Olf Herbarth

Atopic Diseases, Allergic Sensitization, and Exposure to Traffic-related Air Pollution in Children

RATIONALE In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent. OBJECTIVES To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life. METHODS We studied 2,860 children at the age of 4 years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM(2.5)), PM(2.5) absorbance, and long-term exposure to nitrogen dioxide (NO(2)) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants. MEASUREMENTS AND MAIN RESULTS Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM(2.5) absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO(2) exposure was associated with eczema, whereas no association was found for allergic sensitization. CONCLUSIONS This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.

Timing of solid food introduction in relation to atopic dermatitis and atopic sensitization : Results from a prospective birth cohort study

OBJECTIVE. Prophylactic feeding guidelines recommend a delayed introduction of solid foods for the prevention of atopic diseases. Scientific evidence for this is scarce. This study investigates whether a delayed introduction of solids (past 4 months or 6 months) is protective against the development of atopic dermatitis (AD) and atopic sensitization when considering reverse causality. METHODS. Data from 2612 infants in an ongoing birth cohort study were analyzed at 2 years of age. Information on diet and on symptoms and diagnoses of AD was collected semiannually, and information on specific immunoglobulin E levels was collected at 2 years of age. RESULTS. Solid food introduction past the first 4 months of life decreased the odds of symptomatic AD but not for doctor-diagnosed AD, combined doctor-diagnosed and symptomatic AD, or atopic sensitization. Postponing the introduction beyond the sixth month of life was not protective in relation to either definition of AD or atopic sensitization. There was also no evidence for a protective effect of a delayed introduction of solids on AD and atopic sensitization in children of atopic parents. There was clear evidence for reverse causality between early skin or allergic symptoms and the introduction of solids. CONCLUSIONS. This study does not find evidence supporting a delayed introduction of solids beyond the sixth month of life for the prevention of AD and atopic sensitization. We cannot rule out that delaying the introduction of solids for the first 4 months of life might offer some protection. Measures to avoid reverse causality have to be considered in the conduction, analysis, and interpretation of cohort studies on the topic.

Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85×10−20 and 7.08×10−19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78×10−4 and P = 1.95×10−3). The “top” SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28×10−7−4.46×10−8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Traffic-related atmospheric pollutants levels during pregnancy and offspring's term birth weight: a study relying on a land-use regression exposure model.

Background Some studies have suggested that particulate matter (PM) levels during pregnancy may be associated with birth weight. Road traffic is a major source of fine PM (PM with aero-dynamic diameter < 2.5 μm; PM2.5). Objective We determined to characterize the influence of maternal exposure to atmospheric pollutants due to road traffic and urban activities on offspring term birth weight. Methods Women from a birth cohort [the LISA (Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children) cohort] who delivered a non-premature baby with a birth weight > 2,500 g in Munich metropolitan area were included. We assessed PM2.5, PM2.5 absorbance (which depends on the blackness of PM2.5, a marker of traffic-related air pollution), and nitrogen dioxide levels using a land-use regression model, taking into account the type and length of roads, population density, land coverage around the home address, and temporal variations in pollution during pregnancy. Using Poisson regression, we estimated prevalence ratios (PR) of birth weight < 3,000 g, adjusted for gestational duration, sex, maternal smoking, height, weight, and education. Results Exposure was defined for 1,016 births. Taking the lowest quartile of exposure during pregnancy as a reference, the PR of birth weight < 3,000 g associated with the highest quartile was 1.7 for PM2.5 [95% confidence interval (CI), 1.2–2.7], 1.8 for PM2.5 absorbance (95% CI, 1.1–2.7), and 1.2 for NO2 (95% CI, 0.7–1.7). The PR associated with an increase of 1 μg/m3 in PM2.5 levels was 1.13 (95% CI, 1.00–1.29). Conclusion Increases in PM2.5 levels and PM2.5 absorbance were associated with decreases in term birth weight. Traffic-related air pollutants may have adverse effects on birth weight.

Timing of Solid Food Introduction in Relation to Eczema, Asthma, Allergic Rhinitis, and Food and Inhalant Sensitization at the Age of 6 Years: Results From the Prospective Birth Cohort Study LISA

OBJECTIVE. Current prophylactic feeding guidelines recommend a delayed introduction of solids for the prevention of atopic diseases. This study investigates whether a delayed introduction of solids (past 4 or 6 months) is protective against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. METHODS. Data from 2073 children in the ongoing LISA birth cohort study were analyzed at 6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality. RESULTS. A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant allergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms were considered, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months. CONCLUSIONS. This study found no evidence supporting a delayed introduction of solids beyond 4 or 6 months for the prevention of asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. Positive associations between late introduction of solids and food sensitization have to be interpreted with caution. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely.

Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life results of the LARS-study

INTRODUCTION The Leipzig Allergy High-Risk Children Study (LARS) is a prospective nested cohort control study about the influence of chemical indoor exposure in dwellings on the health outcome of atopy-risk children during the first years of life. DESIGN AND METHODS 475 premature children and children with allergic risk factors have been selected out of the 1995/1996 birth cohort in the city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in the infants bedrooms using passive sampling systems for 4 weeks after birth. The babies underwent a medical examination at the age of six weeks and 1 year. The parents answered a questionnaire. RESULTS Correlations between VOC exposures and infections were calculated by multiple logistic regression. Selected VOC show a direct association to actually painted dwellings (OR = 2.4; 95% Cl 1.1-5.3). An increase of risk of pulmonary infections was observed in infants aged 6 weeks if restoration (painting OR 5.6; 95% Cl 1.3-24.0) or flooring connected with painting had occurred during the pregnancy period. Higher concentration of styrene (> 2.0 micrograms/m3, indicator for flooring) elevated the risk of pulmonary infections in six-week-old infants (OR = 2.1; 95% Cl 1.1-4.2). Environmental benzene > 5.6 micrograms/m3 increased the risk of airway infections in six-week-old babies (OR = 2.4; 95% Cl 1.28-4.48). Smoking in the dwelling (OR = 2.0; 95% Cl 1.1-3.5) as well as restoration (OR = 1.9; 95% Cl 1.1-3.5) are also risk factors of the development of wheezing in the one-year-old child. CONCLUSIONS The data give indications in order to prevent allergies and chronic lung diseases in atopy risk children exposure to chemicals from indoor air should be minimised from birth on.

The effect of particle size on cardiovascular disorders — The smaller the worse

BACKGROUND Previous studies observed associations between airborne particles and cardio-vascular disease. Questions, however, remain as to which size of the inhalable particles (coarse, fine, or ultrafine) exerts the most significant impact on health. METHODS For this retrospective study, data of the total number of 23,741 emergency service calls, registered between February 2002 and January 2003 in the City of Leipzig, were analysed, identifying 5326 as being related to cardiovascular incidences. Simultaneous particle exposure was determined for the particle sizes classes <100 nm (UFP), <2.5 μm (PM2.5) and <10 μm (PM10). We used a time resolution of 1 day for both parameters, emergency calls and exposure. RESULTS Within the group of cardiovascular diseases, the diagnostic category of hypertensive crisis showed a significant association with particle exposure. The significant effect on hypertensive crisis was found for particles with a size of <100 nm in diameter and starting with a lag of 2 days after exposure. No consistent influence could be observed for PM2.5 and PM10. The Odds Ratios on hypertensive crisis were significant for the particle size <100 nm in diameter from day 2 post exposure OR=1.06 (95%CI: 1.02-1.10, p=0.002) up to day 7 OR=1.05 (95%CI 1.02-1.09, p=0.005). CONCLUSION Ultrafine particles affect cardiovascular disease adversely, particularly hypertensive crises. Their effect is significant compared with PM2.5 and PM10. It appears necessary, from a public health point of view, to consider regulating this type of particles using appropriate measurands as particle number.

Statistical models to assess the health effects and to forecast ground-level ozone

By means of statistical approaches we attempt to bridge both aspects of the ground-level ozone problem: assessment of health effects and forecasting and warning. Disagreement has been highlighted in the literature recently regarding the adverse health effects of tropospheric ozone pollution. Based on a panel study of children in Leipzig we identified a non-linear (quadratic) concentration-response relationship between ozone and respiratory symptoms. Our results indicate that using ozone as a linear covariate might be a misspecification of the model, which might explain non-uniform results of several field studies in health effects of ozone. We conclude that there is urgent demand for forecasting episodes of high ozone that may help susceptible persons to avoid high exposure. Novel approaches to statistical modelling and data mining are helpful tools in operational smog forecasting. We present a rigorous assessment of the performance of 15 different statistical techniques in an inter-comparison study based on data sets from 10 European regions. To evaluate the results of the inter-comparison exercise we suggest an integrated assessment procedure, which takes the unbalanced study design into consideration. This procedure is based on estimating a statistical model for the performance indices depending on predefined factors, such as site, forecasting technique, forecasting horizon, etc. We find that the best predictions can be achieved for sites located in rural and suburban areas in Central Europe. For application in operational air pollution forecasting we may recommend neural network and generalised additive models, which can handle non-linear associations between atmospheric variables. As an example we demonstrate the application of a Generalised Additive Model (GAM). GAMs are based on smoothing splines for the covariates, i.e., meteorological parameters and concentrations of other pollutants. Finally, it transpired that respiratory symptoms are associated with the daily maximum of the 8-h average ozone concentration, which in turn is best predicted by means of non-linear statistical models. The new air quality directive of the European Commission (Directive 2002/3/EC) accounts for the special relevance of the 8h mean ozone concentration.

Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative

To cite this article: Tischer CG, Hohmann C, Thiering E, Herbarth O, Müller A, Henderson J, Granell R, Fantini MP, Luciano L, Bergström A, Kull I, Link E, von Berg A, Kuehni CE, Strippoli M‐PF, Gehring U, Wijga A, Eller E, Bindslev‐Jensen C, Keil T, Heinrich J & as part of the ENRIECO consortium. Meta‐analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative. Allergy 2011; 66: 1570–1579.