Search

Background: Among the many risk factors for the development of atopic eczema (AE), the influence of air pollution has recently been discussed more often. A systematic review about this topic however is lacking., Aims: Which effects of outdoor air pollution (particles, nitric oxides, sulfur dioxide, ozone or general traffic exhaust emissions) on AE can be demonstrated in a systematic analysis of available environmental epidemiologic studies?, Methods: All environmental epidemiologic studies on AE and air pollution found in the literature database PubMed were identified. The most important key figures of these studies were tabulated, the quality of evidence was graded and the studies described., Results: A total of 57 studies were identified. Only one of the 15 cross-sectional studies with a large-scale exposure assessment found a significant association between AE and air pollution. In contrast 23 of 30 studies with small-scale exposure assessment found a significant association between AE and traffic related emissions-especially from trucks. Of the 30 studies, 14 were cohort studies (1 adult, 13 birth cohorts). The sole adult cohort found an association with intrinsic AE. In the East Asian cohorts (all published since 2015), an association between maternal exposure to traffic-related pollution and incidence of AE in the offspring was found. This was less clear in cohorts from Europe/US or simply not investigated. In 5/5 panel studies (all from South Korea), symptom severity of AE was found to be significantly and positively related to outdoor air pollution., Conclusions: In a systematic analysis of environmental epidemiologic studies about air pollution and AE rather good evidence was found that, based on small-scale exposure measurements, especially truck traffic emissions increased AE prevalence, while large-scale exposure to larger particles (PM10) or SO 2 was without effect. Considering pathophysiologic aspects traffic exhaust emissions seem to affect both skin barrier function and activation of immune responses.

Background: Although many risk factors have been described for atopic eczema in children, little is known about the eczema phenotype in middle-aged or elderly adults., Objective: We sought to examine the association between air pollution, atopy, and eczema in adulthood., Methods: This analysis was based on 834 women from the Study on the influence of Air pollution on Lung Function, Inflammation and Ageing cohort in Germany. Incident symptoms of eczema after age 55 years and prevalent symptoms of eczema 12 months or less before investigation were assessed by means of questionnaire at the second follow-up (2007-2010). Total serum IgE levels were measured at baseline (1985-1994) and in 2007-2010. Exposure to air pollution was assessed by using land-use regression. Adjusted logistic regression models were applied to estimate the association between air pollution and incident and prevalent symptoms of eczema. Weighted genetic risk scores were used to investigate the effect of atopic eczema-related risk alleles on this association., Results: Exposures to oxides of nitrogen (nitrogen dioxide and nitrogen oxides) and particulate matter (fine particulate matter with an aerodynamic diameter of ≤2.5 μm [PM 2.5 ] and particulate matter with an aerodynamic diameter of <10 μm) were significantly associated with increased odds of incident eczema (eg, with PM 2.5 per 4.7 μg/m 3 ; odds ratio, 1.45; 95% CI, 1.06-1.99). These associations were slightly more pronounced with nonatopic eczema (eg, with PM 2.5 ; odds ratio of 1.65 and 95% CI of 1.15-2.34 for participants without hay fever or increased IgE levels). Associations with air pollution were stronger in carriers of fewer risk alleles for atopic eczema., Conclusion: Nonatopic eczema in the elderly is associated with traffic-related air pollutants, and this phenotype differs from genetically driven atopic eczema., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Air pollution has been associated with impaired lung and cognitive function, especially impairment in visuo-construction performance (VCP). In this article, we evaluate whether the effect of air pollution on VCP is mediated by lung function.We used data from the SALIA cohort (baseline 1985-1994 and follow-up 2007-2010) including 587 women aged 55 years at baseline. Particulate matter (PM) and nitrogen dioxide (NO 2 ) exposures at baseline were estimated via land-use regression models. Lung function was characterised by averages between baseline and follow-up. We used age- and height-controlled Global Lung Initiative (GLI) z-scores of forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC. VCP was assessed at follow-up with the CERAD-Plus neuropsychological test battery and causal mediation analysis was conducted.An increase of one interquartile range in FEV 1 and FVC was positively associated with VCP (β=0.18 (95% CI 0.02-0.34) and β=0.23 (95% CI 0.07-0.39), respectively). The proportion of the association between NO 2 on VCP mediated by FEV 1 was 6.2% and this was higher in never smokers (7.2%) and non-carriers of the APOE-ε4 allele (11.2%). However, none of the mediations were statistically significant.In conclusion, air pollution associated VCP was partially mediated by lung function. Further studies on the mechanisms underlying this pathway are required to develop new strategies to prevent air pollution induced cognitive impairment., Competing Interests: Conflict of interest: M.J. Abramson has received investigator initiated grants for unrelated research from Pfizer and Boehringer-Ingelheim, and reimbursement for congress attendance from Sanofi., (Copyright ©ERS 2018.)

Background: Long-term air pollution exposure has been associated with chronic inflammation providing a link to the development of chronic health effects. Furthermore, there is evidence that pathways activated by endoplasmatic reticulum (ER) stress induce airway inflammation and thereby play an important role in the pathogenesis of inflammatory diseases., Objective: We investigated the role of genetic variation of the ER stress pathway on air pollution-induced inflammation., Methods: We used the follow-up examination of the German SALIA study (N=402, age 68-79 years). Biomarkers of inflammation were determined in induced sputum. We calculated biomarker-specific weighted genetic risk scores (GRS) out of eight ER stress related single nucleotide polymorphisms and tested their interaction with PM 2.5 , PM 2.5 absorbance, PM 10 and NO 2 exposure on inflammation by adjusted linear regression., Results: Genetic variation of the ER stress pathway was associated with higher concentration of inflammation-related biomarkers (levels of leukotriene (LT)B 4 , tumor necrosis factor-α (TNF-α), the total number of cells and nitric oxide (NO) derivatives). Furthermore, we observed a significant interaction between air pollution exposure and the ER stress risk score on the concentration of inflammation-related biomarkers. The strongest gene-environment interaction was found for LTB 4 (PM 2.5 : p-value=0.002, PM 2.5 absorbance: p-value=0.002, PM 10 : p-value=0.001 and NO 2 : p-value=0.004). Women with a high GRS had a 38% (95%-CI: 16-64%) higher LTB 4 level for an increase of 2.06μg/m³(IQR) in PM 2.5 (no associations in women with a low GRS)., Conclusion: These results indicate that genetic variation in the ER stress pathway might play a role in air pollution induced inflammation in the lung., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Previous published analyses have focused on the effect of air pollution on asthma and rhinoconjunctivitis throughout early and middle childhood. However, the role of exposure to air pollution in the development of childhood and adolescent asthma and rhinoconjunctivitis remains unclear. We aimed to assess the longitudinal associations between exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence., Methods: We did a population-based birth cohort study of 14 126 participants from four prospective birth cohort studies from Germany, Sweden, and the Netherlands with 14–16 years of follow-up. We linked repeated questionnaire reports of asthma and rhinoconjunctivitis with annual average air pollution concentrations (nitrogen dioxide [NO2], particulate matter [PM] with a diameter of less than 2·5 μm [PM2·5], less than 10 μm [PM10], and between 2·5 μm and 10 μm [PMcoarse], and PM2·5 absorbance [indicator of soot]) at the participants' home addresses. We analysed longitudinal associations of air pollution exposure at participants' birth addresses and addresses at the time of follow-up with asthma and rhinoconjunctivitis incidence and prevalence in cohort-specific analyses, with subsequent meta-analysis and pooled analyses., Findings: Overall, the risk of incident asthma up to age 14–16 years increased with increasing exposure to NO2 (adjusted meta-analysis odds ratio [OR] 1·13 per 10 μg/m3 [95% CI 1·02–1·25]) and PM2·5 absorbance (1·29 per 1 unit [1·00–1·66]) at the birth address. A similar, albeit non-significant, trend was shown for PM2·5 and incident asthma (meta-analysis OR 1·25 per 5 μg/m3 [95% CI 0·94–1·66]). These associations with asthma were more consistent after age 4 years than before that age. There was no indication of an adverse effect of air pollution on rhinoconjunctivitis., Interpretation: Exposure to air pollution early in life might contribute to the development of asthma throughout childhood and adolescence, particularly after age 4 years, when asthma can be more reliably diagnosed. Reductions in levels of air pollution could help to prevent the development of asthma in children., Funding: The European Union.

Introduction: The impact of outdoor air pollution exposure on long-term lung development and potential periods of increased lung susceptibility remain unknown. This study assessed associations between early-life and current residential exposure to air pollution and lung function at 15-years of age in two German birth cohorts., Methods: Fifteen year-old participants living in an urban and rural area in Germany underwent spirometry before and after bronchodilation (N=2266). Annual average (long-term) exposure to nitrogen dioxide (NO(2)), particles with aerodynamic diameters less than 2.5 μg/m(3) (PM2.5) mass and less than 10 μg/m(3) (PM(10)) mass, PM(2.5) absorbance and ozone were estimated to each participant's birth-, 10- and 15-year home address using land-use regression and kriging (ozone only) modelling. Associations between lung function variables and long-term pollutant concentrations were assessed using linear regression models adjusted for host and environmental covariates and recent short-term air pollution exposures., Results: Long-term air pollution concentrations assessed to the birth-, 10- and 15-year home addresses were not associated with lung function variables, before and after bronchodilation, in the complete or study area specific populations. However, several lung function variables were negatively associated with long-term NO2 concentrations among asthmatics. For example, NO(2) estimated to the 15-year home address was associated with the ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC) and the mean flow rate between 25% and 75% of FVC (-3.5%, 95% confidence interval [-6.0, -1.0] and -297.4 ml/s [-592.6, -2.1] per 5.9 μg/m(3) increase in NO(2), respectively). Nearly all effect estimates for the associations between the short-term PM(2.5) mass, PM(10) mass and ozone concentrations and the lung function variables were negative in the complete population., Conclusions: Early-life and current long-term air pollution exposures and lung function at the age of 15 years were not associated in the complete study population. Asthmatics may represent a vulnerable group., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Epidemiological studies have shown effects of long-term exposure to air pollution on cardiovascular and respiratory health. However, studies investigating the effects of air pollution on cognition and brain function are limited. We investigated if neurocognitive functions are associated with air pollution exposure and whether apolipoprotein E (ApoE) alleles modify the association of air pollution exposure with cognition., Methods: We investigated 789 women from the SALIA cohort during the 22-year follow-up examination (2008-2009). Exposure to particulate matter (PM) size fractions and nitrogen oxides (NOx) were assigned to home addresses. Traffic indicators were used to assess residential proximity to high traffic load. Level of cognitive performance was assessed using the CERAD-Plus test. Air pollution effects on cognitive functioning were estimated cross-sectionally using adjusted linear regression models., Results: Air pollution was negatively associated with cognitive function and cognitive performance in the subtests for semantic memory and visuo-construction. Significant associations could be observed for figure copying with an interquartile range increase of NO2 (β=-0.28 (95%CI:-0.44;-0.12)), NOx (β=-0.25 (95%CI:-0.40;-0.09)), PM10 (β=-0.14 (95%CI:-0.26;-0.02)) and PM2.5 (β=-0.19 (95%CI:-0.36;-0.02)). The association with traffic load was significant in carriers of one or two ApoE ɛ4 risk alleles., Conclusion: In this study of elderly women, markers of air pollution were associated with cognitive impairment in the visuospatial domain. The association of traffic exposure is significant in participants carrying the ApoE ε4 risk allele., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear., Objective: We aimed to investigate the association between air pollution and adult onset asthma., Methods: Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect., Results: In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 μg/m3; p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 μg/m3; p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 μg/m3), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 μg/m3), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10-5/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles × meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 μg/m3)., Conclusions: Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed.

Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality., Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter., Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ≤ 2.5 μm (PM2.5) and ≤ 10 μm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis., Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced., Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.

Epidemiological studies indicate that asthmatic children are more susceptible to traffic-related air pollution exposure than non-asthmatic children. Local and systemic inflammation in combination with oxidative stress have been suggested as a possible susceptibility factor. We investigated effect modification by asthma status for the association between air pollution exposure and systemic effects using whole blood cytokine responsiveness as an inflammatory marker. The study was nested within the two German birth cohort studies GINIplus and LISAplus and initially designed as a random sub-sample enriched with asthmatic children. Using data from 27 asthmatic and 59 non-asthmatic six-year-old children we measured the production of Interleukin-6 (IL)-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in whole blood after ex-vivo stimulation with urban particulate matter (EHC-93). Air pollution exposure (nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter with an aerodynamic diameter <10μm (PM10), particulate matter with an aerodynamic diameter <2.5μm (PM2.5mass), coarse particulate matter (PMcoarse) and PM2.5absorbance (PM2.5abs)) was modelled for children´s home addresses applying land-use regression. To assess effect modification by asthma status linear regression models with multiplicative interaction terms were used. In asthmatics exposure to NO2 was associated with higher production of pro-inflammatory cytokines: adjusted means ratio (MR) 2.22 (95% confidence interval 1.22-4.04) for IL-6 per 2.68µg/m³ NO2. The interaction term between asthma status and NO2 exposure was significant. Results for NOx, PM10, PM2.5mass and PM2.5abs were in the same direction. No association between air pollution and cytokine responsiveness was found in the group of non-asthmatic children and in the overall group. Traffic-related air pollution exposure is associated with higher pro-inflammatory cytokine responsiveness in whole blood of asthmatic children., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Evidence for a role of long-term particulate matter exposure on acute respiratory infections is growing. However, which components of particulate matter may be causative remains largely unknown. We assessed associations between eight particulate matter elements and early-life pneumonia in seven birth cohort studies (N total=15,980): BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), INMA (Spain), MAAS (United Kingdom) and PIAMA (The Netherlands). Annual average exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc, each respectively derived from particles with aerodynamic diameters ≤ 10 μm (PM10) and 2.5 μm (PM2.5), were estimated using standardized land use regression models and assigned to birth addresses. Cohort-specific associations between these exposures and parental reports of physician-diagnosed pneumonia between birth and two years were assessed using logistic regression models adjusted for host and environmental covariates and total PM10 or PM2.5 mass. Combined estimates were calculated using random-effects meta-analysis. There was substantial within and between-cohort variability in element concentrations. In the adjusted meta-analysis, pneumonia was weakly associated with zinc derived from PM10 (OR: 1.47 (95% CI: 0.99, 2.18) per 20 ng/m(3) increase). No other associations with the other elements were consistently observed. The independent effect of particulate matter mass remained after adjustment for element concentrations. In conclusion, associations between particulate matter mass exposure and pneumonia were not explained by the elements we investigated. Zinc from PM10 was the only element which appeared independently associated with a higher risk of early-life pneumonia. As zinc is primarily attributable to non-tailpipe traffic emissions, these results may suggest a potential adverse effect of non-tailpipe emissions on health., (Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Long-term exposure to air pollution has been hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country specific., Objectives: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations., Methods: We analyzed 15 population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). We modeled residential exposure to particulate matter and nitrogen oxides with land use regression using a uniform protocol. We assessed traffic exposure with traffic indicator variables. We analyzed systolic and diastolic BP in participants medicated and nonmedicated with BP-lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic BP, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis., Results: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in nonmedicated participants [0.35 mmHg (95% CI: 0.02, 0.68) and 0.22 mmHg (95% CI: 0.04, 0.40) per 4,000,000 vehicles × m/day, respectively]. The estimated odds ratio (OR) for prevalent hypertension was 1.05 (95% CI: 0.99, 1.11) per 4,000,000 vehicles × m/day. Modeled air pollutants and BP were not clearly associated., Conclusions: In this first comprehensive meta-analysis of European population-based cohorts, we observed a weak positive association of high residential traffic exposure with BP in nonmedicated participants, and an elevated OR for prevalent hypertension. The relationship of modeled air pollutants with BP was inconsistent.

Background: Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies., Methods: We conducted a multicenter study in 5 European birth cohorts-BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands)-for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 μm (PM2.5) and smaller than 10 μm (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis., Results: We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass., Conclusions: Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass.

Background: Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only., Aims: The aim of this study was to examine the association of PM composition with cardiovascular mortality., Methods: We used data from 19 European ongoing cohorts within the framework of the ESCAPE (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport related Air Pollution and Health impacts--Integrated Methodologies for Assessing Particulate Matter) projects. Residential annual average exposure to elemental constituents within particle matter smaller than 2.5 and 10 μm (PM2.5 and PM10) was estimated using Land Use Regression models. Eight elements representing major sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc). Cohort-specific analyses were conducted using Cox proportional hazards models with a standardized protocol. Random-effects meta-analysis was used to calculate combined effect estimates., Results: The total population consisted of 322,291 participants, with 9545 CVD deaths. We found no statistically significant associations between any of the elemental constituents in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84-1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% CI: 0.93-1.47), and S in PM2.5 (1.08, 95% CI: 0.95-1.22) and PM10 (1.09, 95% CI: 0.90-1.32)., Conclusion: In a joint analysis of 19 European cohorts, we found no statistically significant association between long-term exposure to 8 elemental constituents of particles and total cardiovascular mortality., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Rationale: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent., Objectives: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE)., Methods: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up., Measurements and Main Results: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators., Conclusions: In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality.

Background: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have been characterized as endocrine-disrupting chemicals (EDCs)., Objectives: Within the Duisburg birth cohort study, we studied associations of prenatal exposure to PCDD/Fs and PCBs with parent-reported sexually dimorphic behavior in children., Methods: We measured lipid-based and WHO2005-TEQ (toxic equivalents established in 2005 by the World Health Organization)-standardized PCDD/Fs and PCBs in maternal blood samples and in early breast milk using gas chromatography/high-resolution mass spectrometry. At the child's age of 6-8 years, parents (mostly mothers) reported sex-typical characteristics, preferred toys, and play activities using the Pre-School Activities Inventory (PSAI), which was used to derive feminine, masculine, and difference (feminine - masculine) scores. We estimated exposure-outcome associations using multivariate linear regression. A total of 91-109 children were included in this follow-up., Results: Mean blood levels of summed WHO2005-TEQ-standardized dioxins (ΣPCDD/Fs) were 14.5 ± 6.4 pg/g blood lipids, and ΣPCBs were 6.9 ± 3.8 pg/g blood lipids, with similar values for milk lipids. Regression analyses revealed some highly significant interactions between sex and exposure-such as for ΣPCBs in milk, pronounced positive (boys: β = 3.24; CI = 1.35, 5.14) or negative (girls: β = -3.59; CI = -1.10, -6.08) associations with reported femininity. Less pronounced and mostly insignificant but consistent associations were found for the masculinity score, positive for boys and negative for girls., Conclusions: Given our results and the findings of previous studies, we conclude that there is sufficient evidence that these EDCs modify behavioral sexual dimorphism in children, presumably by interacting with the hypothalamic-pituitary-gonadal axis., Citation: Winneke G, Ranft U, Wittsiepe J, Kasper-Sonnenberg M, Fürst P, Krämer U, Seitner G, Wilhelm M. 2014. Behavioral sexual dimorphism in school-age children and early developmental exposure to dioxins and PCBs: a follow-up study of the Duisburg Cohort. Environ Health Perspect 122:292-298; http://dx.doi.org/10.1289/ehp.1306533.

Background: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants., Methods: We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis., Findings: The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13)., Interpretation: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value., Funding: European Community's Seventh Framework Program (FP7/2007-2011)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The role of ambient air pollution in the development of chronic obstructive pulmonary disease (COPD) is considered to be uncertain. We review the evidence in the light of recent studies. Eight morbidity and six mortality studies were identified. These were heterogeneous in design, characterisation of exposure to air pollution and methods of outcome definition. Six morbidity studies with objectively defined COPD (forced expiratory volume in 1 s/forced vital capacity ratio) were cross-sectional analyses. One longitudinal study defined incidence of COPD as the first hospitalisation due to COPD. However, neither mortality nor hospitalisation studies can unambiguously distinguish acute from long-term effects on the development of the underlying pathophysiological changes. Most studies were based on within-community exposure contrasts, which mainly assess traffic-related air pollution. Overall, evidence of chronic effects of air pollution on the prevalence and incidence of COPD among adults was suggestive but not conclusive, despite plausible biological mechanisms and good evidence that air pollution affects lung development in childhood and triggers exacerbations in COPD patients. To fully integrate this evidence in the assessment, the life-time course of COPD should be better defined. Larger studies with longer follow-up periods, specific definitions of COPD phenotypes, and more refined and source-specific exposure assessments are needed.

Background: Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight., Methods: We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models., Findings: A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term., Interpretation: Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced., Funding: The European Union., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

In this study, we evaluated the association between prenatal and postnatal exposure to environmental tobacco smoke and the development of insulin resistance in 10 year old children. Fasting blood samples were collected from 470 children participating in two prospective birth cohorts. Of those 276 were selected population based and enriched with 194 children exceeding the 85th percentile of body mass index in this age group. Children already having diabetes type 1 or 2 at the age of 10 years were excluded. Fasting blood insulin and glucose levels and calculated HOMA index for insulin resistance assessment were analysed using generalised additive models. Potential confounders were adjusted for. Insulin resistance was increased by 24% in children frequently exposed to environmental tobacco smoke during childhood (MR(adj) = 1.24, p = 0.001), while glucose levels were not. Exclusion of prenatally exposed children did not attenuate the association (MR(adj) = 1.25, p = 0.006). After stratification, the effect sizes were identical within overweight children and the population based sample of children. Insulin resistance and fasting insulin levels were increasing with increasing numbers of cigarettes smoked in children's home. Maternal smoking during the third trimester of pregnancy increased children's insulin levels (MR(adj) = 1.19, p = 0.037), and even more so, if children were exclusively breastfed after birth (MR(adj) = 1.31, p = 0.016). Increased mean ratios were found for smoking of a third person in addition to maternal smoking. Positive dose-dependent associations and independent effects of postnatal exposure suggest involvement of environmental tobacco smoke in the risk for development of insulin resistance in children., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

In a cross-sectional study performed in 2000, an unexpected positive association between nickel (Ni) in ambient air, urinary Ni content and the prevalence of Ni sensitization in a subgroup of 6-yr-old children living near a steel mill was observed. Between 2005 and 2006, in a different and larger study population, we examined if Ni from ambient air or urinary Ni concentration was related to Ni sensitization in children living next to Ni-emitting steel mills. We studied 749 school beginners living in four Ni-polluted industrial areas of North Rhine-Westphalia, Germany. We assessed Ni in ambient air, Ni in urine from children and mothers, and Ni in tap water, conducted patch tests in children (including the NiSO(4)-dilution test) and collected questionnaire data. Statistics were done by linear and logistic regression analyses, adjusted for covariates. At increased Ni concentration in ambient air (unit of increase: 10 ng/m(3)), urinary Ni concentrations rose in both mothers (9.1%; 95% CI: 6.8-11.4%) and children (2.4%; 95% CI: 0.4-4.4%). The prevalence of Ni sensitization in children was associated with increased Ni from ambient air (unit of increase: 18 ng/m(3); odds ratio 1.28; 95% CI: 1.25-1.32) and urinary Ni concentration (unit of increase: 7.1 μg/L; odds ratio 2.4; 95% CI: 1.20-4.48). Ni in ambient air of areas with Ni-emitting factories contributes to internal Ni exposure in residents via inhalation and, furthermore, is a risk factor for the development of Ni sensitization in children., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Neurobehavioral measures of attention, and clinical features of the attention-deficit hyperactivity disorder (ADHD) have been studied in pediatric environmental lead research. However rarely, if ever, have performance measures of attention or executive functions and questionnaire-based quantitative ADHD-observations been studied in the same subjects. We examined associations between pediatric blood lead concentrations (PbB), as well as those of mercury (Hg), and aluminum (Al), and performance in four different attention tasks, as well as behavioral ratings from an ICD-10 (hyperactivity) and DSM-IV-coded (attention deficit) German questionnaire (FBB-ADHS). Asymptomatic, 8-12 year old children from two Romanian cities were studied, namely Bucharest and Pantelimon, a city near a metal-processing plant. Blood was analyzed for Pb, Al, and Hg. Data from 83 children were available for final analysis. We assessed attention performance by means of four tasks of the computer-based ADHD-taylored German KITAP-battery. We also received questionnaire ratings from parents and teachers covering three ADHD-dimensions. Multiple linear regression analysis was used to estimate associations between the three neurotoxic trace metals in blood and the different ADHD features. After adjusting for eleven potentially confounding variables we found consistent borderline to significant associations between Pb, but not other metals, in blood and various performance- and questionnaire data. False alarm responses (FAR) in the KITAP subtests rather than response latencies exhibited positive associations with PbB. Questionnaire ratings for ADHD dimensions also revealed PbB-related adversity. With any two-fold increase of PbB outcome changed markedly, namely up to 35%. Restriction to children with PbBs<10mug/dl had only a marginal influence on outcome.The converging evidence from performance- and questionnaire data confirms that core elements of ADHD are adversely affected by low environmental PbB even below 10mug/dl, but not by other neurotoxic trace metals. Observed effect-sizes are considerably larger than those typically found for lead-related IQ-deficit, thus suggesting that attention deficit could be the more basic adverse effect of lead in children. This is the first study from Central and Eastern Europe dealing with links between environmental exposure of children to neurotoxic metals and ADHD., (2010 Elsevier Inc. All rights reserved.)

Background and Objective: Nickel is one of the most prevalent causes of contact allergy in the general population. This study focuses on human exposure to airborne nickel and its potential to induce allergic sensitization., Materials and Methods: The study group consisted of 309 children at school-starter age living in the West of Germany in the vicinity of two industrial sources and in a rural town without nearby point sources of nickel. An exposure assessment of nickel in ambient air was available for children in the Ruhr district using routinely monitored ambient air quality data and dispersion modelling. Internal nickel exposure was assessed by nickel concentrations in morning urine samples of the children., Results: The observed nickel sensitization prevalence rates varied between 12.6% and 30.7%. Statistically significant associations were showed between exposure to nickel in ambient air and urinary nickel concentration as well as between urinary nickel concentration and nickel sensitization. Furthermore, an elevated prevalence of nickel sensitization was associated with exposure to increased nickel concentrations in ambient air., Conclusion: The observed associations support the assumption that inhaled nickel in ambient air might be a risk factor for nickel sensitization; further studies in larger collectives are necessary.

Animal studies have suggested that fine particulate matter (PM) can translocate from the upper respiratory tract to the brain and cause brain inflammation. Brain inflammation is involved in the pathogenesis of neurodegenerative diseases. Hypothesizing therefore that long-term exposure to fine PM might contribute to the development of Alzheimer's disease (AD), the objective of this study was to investigate the association between exposure to fine PM and mild cognitive impairment (MCI) which is associated with a high risk of progression to AD. A study group of 399 women aged 68-79 years who lived for more than 20 years at the same residential address has been assessed for long-term exposure to PM and tested for MCI. The exposure assessment comprised background concentration of PM(10) and traffic-related PM indicated by the distance of the residential address to the next busy road. The women were assessed for MCI by a battery of several neuropsychological tests and their odor identification ability. Consistent effects of traffic-related air pollution exposure on test performances including a dose-response relation were found. The associations were adjusted for potential confounders using regression analysis. These results indicate that chronic exposure to traffic-related PM may be involved in the pathogenesis of AD.

There is concern about indoor air quality as a possible cause for health impairment. Exposure to indoor renovation activities has been shown to be associated with airway symptoms and allergic manifestations in children. The aim of this study is to analyse immune markers responsible for disease development in relation to renovation activities. Within the LISAplus (Life style Immune System Allergy) birth cohort study, blood samples of 6-yr-old children were analysed for concentration of the inflammatory markers interleukin (IL)-8, IL-6, tumour necrosis factor-alpha, MCP-1 and IL-10. Data on indoor renovation activities (painting, flooring, new furniture) were assessed with a questionnaire filled in by the parents. Data on cytokine blood concentrations and exposure variables were available for 250 children. Increased levels of IL-8 and MCP-1 in children's blood were related to renovation activities. In particular, new floor covering was associated with increased inflammatory markers. Among floor covering materials only wall-to-wall carpets were associated with elevated IL-8 and Monocyte Chemoattractant Protein-1 (MCP-1) levels. No association between the single renovation activities painting and furnishing and blood concentration of inflammatory markers has been found. Our data shows that IL-8 and MCP-1 may be suitable markers for monitoring inflammatory reactions in relation with renovation activities. Among renovation activities floor covering seems to induce the strongest inflammatory reactions.

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.

Background: The influence of cat allergen exposure in early childhood on the development of sensitization and allergic diseases is complex. Little is known about the natural course of the sensitization development within individuals., Objective: We investigated the association between cat allergen exposure in infancy and cat ownership and cat contact during childhood and the development of cat sensitization and allergic diseases up to age 6 years using a longitudinal analysis approach., Methods: Overall, 2166 children from an ongoing birth cohort study were included in the analysis. House dust samples were collected 3 months after birth. Cat allergen levels were extracted. Blood samples were collected when the children were 2 and 6 years old. Information on the allergic symptoms of children and doctor-diagnosed allergic disease were collected at each follow-up using questionnaires., Results: Cat allergen exposure in infancy was positively associated with sensitization at age 2 years but not at age 6 years. No associations existed between cat allergen exposure in infancy and allergic symptoms and diseases up to age 6 years. Cumulative allergen exposure from cat ownership and regular cat contact increased the risk of cat sensitization up to age 6 years., Conclusion: Cat allergen exposure in infancy increases the risk of sensitization development in early childhood but not in school-age children. Cumulative allergen exposure from cat ownership and regular cat contact during childhood contribute to sensitization development up to school age., Clinical Implications: Cat allergen avoidance at home alone might be not effective to prevent the development of allergic sensitization in young children.

Background: There is growing epidemiological evidence that short-term and long-term exposure to high levels of air pollution may increase cardiovascular morbidity and mortality. In addition, epidemiological studies have shown an association between air pollution exposure and respiratory health. To what extent the association between cardiovascular mortality and air pollution is driven by the impact of air pollution on respiratory health is unknown. The aim of this study was to investigate whether respiratory health at baseline contributes to the effects of long-term exposure to high levels of air pollution on cardiovascular mortality in a cohort of elderly women., Method: We analyzed data from 4750 women, aged 55 at the baseline investigation in the years 1985-1994. 2593 of these women had their lung function tested by spirometry. Respiratory diseases and symptoms were asked by questionnaire. Ambient air pollution exposure was assessed by the concentrations of NO2 and total suspended particles at fixed monitoring sites and by the distance of residency to a major road. A mortality follow-up of these women was conducted between 2001 and 2003. For the statistical analysis, Cox' regression was used., Results: Women with impaired lung function or pre-existing respiratory diseases had a higher risk of dying from cardiovascular causes. The impact of impaired lung function declined over time. The risk ratio (RR) of women with forced expiratory volume in one second (FEV1) of less than 80% predicted to die from cardiovascular causes was RR = 3.79 (95%CI: 1.64-8.74) at 5 years survival time and RR = 1.35 (95%CI: 0.66-2.77) at 12 years. The association between air pollution levels and cardiovascular death rate was strong and statistically significant. However, this association did only change marginally when including indicators of respiratory health into the regression analysis. Furthermore, no interaction between air pollution and respiratory health on cardiovascular mortality indicating a higher risk of those with impaired respiratory health could be detected., Conclusion: Respiratory health is a predictor for cardiovascular mortality. In women followed about 15 years after the baseline investigation at age 55 years long-term air pollution exposure and impaired respiratory health were independently associated with increased cardiovascular mortality.

Background: Living close to major roads or highways has been suggested to almost double the risk of dying from cardiopulmonary causes. We assessed whether long-term exposure to air pollution originating from motorized traffic and industrial sources is associated with total and cause-specific mortality in a cohort of women living in North Rhine-Westphalia, Germany., Methods: The study was a follow-up of a series of cross-sectional studies carried out during the 1980s and 1990s on the health of women (age 50-59 years). Approximately 4800 women were followed up for vital status and migration. Exposure to air pollution was defined by distance to major roads calculated from Geographic Information System data and by 1- and 5-year average nitrogen dioxide (NO2) and particle (PM10) concentrations calculated from air monitoring station data. We analyzed associations between exposure and mortality using Cox's proportional hazards models adjusting for confounders. Relative risks (RRs) refer to an interquartile range increase in exposure (16 microg/m for NO2; 7 microg/m for PM10)., Results: During the follow-up period, 8% of the women died, 3% from cardiopulmonary causes. Cardiopulmonary mortality was associated with living within a 50-meter radius of a major road (adjusted RR = 1.70; 95% confidence interval = 1.02-2.81), with NO2 (1.57; 1.23-2.00 for 1-year average), and with PM10 (1.34; 1.06-1.71 for 1-year average). Exposure to NO2 was also associated with all-cause mortality (1.17; 1.02-1.34). No association was seen with noncardiopulmonary nonlung cancer mortality., Conclusions: Living close to major roads and chronic exposure to NO2 and PM10 may be associated with an increased mortality due to cardiopulmonary causes.

Background: Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements., Methods: In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level., Results: The prevalence of COPD (GOLD stages 1-4) was 4.5%. COPD and pulmonary function were strongest affected by PM10 and traffic related exposure. A 7 microg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced., Conclusion: Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.

Particles in the air influence mortality and morbidity even in concentrations which were considered harmless. This report examines their role in allergies. Studies on children from areas with different degrees of pollution show that the "classical" type of air pollution with high amounts of coarse particles apparently does not induce allergies. Nearly all studies, which characterized exposure on a smaller spatial scale, found that symptoms of asthma and allergic rhinitis were more common in children exposed to traffic-related pollution. Time series and panel studies demonstrate that particle pollution contributes to asthma aggravation. Whether this applies to eczema or allergic rhinitis has hardly been investigated. Overall the studies suggest a special role for traffic-related particles.

Maternal smoking has been repeatedly found to be the most important determinant of children's exposure to environmental tobacco smoke (ETS). Here, we further investigated predictors for the urinary cotinine/creatinine ratio (CCR, ng/mg) in 1220 preschool children for the year 1996. Children from smoking homes (35.1%) had significantly higher CCR than children from nonsmoking homes (mean: 55.5 vs. 14.9 ng/mg). The level of education of the parents was a strong predictor for CCRs even after adjusting for number of cigarettes smoked, maternal smoking and dwelling space. Additionally, dwelling space was inversely related to children's urinary cotinine level. The CCR- levels in children investigated in 1996 and 1998 were significantly correlated (Pearson's r=0.67). The parents of 806 children agreed for a visit to their homes. In 79 of the 536 (14.7%) of the self-reported, nonsmoking households, smoking was admitted during the visit. The mean urinary CCR of these children was 25.2 ng/mg. We conclude that in addition to parental smoking behaviour, other variables such as dwelling space and social and educational status predict the children's exposure to ETS. Our data also revealed that a considerable percentage of parents denied the ETS exposure of their children at home.

Background: There is uncertainty whether environmental levels of exposure to polychlorinated biphenyls (PCBs) adversely affect mental and motor development in early childhood. We aimed to establish whether such an effect is of only prenatal or additional postnatal origin, and if a favourable home environment can counteract this effect., Methods: Between 1993 and 1995 we recruited 171 healthy mother-infant pairs and prospectively measured psychodevelopment in newborn infants aged 7, 18, 30, and 42 months. We estimated prenatal and perinatal PCB exposure of newborn babies in cord blood and maternal milk. At 42 months we measured postnatal PCB concentrations in serum. At 18 months the quality of the home environment was assessed using the Home Observation for Measurement of the Environment scale. Mental and psychomotor development of the children were assessed using the Bayley Scales of Infant Development until 30 months and the Kaufman Assessment Battery for Children at 42 months., Findings: Negative associations between milk PCB and mental/motor development were reported at all ages, becoming significant from 30 months onwards. Over 30 months, for a PCB increase from 173 (5th percentile) to 679 ng/g lipids in milk (95th percentile) there was a decrease of 8.3 points (95% CI -16.5 to 0.0) in the Bayley Scales of Infant Development mental scores, and a 9.1 point decrease (95% CI -17.2 to -1.02) in the Bayley Scales of Infant Development motor scores. There was also a negative effect of postnatal PCB exposure via breastfeeding at 42 months. Home environment had a positive effect from 30 months onwards (Bayley Scales of Infant Development mental score increase of 9.4 points [95% CI 2.2-16.7])., Interpretation: Prenatal PCB exposure at current European background levels inhibits, and a favourable home environment supports, mental and motor development until 42 months of age. PCB exposure also has an effect postnatally.

Objective: The influence of area of residence on haemoglobin (Hb) adducts of 4-aminobiphenyl (4-ABP), o-, m-, p-toluidine and o-anisidine was investigated in children from three different-sized Bavarian cities - Munich, Augsburg and Eichstätt, with 1,300,000, 250,000 and 13,000 inhabitants, respectively--and was compared with that of exposure to environmental tobacco smoke (ETS)., Methods: Blood samples from Munich (n = 34) and Eichstätt (n = 64) were from children attending the Paediatric Clinic of the Technical University of Munich (TUM) or a practice in Eichstätt, respectively. Blood samples (n = 126) together with urine samples (n = 88) were collected from Augsburg children during school medical examination. Personal data including possible sources of ETS exposure were obtained at the interview. Hb adduct levels were analysed by a gas chromatographic method, using mass spectrometry with selected-ion monitoring. Urinary cotinine was determined by radioimmunoassay., Results: 4-ABP Hb adduct levels in children from Munich were 1.5 and 1.2 times higher than those in children from Eichstätt and Augsburg (P < 0.001). Children from Munich also had significantly higher Hb adduct levels of monocyclic aromatic amines than did children from Eichstätt and, except for o-toluidine, children from Augsburg (P < 0.005). Compared with children from Eichstätt, children from Augsburg had higher Hb adduct levels of 4-ABP, o- and m-toluidine (P < 0.01) but not p-toluidine and o-anisidine. In a multivariate analysis, gender, age and body mass index had no consistent influence on Hb adducts. ETS exposure resulted in a slight, nonsignificant increase in 4-ABP Hb adduct levels. In contrast, adduct levels from monocyclic aromatic amines were consistently decreased in ETS-exposed children (significant for o- and m-toluidine, P<0.05)., Conclusions: Hb adducts from aromatic amines in children were strongly influenced by site of residence, whereas ETS exposure did not significantly increase the adduct levels.JECT

The fall of the Berlin wall in 1989 offered the unique opportunity to compare populations of a similar genetic and geographic background which had been living under quite different environmental exposure conditions for over 40 years. Since 1990 comparative epidemiological studies were performed between various regions in former East and West Germany with yearly questionnaires and 3 years' physical, dermatological, allergological and exposure examination in a total of about 30,000 preschool children. There were striking differences between the various German regions with higher prevalence rates of respiratory atopy (hay fever, asthma) and atopic sensitization (prick test, RAST) in West Germany, while atopic eczema was significantly higher in East Germany (17.5 vs. 11.4% in West Germany). Total serum IgE levels were markedly higher in children in the east of Germany, similarly to the prevalence of parasitic infestation (questionnaire data as well as positive ascaris RAST). In multivariate logistic regression analysis the following factors were significantly associated with atopic eczema: animal contact (odds ratio, OR 2.9), animal furs in the bedroom (OR 2.2), use of gas without ventilation (OR 1.7) and living near road with heavy traffic (OR 1.7). Furthermore, socioeconomic factors measured as parental educational status (university vs. elementary school) were significantly associated (OR 2.3) with atopy. Respiratory tract infections and irritant responses decreased together with decreasing SO2 and suspended particulate air pollution in East Germany from 1991 to 1997. It is concluded that environmental factors from the physical, chemical, biological, and psychological environment (characteristic of a 'modern' or 'western' society) do influence the development of atopic sensitization and disease.

Within a larger environmental health screening program neurobehavioral measures were taken in 384 6-year-old children (mean age 74 months) in the cities of Leipzig, Gardelegen, and Duisburg. Lead concentrations in venous blood samples (PbB) and urinary mercury excretion in 24-h samples (HgU) were measured as markers of environmental exposure by electrothermal AAS. Dependent variables included two subtests from the WISC [vocabulary (V) and block design (BD)] as well as five tests from the NES2 [pattern comparison, pattern memory, tapping, simple reaction time, and the continuous performance test (CPT; child version)]. In addition, visual functions [visual acuity (TITMUS-test) and contrast sensitivity (FACT)] were tested as covariates. The overall average PbB (geometric mean) was 42.5 microg/l (upper 95% value = 89 microg/l). The overall average mercury excretion (HgU) was 0.16 microg/24 h. Whereas no significant or borderline associations between HgU and any of the target variables was found, significant negative associations were observed between PbB and verbal intelligence (WISC vocabulary but not WISC Block Design) and false-positive responses (false alarms), as well as false-negative responses (miss) in the CPT. Whereas parental education was the most important confounder for WISC performance, visual contrast sensitivity and computer familiarity also proved predictive for performance in several computer-based NES subtests. It is concluded that non-IQ measures, namely measures of sustained attention, are negatively affected in children with 95% of blood-lead levels below 90 microg/l, even after adjustment for intelligence and contrast sensitivity, whereas the causative role of lead in altering IQ functions remains somewhat equivocal, because important covariates could not be controlled for.

Neurobehavioural toxicity in occupational lead-exposure has typically not been observed at blood lead-concentrations (PbB) below 400 micrograms/l (e.g. 1, 2), whereas in environmentally exposed children such deficit has been reported to occur down to PbB of 100-150 micrograms/l and, perhaps, even below this range (4). Both cross-sectional and prospective studies have arrived at similar conclusions in this respect. The preferred endpoint in most such studies has been the IQ-measure, which has good psychometric qualities, is sufficiently well standardized to be comparable across studies, and exhibits attractive simplicity for the regulator in a public health context. Metaanalyses on both cross sectional and prospective studies in lead exposed children have concluded that a typical doubling of PbB from 100 to 200 micrograms/l is associated with an average loss of IQ of 1-3 points (3, 4). It should also be pointed out, however, that the IQ-focus has also interfered with systematic efforts to identify more specific lead-induced functional deficits by means of more detailed neurobehavioral analyses (5). Some neuropsychological findings in lead exposed children suggest that part of the impairment resembles performance deficit found to be characteristic for children presenting with signs and symptoms of attention deficit disorder.

When comparing neurobehavioural observations from occupational lead-exposure of adults on the one hand, and environmental lead exposure of children on the other, it appears that the developing relative to the mature brain is more at risk. Neurobehavioural toxicity in occupational lead-exposure has typically not been observed at blood lead-concentrations (PbBs) below 400 micrograms/l, whereas ih environmentally exposed children such deficit has been reported to occur down to PbB of 100-150 micrograms/l and, perhaps, even below this range. Both cross-sectional and prospective studies have arrived at similar conclusions in this respect. The preferred endpoint in most such studies has been the IQ-measure, which has good psychometric qualities, is sufficiently well standardized to be comparable across studies, and exhibits attractive simplicity for the regulator in a public health context. At the same time, however, this IQ-focus has also interfered with systematic efforts to identify more specific lead-induced functional deficits by means of more detailed neurobehavioural analyses (Bellinger 1995). Metanalyses on both cross sectional and prospective studies in lead-exposed children have concluded that a typical doubling of PbB from 100 to 200 micrograms/l is associated with an average IQ-loss of 1-3 points (Pocock et al. 1994; WHO 1995), and no threshold has as yet been identified. Since, however, cause-effect contingencies necessarily remain doubtful in epidemiological studies if the observed effects are as subtle as these, experimental studies in animals have become helpful in supporting the causative role of lead to produce neurobehavioural deficit at steady-state PbB down to about 150 to 200 micrograms/l. Such deficit has been demonstrated by means of a variety of learning/memory models with positive and negative reinforcement contingencies in the rat--and in primates as well. It has also been shown in such studies that neurobehavioural deficit subsequent to early developmental exposure extends long into adulthood after cessation of exposure at weaning. It, therefore, appears that the neurobehavioural teratology of lead has more convincingly been demonstrated in animal models than in human exposure conditions, so far. A coherent theory to explain the particular vulnerability to lead of the developing brain is still lacking. Recent data do suggest, however, that Pb-induced disruption of calcium homeostasis in the immature brain might interfere with normal brain development.

The effects of chronic low-level tetrachloroethene (TCE) exposure on functions of the central nervous system (CNS) were measured in subjects living in the neighborhood of dry cleaning shops with a mean residential time of 10.6 years. Neurobehavioral tests were performed using a German version of the NES battery. Additionally, a pattern reversal visual-evoked potentials (VEPs) were recorded. the mean blood TCE concentration in the subjects was 17.8 micrograms/liter and the median indoor TCE air concentration measured in the residences was 1.36 mg/m3. The outcome of the NES subtests for vigilance, simple reaction time, as well as visual memory differed statistically significantly between the exposed subjects and the controls, whereas for VEP latencies the differences were statistically not significant. It is concluded that despite the low exposure levels, CNS functions might be affected by TCE in subjects living close to a dry cleaning facility if the exposure lasts for several years.

Lead and cadmium levels in blood and deciduous teeth (shed incisors only) of 6-year-old German children were determined in 1991 in a large epidemiological study carried out in rural and urban areas of western Germany (Duisburg, Essen, Gelsenkirchen, Dortmund, Borken) and eastern Germany (Leipzig, Halle, Magdeburg, Osterburg, Gardelelegen, Salzwedel). In total, blood lead and cadmium levels of 2311 German children and tooth lead and cadmium levels of 790 German children were analyzed. Blood lead levels were generally low in all study areas with geometric means between 39.3 micrograms/l and 50.8 micrograms/l in the western German and between 42.3 micrograms/l and 68.1 micrograms/l in the eastern German study areas. The mean blood lead level of Turkish children (n = 213) living in the western German study areas was 50.1 micrograms/l and thus 5.6 micrograms/l higher than the overall geometric mean of the western German children. The higher exposure may be explained by a higher oral uptake from food and different living conditions. These children were excluded from multiple regression analysis because they were all living in the western study areas. The mean tooth lead levels ranged between 1.50 and 1.74 micrograms/g in the western and between 1.51 micrograms/g and 2.72 micrograms/g in the eastern study areas. Thus, they show a distribution pattern similar to blood. Blood and tooth lead levels were higher in urban than in rural areas and higher in the eastern German than in the western German study areas. With regard to the blood and tooth cadmium concentrations, no significant differences between the study areas could be found.(ABSTRACT TRUNCATED AT 250 WORDS)