Search

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. [ABSTRACT FROM AUTHOR]

Background Nutritional intervention with hydrolysed infant formulas has been shown efficacious in preventing eczema in children predisposed to allergy. However, this preventive effect has never been related to the natural course of eczema in children with or without a family history of allergy. The aim of this study therefore was to compare the course of eczema in predisposed children after nutritional intervention to the natural course of eczema. Method The prospective German birth cohort study GINIplus includes a total of 5991 children, subdivided into interventional and non-interventional groups. Children with a familial predisposition for allergy whose parents agreed to participate in the prospective, double-blind intervention trial ( N=2252) were randomly assigned at birth to one of four formulas: partially or extensively hydrolysed whey, extensively hydrolysed casein (eHF-C) or standard cow's milk formula. Children with or without familial predisposition represented the non-interventional group ( N=3739). Follow-up data were taken from yearly self-administered questionnaires from 1 up to 6 years. The outcome was physician-diagnosed eczema and its symptoms. The cumulative incidence of eczema in predisposed children with or without nutritional intervention was compared with that of non-predisposed children who did not receive intervention. Cox regression was used to adjust for confounding. Results Predisposed children without nutritional intervention had a 2.1 times higher risk for eczema [95% confidence interval (CI) 1.6–2.7] than children without a familial predisposition. The risk was smaller with nutritional intervention even levelling out to 1.3 (95% CI 0.9–1.9) in children fed eHF-C formula. Conclusion Although direct comparability is somewhat restricted, the data demonstrate that early intervention with hydrolysed infant formulas can substantially compensate up until the age of 6 years for an enhanced risk of childhood eczema due to familial predisposition to allergy. Cite this as: A. v. Berg, U. Krämer, E. Link, C. Bollrath, J. Heinrich, I. Brockow, S. Koletzko, A. Grübl, B. Filipiak-Pittroff, H.-E. Wichmann, C.-P. Bauer, D. Reinhardt, D. Berdel and the GINIplus study group, Clinical & Experimental Allergy, 2010 (40) 627–636. [ABSTRACT FROM AUTHOR]

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. Cite this as: U. Krämer, H. Oppermann, U. Ranft, T. Schäfer, J. Ring and H. Behrendt, Clinical & Experimental Allergy, 2010 (40) 289– 298. [ABSTRACT FROM AUTHOR]

Psoriasis, a skin disease with autoimmune features, can be triggered and exacerbated by genetic and environmental factors. Chemicals can break tolerance to self-antigens by interfering with antigen processing and presentation; therefore, proteins involved in antigen processing may affect susceptibility. We test here whether variants of immunoproteasome subunits LMP2 and LMP7, or antigen peptide transport proteins TAP1 (transporters associated with antigen presentation) and TAP2 are associated with psoriasis. We analyzed 7 single-nucleotide polymorphisms in 321 Caucasian (German) psoriasis patients and 235 unrelated controls by time-of-flight mass spectrometry, using the Sequenom platform. We found strong associations of psoriasis with variant alleles of LMP and TAP (ORTAP_687: 3.3, 95% CI: 1.9–5.7). Genotype effects were generally stronger for males and LMP effects were mainly seen for psoriasis arthropathica. Our results will help define behavioral or drug treatment suggestions to patients and contribute to a better understanding of the role of low molecular weight chemicals in genetic susceptibility to autoimmune diseases.Genes and Immunity (2007) 8, 513–517; doi:10.1038/sj.gene.6364404; published online 21 June 2007 [ABSTRACT FROM AUTHOR]

The principles of maedi-visna eradication programmes were applied to a field trial for the eradication of ovine pulmonary adenocarcinoma (OPA). In two maternal flocks the prevalence of gross and histological lesions in slaughtered animals was 18.3 per cent and 29.8 per cent, respectively. The lambing period was supervised for three consecutive years from 1999 to 2001, during which the lambs were taken away from their mothers at birth, deprived of maternal colostrum, and hand-reared away from other sheep. Over the three-year period, 322 hand-reared animals, mainly male lambs between 10 and 14 months old, were slaughtered; their lungs were examined grossly, 52.5 per cent of them were examined histologically, and 105 samples of caudal mediastinal lymph nodes were examined by PCR. NO OPA tumours were detected in the slaughter specimens from the derived flock, but one lamb had histological lesions in one lung location; intrauterine transmission was ruled out in this case. No clinical OPA has subsequently been observed in the hand-reared flock. Bronchoalveolar lavage samples from the breeding stock were examined by PCR in order to rule out further subclinical cases of OPA. NO Jaagsiekte retrovirus was detected in any of the 488 samples. [ABSTRACT FROM AUTHOR]

Background Mite allergen exposure is an important risk factor for specific IgE production and is associated with asthma, hay fever and eczema. Whether these associations are independent of mite species has not been investigated so far. Objectives To investigate the influence of exposure to the major house dust mite (HDM) allergens Der p 1 and Der f 1 on sensitization, respiratory symptoms, and especially on eczema and related skin symptoms in 6–7-year-old children. Methods In a cross-sectional study in Augsburg (Bavaria, Germany) 1669 school beginners (mean age 6·5 years) were investigated in 1996. The concentrations of Der p 1 and Der f 1 were measured in dust samples from mattresses of 1081 children by enzyme-linked immunosorbent assay. The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and determination of specific serum IgE concentrations by radioallergosorbent test. Information about covariates was taken from questionnaires and interview data. Logistic regression was used to adjust for confounding. Results The mean concentrations of Der p 1 and Der f 1 were 0·68 and 0·79 µg g−1 dust, respectively. The relationship between the two species-specific allergens in individual homes was poor (Pearson correlation 0·2). Influencing variables were bedroom-sharing (Der p 1) and social status of the parents (Der f 1). Respiratory diseases were positively associated with both allergen concentrations [odds ratio (OR) between 1·1 and 2·6]. These associations were significant for sneezing attacks (Der p 1 and Der f 1). Reported prevalence of current (in the last 12 months) itchy skin rash was significantly associated with exposure to Der f 1 only (OR 2·4, P < 0·003); also a diagnosis of atopic eczema on the day of investigation was positively associated with Der f 1 only (OR 1·8, P = 0·14). Conclusions Studies on the effects of HDM exposure on eczema and allergies should consider specific effects of different mite species. This might have implications on assessment of allergen exposure and consecutive prevention or therapeutic measures. [ABSTRACT FROM AUTHOR]

The prevalence of atopic diseases has increased dramatically during recent decades; the reasons are not known. Among various plausible hypotheses the so-called hygiene hypothesis (jungle hypothesis) has gained public interest recently. According to this hypothesis improved hygiene leading to a decreased stimulation of the immune system by infections, parasites, vaccinations or contact with immunostimulating agents has led to an immunodeviation with T helper (Th)2-enhancing effects followed by increased occurrence of IgE-mediated allergies.The hygiene hypothesis is not defined precisely, and some questions remain open: the influence of actual infectious disease or specific vaccinations, the nature of infectious agents (virus, bacteria, fungi, parasites), the definition of the term‘hygiene’, the nature of other immunostimulating agents and the effects upon different atopic diseases. As arguments in favour of the hygiene hypothesis, the following study results are quoted: children of farmers have less allergies; children from academic parents show an increased risk of atopic diseases; children from anthroposophic families have decreased allergy prevalence rates; effects of endotoxin and CD14 gene polymorphism; and the protective influence of gut flora with high amounts of lactobacilli. The following findings argue against the hygiene hypotheses: parasite infections are associated with an increased risk of urticaria and atopic eczema; some microorganisms e.g. respiratory syncytial virus (RSV),Bordetella pertussisenhance IgE production; patients with active tuberculosis have high Th2 reactions; pertussis vaccination has a protective effect; high allergy prevalences in very poor regions (inner city slums in the United States, Africa, Southern America); germfree conditions prevent the spontaneous outbreak of atopic eczema in certain mouse strains, many other influences (e.g. traffic exhaust exposure) are associated with allergy and sensitization. Comparing the prevalence of atopic diseases and sensitization in East and West German children after reunification there was a striking difference with regard to higher prevalence rates of respiratory atopic diseases in West German children compared to the East, which was not seen for atopic eczema. No single factor has been established to explain this East–West German difference. When differences in pertussis vaccination strategy (in West Germany in the 1980s only about 50% of the children were vaccinated, while in East Germany this was obligatory for everyone) were included in the analysis, it became obvious that 20% of West German children were suffering from pertussis infection compared to 0.5% of East German children and pertussis infection increased the risk for atopic respiratory disease, although not for eczema and sensitization. When pertussis vaccination and infection was included among the confounders to be adjusted for in the multivariate logistic regression, the East–West German difference disappeared for asthma and wheezing, so it can be concluded that pertussis vaccination does prevent pertussis infection and thereby prevents asthma and wheezing independent of atopic sensitization. Furthermore, it has become clear that pollens are not only allergen carriers but also produce proinflammatory mediators of eicosanoid-like activity. These pollen-associated lipid mediators (PALMs) − among them pollotrienes − are able to attract neutrophils and activate the innate immune system. They should be regarded together with pollutants and allergens as modulating factors in the determination of allergic disease development.From a critical evaluation of the evidence it is concluded that the hygiene hypothesis represents an attractive theory and stimulus for further research, particularly the more precise aspect of the jungle hypothesis, with an inverse relationship between parasite infestation and respiratory atopy. It seems that the hygiene hypothesis fits only for atopic respiratory but not for atopic skin disease. Regarding the partly controversial data it is too early to give practical recommendations for allergy prevention based on this hypothesis. There is no rationale to recommend avoidance of vaccinations or adequate body cleaning measures. Effective programmes for primary prevention will be possible only after increased research efforts have elucidated the true causes of increased allergy prevalence. [ABSTRACT FROM AUTHOR]

The negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known. Whether there is an effect on atopic eczema is not clear. To determine the impact of ETS on atopic eczema, allergic sensitization and allergic airway diseases in 1669 school beginners. The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and specific immunoglobulin E measurement. Exposure assessments were based on measurement of cotinine [expressed as cotinine to creatine ratio (CCR)] in spot urine samples ( n = 1220) together with questionnaire and interview data on smoking behaviour of the parents. In the total study group, prevalence of atopic eczema diagnosed on examination was significantly associated with urinary CCR values. The odds ratio (OR) and 95% confidence interval (CI), calculated for an increase of 100 ng mg−1 CCR was 1·97 (95% CI 1·23–3·16). The prevalence of skin manifestations according to questionnaire data as well as a history of asthma, wheezing, and hay fever were positively although not significantly associated with ETS exposure. When genetically predisposed children (defined by the presence of parental atopy) were compared with children whose parents had no atopy, the ORs of allergic outcome variables were generally higher in the first group. In the group of predisposed children, significant associations with urinary CCR were found for allergic sensitization against house dust mites as measured by skin prick test (OR 3·10, 95% CI 1·63–5·90). Children are at a higher risk of developing an atopic eczema when exposed to ETS and genetically predisposed children are at higher risk of developing a sensitization against house dust mites. [ABSTRACT FROM AUTHOR]

Background Prevalence data for atopic eczema based on a dermatological examination have not so far been available for East and West Germany. Possible differences in the proportions of extrinsic and intrinsic types of eczema, and how far these could explain differences in the prevalence of eczema, need to be clarified. Objectives To compare the prevalence of atopic eczema in pre-school children between different locations in East and West Germany, and over a period of 7 years, at three time points. Additionally, to determine the proportions of intrinsic and extrinsic types of eczema by taking skin prick test reactivity into account. Methods Repeated cross-sectional studies in 1991, 1994 and 1997 in 5–6-year-old pre-school children at five different locations in West Germany (n = 2075) and six in East Germany (n = 1926) were carried out. Individuals with eczema were identified by an examination performed by physicians of the Department of Dermatology. In addition, a skin prick test and a standardized questionnaire were used. Results The overall prevalence of atopic eczema in these children was 10·4%. At all three times of investigation (1991, 17·5% vs. 11·2%; 1994, 12·6% vs. 8·7%; 1997, 11·2% vs. 4·5%) and in the total group (12·9% vs. 8·2%), the prevalence was significantly higher in East than in West Germany. After controlling for influences of sex, parental history of atopic diseases, observer and socio-economic status in multiple logistic regression analyses, these differences remained significant for 1991, 1994 and for the overall group (odds ratio, OR 1·78, 95% confidence interval, CI 1·43–2·21). Girls (OR 1·56, 95% CI 1·27–1·92) and children whose parents had a higher level of school education (OR 1·17, 95% CI 1·00–1·37) were affected more frequently. Of all children, 26·6%, and of those with eczema, 41·9% exhibited at least one reaction in the prick test (OR 2·21, 95% CI 1·75–2·80; sensitization in eczema vs. no eczema). Whereas 50·4% of the children with eczema in West Germany were sensitized, only 36·5% of the diseased children in East Germany reacted positively in the prick test (OR 1·77, 95% CI 1·12–2·79). Conclusions These results are in accordance with findings regarding allergic sensitization and hay fever and might indicate that factors other than allergy are responsible for the higher prevalence of atopic eczema in East Germany. [ABSTRACT FROM AUTHOR]

Presents details and findings of a study which 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. How infections in early childhood may prevent allergies from developing later in life; How attendance of nursery schools promotes cross infections; Background; Methods; Findings; Interpretation.

Abstract: Since 1988, 82 heart transplants have been performed in 80 infants and children. Diagnoses pretransplant were: hypoplastic left heart syndrome (HLHS) (n = 43); cardiomyopathy (n = 19); endocardial fibroelastosis (n = 6); and other complex congenital heart diseases (n = 12). Age at transplantation was < 1 yr in 61 patients. Overall survival rate was 79% at 1 yr and 73% at 5 and 10 yr. To date, 20 patients have died after transplantation. Causes of death were: rejection (eight patients); right ventricular failure (four patients); transplant coronary artery disease (TCAD) (two patients); and other causes (six patients). In the majority of patients somatic growth is not impaired, and renal function is reduced (but stable) in all patients. Two patients developed post-transplant lymphoproliferative disease, which was treated successfully. Major long-term morbidity is neurologic deficit – severe in three patients and minor in six. TCAD was present or suspected in six surviving patients. We conclude that heart transplantation in infants and children can be performed with good early and late results. Quality of life is excellent in most patients. TCAD, however, will become an increasing problem in the long term. [ABSTRACT FROM AUTHOR]

Abstract: Acute rejection of the donor heart is a major cause of mortality in infant heart transplant recipients. The early diagnosis of acute cardiac rejection (ACR) is crucial. Non-invasive methods have shown poor sensitivity in detecting rejection when compared to endomyocardial biopsies (EMB). We assessed troponin I as a new marker to diagnose cardiac rejection. Serum cardiac troponin I (cTNI) levels were retrospectively analysed in 25 heart transplant patients (ages, 2 wk to 13 yr; mean age, 3 months) presenting 36 acute rejections. In early post-operative rejection and initially elevated cTNI levels, rejection was associated with a second increase of serum cTNI concentrations in 21% of the patients (p = 0.15). If cTNI levels were in normal range before ACR an elevation was monitored in 59% of the rejection periods (p < 0.05). In 25% of the cases (n = 9) cTNI levels remained in normal range during the rejection episode (<0.6 ng/mL), in 22% (n = 8) cTNI levels did not exceed pathological values from 0.6 to 1.5 ng/mL and in 53% (n = 19) the measured levels went beyond 1.5 ng/mL. Maximum concentrations of cTNI were measured mostly 12 d from the moment rejection was suspected (day 1) in patients (median day 3). However, cTNI levels were elevated for 2–43 d after ACR was diagnosed (median 10 d). Twenty per cent of the patients with grade 3 rejection (ISHLT) and 75% of the patients with grade 4 rejection had a corresponding elevated cTNI level (p = 0.013). No false-positive elevations of cTNI were documented. The present data demonstrate that cTNI is a not a sensitive but a specific marker of ACR in children. [ABSTRACT FROM AUTHOR]

Abstract DESY Hamburg operates a test beam facility with three independent beam lines at the DESY II synchrotron. It is world-wide one of very few facilities providing test beams in the GeV range. To this end, it offers electron/positron beams with user-selectable momenta from 1-6 GeV/c. The available infrastructure for the users is unique, including a high field solenoidal magnet and permanently installed high-precision pixel beam telescopes. This publication gives a detailed description of the facility, the available infrastructure, and the simulated and measured performance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The DESY II Test Beam Facility is a key infrastructure for modern high energy physics detector development, providing particles with a small momentum spread in a range from 1 to 6 GeV to user groups e.g. from the LHC experiments and Belle II as well as generic detector R&D. Beam telescopes are provided in all three test beam areas as precise tracking reference without time stamping, with triggered readout and a readout time of > 115 μ s. If the highest available rates are used, multiple particles are traversing the telescopes within one readout frame, thus creating ambiguities that cannot be resolved without additional timing layers. Several upgrades are currently investigated and tested: Firstly, a fast monolithic pixel sensor, the TelePix , to provide precise track timing and triggering on a region of interest is proposed to overcome this limitation. The TelePix is a 180 nm HV-CMOS sensor that has been developed jointly by DESY, KIT and the University of Heidelberg and designed at KIT. In this publication, the performance evaluation is presented: The difference between two amplifier designs is evaluated. A high hit detection efficiency of above 99.9 % combined with a time resolution of below 4 ns at negligible pixel noise rates is determined. Finally, the digital hit output to provide region of interest triggering is evaluated and shows a short absolute delay with respect to a traditional trigger scintillator as well as an excellent time resolution. Secondly, a fast LGAD plane has been proposed to provide a time resolution of a few 10 ps, which is foreseen to drastically improve the timing performance of the telescope. Time resolutions of below 70 ps have been determined in collaboration with the University of California, Santa Barbara. [ABSTRACT FROM AUTHOR]

Several Brassicaceae species are able to hyperaccumulate extraordinarily high levels of heavy metals in their aboveground tissues. This rare and complex trait named metal hyperaccumulation may offer effective protection against antagonists. Several laboratory studies provide evidence that metal hyperaccumulation acts as an elemental defense. Here, we investigated whether this elemental defense can be confirmed in the field and whether plant growth is affected when plants can hyperaccumulate metals from the soil. Plants of Arabidopsis halleri (L.) O'Kane & Al-Shehbaz, which can hyperaccumulate cadmium (Cd) and zinc (Zn), were cultivated in pots in unamended (control) or metal-amended soil (test) for 2 months. The pots containing the plants were then transferred to a common garden. Leaf-damaging insect visitors were monitored over a period of 3 months. Plant size and shoot mass were measured directly before and at the end of the field exposure. Furthermore, before and at the end of the field exposure we determined leaf concentrations of Cd and Zn, as well as glucosinolates, which are characteristic secondary metabolites of the Brassicaceae that are known to act potentially as organic defense compounds. Growth of the test plants on metal-amended soil led to a significant increase in leaf Cd and Zn concentrations when compared to control plants on unamended soil. After two initial months of growth under standardized greenhouse conditions, plants grown on different soils did not differ in size or biomass. In contrast, by the end of the 3-month field exposure, test plants were larger than control plants. During field exposure, control plants were visited by more herbivores, suggesting that plants growing on metal-amended soil were well defended against herbivores. Total glucosinolate concentrations were significantly higher in test compared to control plants only after the initial growth period under standardized conditions, but not by the end of the field exposure, pointing to joint effects of defenses particularly in young plants. Our results demonstrate that metal hyperaccumulation affords an effective elemental defense and enables increased growth under field conditions. [ABSTRACT FROM AUTHOR]

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 ( GA2LEN) 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. [ABSTRACT FROM AUTHOR]

Background Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. Objective We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. Methods The Global Asthma and Allergy Network of Excellence ( GA2 LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis ( CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and Ig E sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. Results One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females ( Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. Conclusions and Clinical Relevance Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures. [ABSTRACT FROM AUTHOR]

Background Specific IgE to Staphylococcus aureus enterotoxins ( SE-IgE) has been associated with asthma. In the general population, we aimed to determine the prevalence of and risk factors for serum SE-IgE and to examine the association with asthma. Methods A postal questionnaire was sent to a random sample of adults in 19 centers across Europe. A random sample of respondents was invited for clinical examination upon which they answered a questionnaire, underwent skin prick tests ( SPTs) for common aeroallergens, and provided blood for measurement of total IgE and SE-IgE. Risks were analyzed within centers using weighted logistic regression, and overall estimates calculated using fixed-effects meta-analysis. Results 2908 subjects were included in this analysis. Prevalence of positive SE-IgE was 29.3%; no significant geographic variation was observed. In contrast to positive skin prick tests, SE-IgE was more common in smokers (<15 pack-year: OR 1.11, P = 0.079, ≥15 pack-year: OR 1.70, P < 0.001), and prevalence did not decrease in older age-groups or in those with many siblings. Total IgE concentrations were higher in those with positive SE-IgE than in those with positive SPT. SE-IgE was associated with asthma ( OR 2.10, 95% confidence interval [1.60-2.76], P = 0.001) in a concentration-dependent manner. This effect was independent of SPT result and homogeneous across all centers. Conclusions We report for the first time that SE-IgE is common in the general population throughout Europe and that its risk factors differ from those of IgE against aeroallergens. This is the first study to show that SE-IgE is significantly and independently associated with asthma in the general population. [ABSTRACT FROM AUTHOR]

Previous studies have found inconsistent results on the association between asthma in children and gas cooking emissions. We aimed to assess the effects of the long-term exposure to gas cooking on the onset of asthma and respiratory symptoms, focusing on wheezing, in children from two German birth cohorts: LISAplus and GINIplus. A total of 5078 children were followed until the age of 10 years. Asthma, wheezing, gas cooking, and exposure to other indoor factors were assessed through parental reported questionnaires administered periodically. Logistic and multinomial regressions adjusting for potential confounders were performed. The prevalence of asthma and persistent wheezing was higher among children exposed to gas cooking but the results were not statistically significant. Exposure to gas cooking was positively associated ( P-value < 0.05) with exposure to other indoor factors (dampness, environmental tobacco smoke, and pets). Our results did not show a statistically significant association between the exposure to gas cooking and children's respiratory health. Practical Implications These analyses are consistent with the assumption of no effect of the exposure to low doses of nitrogen dioxide. The strong positive associations found between gas cooking and other indoor factors highlight the importance of considering other indoor factors when assessing health effects of gas cooking. Low-dose exposure to indoor nitrogen dioxide through gas cooking might not contribute to increase the risk of asthma and respiratory symptoms in children. [ABSTRACT FROM AUTHOR]

To cite this article: Flexeder C, Thiering E, Brüske I, Koletzko S, Bauer C.-P, Wichmann H.-E, Mansmann U, von Berg A, Berdel D, Krämer U, Schaaf B, Lehmann I, Herbarth O, Heinrich J. Growth velocity during infancy and onset of asthma in school-aged children. Allergy 2012; 67: 257-264. Abstract Background: Growth velocities during infancy might affect the risk of asthma in childhood. This study examines the association between peak height and weight velocities during the first 2 years of life and onset of asthma and wheeze up to 10 years of age. Methods: Data from 9086 children who participated in the GINIplus and LISAplus birth cohorts were analyzed. Information on asthma was requested annually from 1 to 10 years and information on wheeze at 1, 2, 4, 6, and 10 years. Peak height and weight velocities were calculated using height and weight measurements obtained between birth and 2 years of age. Cox proportional hazards models and generalized linear mixed models were calculated after adjustment for potential confounding factors including birth weight and body mass index at 10 years of age. Results: Per interquartile range increase in peak weight velocity (PWV), the risk of asthma increased significantly (adjHR: 1.22; CI: 1.02-1.47). The relationship between peak height velocity (PHV) and onset of asthma was nonsignificant (adjHR: 1.08; CI: 0.88-1.31). Wheeze was not significantly associated with PHV or with PWV (adjOR: 1.07; CI: 0.64-1.77 and adjOR: 1.11; CI: 0.68-1.79, respectively). Conclusions: Weight gain during infancy is positively associated with physician-diagnosed asthma in school-aged children. [ABSTRACT FROM AUTHOR]

To cite this article: Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T, Gjomarkaj M, Forsberg B, Gunnbjornsdottir M, Minov J, Brozek G, Dahlen SE, Toskala E, Kowalski ML, Olze H, Howarth P, Krämer U, Baelum J, Loureiro C, Kasper L, Bousquet PJ, Bousquet J, Bachert C, Fokkens W, Burney P. Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe. Allergy 2012; 67: 91-98. Abstract Background: The prevalence of asthma and its association with chronic rhinosinusitis (CRS) have not been widely studied in population-based epidemiological surveys. Methods: The Global Allergy and Asthma Network of Excellence (GA2LEN) conducted a postal questionnaire in representative samples of adults living in Europe to assess the presence of asthma and CRS defined by the European Position Paper on Rhinosinusitis and Nasal Polyps. The prevalence of self-reported current asthma by age group was determined. The association of asthma with CRS in each participating centre was assessed using logistic regression analyses, controlling for age, sex and smoking, and the effect estimates were combined using standard methods of meta-analysis. Results: Over 52 000 adults aged 18-75 years and living in 19 centres in 12 countries took part. In most centres, and overall, the reported prevalence of asthma was lower in older adults (adjusted OR for 65-74 years compared with 15-24 years: 0.72; 95% CI: 0.63-0.81). In all centres, there was a strong association of asthma with CRS (adjusted OR: 3.47; 95% CI: 3.20-3.76) at all ages. The association with asthma was stronger in those reporting both CRS and allergic rhinitis (adjusted OR: 11.85; 95% CI: 10.57-13.17). CRS in the absence of nasal allergies was positively associated with late-onset asthma. Conclusion: Geographical variation in the prevalence of self-reported asthma was observed across Europe, but overall, self-reported asthma was more common in young adults, women and smokers. In all age groups, men and women, and irrespective of smoking behaviour, asthma was also associated with CRS. [ABSTRACT FROM AUTHOR]

To cite this article: Standl M, Sausenthaler S, Lattka E, Koletzko S, Bauer C-P, Wichmann H-E, von Berg A, Berdel D, Krämer U, Schaaf B, Lehmann I, Herbarth O, Klopp N, Koletzko B, Heinrich J. FADS gene cluster modulates the effect of breastfeeding on asthma. Results from the GINIplus and LISAplus studies. Allergy 2012; 67: 83-90. Abstract Background: The protective effect of breastfeeding (BF) on the development of asthma has been widely recognized, even if not all results have been consistent. Gene variants of the FADS gene cluster have a major impact on fatty acid composition in blood and in breast milk. Therefore, we evaluated the influence of the FADS1 FADS2 gene cluster polymorphisms on the association between BF and asthma. Methods: The analysis was based on data ( N = 2245) from two German prospective birth cohort studies. Information on asthma and BF during the first 6 months was collected using questionnaires completed by the parents. Logistic regression modelling was used to analyse the association between exclusive BF and ever having asthma stratified by genotype. Results: In the stratified analyses, BF for 3 or 4 months after birth had a protective effect for heterozygous and homozygous carriers of the minor allele (adjusted odds ratio between 0.37 (95% CI: 0.18-0.80) and 0.42 (95% CI: 0.20-0.88). Interaction terms of BF with genotype were significant and ranged from −1.17 ( P-value: 0.015) to −1.33 (0.0066). Moreover, heterozygous and homozygous carriers of the minor allele who were exclusively breastfed for 5 or 6 months after birth had a reduced risk of asthma [0.32 (0.18-0.57) to 0.47 (0.27-0.81)] in the stratified analyses. For individuals carrying the homozygous major allele, BF showed no significant effect on the development of asthma. Conclusions: The association between exclusive BF and asthma is modified by the genetic variants of FADS genotypes in children. [ABSTRACT FROM AUTHOR]

Summary 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. Cite this as: M. Standl, S. Sausenthaler, E. Lattka, S. Koletzko, C.-P. Bauer, H.-E. Wichmann, A. von Berg, D. Berdel, U. Krämer, B. Schaaf, S. Röder, O. Herbarth, N. Klopp, B. Koletzko and J. Heinrich for the GINIplus and LISAplus Study Group, Clinical & Experimental Allergy, 2011 (41) 1757-1766. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA2LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP3OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. Method: A postal questionnaire was sent to a random sample of adults aged 15-75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP3OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year - with at least one symptom being nasal blockage or discharge. Results: Information was obtained from 57 128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP3OS criteria was 10.9% (range 6.9-27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6-1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP3OS-diagnosed CRS. Conclusion: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe. [ABSTRACT FROM AUTHOR]

Background: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA2LEN European survey. Methods: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chancecorrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. Results: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers ()3.0%, 95% CI: )5.0 to )1.0%, I2 = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Conclusion: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Previous studies have reported a protective association between high levels of exposure to endotoxin during infancy and the development of subsequent eczema within the first 6 months of life. Aim. To investigate the association between exposure in infancy to endotoxin from mattress dust and the development of eczema up to age of 6 years in 2166 children participating in the German Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood (LISA) study, an ongoing population-based birth-cohort study. Methods. Endotoxin levels in house dust samples collected at 3 months after birth were quantified using the kinetic Limulus amebocyte lysate assay. Specific IgE antibodies to common food and aeroallergens were measured using radioallergosorbent test, fluorenzyme immunoassay (Pharmacia CAP system) when children were 2 and 6 years old. Information on eczema symptoms and physician-diagnosed eczema were collected at each follow-up using a questionnaire. Results. No association was found between endotoxin exposure from mattresses (the mattresses of each child and their parents were examined) during infancy and the development of eczema symptoms or doctor-diagnosed eczema by 6 years of age (OR = 1.1, 95% CI 0.5–2.3, and OR = 1.1, 95% CI 0.4–3.3, respectively). No association was found when children with only atopic eczema. Conclusion. Endotoxin exposure during infancy is unlikely to have a large long-term effect on the development of eczema, especially the atopic form. [ABSTRACT FROM AUTHOR]

Background Food allergy is common, especially in childhood, where 6–8% of children are affected. Identification of early and efficient markers for later development of food allergy is very important. Objective We examined the ability of repeated measurements of food sensitization in early childhood to predict doctor-diagnosed food allergy (DDFA) at the age of 6 years. Methods The analysis was based on data from a prospective birth cohort study. Information was collected by parental questionnaires, and blood samples were obtained at 2 and 6 years of age. Children with repeated determination of sensitization to food allergens at 2 and 6 years of age were categorized into the sensitization phenotypes: no, early onset, late onset and persistent sensitization. The association between sensitization phenotypes and DDFA was prospectively investigated using multiple logistic regression analyses. Results Of 3097 children recruited at birth, a complete follow-up of IgE measurements and questionnaires at 1.5, 2 and 6 years were available for 1082 children. Early food allergen sensitization (fx5) was a strong risk for DDFA at 6 years [odds ratio (OR)=4.7; 95% confidence intervals (95% CI) 2.0–11.2] and for a new onset of DDFA at 6 years (OR=4.1; 95% CI 1.5–11.3). Additionally, persistent food allergen sensitization increased the risk of DDFA at 6 years (OR=6.1; 95% CI 2.7–13.7). Early sensitized children with a history of parental atopy showed the highest risk for DDFA at 6 years. Conclusion Food-sensitized children during the first 2 years of life, especially with a family history of atopy, might be considered as a susceptible subgroup that requires specific attention concerning the development of food allergy-related symptoms. >Cite this as: E. Schnabel, S. Sausenthaler, B. Schaaf, T. Schäfer, I. Lehmann, H. Behrendt, O. Herbarth, M. Borte, U. Krämer, A. von Berg, H.-E. Wichmann, J. Heinrich, and for the LISA Study Group, Clinical & Experimental Allergy, 2010 (40) 450–457. [ABSTRACT FROM AUTHOR]

Alternative splicing of pre-mRNA increases proteomic diversity, a crucial mechanism in defining tissue identity. We demonstrate differentially spliced interleukin (IL)-7 in distinct anatomic areas in the adult, in developing human brains and in normal human neuronal progenitor (NHNP) cells. IL-7c (c, the canonical form spanning all six exons) or its variants IL-7δ5, δ4 or δ4/5 were cloned and expressed as recombinant proteins. IL-7 and splice variants were able to shift the differentiation of NHNP cells as compared with the diluent control (P<0.01) defined by anti-β (III)-tubulin and glial fibrillary acidic protein expression, with different degrees (IL-7c>δ4/5>IL-7δ5); IL-7δ4 exhibited a significantly weaker potency. Differentiation was confirmed by transcriptome analysis of IL-7c-stimulated neural NHNP cells, resulting in 58 differentially expressed genes; some of these are involved in neural differentiation, for example, the developmentally regulated transcription factor krüppel-like factor 12, musashi 2, a translational regulator of cell fate or the sonic hedgehog receptor patch 1. This suggests that IL-7 influences neural development at a molecular level by participating in human brain architecture through glia cell formation: a paradigm that alternative splicing in cytokines, for example, for IL-7, has a physiological role in human organ development and progenitor cell differentiation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 GA2LEN, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To analyse time trends in overweight and obesity from 1991 to 2000 in samples of German children and to test the hypothesis of a trend difference between the samples from East and West Germany during this time period. Design: Repeated cross-sectional studies using data of 35 434 five to seven-year-old children from school entry examinations in several rural and urban areas in East and West Germany (between 1991 and 2000). The main outcome measures were overweight and obesity. Weight and height were measured and body mass index was calculated. International cut-off points were used to classify overweight and obesity. Results: From 1991 to 2000, the prevalence of overweight increased from 10.0% to 17.5% in the East and from 14.8% to 22.2% in the West. The prevalence of obesity increased from 2.1% to 5.7% in the East and from 3.6% to 7.6% in the West. All increases were significant. There was no evidence of a trend difference between the East and the West German samples. Conclusions: Unlike in other countries in transition, prevalences of childhood overweight and obesity were increasing in samples of East German children after reunification in 1990, possibly as a result of the rapid adoption of a western lifestyle in the East. Although prevalences were generally higher in the West German samples, there was no evidence that the increase was levelling off in the West. Overall, trends were similar in the East and West German samples. [ABSTRACT FROM AUTHOR]

Background: Early childhood influences are important for the development of the allergic phenotype. In East Germany, tremendous lifestyle changes took place after 1990 and it can be hypothesized that the allergic phenotypes in mothers and their children are less similar than in West Germany. This was investigated in our study done in mothers and their 6-year-old children from East and West Germany in the year 2000. Methods: 1,393 mother-child pairs participated. A subgroup of 774 pairs gave blood for the determination of specific IgE. Regional differences in mother-child correlations and in prevalence of mother-child combinations with respect to allergic sensitization and disease were examined by logistic regression analysis. Results: The adjusted association in positive allergic sensitization between mothers and their children was not significant in East Germany (OR 1.23, 95% CI: 0.68–2.24) but highly significant in West Germany (OR 2.89, 95% CI: 1.73–4.80). The probability for the combination of ‘negative’ mother and ‘positive’ child was significantly higher in East than in West Germany. Conclusions: Mother-child transmission of atopy predisposition can even be cancelled by environmental changes. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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-γ 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. [ABSTRACT FROM AUTHOR]

Background Epidemiological studies indicate environmental pollutants to be involved in the increase in the prevalence of allergic diseases. In human exposure studies, volatile organic compounds (VOCs) have been shown to cause exacerbations of allergic asthma whereas, no data concerning atopic eczema (AE) are available. Objective We investigated the effect of airborne VOCs on the skin of patients with AE and controls in the presence or absence of house dust mite allergen, Der p 1. Methods In a double-blind crossover study, 12 adults with AE and 12 matched healthy volunteers were exposed on their forearms to Der p 1 and subsequently to a mixture of 22 VOCs (M22, 5 mg/m3) in a total body exposure chamber for 4 h. Transepidermal water loss (TEWL) and skin blood flow were measured in all subjects before, during and after exposure. Additionally, an atopy patch test (APT) with Der p 1 was applied to the skin after exposure. Results A significant increase in transepidermal water loss was observed 48 h after exposure to VOCs as compared with exposure with filtered air in all individuals (mean difference: +34%; 95% Confidence Interval: 7–69%). Prior Der p 1 exposure resulted in a significant rise of dermal blood flow after 48 h in patients with AE but not in controls. Six out of seven patients showed enhanced atopy patch test (APT) reactions to HDM allergen after previous exposure to VOCs. Conclusion Our results show that exposure to VOCs – at concentrations commonly found in indoor environments – can damage the epidermal barrier and enhance the adverse effect of Der p 1 on sensitized subjects with AE. These findings may contribute to a better understanding of the mechanisms underlying the increase in prevalence and exacerbation of AE. [ABSTRACT FROM AUTHOR]

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 (⩾ 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. [ABSTRACT FROM AUTHOR]

New phases of the homologous series (YC)n(NiB)m have been detected locally in samples with nominal composition YNi2−xB2−xC (x=0.2, 0.35 and 0.5). The existence of the already published phases YNi2B2C, YNiBC and Y3Ni4B4C3 in these samples has been verified clearly by TEM (electron diffraction, EDX), REM (WDX) and X-ray diffraction, while Y3Ni4B4C3 was investigated by single crystal X-ray diffraction for the first time. The new phases Y5Ni8B8C5 and Y5Ni6B6C5 were identified by electron diffraction and verified by EDX investigation with regard to their composition. The space group is I4/mmm-edba and the Pearson symbol tI12. Chemical stacking faults were observed in YNiBC, YNi2B2C, Y3Ni4B4C3 and Y5Ni8B8C5. After annealing at 1450 °C, the phases Y3Ni4B4C3, Y5Ni8B8C5 and Y5Ni6B6C5 could not be detected anymore. All the samples became superconducting in the temperature range from 11.4 to 13.6 K. [Copyright &y& Elsevier]

Epitaxial thin films of the superconducting borocarbide compound YNi2B2C have been grown on single-crystal MgO (001) substrates using pulsed laser deposition. The deposition temperature has a strong influence on the structural properties of the films, which in turn affect the superconducting transition temperature, Tc. The resulting phases and their orientations with respect to the substrate have been investigated by X-ray diffraction and HRTEM, using cross-section samples. For deposition temperatures around 750 °C, c-axis oriented growth of YNi2B2C films occurs preferentially. At lower temperatures a weaker a-axis orientation was found by X-ray diffraction, whereas by HRTEM grains with a-axis and a weak c-axis orientation could be identified. An interfacial layer some 100 nm thick was formed bordering on the substrate, comprising mainly Y2O3 but also other epitaxially grown phases such as YNi4B. The growth directions of Y2O3 are [001] at 750 °C and [111] at lower temperatures. The in-plane orientations and the lattice mismatches of the bordering phases were also investigated. [Copyright &y& Elsevier]

Non-invasive investigations of skin morphology and function are standard tools to study the pathophysiology of several cutaneous disorders, yet they have not been used in population-based epidemiological studies. Here we examined skin surface pH, stratum corneum hydration, trans-epidermal water loss (TEWL) and skin roughness by profilometry in a study population comprising 377 primary school children (8-9 years old) as part of a multicentre survey on risk factors for allergic diseases in school children. Skin surface pH showed significant higher values (p=0.029) in the group with atopic eczema (n=45) compared with the group without atopic eczema; all other parameters did not differ significantly between children with and without atopic eczema. With increasing skin dryness there was a significant increase in pH values (p=0.004). Stratum corneum hydration showed a significant decrease with increasing dryness (p<0.001). Measurement of skin roughness also revealed a significant linear relationship with skin dryness (p=0.02). It is concluded that measurement of skin surface pH, corneometry and profilometry are useful non-invasive techniques to objectively assess skin dryness in epidemiological studies regarding atopic skin disease. [ABSTRACT FROM AUTHOR]

Background Acquiring and retaining novel motor skills plays a fundamental role in human behavior. Theoretical models suggest that distinct cortico-striatal and cortico-cerebellar loops mediate motor learning. Parkinson’s disease (PD) and spino-cerebellar ataxia (SCA) are neurodegenerative disorders which affect the basal ganglia and the cerebellum, respectively. These disorders can serve as models of how impairments in specific nodes of above-mentioned cortico-striato-cerebellar network affect network interactions and motor skill learning. The goal of this study was to investigate the critical impact of basal ganglia and cerebellar nodes on whole-brain activation patterns as well as network interactions during motor sequence learning. Based on previous studies in PD patients and cerebellar deformations patients, we hypothesized that dysfunction of cerebellum would have a global effect on the cortico-striatal-cerebellar network. By contrast, PD patients who show learning effects, will show compensatory effects in this network. Methods FMRI was measured in a group of 13 SCA patients (SARA score > 17), 12 PD patients (UPDRS < 40), and age-matched (to each group) controls while they performed the serial reaction time task. In this task, in a hidden 12-element complex sequence of movements is to be learned implicitly. The task was comprised of sequence blocks in which participants could learn the underlying pattern, interleaved with random blocks in which no pattern of finger movements was underlying the responses. Dynamic causal modelling (DCM) was used to investigate causal network interactions. Results As hypothesized, patients with SCA did not show behavioral evidence for learning whereas learning was evident in PD patients and controls. We found significant learning-related increase in activation in parahippocampal cortex (PHC) and cerebellar crus I when comparing SCA patients to controls. The cerebellar activity increase was observed in the non-learners of the SCA group (determined by reaction time difference between conditions), whereas learners showed activity decrease. When comparing PD to controls, we found a similar effect in PHC as well as in the substantia nigra. Comparing the two patient groups we found that learning activated bilateral caudate nucleus as well as inferior parietal lobule in SCA compared to PD, despite the lack of behavioral evidence for learning in the SCA group. DCM analysis of the cortico-striato network revealed that connection from SMA to M1 was negatively modulated by learning in controls and the learners of the SCA group, whereas the non-leaners showed a reverse pattern. Conclusions These results suggest that both degeneration in cerebellum (SCA) and degeneration in the basal ganglia (PD) affect remote brain regions, such as the parahippocampal cortex related to learning and memory processes. The correlation of activity in cerebellar crus I with behavioral measures in the SCA group suggests a pathological increase in activity which prevents learning. Bilateral activation of caudate nucleus in the SCA group suggests recruitment of basal ganglia territories for learning, perhaps as compensation for cerebellar degeneration. Finally, we present first evidence for the influence of cerebellar degeneration on causal cortico-cortical interactions relevant for motor learning. [ABSTRACT FROM AUTHOR]

Introduction In the brain, estrogen plays an important role in neural plasticity and its decline during menopause might result in cognitive impairment and predispose to the development of dementia. Two estrogen receptors – α and ß – mediate estrogen actions either as ligand-activated dimeric transcription factors or as membrane-embedded ER monomers. Objective To analyze ERß-variants and ApoE-genotype in the population-based SALIA cohort of 834 non-demented, elderly women. Aims We aimed to explore, whether ERß variants may impact on cognitive performance in interaction with air pollution and APOE. Methods DNA was isolated from lymphocytes. ApoE-epsilon-variants and ERß SNPs rs944045, rs1256062, rs10144225 and rs2274705 were determined by LCG /KBioscience (Hoddesdon, UK). All participants were assessed for cognitive impairment by the CERAD-Plus test battery. Subtests were merged to a total z-score, that corrected for gender, age and time of education. Long-term exposure to air pollution was backextrapolated from data collected by monitoring stations using a geographic information system. Results SNP analysis revealed that 3 ERß variants (rs1256062, rs10144225 and rs2274705) were significantly correlated with lower CERAD z total scores and especially with decline in episodic memory. These effects were strengthened in APOE-epsilon-E4 carriers. Air pollution (NO 2 , PM2,5) did not worsen the CERAD z total score of the women, but interacting with the ERß variants PM2,5 affected their visuoconstructive practice and NO 2 their semantic memory. Conclusion In this population-based, prospective study a gene-gene interaction effect of ApoE and ERß on cognitive performance appeared. Moreover, significant gene-environment interactions on cognition were found for air pollution. [ABSTRACT FROM AUTHOR]