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Biomedical subjects

H E Wichmann

Publications and source records attributed to H E Wichmann.

At least 37 records · Page 2Linked to original sources

Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitisation during the first year of life.

AIMS: To investigate the effect of caesarean section on gastrointestinal symptoms, atopic dermatitis, and sensitisation to nutritional allergens in infants. METHODS: A total of 865 healthy full term neonates with parental history of allergy participating in the prospective German Infant Nutritional Intervention Program (GINI) were exclusively breast fed during the first four months of life and had a one year follow up. Data were obtained by follow up visits at age 1, 4, 8, and 12 months, weekly diaries for the first six months, and measurement of total and specific IgE at birth and 12 months. RESULTS: Infants born by caesarean section (147/865, 17%) had a greater risk of diarrhoea (OR(adj) 1.46, 95% CI 1.022 to 2.10) and sensitisation to food allergens, both in adjusted (OR(adj) 2.06, 95% CI 1.123 to 3.80) and stratified analyses (by cord blood IgE). Caesarean delivery was not associated with colicky pain and atopic dermatitis. CONCLUSION: Caesarean delivery might be a risk factor for diarrhoea and sensitisation in infants with family history of allergy. Further research in this area seems warranted as choosing caesarean section becomes increasingly popular.

Adult↗

Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults.

BACKGROUND: Several studies have shown linkage of chromosome 12q 13-24 with atopy related phenotypes. Among candidate genes in this region is STAT6 (signal transducer and activator of transcription), which is essential for Th2 cell differentiation, recruitment, and effector function. METHODS: We evaluated six polymorphisms of STAT6 for evidence of associations with serum IgE levels and atopic diseases in a population based cross sectional cohort of 1407 German adults. Genotyping was performed using the matrix assisted laser desorption ionisation-time of flight mass spectrometry method. Haplotypes were estimated using the SAS/Genetics module, and population-derived IgE percentiles (50% IgE>53 kU/l, 66% IgE>99 kU/l and 90% IgE>307 kU/l) were modelled as outcome variables in haplotype trend regression analysis. RESULTS: All polymorphisms were genotyped successfully. Haplotype reconstruction revealed 8/64 possible haplotypes, reaching estimated frequencies of 1% or more. One polymorphism in intron 2 (rs324011) showed a significant association with total serum IgE (p = 0.015). A STAT6 risk haplotype for elevated IgE showing odds ratios of 1.7 (p = 0.015) for IgE cut-off 100 kU/l, and 1.54 (p = 0.032), 1.6 (p = 0.025), and 2.54 (p = 0.007) for IgE percentiles 50%, 66%, and 90%, respectively was detected. The increased risk of this haplotype was confirmed by linear haplotype trend regression on log transformed IgE values (p = 0.007). Analysis further revealed a risk haplotype for specific sensitisation and a risk haplotype for asthma. CONCLUSION: The data indicate that genetic variants within STAT6 contribute significantly to IgE regulation and manifestation of atopic diseases.

Adult↗

On the potential of measurement error to induce differential bias on odds ratio estimates: an example from radon epidemiology.

It is well established that odds ratios estimated by logistic regression are subject to bias if exposure is measured with error. The dependence of this bias on exposure parameter values, particularly for multiplicative measurement error, and its implications in epidemiology are not, however, as fully acknowledged. We have been motivated by a German West case-control study on lung cancer and residential radon, where restriction to a subgroup exhibiting larger mean and variance of exposure than the entire group has shown higher odds ratio estimates as compared to the full analysis. By means of correction formulae and simulations, we show that bias from additive classical type error depends on the exposure variance, not on the exposure mean, and that bias from multiplicative classical type error depends on the geometric standard deviation (in other words on the coefficient of variation of exposure), but not on the geometric mean of exposure. Bias from additive or multiplicative Berkson type error is independent of exposure distribution parameters. This indicates that there is a potential of differential bias between groups where these parameters vary. Such groups are commonly compared in epidemiology: for example when the results of subgroup analyses are contrasted or meta-analyses are performed. For the German West radon study, we show that the difference of measurement error bias between the subgroup and the entire group exhibits the same direction but not the same dimension as the observed results. Regarding meta-analysis of five European radon studies, we find that a study such as this German study will necessarily result in smaller odds ratio estimates than other studies due to the smaller exposure variance and coefficient of variation of exposure. Therefore, disregard of measurement error can not only lead to biased estimates, but also to inconsistent results and wrongly concluded effect differences between groups.

Air Pollutants, Radioactive↗

Mechanistic modelling in large case-control studies of lung cancer risk from smoking.

The two-step clonal expansion (TSCE) model is applied to large case-control studies, frequency matched for age, which allow estimation of the RR of lung tumour risk caused by smoking. For estimating background hazard rates, mortality data from the study areas are used to supplement the case-control data. Two approaches are used to analyse the data, based on the unconditional and the conditional likelihoods. They are demonstrated to give nearly identical results. Some model diagnostics are performed and demonstrate a good model fit. Our results indicate that smoking acts on the promotion and transformation parameters, but not on the initiation parameter of the TSCE model. The fitted relative risk of current smokers peaks between ages 50 and 60 years. The relative risk of male ex-smokers decreases strongly with time since end of exposure, but does not reach the risk of non-smokers, and does not decrease as much as for female ex-smokers.

Adult↗

Vaccination against Haemophilus influenzae type b and atopy in east German schoolchildren.

INTRODUCTION: Although routine childhood immunisations are known to prevent severe diseases there is an ongoing discussion on possible side effects in later life. In this paper we investigated the association of Haemophilus influenzae type b (Hib)-vaccination and atopic diseases and allergic sensitisation in children in Eastern Germany. METHODS: From 1998-1999 a cross-sectional survey of school children aged 5 to 14 years on long-term health effects of air pollution was conducted in three regions of Eastern Germany. Atopic outcome was defined by parental reporting of wheezing and doctor's diagnosed asthma (including asthma-like bronchitis), hay fever and eczema. Specific serum IgE against 5 aeroallergens were analysed by RAST-technique. Vaccination status was assessed by vaccination records from the respective local health authorities. Analysis is restricted to 1943 children with complete information on age, gender, place of residence, parental education and 1676 children with available blood data. RESULTS: Lifetime prevalence were 4.9% for asthma, 21.1% for wheezing, 6.6% for hay fever, 11.4% for eczema. 32% of the children had at least one specific IgE RAST>0. Hib-vaccination coverage was 42 % overall, 93 % in 5-7 yr olds, 59 % in 8-10 yr olds and 11 % in 11-14 yr olds. Odds Ratios adjusted for age, gender, place of residence, and parental education were 1.86 (1.05-3.32) for asthma, 1.55 (0.95-2.54) for hay fever, 1.03 (0.70-1.50) for eczema and 1.25 (0.94-1.67) for at least 1 specific IgE RAST>0. CONCLUSION: We found little evidence for an association between Hib-vaccination and some atopic outcomes and causality cannot be ascertained. Our findings do not give sufficient support to question the value of Hib vaccination given the substantial contribution of mass immunisations to public health. Specific research on possible long-term effects of vaccines is needed to enable final conclusions on this topic.

Adolescent↗

Predictors of high endotoxin concentrations in the settled dust of German homes.

Endotoxin concentrations in settled house dust were measured within the collaborative study named INGA (Indoor Exposure and Genetics in Asthma) together with other asthma-related indoor factors in 405 randomly selected homes in two German cities. Endotoxin was assayed using the quantitative kinetic chromogenic Limulus Amebocyte Lysate (LAL) method. The mean concentration of 2,274 ng endotoxin/g dust in living rooms is about two orders of magnitude below mean occupational exposure (e.g. agriculture). Endotoxin concentrations are higher in old buildings (means ratio = (MR) 1.52, 95% C.I.: 1.14; 2.04), and in the lower storey of the dwelling (MR = 1.30, 95% C.I.: 1.04; 1.62). Furthermore, higher endotoxin concentrations are associated with longer occupancy in the apartment (MR = 1.63, 95% C.I.: 1.21; 2.18), high utilisation of the apartment during the sampling period (MR = 2.52, 95% C.I.: 1.42; 4.47), infrequent vacuum cleaning of the carpets (MR = 1.67; 95% C.I.: 1.10; 2.54), an indifferent attitude to ventilation (MR = 1.37; 95% C.I.: 1.03; 1.82), keeping cats (MR = 1.91; 95% C.I.: 1.43; 2.55) and dogs (1.57; 95% C.I.: 1.08; 2.30), as well as the occurrence of mice (MR = 1.39; 95% C.I.: 1.00; 1.93). The season and indoor climate (operative temperature and relative humidity) did not effect endotoxin concentration. These results indicate that high endotoxin concentration in settled dust is an indicator of poor hygienic conditions in homes.

Adult↗

T cell reactivity in neonates from an East and a West German city--results of the LISA study.

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

Cohort Studies↗

[European Community Respiratory Health Survey in Adults (ECRHS)].

The European Community Respiratory Health Survey (ECRHS) was the first study to assess the geographical variation in asthma, allergy, and allergic sensitization in adults using the same instruments and definitions. The database of the ECRHS includes information from approximately 140 000 individuals aged 20 - 44 years from 22 countries. The aim of this review is to summarize the results of the ECRHS and to present the specific contribution of the German centers in Hamburg and Erfurt. The prevalence ranged from 2.0 - 11.9 % for asthma, 9.5 - 40.9 % for allergic rhinitis, 4.0 - 32.0 % for wheeze, 3.4 - 27.9 % for bronchial hyperreactivity, and 16.2 - 44.5 % for allergic sensitisation against common aeroallergens. Although the prevalence of these atopic disorders were found to be consistently higher for the Hamburg center compared to the Erfurt center, strong regional differences in the prevalences were also found within several other European countries. Overall Europe, the lowest prevalences were seen in the Eastern and Middle European countries with the center Erfurt, followed by the Mediterranean region. The highest prevalences were reported for all English speaking centers. Strong geographic variation was reported for medication for asthma. Asthma seems to be undertreated in several countries. Environmental exposures and in particular indoor factors, and exposures at the workplace are playing a major role for asthma in adulthood. Furthermore, protective effects on atopy were found for exposures to pets (dogs) and a large number of siblings in early childhood. In conclusion, the ECRHS has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and likely due to environmental factors.

Adult↗

Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany.

Trends in prevalence of atopic diseases and allergic sensitization in children from Eastern Germany during the 1990s were analysed. The study consisted of three regional cross-sectional surveys of a total of 7,632 children (aged 5-14 yrs) in 1992-1993, 1995-1996, and 1998-1999. Information was gathered on atopic diseases and potential predictors by a parental questionnaire. Allergic sensitization for birch, grass, mite, cat, and cladosporium were assessed by radioallergosorbent test (RAST). After adjustment for age, sex and the study area of the participants, prevalence increased between the first and third survey for hay fever, for asthma and for atopic eczema. The adjusted prevalence of allergic sensitization (RAST > 0.35 kU x L(-1)) showed a decrease, whereas the prevalence of strong sensitization (RAST > or = 17.5 kU x L(-1)) increased significantly, specifically in cohorts born after 1989. Further adjustment for possible determinants of these atopic diseases did not change the trend estimates. A clear increase in the prevalence of atopic diseases, with the exception of hay fever, was observed as well as a shift towards a stronger allergic sensitization, which might affect the onset of clinical manifestations of atopic diseases. Differences in the epidemiology of respiratory symptoms, illnesses and allergies between populations living in the former East Germany and those living in the former West Germany have been reported. Among East German children, lower prevalence rates of asthma, and positive skin-prick tests were observed compared to West German children in the early 1990s. Similarly, among East German adults, lower specific immunoglobulin (Ig) E levels and lower prevalence rates of asthma, wheezing, positive methacholine-challenge tests, allergic rhinitis, and positive skin-prick tests have been reported compared to those of West German adults.

Adolescent↗

Traffic-related air pollution and respiratory health during the first 2 yrs of life.

As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 microm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 microg m(-3), 1.38-4.39 x 10(-5) m(-1), and 19.5-66.9 microg x m3, respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI)): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% CI): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.

Air Pollution↗

Increased asthma medication use in association with ambient fine and ultrafine particles.

The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01-0.1 microm in diameter (NC(0.01-0.1), mean 17,300 x cm(-3), and mass concentrations of fine particles 0.01-2.5 microm in diameter (MC(0.01-2.5)), mean 30.3 microg x m(-3), were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled beta2-agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. Beta2-agonist use was associated with 5-day mean NC(0.01-0.1) and MC(0.01-2.5). The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.

Adrenergic beta-Agonists↗

Allergens and endotoxin on mothers' mattresses and total immunoglobulin E in cord blood of neonates.

The current authors examined whether mite and cat allergen and bacterial endotoxin levels in dust of the mothers' mattresses were associated with cord blood immunoglobulin (Ig)E (CB-IgE) levels in newborns. Data from 1,332 term and normal weight neonates, from an ongoing birth cohort study, influences of life-style related factors on the immune system and the development of allergies in childhood (LISA), with complete information on exposure to biocontaminants in mattress dust and CB-IgE were analysed. Two thirds of CB-IgE were undetectable (<0.35 kU x L(-1)). Thus, 0.35 and 0.45 kU x L(-1) (4th quartile) were chosen as cut-offs. Nonparametric smoothing (generalised additive models) showed statistically significant confounder-adjusted associations between elevated CB-IgE levels (> or = 0.45 kU x L(-1)) and log-transformed exposures to cat (linear), mite (inverse u-shaped), and endotoxin (u-shaped). After adjustment for covariables, elevated CB-IgE levels (logistic regression using the 1st-4th quartiles of exposure) were positively associated with high cat-allergen exposure and medium exposure to mite allergen, but were inversely associated with exposure to endotoxin. The associations were similar, but somewhat weaker, when 0.35 kU x L(-1) was used as cut-off. These results, showing an association between prenatal allergen and endotoxin exposures and immunoglobulin E production, suggest that the development of foetal immune responses may be affected.

Allergens↗

Indoor exposure to molds and allergic sensitization.

Evidence that indoor dampness and mold growth are associated with respiratory health has been accumulating, but few studies have been able to examine health risks in relation to measured levels of indoor mold exposure. In particular, little is known about the contribution of indoor molds to the development of allergic sensitization. As a part of an ongoing study examining the effects of ambient air pollutants on respiratory health and atopic diseases in German school children, we examined the relation between viable mold levels indoors and allergic sensitization in 272 children. We examined whether allergic sensitization in children is associated with higher fungal spore count in settled house dust sampled from living room floors. Adjusting for age, sex, parental education, region of residency, and parental history of atopy, we found that mold spore counts for Cladosporium and Aspergillus were associated with an increased risk of allergic sensitization. Sensitized children exposed to high levels of mold spores (> 90th percentile) were more likely to suffer from symptoms of rhinoconjunctivitis. We conclude that elevated indoor concentrations of molds in wintertime might play a role in increasing the risk of developing atopic symptoms and allergic sensitization not only to molds but also to other common, inhaled allergens. These effects were strongest in the group of children who had lived in the same home since birth.

Adolescent↗

Predictors of cat allergen (Fel d 1) in house dust of German homes with/without cats.

BACKGROUND: Exposure to cat allergen is a major risk factor for sensitization and the development of asthma in many parts of the world. The study was designed to examine the levels of cat allergen (Fel d 1) in homes of two German cities and to detennine predictors of Fel d 1 exposure. METHODS: We collected dust samples from 405 randomly selected homes in Hamburg (n = 201) and Erfurt (n = 204). In each apartment dust samples were taken from living room floor (LR), bedroom floor (BR), and mattress surface (MA) using vacuum sampling and analyzed by two-site monoclonal antibody ELISA. Environmental variables were assessed by questionnaire to obtain information on factors supposed to have an impact on the Fel d 1 levels in house dust. The effects of possible predictors of Fel d 1 were assessed by multiple linear regression models. RESULTS: Fel d 1 was present in 98% of the homes (395/405), ranging from 0.015 to 7.278 microg/g dust (GM 0.486 microg/g). The levels were similar in floors (GM for LR 0.575 microg/g and BR 0.469 microg/g) and in MA (GM 0.424 microg/g). Higher allergen concentrations (> 2 microg/g) were detected in 99% of the homes keeping cats, in 55% of homes that had had a cat during the last year, and in 28% of the homes without a cat. Fel d 1 levels were significantly higher in homes with a cat (628-682-fold, MA, floor) and in homes in which a cat had previously lived (11-12-fold, floor, MA) than in homes that never had a cat. Furthermore, after controlling for possible other confounders, Fel d 1 levels were significantly higher in summer and in homes with low frequency of cleaning and low ventilation rate. CONCLUSION: It could be confirmed that keeping a cat has the highest impact on Fel d 1 concentration. Besides, a continuous influx of Fel d 1 in homes without cat, as a result of direct or indirect cat contact outside the home, is likely. High frequencies of dusting and ventilation might reduce cat allergens in homes with and without cats.

Allergens↗

Early antibiotic treatment and later asthma.

The reasons for the asthma epidemic are poorly understood. As the asthma prevalence follows the geographical and temporal trend of antibiotic use into clinical medicine, we examined a possible association in a population-based study of 2,512 children age 5-14 in East Germany. Wheezing was associated with increasing number of antibiotic courses (never versus one time odds ratio 1.9, P = 0.012, 2 to 5 times odds ratio 3.0, P<0.001 and more than 5 times, odds ratio 6.9, P<0.001) which was also seen for asthma diagnosis. The risk increased with earlier administration (never versus second year odds ratio 4.6, month 7-12 odds ratio 5.4 and birth until month 6 odds ratio 7.9, all P<0.001). Also non pulmonary treatment indication was associated with later wheezing (odds ratio 3.9, P<0.001). The most likely possible explanation is reverse causation indicating that frequent upper respiratory infections, an early symptom of asthma, are treated with antibiotics. Antibiotic therapy could also be a proxy of another closely associated genetic or environmental factor. The high dose effect, the time dependency of the administration and the effect by non-pulmonary indications raises the possibility that early antibiotic treatment could itself be related to later asthma.

Adolescent↗

Lung cancer and cigarette smoking in Europe: an update of risk estimates and an assessment of inter-country heterogeneity.

Ten case-control studies have been carried out in 6 European countries to investigate the major risk factors for lung cancer. Carcinogenic effect from cigarette smoke was the most relevant interest in our study, which has included 7,609 cases of lung cancer and 10,431 controls, mainly population based. The results indicate elevated odds ratios (ORs; 23.9 among men and 8.7 among women) with attributable risks exceeding 90% for men and close to 60% for women. A large, and statistically significant, variability of the results across countries was detected after adjusting for the most common confounding variables, and after controlling, at least in part, for the instability of the ORs due to the small number of non-smokers in some of the study subsets. This pattern of lung cancer risk associated with cigarettes smoke, across different European regions, reflects inherent characteristics of the studies as well as differences in smoking habits, particularly calendar periods of starting, and it is likely to have been influenced by effect modifiers like indoor radon exposure, occupation, air pollution and dietary habits.

Aged↗

Indoor and outdoor BTX levels in German cities.

On the basis of the ongoing study INGA (INdoor exposure and Genetics in Asthma), Germany's most detailed and standardized epidemiological study on indoor exposure to both allergens in house dust and volatile compounds in the air of the home environment has been performed. The purpose of this paper is to describe the spatial and seasonal variability of indoor and outdoor BTX (Benzene, toluene, ethyl benzene, ortho-xylene, meta- and para-xylene) concentrations for the study period from June 1995 to November 1996. Within this framework, air concentrations of volatile organic compounds (BTX) were measured in 204 households in Erfurt (Eastern Germany) and 201 households in Hamburg (Western Germany). BTX sampling was conducted over one week using OVM 3500 passive diffusion sampling devices in the indoor (living room and bedroom) and outdoor environment (outside the window of the living room). Indoor and outdoor median BTX concentrations in Erfurt were slightly, but significantly higher than those in Hamburg. This gap was most pronounced in the levels of indoor toluene (37.3 microg/m3 for Erfurt and 20.5 microg/m3 for Hamburg, P < 0.0001). In both cities, winter indoor and outdoor concentrations for the five compounds exceeded the summer values. Outdoor concentrations of ethyl benzene and ortho-xylene were very low (50% < L.D.). In general, the indoor BTX air concentrations were significantly higher than the outdoor concentra- tions, the lowest I/O ratios were found in the case of benzene. Living room and bedroom values for the five compounds were highly correlated (Spearman coefficient 0.5-0.9). Despite the better insulation of the homes in West Germany, no indication for the expected higher indoor concentrations of BTX in the West could be found. The strong and yet undiscovered indoor source for toluene in East Germany might lead to a further increase in the indoor air load in those homes in the East, which undergo renovations which will lead to improved insulation.

Air Pollutants↗