Christina Tischer

Maternal smoking in pregnancy and asthma in preschool children: a pooled analysis of eight birth cohorts.

RATIONALE Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of childhood wheezing and asthma, previous studies were not able to differentiate the effects of prenatal from postnatal exposure. OBJECTIVES To assess the effect of exposure to maternal smoking only during pregnancy on wheeze and asthma among preschool-age children. METHODS A pooled analysis was performed based on individual participant data from eight European birth cohorts. Cohort-specific effects of maternal smoking during pregnancy, but not during the first year, on wheeze and asthma at 4 to 6 years of age were estimated using logistic regression and then combined using a random effects model. Adjustments were made for sex, parental education, parental asthma, birth weight, and siblings. MEASUREMENTS AND MAIN RESULTS Among the 21,600 children included in the analysis, 735 children (3.4%) were exposed to maternal smoking exclusively during pregnancy but not in the first year after birth. In the pooled analysis, maternal smoking only during pregnancy was associated with wheeze and asthma at 4 to 6 years of age, with adjusted odds ratios of 1.39 (95% confidence interval, 1.08-1.77) and 1.65 (95% confidence interval, 1.18-2.31), respectively. The likelihood to develop wheeze and asthma increased statistically significantly in a linear dose-dependent manner in relation to maternal daily cigarette consumption during the first trimester of pregnancy. CONCLUSIONS Maternal smoking during pregnancy appears to increase the risk of wheeze and asthma among children who are not exposed to maternal smoking after birth.

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.

European birth cohorts for environmental health research

Background: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. Objectives: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. Methods: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother–child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. Results: Questionnaires were completed by 37 cohort studies of > 350,000 mother–child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12–19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. Conclusion: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.

The role of cats and dogs in asthma and allergy – a systematic review

Studies have reported contradictory effects of cat and dog exposure on allergy, resulting in inconsistent recommendations on animal avoidance. We conducted a systematic review of observational studies published in English from 2000 to January 2009. It shows in this review that the reported exposure-response relationships are contradictory. A total of 17 and 13 birth cohort studies on cat and dog exposure, respectively, are included in the review. Most of the birth cohort studies found that cat or dog exposure in early life had no effect on the development of asthma or wheezing symptoms and dog exposure during infancy was found to protect children from developing sensitization against aeroallergens. A total of 7 and 6 prospective studies in school-age children or adults on cat and dog exposure, respectively, are included in this review and most of these studies suggested an inverse association between cat exposure and asthma and wheezing symptoms. As for cross-sectional studies, 26 and 21 studies on cat and dog exposure, respectively, are included in this review, which cover a broad range of age groups and geographical areas, and reported inconsistent results. The evidence summarised in this systematic review needs to be interpreted with caution, the inconsistent study results may be due to study design, exposure assessment, and avoidance measure. The exposure-response relationships may also alter in geographical areas where the community prevalence of cats and dogs are significantly different. However, as the evidence of the effects of pet keeping on subsequent development of asthma or allergic diseases presented in this review are not overwhelmingly strong, the decision of whether to keep a cat or a dog in the family should be based on arguments other than the concern of developing asthma and allergy.

Respiratory health in children, and indoor exposure to (1,3)-β-D-glucan, EPS mould components and endotoxin.

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-&bgr;-d-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-&bgr;-d-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case–control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-&bgr;-d-glucan, EPS and endotoxin were measured in settled house dust sampled from children’s mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children’s mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39–0.92) and 0.55 (95% CI 0.31–0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31–0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children’s mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.

A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project

The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 μm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five European birth cohorts: MAAS (England, UK), BAMSE (Sweden), PIAMA (the Netherlands), GINI and LISA (both Germany, divided into north and south areas). Land-use regression models were developed for each study area and used to estimate outdoor air pollution exposure at the home address of each child. Information on asthma and current wheeze prevalence at the ages of 4–5 and 8–10 years was collected using validated questionnaires. Multiple logistic regression was used to analyse the association between pollutant exposure and asthma within each cohort. Random-effects meta-analyses were used to combine effect estimates from individual cohorts. The meta-analyses showed no significant association between asthma prevalence and air pollution exposure (e.g. adjusted OR (95%CI) for asthma at age 8–10 years and exposure at the birth address (n=10377): 1.10 (0.81–1.49) per 10 μg·m-3 nitrogen dioxide; 0.88 (0.63–1.24) per 10 μg·m-3 PM10; 1.23 (0.78–1.95) per 5 μg·m-3 PM2.5). This result was consistently found in initial crude models, adjusted models and further sensitivity analyses. This study found no significant association between air pollution exposure and childhood asthma prevalence in five European birth cohorts. No significant association between air pollution and childhood asthma prevalence in five European birth cohorts http://ow.ly/Cdbba

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large‐scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy‐related diseases. To complement the population‐based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Paving the way of systems biology and precision medicine in allergic diseases

MeDALL (Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large‐scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy‐related diseases. To complement the population‐based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts: an allergic comorbidity cluster

Asthma, rhinitis and eczema often co‐occur in children, but their interrelationships at the population level have been poorly addressed. We assessed co‐occurrence of childhood asthma, rhinitis and eczema using unsupervised statistical techniques.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen‐specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono‐ and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE‐mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re‐occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE‐mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.