Publications by authors named "Olf Herbarth"

94 Publications

Modified Nucleosides - Molecular Markers Suitable for Small-volume Cancer?

Anticancer Res 2018 Nov;38(11):6113-6119

LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.

Background: Modified nucleosides (mNS) in urine are shown to be encouraging markers in cancer, mostly in patients presenting with high tumor mass such is breast and lung cancer. To our knowledge, mNS have not been investigated in head and neck squamous cell carcinoma (HNSCC). HNSCC is characterized by early metastasis into locoregional lymph nodes and slow infiltrating growth, but even in the advanced stage exhibits only a relatively low cancer volume. Therefore, reliable distinction between HNSCC and healthy controls by urinary mNS might pose substantial analytical problems and even more as patients with HNSCC mostly have an increased exposure to tobacco smoke and excessive alcohol consumption which affect the renal mNS pattern.

Materials And Methods: Urinary mNS in samples of 93 therapy-naive patients with HNSCC and 242 healthy controls were quantified by reversed-phase high-performance liquid chromatography. Considering that the circadian rhythm causes diuresis-induced variations in concentration, the mNS-to-creatinine ratio was chosen to compare patients and controls. For sensitivity and specificity in discriminating between patients and controls, the corresponding curve was plotted. Additionally, logistic regression was carried out and a multilayer perceptron neuronal network (NN) was created.

Results: Fifteen mNS were detectable in cases and controls; concentrations of 11 were found to be significantly different. The sensitivity and specificity depend on the total volume of the lesion; HNSCC with volume <20 ml was reliably detected, but those with a volume of 20 ml or greater produced amounts of mNS which led to the most accurate detection of HNSCC based on HNSCC-specific mNS patterns.

Conclusion: Analysis of urinary mNS allows for detection of small-volume HNSCC, with acceptable specificity and sensitivity if the tumor volume exceeds 20 ml.
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http://dx.doi.org/10.21873/anticanres.12962DOI Listing
November 2018

The volatilome - investigation of volatile organic metabolites (VOM) as potential tumor markers in patients with head and neck squamous cell carcinoma (HNSCC).

J Otolaryngol Head Neck Surg 2018 Jul 3;47(1):42. Epub 2018 Jul 3.

Institute of Environmental Medicine and Hygiene, Faculty of Medicine, University of Leipzig, Liebigstr. 27, 04103, Leipzig, Germany.

Background: Different organisms such as bacteria, molds and humans produce and release a relative unknown class of metabolites which are responsible for the individual olfactory pattern. These volatile organic metabolites (VOM) represent a kind of biosignature that reflects the sum of all multifactorial influences, including genetics, environmental factors, nutritional and disease status. As a result of pathological processes the individual body odor can be influenced by newly produced or altered compositions of the VOM. Until now, human VOM have been detected in various body media, such as on the skin, in the exhaled air as well as in body fluids such as saliva, mother's milk, sweat, blood and urine.

Methods: In this retrospective case-control study urinary VOM of 53 therapy-naive patients with head and neck squamous cell carcinoma (HNSCC) and 82 healthy controls were semi-quantified by headspace solid-phase micro extraction (SPME) gas chromatography (GC) mass spectrometry (MS). At first, the procedure was optimized in respect to the extraction parameters. By using Student's t-test significant differences in the VOM pattern with the corresponding p-values were obtained. For multivariate metabolite pattern recognition the hierarchical cluster analysis by Ward was applied, followed by the supervised partial least squares-discriminant analysis (PLS-DA).

Results: In total 81 VOMs could identified in the urine samples of all study participants, of which 25 were significantly increased and of which were 10 significantly reduced in HNSCC-patients compared to the controls. In addition, the multivariate statistics confirmed that on the basis of the renal excreted pattern of the volatile metabolites a high discrimination can be carried out between patients with a tumor in the head and neck region and controls. The substance group of the saturated, unbranched aldehydes makes a substantial contribution in this context.

Conclusions: The systematic pattern analysis of urinary VOMs appears to have potential clinical application as a diagnostic tool for cancer, especially HNSCC.
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http://dx.doi.org/10.1186/s40463-018-0288-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029417PMC
July 2018

The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.

Int J Cancer 2015 Dec 6;137(12):2846-57. Epub 2015 Jul 6.

LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103, Leipzig, Germany.

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.
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http://dx.doi.org/10.1002/ijc.29649DOI Listing
December 2015

Helicobacter pylori prevalence in children influenced by non-specific antibiotic treatments.

Cent Eur J Public Health 2014 Mar;22(1):48-53

Objective: Helicobacter pylori (H.p.) infections play a very important role in the development of ulcerations and malignancies of the gastrointestinal tract. It is assumed that the primary infection occurs during childhood, depending on numerous environmental factors among them hygiene and social status. Our aim was to determine whether treatment with antibiotics affects the persistence of H.p. infection.

Methods: In 2006, we conducted an epidemiological study among all grade 8 students in the city of Leipzig (mean age 14.6 years). To determine the prevalence of H.p. infection, a voluntary H.p. test (13C-urea breath test) was performed in all participants.

Results: The H.p. prevalence was 6.3% (N = 1,598). A significant difference was found between those students who had been treated with an antibiotic at least once prior to the test and those who had never received any antibiotics (4.0% and 11.1%, respectively, p < 0.001). H.p. prevalence decreased with increasing numbers of antibiotic treatments.

Conclusion: In adolescence, treatment with "non-H.p. specific" antibiotics appears to significantly affect H.p. prevalence. Moreover, the actual persistence of H.p. in "chronic persistent" H.p. infections appears to fluctuate at least in younger years. Thus, any "non-H.p. specific" antibiotic treatment should be considered in the diagnosis and treatment of H.p. infections and should be taken into account as an important confounder in future epidemiological studies.
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http://dx.doi.org/10.21101/cejph.a3890DOI Listing
March 2014

Improvement of health risk factors after reduction of VOC concentrations in industrial and urban areas.

Environ Sci Pollut Res Int 2014 3;21(16):9676-88. Epub 2014 May 3.

Facultad de Ciencias Exactas, CIMA-Centro de Investigaciones del Medio Ambiente, Universidad Nacional de La Plata, La Plata, Argentina.

After reductions of fugitive and diffuse emissions by an industrial complex, a follow-up study was performed to determine the time variability of volatile organic compounds (VOCs) and the lifetime cancer risk (LCR). Passive samplers (3 M monitors) were placed outdoors (n = 179) and indoors (n = 75) in industrial, urban, and control areas for 4 weeks. Twenty-five compounds including n-alkanes, cycloalkanes, aromatics, chlorinated hydrocarbons, and terpenes were determined by GC/MS. The results show a significant decrease of all VOCs, especially in the industrial area and to a lesser extent in the urban area. The median outdoor concentration of benzene in the industrial area declined compared to the former study, around 85% and about 50% in the urban area, which in the past was strongly influenced by industrial emissions. Other carcinogenic compounds like styrene and tetrachloroethylene were reduced to approximately 60%. VOC concentrations in control areas remained nearly unchanged. According to the determined BTEX ratios and interspecies correlations, in contrast to the previous study, traffic was identified as the main emission source in the urban and control areas and showed an increased influence in the industrial area. The LCR, calculated for benzene, styrene, and tetrachloroethylene, shows a decrease of one order of magnitude in accordance to the decreased total VOC concentrations and is now acceptable according to values proposed by the World Health Organization.
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http://dx.doi.org/10.1007/s11356-014-2904-xDOI Listing
June 2015

Modified nucleosides as biomarkers for early cancer diagnose in exposed populations.

Environ Toxicol 2015 Jul 24;30(8):956-67. Epub 2014 Feb 24.

Environmental Medicine and Hygiene, Faculty of Medicine, University of Leipzig, Liebigstrasse 27, 04103, Leipzig, Germany.

There is increasing worldwide interest in developing of markers for tumor diagnosis and identification of individuals who are at high cancer risk. Cancer, like other diseases accompanied by metabolic disorders, causes characteristic effects on cell turnover rate, activity of modifying enzymes, and RNA/DNA modifications. This results in an increased excretion of modified nucleosides in cancer patients. Therefore, for many years modified nucleosides have been suggested as tumor markers. The aim of the study was to elucidate further the usefulness of urinary nucleosides as possible markers at early detection of cancer in persons which are exposed against tumor promoting influences during their working life. Uranium miners are exposed to many kinds of pollutants that can cause health damage even lead to carcinogenesis. We analyzed modified nucleosides in urine samples from 92 miners who are at high risk for lung cancer to assess the levels of nucleosides by a multilayer perceptron (MLP) classifier - a neural network model. Eighteen nucleosides/metabolites were detected with reversed-phase high-pressure liquid chromatography (RP-HPLC). A valid set of urinary metabolites were selected and multivariate statistical technique of multilayer perceptron neural network were applied. In a previous study, MLP shows a sensitivity and specificity of 97 and 85%, respectively. MLP classification including the most relevant markers/nucleosides clearly demonstrates the elevation of RNA metabolism in miners, which is associated with possible malignant disease. We found that there were 30 subjects with early health disorders among 92 uranium workers based on MLP technique using modified nucleosides. The combination of RP-HPLC analysis of modified nucleosides and subsequent MLP analyses represents a promising tool for the development of a non-invasive prediction system and may assist in developing management and surveillance procedures.
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http://dx.doi.org/10.1002/tox.21970DOI Listing
July 2015

GSTP1 and TNF Gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) study.

Environ Health Perspect 2014 Apr 24;122(4):418-24. Epub 2014 Jan 24.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma.

Objective: Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma.

Methods: Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7-8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, ozone] were assigned to each child's birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated.

Results: Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 μg/m3 NO2] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype.

Conclusions: Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution.
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http://dx.doi.org/10.1289/ehp.1307459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984232PMC
April 2014

Healthcare use and costs associated with children's behavior problems.

Eur Child Adolesc Psychiatry 2014 Aug 11;23(8):701-14. Epub 2013 Dec 11.

Institute of Epidemiology I, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany,

The objective of the study was to investigate associations between severity of behavior problems, specific symptom domains with healthcare use and costs in school-aged children. A cross-sectional study using data from the 10-year follow-up of two population-based birth cohorts was conducted on four rural and urban communities in Germany. There were 3,579 participants [1,834 boys (51%), 1,745 girls (49%)] on average aged 10.4 years. The severity levels (normal, at risk, abnormal) and symptom domains of behavioral problems were assessed by parent-reported strengths and difficulties questionnaire (SDQ).The outcomes were medical use categories (physicians, therapists, hospital, and rehabilitation), medical costs categories and total direct medical use and costs (calculated from parent-reported utilization of healthcare services during the last 12 months). Total direct medical costs showed a graded relationship with severity level (adjusted p < 0.0001). Average annual cost difference in total direct medical costs between at risk and normal total difficulties was Euro () 271 (SD 858), and 1,237 (SD 2,528) between abnormal and normal total difficulties. A significant increase in physician costs showed between children with normal and at risk total difficulties (1.30), and between normal and abnormal total difficulties (1.29; p < 0.0001). Between specific symptom domains, children with emotional symptoms showed highest costs for physicians, psychotherapist, and hospitalization as well as total direct medical costs. Children with hyperactivity/inattention showed highest costs for therapists and emergency room costs. Healthcare use and costs are related to the severity of child behavior problems. In general, children's costs for psychotherapy treatments have been low relative to general medical treatments which may indicate that some children with behavioral problems did not get appropriate care. To some degree, medical conditions may be attributable to some of the high hospitalization costs found in children with emotional symptom.
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http://dx.doi.org/10.1007/s00787-013-0504-9DOI Listing
August 2014

Traffic, asthma and genetics: combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution's impact on childhood asthma.

Eur J Epidemiol 2013 Jul 24;28(7):597-606. Epub 2013 Jul 24.

School of Population and Public Health, University of British Columbia, 2206 East Mall, Vancouver, BC, V6T1Z3, Canada.

Associations between traffic-related air pollution and incident childhood asthma can be strengthened by analysis of gene-environment interactions, but studies have typically been limited by lack of study power. We combined data from six birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and candidate genes. Individual-level assessment of traffic-related air pollution exposure was estimated using land use regression or dispersion modeling. A total of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study; 6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1 rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for investigating the effect of genotype on the association between air pollution and childhood allergic disease.
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http://dx.doi.org/10.1007/s10654-013-9828-5DOI Listing
July 2013

Children with ADHD symptoms have a higher risk for reading, spelling and math difficulties in the GINIplus and LISAplus cohort studies.

PLoS One 2013 27;8(5):e63859. Epub 2013 May 27.

Max Planck Institute of Psychiatry, Munich, Germany.

Attention-deficit/hyperactivity disorder (ADHD) and dyslexia belong to the most common neuro-behavioral childhood disorders with prevalences of around 5% in school-aged children. It is estimated that 20-60% of individuals affected with ADHD also present with learning disorders. We investigated the comorbidity between ADHD symptoms and reading/spelling and math difficulties in two on-going population-based birth cohort studies. Children with ADHD symptoms were at significantly higher risk of also showing reading/spelling difficulties or disorder (Odds Ratio (OR) = 2.80, p = 6.59×10⁻¹³) as compared to children without ADHD symptoms. For math difficulties the association was similar (OR = 2.55, p = 3.63×10⁻⁰⁴). Our results strengthen the hypothesis that ADHD and learning disorders are comorbid and share, at least partially, the same underlying process. Up to date, it is not clear, on which exact functional processes this comorbidity is based.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063859PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664565PMC
November 2013

Childhood allergic rhinitis, traffic-related air pollution, and variability in the GSTP1, TNF, TLR2, and TLR4 genes: results from the TAG Study.

J Allergy Clin Immunol 2013 Aug 30;132(2):342-52.e2. Epub 2013 Apr 30.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Associations between traffic-related air pollution (TRAP) and allergic rhinitis remain inconsistent, possibly because of unexplored gene-environment interactions.

Objective: In a pooled analysis of 6 birth cohorts (Ntotal = 15,299), we examined whether TRAP and genetic polymorphisms related to inflammation and oxidative stress predict allergic rhinitis and sensitization.

Methods: Allergic rhinitis was defined with a doctor diagnosis or reported symptoms at age 7 or 8 years. Associations between nitrogen dioxide, particulate matter 2.5 (PM2.5) mass, PM2.5 absorbance, and ozone, estimated for each child at the year of birth, and single nucleotide polymorphisms within the GSTP1, TNF, TLR2, or TLR4 genes with allergic rhinitis and aeroallergen sensitization were examined with logistic regression. Models were stratified by genotype and interaction terms tested for gene-environment associations.

Results: Point estimates for associations between nitrogen dioxide, PM2.5 mass, and PM2.5 absorbance with allergic rhinitis were elevated, but only that for PM2.5 mass was statistically significant (1.37 [1.01, 1.86] per 5 μg/m(3)). This result was not robust to single-cohort exclusions. Carriers of at least 1 minor rs1800629 (TNF) or rs1927911 (TLR4) allele were consistently at an increased risk of developing allergic rhinitis (1.19 [1.00, 1.41] and 1.24 [1.01, 1.53], respectively), regardless of TRAP exposure. No evidence of gene-environment interactions was observed.

Conclusion: The generally null effect of TRAP on allergic rhinitis and aeroallergen sensitization was not modified by the studied variants in the GSTP1, TNF, TLR2, or TLR4 genes. Children carrying a minor rs1800629 (TNF) or rs1927911 (TLR4) allele may be at a higher risk of allergic rhinitis.
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http://dx.doi.org/10.1016/j.jaci.2013.03.007DOI Listing
August 2013

Association of atopic and non-atopic asthma with emotional symptoms in school children.

Pediatr Allergy Immunol 2013 May;24(3):230-6

Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

Objective: To date, there is conflicting evidence whether the association between asthma and depression depends on the atopic or non-atopic asthma phenotype. This study investigates associations between emotional symptoms and atopic and non-atopic asthma in school-aged children.

Methods: Cross-sectional data on asthma and allergic diseases at the 10-year follow-up of two birth cohorts were collected by parent-reported physician diagnoses. Specific IgE levels including most common inhalant allergens (SX1) and food allergens (FX5) were measured by RAST-CAP FEIA. Atopic asthma was defined as asthma ever and positive specific IgE test, non-atopic asthma as asthma ever and no IgE sensitization. Emotional symptoms were assessed by parent-reported strength and difficulty questionnaire. Logistic regression modeling were applied to determine likelihood of emotional symptoms in children with atopic and non-atopic asthma controlling for socio-demographic factors, body mass index, atopic eczema, allergic rhinitis, and pubertal development.

Results: Non-atopic asthma was associated with about 3-fold higher likelihood of emotional symptoms compared to children with no asthma (ORadj = 2.90, CI95% = 1.46-5.73). Atopic asthma was not associated with emotional symptoms (ORadj = 1.35, CI95% = 0.81-2.26).

Conclusions: Atopic and non-atopic asthma in children might have different etiologies, whereas for non-atopic asthma, emotional symptoms are relevant, this is not the case in atopic asthma. The relationship between the non-atopic asthma phenotype and emotional symptoms might be dependent on gender.
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http://dx.doi.org/10.1111/pai.12056DOI Listing
May 2013

Physical activity and its correlates in children: a cross-sectional study (the GINIplus & LISAplus studies).

BMC Public Health 2013 Apr 16;13:349. Epub 2013 Apr 16.

Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany.

Background: Physical inactivity among children is an increasing problem that adversely affects children's health. A better understanding of factors which affect physical activity (PA) will help create effective interventions aimed at raising the activity levels of children. This cross-sectional study examined the associations of PA with individual (biological, social, behavioral, psychological) and environmental (East vs. West Germany, rural vs. urban regions) characteristics in children.

Methods: Information on PA and potential correlates was collected from 1843 girls and 1997 boys using questionnaires during the 10-year follow-up of two prospective birth cohort studies (GINIplus and LISAplus). Study regions represent urban and rural sites as well as East and West of Germany. Logistic regression modeling was applied to examine cross-sectional associations between individual as well as environmental factors and PA levels.

Results: Five of fourteen variables were significantly associated with PA. Among children aged 10, girls tended to be less active than boys, especially with respect to vigorous PA (OR = 0.72 for summer). Children who were not a member of a sports club showed a substantially reduced amount of PA in winter (OR = 0.15). Rural environments promote moderate PA, particularly in winter (OR = 1.88), whereas an increased time outdoors primarily promotes moderate PA in summer (OR = 12.41). Children with abnormal emotional symptoms exhibited reduced physical activity, particularly in winter (OR = 0.60). BMI, puberty, parental BMI, parental education, household income, siblings, TV/PC consumption, and method of arriving school, were not associated with PA.

Conclusions: When considering correlates of PA from several domains simultaneously, only few factors (sex, sports club membership, physical environment, time outdoors, and emotional symptoms) appear to be relevant. Although the causality needs to be ascertained in longitudinal studies, variables which cannot be modified should be used to identify risk groups while modifiable variables, such as sports club activities, may be addressed in intervention programs.
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http://dx.doi.org/10.1186/1471-2458-13-349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641958PMC
April 2013

No cross-sectional and longitudinal association of ferritin and symptoms of attention-deficit-/hyperactivity disorder in a large population-based sample of children: results from the GINIplus and LISAplus studies.

Atten Defic Hyperact Disord 2013 Sep 13;5(3):313-20. Epub 2013 Apr 13.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Clinic of Munich, Nußbaumstr. 5 a, 80336 Munich, Germany.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with alterations in iron metabolism, and low ferritin concentrations in peripheral blood have inconsistently been reported in clinically referred samples of children with ADHD. This study examined whether higher peripheral concentrations of ferritin, the major iron storage protein, are associated with decreased symptoms of ADHD in 2,805 children aged 10 years participating in two large population-based birth cohorts (GINIplus and LISAplus). Whether high ferritin concentrations at age 4 months predict lower ADHD symptoms at age 10 years was also investigated using a longitudinal approach in a subsample of 193 children. No indications for an association between peripheral ferritin concentrations and ADHD symptoms were found in this large population-based study. Re-evaluating iron substitution as a therapeutic measure for ADHD may be warranted.
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http://dx.doi.org/10.1007/s12402-013-0108-8DOI Listing
September 2013

Size-fractioned particulate air pollution and cardiovascular emergency room visits in Beijing, China.

Environ Res 2013 Feb 30;121:52-63. Epub 2013 Jan 30.

Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany.

Background: Although short-term exposure to ambient particulate matter has increasingly been linked with cardiovascular diseases, it is not quite clear how physical characteristics of particles, such as particle size may be responsible for the association. This study aimed at investigating whether daily changes in number or mass concentrations of accurately size-segregated particles in the range of 3nm-10μm are associated with daily cardiovascular emergency room visits in Beijing, China.

Methods: Cardiovascular emergency room visit counts, particle size distribution data, and meteorological data were collected from Mar. 2004 to Dec. 2006. Particle size distribution data was used to calculate particle number concentration in different size fractions, which were then converted to particle mass concentration assuming spherical particles. We applied a time-series analysis approach. We evaluated lagged associations between cardiovascular emergency room visits and particulate number and mass concentration using distributed lag non-linear models up to lag 10. We calculated percentage changes of cardiovascular emergency room visits, together with 95% confidence intervals (CI), in association with an interquartile range (IQR, difference between the third and first quartile) increase of 11-day or 2-day moving average number or mass concentration of particulate matter within each size fraction, assuming linear effects. We put interaction terms between season and 11-day or 2-day average particulate concentration in the models to estimate the modification of the particle effects by season.

Results: We observed delayed associations between number concentration of ultrafine particles and cardiovascular emergency room visits, mainly from lag 4 to lag 10, mostly contributed by 10-30nm and 30-50nm particles. An IQR (9040cm(-3)) increase in 11-day average number concentration of ultrafine particles was associated with a 7.2% (1.1-13.7%) increase in total, and a 7.9% (0.5-15.9%) increase in severe cardiovascular emergency room visits. The delayed effects of particulate mass concentration were small. Regarding immediate effects, 2-day average number concentration of Aitken mode (30-100nm) particles had strongest effects. An IQR (2269cm(-3)) increase in 2-day average number concentration of 30-50nm particles led to a 2.4% (-1.5-6.5%) increase in total, and a 1.7% (-2.9-6.5%) increase in severe cardiovascular emergency room visits. The immediate effects of mass concentration came mainly from 1000-2500nm particles. An IQR (11.7μgm(-3)) increase in 2-day average mass concentration of 1000-2500nm particles led to an around 2.4% (0.4-4.4%) increase in total, and a 1.7% (-0.8-4.2%) increase in severe cardiovascular emergency room visits. The lagged effect curves of number and mass concentrations of 100-300nm particles or 300-1000nm particles were quite similar, indicating that using particulate number or mass concentrations seemed not to affect the cardiovascular effect (of particles within one size fraction). The effects of number concentration of ultrafine particles, sub-micrometer particles (3-1000nm) and 10-30nm particles were substantially higher in winter comparing with in summer.

Conclusions: Elevated concentration levels of sub-micrometer particles were associated with increased cardiovascular morbidity. Ultrafine particles showed delayed effects, while accumulation mode (100-1000nm) particles showed immediate effects. Using number or mass concentrations did not affect the particle effects.
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http://dx.doi.org/10.1016/j.envres.2012.10.009DOI Listing
February 2013

Exposure to second-hand smoke and direct healthcare costs in children - results from two German birth cohorts, GINIplus and LISAplus.

BMC Health Serv Res 2012 Oct 2;12:344. Epub 2012 Oct 2.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Member of the German Center for Lung Research, Neuherberg, Germany.

Background: Although the negative health consequences of the exposure to second hand tobacco smoke during childhood are already known, evidence on the economic consequences is still rare. The aim of this study was to estimate excess healthcare costs of exposure to tobacco smoke in German children.

Methods: The study is based on data from two birth cohort studies of 3,518 children aged 9-11 years with information on healthcare utilisation and tobacco smoke exposure: the GINIplus study (German Infant Study On The Influence Of Nutrition Intervention Plus Environmental And Genetic Influences On Allergy Development) and the LISAplus 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). Direct medical costs were estimated using a bottom-up approach (base year 2007). We investigated the impact of tobacco smoke exposure in different environments on the main components of direct healthcare costs using descriptive analysis and a multivariate two-step regression analysis.

Results: Descriptive analysis showed that average annual medical costs (physician visits, physical therapy and hospital treatment) were considerably higher for children exposed to second-hand tobacco smoke at home (indoors or on patio/balcony) compared with those who were not exposed. Regression analysis confirmed these descriptive trends: the odds of positive costs and the amount of total costs are significantly elevated for children exposed to tobacco smoke at home after adjusting for confounding variables. Combining the two steps of the regression model shows smoking attributable total costs per child exposed at home of €87 [10-165] (patio/balcony) and €144 [6-305] (indoors) compared to those with no exposure. Children not exposed at home but in other places showed only a small, but not significant, difference in total costs compared to those with no exposure.

Conclusions: This study shows adverse economic consequences of second-hand smoke in children depending on proximity of exposure. Tobacco smoke exposure seems to affect healthcare utilisation in children who are not only exposed to smoke indoors but also if parents reported exclusively smoking on patio or balcony. Preventing children from exposure to second-hand tobacco smoke might thus be desirable not only from a health but also from an economic perspective.
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http://dx.doi.org/10.1186/1472-6963-12-344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506539PMC
October 2012

Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts.

PLoS One 2012 29;7(8):e43214. Epub 2012 Aug 29.

Department of Paediatrics, Oslo University Hospital, Ullevål, Norway.

Objective: To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6-10 years.

Design: Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. EXPOSURE DEFINITION: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. OUTCOME DEFINITION: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years of age.

Data Synthesis: Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.

Results: We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with "no pets" (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84) (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.

Conclusions: Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6-10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043214PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430634PMC
February 2013

Is there a relationship between hyperactivity/inattention symptoms and poor oral health? Results from the GINIplus and LISAplus study.

Clin Oral Investig 2013 Jun 29;17(5):1329-38. Epub 2012 Aug 29.

German Research Center for Environmental Health, Institute of Epidemiology I, Helmholtz Zentrum Muenchen, Ingolstaedter Landstrasse 1, Neuherberg, Germany.

Objectives: A few clinical observations reported that children with attention deficit hyperactivity disorder (ADHD) have poor oral health compared to children without ADHD. However, evidence is not conclusive. We assess the association between hyperactivity/inattention and oral health in a population-based study.

Material And Methods: As part of the ongoing birth cohort studies German Infant Nutritional Intervention-plus (GINIplus) and Influences of lifestyle-related factors on the immune system and the development of allergies in childhood-plus (LISAplus), 1,126 children at age 10 years (±10.2) from Munich (Germany) were included in the present analysis. During the dental examination, oral hygiene, non-cavitated and cavitated caries lesions, dental trauma, and enamel hypomineralization (EH) in the permanent dentition (MIH/1) were recorded. Children with a Molar-Incisor-Hypomineralization were subcategorized into those with EH on at least one first permanent molar (MIH/1A), and on at least one first permanent molar and permanent incisor (MIH/1B). Data on children's hyperactivity/inattention symptoms were collected by parent-reported Strength and Difficulties Questionnaire. Logistic regressions and zero-inflated Poisson regression models were applied adjusted for gender, parental education, parental income, and methylphenidate or atomoxetine medication.

Results: Logistic regressions showed that non-cavitated caries lesions were positively related with the presence of hyperactivity/inattention (ORadj = 1.51,CI95% = 1.08-2.11). When adjusted for parental background, an association showed between hyperactivity/inattention symptoms and MIH/1A but did not reach statistical significance (ORadj = 1.59,CI95% = 1.00-2.53).

Conclusions: Children with borderline and abnormal values of hyperactivity/inattention symptoms showed more non-cavitated caries lesions. Severe levels of hyperactivity/inattention may contribute to a higher risk for MIH/1A in school age.

Clinical Relevance: Adequate dental preventive care for children with hyperactivity/inattention, especially from a low social background, is of importance for optimal caries prevention.
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http://dx.doi.org/10.1007/s00784-012-0829-7DOI Listing
June 2013

Utilization and costs of conventional and alternative pharmaceuticals in children: results from the German GINIplus and LISAplus birth cohort studies.

Pharmacoepidemiol Drug Saf 2012 Oct 1;21(10):1102-11. Epub 2012 Aug 1.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg, Germany.

Purpose: The socioeconomic determinants for drug utilization, especially in children, have not been investigated sufficiently so far. The study's aim was the estimation of prevalences and determinants of conventional, homeopathic and phytotherapeutic drugs and expenditures.

Methods: Population-based data on drug utilization of 3,642 children in two German birth cohorts (GINIplus and LISAplus, 10-year follow-up) were collected using a self-administered questionnaire. For analysis, the reported drugs (use within the last four weeks) were classified into the therapeutic categories of 'conventional medicine', 'homeopathy', 'phytotherapy' and 'others'. Drug costs were estimated using pharmaceutical identification numbers.

Results: In all, 42.3% of the children reported drug use; 24.1% of the drugs were homeopathic and 11.5% were phytotherapeutic. The proportion of children who took at least one homeopathic remedy was 14.3%. Drugs prescribed by physicians were dominated by conventional medicine (76.5%), whereas in non-prescribed drugs, both homeopathy and conventional medicine accounted for 37% each. Boys (OR = 0.78) used less homeopathy than girls. Income showed only a weak influence. Education had a strong effect on the use of phytotherapy such that children of mothers with higher school education (>10 years vs. <10 years) used more phytotherapy (OR = 2.01). If out-of-pocket payments arose (n = 613), the mean was €20. On average, total drug expenditures summed up to €39 in 4 weeks for drug users if only clearly identifiable prices for drugs were considered (58% of all data).

Conclusions: Utilization of homeopathy is common in children from the analyzed cohort. User profiles of homeopathy and phytotherapy differ from each other and should be analyzed separately.
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http://dx.doi.org/10.1002/pds.3323DOI Listing
October 2012

Genetic association between obstructive bronchitis and enzymes of oxidative stress.

Metabolism 2012 Dec 26;61(12):1771-9. Epub 2012 Jun 26.

UFZ-Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Leipzig, Germany.

Objective: Obstructive respiratory diseases, mainly the chronic obstructive pulmonary disease (COPD) and asthma, are associated with functional polymorphisms of xenobiotic-metabolizing enzymes (XMEs). To date, association for obstructive bronchitis has not been described.

Material/methods: In this study, we investigated the genotypes from 26 functional polymorphisms of 20 XMEs in children (n, 1028) at the age of 6 years from the German prospective birth cohort study (LISAplus) and analyzed the associations between genotypes and obstructive bronchitis.

Results: For the first time, we found noteworthy gene-disease associations for the functional PON1 M55L and EPHX1 H139R polymorphisms and gene-environment associations for the functional COMT V158M and NQO1 P187S polymorphisms after stratification for maternal active smoking behaviour during pregnancy. The noteworthy associations were substantiated by the biological findings that all the risk genotypes belong to genes involved in oxidative stress and code for proteins with a fast enzymatic activity or concomitantly appear in common estrogene-metabolizing pathway (COMT, NQO1).

Conclusion: The oxidative stress has to be taken into account in mechanism of the obstructive bronchitis in early childhood. The risk genotypes may serve as risk factors for respiratory obstruction rather than for signs of COPD or asthma.
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http://dx.doi.org/10.1016/j.metabol.2012.05.013DOI Listing
December 2012

Food intake, diet quality and behavioral problems in children: results from the GINI-plus/LISA-plus studies.

Ann Nutr Metab 2012 1;60(4):247-56. Epub 2012 Jun 1.

Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

Background/aims: To assess the association between food intake and diet quality and behavioral problems at the 10-year follow-up of the two population-based birth cohorts of the studies German Infant Nutritional Intervention and 'Influences of lifestyle-related factors on the immune system and the development of allergies in childhood'.

Methods: Cross-sectional data on food intake over the past year were collected by a parent-reported food frequency questionnaire. Diet quality was based on reference values of food amounts of the optimized mixed diet. Behavioral problems were assessed by a parent-reported Strengths and Difficulties Questionnaire. Relationships between food category intake, diet quality and behavior problems were examined using multivariable regression modeling adjusted for gender, sociodemographic characteristics, body mass index, physical exercise, television viewing/PC use and total energy intake. A total of 3,361 children with complete data were analyzed.

Results: Children with increased intake of confectionery had increased odds of having emotional symptoms [adjusted odds ratio (OR(adj)) 1.19, 95% confidence interval (CI) 1.08-1.32] compared to children with low intake. A higher diet quality score was associated with lower likelihood of emotional symptoms (OR(adj) 0.89, 95% CI 0.80-0.98). The unadjusted significant relationship between diet quality and hyperactivity/inattention was attenuated by adjusting for several confounders to an OR(adj) of 0.92 (95% CI 0.82-1.03).

Conclusions: Increased consumption of high-sugar products and lower diet quality are associated with a higher likelihood of emotional symptoms in children.
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http://dx.doi.org/10.1159/000337552DOI Listing
November 2012

FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children: results from the GINIplus and LISAplus studies.

PLoS One 2012 21;7(5):e37780. Epub 2012 May 21.

Institute of Epidemiology I, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.

Background: Elevated cholesterol levels in children can be a risk factor for cardiovascular diseases in later life. In adults, it has been shown that blood lipid levels are strongly influenced by polymorphisms in the fatty acid desaturase (FADS) gene cluster in addition to nutritional and other exogenous and endogenous determinants. Our aim was to investigate whether lipid levels are determined by the FADS genotype already in children and whether this association interacts with dietary intake of n-3 fatty acids.

Methods: The analysis was based on data of 2006 children from two German prospective birth cohort studies. Total cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped. Dietary n-3 fatty acid intake was assessed by food frequency questionnaire. Linear regression modeling was used to assess the association between lipid levels, n-3 fatty acid intake and FADS genotype.

Results: Individuals carrying the homozygous minor allele had lower levels of total cholesterol [means ratio (MR) ranging from 0.96 (p = 0.0093) to 0.98 (p = 0.2949), depending on SNPs] and LDL [MR between 0.94 (p = 0.0179) and 0.97 (p = 0.2963)] compared to homozygous major allele carriers. Carriers of the heterozygous allele showed lower HDL levels [β between -0.04 (p = 0.0074) to -0.01 (p = 0.3318)] and higher triglyceride levels [MR ranging from 1.06 (p = 0.0065) to 1.07 (p = 0.0028)] compared to homozygous major allele carriers. A higher n-3 PUFA intake was associated with higher concentrations of total cholesterol, LDL, HDL and lower triglyceride levels, but these associations did not interact with the FADS1 FADS2 genotype.

Conclusion: Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037780PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357401PMC
December 2012

Peak growth velocity in infancy is positively associated with blood pressure in school-aged children.

J Hypertens 2012 Jun;30(6):1114-21

Helmholtz Zentrum Munich, Center for Environment and Health, Institute of Epidemiology I, Neuherberg, Germany.

Objectives: Rapid growth velocity in early life may be a risk factor for obesity, elevated blood pressure, and adverse metabolic markers in childhood, but results are not consistent. We analysed the association between peak growth velocity during the first 2 years of life and blood pressure, fasting glucose and insulin at 10 years of age.

Methods: A prospective German birth cohort (LISAplus) provided data on growth, blood pressure, glucose, and insulin for 1127 children up to the age of 10 years. All children had a birth weight of at least 2500 g. Growth was modelled using nonlinear mixed-effect Reed1 models. Associations between peak growth velocities and metabolic outcomes were calculated with linear regression models. Potential confounders were sequentially adjusted for.

Results: Higher peak height velocity (PHV) and peak weight velocity (PWV) in infancy were associated with significant increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in children at 10 years. For each 10.2 cm/year [2 standard deviation (SD)] increase in PHV, SBP increased by 2.94 mmHg [95% confidence interval (CI) 1.34, 4.54] after adjustment for potential confounders including birth weight and body mass index. A 5.1 kg/year (2 SD) higher PWV was associated with a 2.13 mmHg (95% CI 0.51, 3.74) increase in SBP and a 1.91 mmHg (95% CI 0.52, 3.30) increase in DBP. No consistent associations were found between PHV or PWV and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index after multiple adjustments.

Conclusions: Blood pressure and metabolic outcomes at school age may be associated with growth patterns in early life, regardless of relative weight during school age.
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http://dx.doi.org/10.1097/HJH.0b013e328352d699DOI Listing
June 2012

Indoor factors and behavioural problems in children: the GINIplus and LISAplus birth cohort studies.

Int J Hyg Environ Health 2013 Mar 7;216(2):146-54. Epub 2012 Apr 7.

Centre for Research in Environmental Epidemiology, Spain.

Indoor microbial agents exposure is associated to depressive symptoms in adults and persistent exposure to indoor mould is associated to poorer cognitive function in children. In our study, we aimed to assess the effects of the exposure to indoor factors associated with increased microbial exposure (mould, dampness and pets) on behavioural problems in children aged 10 years, participating in two German birth cohorts. A total of 4860 children were followed until the age of 10 years, and the strengths and difficulties questionnaire (SDQ) was administered to the parents. Indoor factors were assessed through parental reported questionnaires in periodical surveys. Logistic and multinomial regressions adjusting for potential confounders were performed. Prevalences of borderline/abnormal total scores in the SDQ at 10 years of age were higher in children exposed to mould (aOR=1.23, 95%CI=1.00-1.56), dampness (aOR=1.51, 95%CI=1.10-2.07), and pets (aOR=1.48, 95%CI=1.20-1.94). The dimension "emotional symptoms" showed statistically significant risk estimates for mould and pets, meanwhile "conduct problems" and "hyperactivity/inattention" dimensions only did for pets. No significant associations were found for the "peer relationship problems" dimension. We found a significant strong interaction between dampness and pet, the risk of borderline/abnormal scores in the "total difficulties" scale and the "emotional symptoms" dimension for pets' was at least twice the risk in children with reported dampness than in children without. Our findings point to a potential effect of microbial exposure on children's behavioural problems, especially on emotional disorders, probably mediated through neurotoxicity and immune system activation.
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http://dx.doi.org/10.1016/j.ijheh.2012.03.006DOI Listing
March 2013

The hygiene hypothesis does not apply to atopic eczema in childhood.

Chem Immunol Allergy 2012 13;96:15-23. Epub 2012 Mar 13.

There is evidence that environmental factors are important for the development of eczema. Different mechanisms have been discussed in the literature, the best known of which is the hygiene hypothesis. However, epidemiological data give reason for questioning this hypothesis with regard to childhood eczema. We present results from two German birth cohort studies (LISAplus and GINIplus) concerning regional prevalence patterns of eczema and the association of eczema with day care center attendance and older siblings. Our findings are not in line with the hygiene hypothesis and question its validity with regard to eczema. It seems reasonable to assume that the effect of environmental factors is somehow disease-specific.
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http://dx.doi.org/10.1159/000331805DOI Listing
July 2012

Predictive value of food sensitization and filaggrin mutations in children with eczema.

J Allergy Clin Immunol 2011 Dec 26;128(6):1235-1241.e5. Epub 2011 Oct 26.

Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Background: It was reported that in infants with eczema and food sensitization, the presence of a filaggrin (FLG) null mutation predicts future asthma with a specificity and positive predictive value of 100%.

Objectives: We sought to evaluate the predictive value of food sensitization and food allergy, FLG haploinsufficiency, and their combination in infants with early-onset eczema for persistent eczema and childhood asthma.

Methods: The German Infant Nutritional Intervention (GINI) and Influence of Lifestyle-related Factors on the Immune System and the Development of Allergies in Childhood (LISA) birth cohorts, as well as a collection of 65 cases of early-onset eczema with and without food allergy were investigated.

Results: The risk for asthma was significantly increased by food sensitization (positive diagnostic likelihood ratios [PLRs] of 1.9 [95% CI, 1.1-3.4] in the GINI cohort and 5.5 [95% CI, 2.8-10.8] in the LISA cohort) and the presence of an FLG mutation (PLRs of 2.9 [95% CI, 1.2-6.6] in the GINI cohort and 2.8 [95% CI, 1.0-7.9] in the LISA cohort) with a rather high specificity (79.1% and 92.9% in the GINI cohort and 89.0% and 91.7% in the LISA cohort, respectively) but low sensitivity (40.0% and 39.3% in the GINI cohort and 31.6% and 23.5% in the LISA cohort, respectively). Likewise, the risk for persistent eczema was increased. In the clinical cases neither food allergy nor FLG mutations had a significant effect. The combination of both parameters did not improve prediction and reached positive predictive values of 52.3% (GINI cohort), 66.9% (LISA cohort), and 30.6% (clinical cases), assuming an asthma prevalence in children with early eczema of 30%.

Conclusion: Early food sensitization and the presence of an FLG mutation in infants with early eczema increase the risk for later asthma, but the combination of the 2 factors does not represent a clinically useful approach to reliably identify children at risk.
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http://dx.doi.org/10.1016/j.jaci.2011.09.014DOI Listing
December 2011

Sub-micrometer particulate air pollution and cardiovascular mortality in Beijing, China.

Sci Total Environ 2011 Nov 21;409(24):5196-204. Epub 2011 Sep 21.

Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany.

Background: While the link between particulate matter and cardiovascular mortality is well established, it is not fully investigated and understood which properties of the aerosol might be responsible for the health effects, especially in polluted mega-city areas.

Objectives: Our goal was to explore the association between daily cardiovascular mortality and different particle metrics in the sub-micrometer range in Beijing, China.

Methods: We obtained daily counts of cause-specific cardiovascular deaths in the Beijing urban area for the period March 2004 to August 2005. Concurrently, continuous measurements of particle number size distributions were performed. Particle number concentrations (NC) between 0.003 μm and 0.8 μm were converted to particle mass and surface area concentrations assuming spherical particles. Semi-parametric Poisson regression models adjusting for trend, seasonality, day of the week, and meteorology were used to estimate immediate, delayed and cumulative particle effects. Additionally, effect modification by air mass origin was investigated.

Results: We observed associations between daily cardiovascular mortality and particle NC for a 2-days delay. Moreover, nearly all particle metrics showed 2-days delayed associations with ischemic heart disease mortality. The strongest association was found for particle NC in the size range 0.03-0.1 μm (7.1% increase in daily mortality with a 95%-confidence interval of 2.9%-11.5%, per an increase of 6250 particles/cm3). Results for surface and mass concentrations with a lag of two days indicated effect modification by air mass origin, whereas effects of particle NC were not modified.

Conclusions: Results show an elevated risk of cardiovascular mortality in Beijing from short-term exposure to particulate air pollution in the sub-micrometer range. Results also indicate that locally produced smaller particles and regionally transported particles may exhibit different effects in Beijing.
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http://dx.doi.org/10.1016/j.scitotenv.2011.08.023DOI Listing
November 2011

Associations between size-segregated particle number concentrations and respiratory mortality in Beijing, China.

Int J Environ Health Res 2012 19;22(2):119-33. Epub 2011 Aug 19.

Helmholtz-Centre for Environmental Research (UFZ), Core Facility-Studies, Leipzig, Germany.

Numerous studies have described the adverse associations between particle mass and respiratory health. The aim of the study was to analyze the associations of particle properties, especially size-segregated particle number concentrations (PNC), and respiratory mortality in Beijing, P.R. China. We gathered daily values of respiratory mortality and air pollution data of the Beijing urban area. Generalized additive models were used to estimate the associations. Single pollutant models showed that delayed concentrations of SO(2), total PNCs, and PNC of 300-1000 nm were adversely associated with total respiratory mortality. There was an indication that adverse health effects of PNCs might be stronger for stagnant air masses. Two-pollutant models verified the independence of associations of total PNCs of other pollutants (SO(2), NO(2), and PM(10)). In conclusion, particle number concentrations, especially accumulation mode particles, might be factors influencing the adverse associations between particulate matter and respiratory health.
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http://dx.doi.org/10.1080/09603123.2011.605878DOI Listing
July 2012

The effect of particle size on cardiovascular disorders--the smaller the worse.

Sci Total Environ 2011 Sep 10;409(20):4217-21. Epub 2011 Aug 10.

Helmholtz Centre for Environmental Research GmbH - UFZ, Leipzig, Germany.

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.
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http://dx.doi.org/10.1016/j.scitotenv.2011.05.049DOI Listing
September 2011

Passive smoking and behavioural problems in children: results from the LISAplus prospective birth cohort study.

Environ Res 2011 Nov 20;111(8):1173-9. Epub 2011 Jul 20.

Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology I, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.

Objective: To analyse the association between pre- and postnatal exposure to tobacco smoke and child behavioural problems and to further investigate the influence of trimester-specific exposure to maternal smoking and the impact of paternal smoking at home on the same outcome.

Methods: Data of 3097 German children recruited at birth for a population-based, prospective study were used. Detailed information on children's tobacco smoke exposure was collected by self-administered questionnaires at each follow-up. Behavioural outcomes were measured by the Strengths and Difficulties Questionnaire applied at 10-year follow-up.

Results: Children exposed to environmental tobacco smoke at home showed increased risks of hyperactivity/inattention problems. Only smoking during the entire pregnancy increased the risk for conduct and hyperactivity/inattention problems (proportional odds ratio (pOR)=1.58, 95% confidence interval (CI)=1.06-2.37 and pOR=1.67, CI=1.03-2.72). Pre- and postnatal exposure to paternal smoking was associated with hyperactivity/inattention problems in children of non-smoking mothers (pOR=1.97, CI=1.06-3.65). Effect estimates were adjusted for study centre, sex, parental educational level, mother's age at birth, having a single parent and time spent in front of a screen.

Conclusions: Not only maternal smoking during pregnancy but also paternal smoking at home should be considered as a risk for hyperactivity/inattention problems in children.
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http://dx.doi.org/10.1016/j.envres.2011.06.011DOI Listing
November 2011