed predominantly after their second birthday. Genetic and lifestyle factors may contribute to this difference.

Since 1991, annual questionnaire-based surveys have been conducted in order to document the state of health of school beginners in industrial centres and in non-industrial areas in the German states of Sachsen-Anhalt, Saxony and North Rhine-Westphalia. As early as 1994, the results of these studies had shown that the considerable reduction of air pollution by SO2 and dust had resulted in a noticeable decrease of upper respiratory irritations and infections in children residing in formerly heavily polluted East German regions. There was, however, no evidence of a connection between outdoor air pollution and symptoms of allergy and sensitisation. These symptoms were even more frequent in school beginners living in North Rhine-Westphalia than in East German children. With regard to the improvement of outdoor air quality, from 1997 on the study was focussed on a comparison of the prevalence of respiratory diseases, allergies and sensitizations in East and West German children with respect to other eventual risk factors including those originating from indoor conditions. From the beginning, every three years the school beginners were tested for eventual sensitizations using the skin prick test and RAST. Up to 1997, data were recovered from a total of 26121 children. The response rate amounted to 83%. A total of 5338 children were investigated by RAST and 4293 by skin prick testing. After three school years, a total of 1342 children, now nine years old, were questioned anew. The life prevalence of hay fever was 0.5-1.0% in East German children born before 1990 and 3.5-4.0% in those born after the political shift of 1990. Thus, the latter prevalence rate resembled that of West German children. Notably, the increase was true of hay fever symptoms (running or obstipated nose, reddened eyes) and not of bronchial asthma and atopic eczema. The 9-year-old children questioned in 1997, however, did not declare more often ever having suffered from hay fever than those of the same age questioned in 1994. Up to now, the incidence of sensitizations against specific allergens has not changed. Generally, the pattern of sickness and symptoms of 6-year old East German children has become quite similar to that of West German children.

Background: East-West comparison studies in Europe find higher prevalences of infectious airway diseases and lower prevalences of allergies in eastern areas. Pollution from sulphur dioxide (SO2) or total suspended particles (TSP) are discussed as causes of this difference., Methods: In four differently polluted areas of East Germany where pollution decreased dramatically between 1989 and 1995 cross-sectional studies in about 7-year-old children were repeated every year between 1991 and 1995. In two differently polluted areas of West Germany studies with the same design were done in 1991 and 1994. In all, 19090 children participated in the study. Thirteen different questions about airway diseases and allergies were evaluated. Logistic regression was used to adjust for confounding., Results: With the exception of pneumonia, all infectious airway diseases and irritations of the airways show a steeper temporal decrease in East than in West Germany or are positively associated with either SO2 or TSP in East Germany. For allergies and related symptoms no differences in time trends could be detected or no association with SO2 or TSP could be seen in East Germany., Conclusion: Most airway diseases were more frequent in East than in West Germany in 1991 and were associated with SO2 or TSP. The decrease in these pollutants between 1991 and 1995 has already had a favourable effect. An effect of SO2 or TSP pollution on allergies and related symptoms could not be detected. This pollution does not protect against the development of allergies.

Background: Infections in early childhood may prevent allergies in later life. If this hypothesis is true, early exposure to childcare outside the home would protect against atopy by promotion of cross infections. We investigated whether children who attend a nursery at a young age have a lower rate of atopy and fewer allergies than children who attend from an older age., Methods: In a cross-sectional study carried out in 1992-93, we examined 2471 children in three age-groups (5-7, 8-10, and 11-14 years) from the towns of Bitterfeld, Hettstedt, and Zerbst in eastern Germany. The children's parents answered a questionnaire about allergies and symptoms, attendance at day care, and related factors. Sensitisation was assessed by skin-prick tests and measurement of allergen-specific IgE antibodies in serum., Findings: In 669 children from small families (up to three people), the prevalence of atopy was higher among children who started to attend day nursery at an older age than in those who started to attend at a younger age (p<0.05). Compared with children who first attended at age 6-11 months, the adjusted odds ratios for a positive skin-prick test were 1.99 (95% CI 1.08-3.66) for children who attended at age 12-23 months and 2.72 (1.37-5.40) for those who attended at age 24 months and older. In 1761 children from large families (more than three people), age of entry to day nursery had no effect on atopy., Interpretation: Our findings accord with the hypothesis that early infection may protect against allergies in later life.

The fall of the Berlin wall in 1989 offered the unique opportunity to compare populations of a similar genetic and geographic background which had been living under quite different environmental exposure conditions for over 40 years. Since 1990 comparative epidemiological studies were performed between various regions in former East and West Germany with yearly questionnaires and 3 years' physical, dermatological, allergological and exposure examination in a total of about 30,000 preschool children. There were striking differences between the various German regions with higher prevalence rates of respiratory atopy (hay fever, asthma) and atopic sensitization (prick test, RAST) in West Germany, while atopic eczema was significantly higher in East Germany (17.5 vs. 11.4% in West Germany). Total serum IgE levels were markedly higher in children in the east of Germany, similarly to the prevalence of parasitic infestation (questionnaire data as well as positive ascaris RAST). In multivariate logistic regression analysis the following factors were significantly associated with atopic eczema: animal contact (odds ratio, OR 2.9), animal furs in the bedroom (OR 2.2), use of gas without ventilation (OR 1.7) and living near road with heavy traffic (OR 1.7). Furthermore, socioeconomic factors measured as parental educational status (university vs. elementary school) were significantly associated (OR 2.3) with atopy. Respiratory tract infections and irritant responses decreased together with decreasing SO2 and suspended particulate air pollution in East Germany from 1991 to 1997. It is concluded that environmental factors from the physical, chemical, biological, and psychological environment (characteristic of a 'modern' or 'western' society) do influence the development of atopic sensitization and disease.

Earlier epidemiologic studies within Germany found a higher frequency of allergic sensitization in West Germany. The reasons for that and the role of environmental factors in the process of allergic sensitization are not fully understood. This study aimed to determine the prevalence of positive skin-prick test results 5 years after unification and to investigate risk factors for allergic sensitization in preschool children. A total of 1235 children (5-6 years) from two West and five East German locations were skin-prick tested after the compulsory school entrance examination. Six common aero- (birch, grass, mugwort pollen, cat, HDM, alternaria) and two food allergens (egg, milk) were used and additional information was obtained by questionnaire. Of the tested children 23.3% exhibited at least one positive reaction. The prevalence of sensitization to the single allergens was as follows: grass (14.4%), birch (6.6%), mugwort pollen (4.5%), cat (8.5%), HDM (5.5%), alternaria (4.9%), egg (2.8%), and milk (3.9%). In the crude analysis significantly more children were sensitized in the East German city Magdeburg (40.2%) compared to the West German control region Borken (23.5%) (OR 2.20, CI 1.47-3.29). Dampness and visible molds were reported in 8.8% of all households, but significantly more often for East German apartments (10.3% versus West Germany 1.9%, OR 5.85, CI 2.55-16.53). Dampness and molds were associated with a higher frequency of sensitizations (40.6% versus 27.6% in unaffected homes). After controlling for sex, parental atopy, SES, family size, and smoking during pregnancy, this association remained statistically significant (OR 1.93, CI 1.19-3.12). With regard to single allergens, dampness and visible molds were significantly associated with sensitization to HDM (OR 3.37, CI 1.63-6.96), cat (OR 3.19, CI 1.11-5.74), and mugwort pollen (OR 2.86, CI 1.29-6.35). In addition, family size was inversely and linearly associated with the frequency of sensitization (OR for four, three, and two-person households: 1.10 (0.74-1.63), 1.57 (1.06-2.42), 2.70 (1.39-5.24), respectively, when compared to family size of five or more). Neither parental predisposition for atopic diseases nor parental education level influenced the prick test reactivity. We conclude that in addition to genetic predisposition, environmental factors like indoor climate and probably infectious stimuli (family size) play an important role in the process of allergic sensitization in children.