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Introduction: The beneficial effect of improving air quality on lung function in the elderly remains unclear. We examined associations between decline in air pollutants and lung function, and effect modifications by genetics and body mass index (BMI), in elderly German women., Methods: Data were analysed from the prospective SALIA (Study on the influence of Air pollution on Lung function, Inflammation and Aging) study (n=601). Spirometry was conducted at baseline (1985-1994; age 55 years), in 2007-2010 and in 2012-2013. Air pollution concentrations at home addresses were determined for each time-point using land-use regression models. Global Lung Initiative 2012 z-scores were calculated. Weighted genetic risk scores (GRSs) were determined from lung function-related risk alleles and used to investigate interactions with improved air quality. Multiple linear mixed models were fitted., Results: Air pollution levels decreased substantially during the study period. Reduction of air pollution was associated with an increase in z-scores for forced expiratory volume in 1 s (FEV 1 ) and the FEV 1 /forced vital capacity ratio. For a decrease of 10 µg·m -3 in nitrogen dioxide (NO 2 ), the z-score for FEV 1 increased by 0.14 (95% CI 0.01-0.26). However, with an increasing number of lung function-related risk alleles, the benefit from improved air quality decreased (GRS×NO 2 interaction: p=0.029). Interactions with BMI were not significant., Conclusions: Reduction of air pollution is associated with a relative improvement of lung function in elderly women, but also depends on their genetic make-up., Competing Interests: Conflict of interest: D. Hüls has nothing to disclose. Conflict of interest: D. Sugiri has nothing to disclose. Conflict of interest: M.J. Abramson reports grants from Pfizer, grants from Boehringer Ingelheim, assistance with conference attendance and honoraria for consultancy from Sanofi, outside the submitted work. Conflict of interest: B. Hoffmann has nothing to disclose. Conflict of interest: H. Schwender has nothing to disclose. Conflict of interest: K. Ickstadt has nothing to disclose. Conflict of interest: U. Krämer has nothing to disclose. Conflict of interest: T. Schikowski has nothing to disclose., (Copyright ©ERS 2019.)

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.)

Background: Exposure to air pollution during pregnancy may increase attention-deficit/hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs., Methods: Air pollution concentrations (nitrogen dioxide [NO2] and particulate matter [PM]) were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified children as having ADHD symptoms within the borderline/clinical range and within the clinical range using validated cutoffs. We combined all adjusted area-specific effect estimates using random-effects meta-analysis and multiple imputations and applied inverse probability-weighting methods to correct for loss to follow-up., Results: We classified a total of 2,801 children as having ADHD symptoms within the borderline/clinical range, and 1,590 within the clinical range. Exposure to air pollution during pregnancy was not associated with a higher odds of ADHD symptoms within the borderline/clinical range (e.g., adjusted odds ratio [OR] for ADHD symptoms of 0.95, 95% confidence interval [CI] = 0.89, 1.01 per 10 µg/m increase in NO2 and 0.98, 95% CI = 0.80, 1.19 per 5 µg/m increase in PM2.5). We observed similar associations for ADHD within the clinical range., Conclusions: There was no evidence for an increase in risk of ADHD symptoms with increasing prenatal air pollution levels in children aged 3-10 years. See video abstract at, http://links.lww.com/EDE/B379.

Background: Studies linking particulate matter (PM) with heart failure (HF) show inconsistent results. However, the association of air pollution with diastolic function, an important determinant of heart failure, has not been studied yet and is addressed in the presented study., Methods: 402 women (69-79 years) of the clinical follow-up (2007-2010) of the ongoing population-based prospective SALIA (Study on the influence of Air pollution on Lung function, Inflammation and Ageing) cohort were examined using Doppler echocardiography: Of the 291 women with preserved ejection fraction, the ratio of peak early diastolic filling velocity and peak early diastolic mitral annulus velocity (E/E') was collected in 264 and left atrial volume index (LAVI) in 262 women. Residential long-term air pollution exposure (nitrogen oxides, size-fractioned PM) was modeled at baseline and at follow-up, applying land use regression models. We used linear regression to model the cross-sectional associations of air pollutants per interquartile range (IQR) with different measures of diastolic function, adjusting for personal risk factors., Results: Median concentrations of annual NOx, NO2, PM2.5, and PM10 at follow-up were 37.7, 25.9, 17.4 and 26.4μg/m(3), respectively. In the fully adjusted models, LAVI was associated with an IQR increase in PM2.5 (1.05 [0.99; 1.12]) and NOx (1.04 [1.00; 1.09]) at follow-up, and with NOx and NO2 (both 1.05 [1.00; 1.11]) at baseline. None of the pollutants were clearly associated with E/E'., Conclusions: In this analysis of elderly women, we found suggestive evidence for an association of air pollution with impaired diastolic function., (Copyright © 2016. Published by Elsevier GmbH.)

Background: Evidence is growing that air pollutants deteriorate glucose metabolism and insulin sensitivity by oxidative stress and inflammation. This might affect HbA1c levels and insulin requirements in type 1 diabetes. There are no data available on this association., Methods: Air pollution values of respirable particulate matter (PM10), nitrogen dioxides (NO2), and accumulated ozone (O3-AOT40) were obtained from the federal environmental agency (Umweltbundesamt II) and assigned to place of residence of 840 participants from a nation-wide population-based type 1 diabetes registry (German Diabetes Center, Düsseldorf, Germany). Information on HbA1c, social status, treatment and co-morbidities was collected by self-administered questionnaires. Complete information was available for 771 patients aged 11-21 years at the time of study., Results: In linear regression models, no adverse effects of air pollutants (PM10, NO2 or O3-AOT40 on HbA1c level were found, but O3-AOT40 was inversely associated with HbA1c (mmol/mol) in the crude (estimate per IQR: -1.86; 95% CI: (-3.27; -0.44); p=0.01) and the best model adjusting for lifestyle, socioeconomic factors, clinical information, and season (-1.50; (-2.82; -0.17); 0.034). After adding area of residency as random effect to the crude and the best model, the association was no longer significant (-1.64; (-3.84; 0.56); 0.14); (-1.56; (-3.67; 0.55); 0.14). Adjustment for further possible confounders did not affect the estimates seriously. None of the pollutants was associated with insulin dose (IU/kg body weight)., Conclusions: Investigated pollutants had no adverse effect on metabolic control in children and young adults with type 1 diabetes in this cross-sectional study. The weak inverse association of accumulated ozone with HbA1c might be due to confounding by regional characteristics or regional aspects of care., (Copyright © 2016 Elsevier GmbH. 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.

An increasing number of epidemiological studies suggest that adverse health effects of air pollution may be related to particulate matter (PM) composition, particularly trace metals. However, we lack comprehensive data on the spatial distribution of these elements. We measured PM2.5 and PM10 in twenty study areas across Europe in three seasonal two-week periods over a year using Harvard impactors and standardized protocols. In each area, we selected street (ST), urban (UB) and regional background (RB) sites (totaling 20) to characterize local spatial variability. Elemental composition was determined by energy-dispersive X-ray fluorescence analysis of all PM2.5 and PM10 filters. We selected a priori eight (Cu, Fe, K, Ni, S, Si, V, Zn) well-detected elements of health interest, which also roughly represented different sources including traffic, industry, ports, and wood burning. PM elemental composition varied greatly across Europe, indicating different regional influences. Average street to urban background ratios ranged from 0.90 (V) to 1.60 (Cu) for PM2.5 and from 0.93 (V) to 2.28 (Cu) for PM10. Our selected PM elements were variably correlated with the main pollutants (PM2.5, PM10, PM2.5 absorbance, NO2 and NOx) across Europe: in general, Cu and Fe in all size fractions were highly correlated (Pearson correlations above 0.75); Si and Zn in the coarse fractions were modestly correlated (between 0.5 and 0.75); and the remaining elements in the various size fractions had lower correlations (around 0.5 or below). This variability in correlation demonstrated the distinctly different spatial distributions of most of the elements. Variability of PM10&#95;Cu and Fe was mostly due to within-study area differences (67% and 64% of overall variance, respectively) versus between-study area and exceeded that of most other traffic-related pollutants, including NO2 and soot, signaling the importance of non-tailpipe (e.g., brake wear) emissions in PM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.)

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO₂, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO₂ exposure was associated with lower levels of FEV₁ (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV₁ (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe., (Copyright ©ERS 2015.)

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.

The role of air pollution in chronic obstructive pulmonary disease (COPD) remains uncertain. The aim was to assess the impact of chronic exposure to air pollution on COPD in four cohorts using the standardised ESCAPE exposure estimates. Annual average particulate matter (PM), nitrogen oxides (NOx) and road traffic exposure were assigned to home addresses using land-use regression models. COPD was defined by NHANES reference equation (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than the lower limit of normal) and the Global Initiative for Chronic Obstructive Lung Disease criterion (FEV1/FVC <0.70) and categorised by severity in non-asthmatics. We included 6550 subjects with assigned NOx and 3692 with PM measures. COPD was not associated with NO2 or PM10 in any individual cohort. In meta-analyses only NO2, NOx, PM10 and the traffic indicators were positively, although not significantly, associated with COPD. The only statistically significant associations were seen in females (COPD prevalence using GOLD: OR 1.57, 95% CI 1.11-2.23; and incidence: OR 1.79, 95% CI 1.21-2.68). None of the principal results were statistically significant, the weak positive associations of exposure with COPD and the significant subgroup findings need to be evaluated in further well standardised cohorts followed up for longer time, and with time-matched exposure assignments., (©ERS 2014.)

Background: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood., Methods: We analyzed data from 6 European population-based birth cohorts-GENERATION R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)-that recruited mother-infant pairs from 1997 to 2008. Air pollution levels-nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5-10 μm (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup-at birth addresses were estimated by land-use regression models, based on monitoring campaigns performed primarily between 2008 and 2011. Levels were back-extrapolated to exact pregnancy periods using background monitoring sites. Cognitive and psychomotor development was assessed between 1 and 6 years of age. Adjusted region-specific effect estimates were combined using random-effects meta-analysis., Results: A total of 9482 children were included. Air pollution exposure during pregnancy, particularly NO2, was associated with reduced psychomotor development (global psychomotor development score decreased by 0.68 points [95% confidence interval = -1.25 to -0.11] per increase of 10 μg/m in NO2). Similar trends were observed in most regions. No associations were found between any air pollutant and cognitive development., Conclusions: Air pollution exposure during pregnancy, particularly NO2 (for which motorized traffic is a major source), was associated with delayed psychomotor development during childhood. Due to the widespread nature of air pollution exposure, the public health impact of the small changes observed at an individual level could be considerable.

Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death., Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and 10 μm to 2.5 μm (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates., Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 μg/m and for PM10, 1.22 (0.91-1.63) per 10 μg/m., Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.

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: There is growing evidence that air pollutants are associated with the risk of type 2 diabetes. Subclinical inflammation may be a mechanism linking air pollution with diabetes. Information is lacking whether air pollution also contributes to worse metabolic control in newly diagnosed type 2 diabetes. We examined the hypothesis that residential particulate matter (PM10) is associated with HbA1c concentration in newly diagnosed type 2 diabetes., Methods: Nationwide regional levels of particulate matter with a diameter of ≤ 10 µm (PM10) were obtained in 2009 from background monitoring stations in Germany (Federal Environmental Agency) and assigned to place of residency of 9,102 newly diagnosed diabetes patients registered in the DPV database throughout Germany (age 65.5 ± 13.5 yrs; males: 52.1%). Mean HbA1c (%) levels stratified for air pollution quartiles (PM10 in µg/m(3)) were estimated using linear regression models adjusting for age, sex, BMI, diabetes duration, geographic region, year of ascertainment, and social indicators., Findings: In both men and women, adjusted HbA1c was significantly lower in the lowest quartile of PM10 exposure in comparison to quartiles Q2-Q4. Largest differences in adjusted HbA1c (95% CI) were seen comparing lowest quartiles of exposure with highest quartiles (men %: -0.42 (-0.62; -0.23)/mmol/mol: -28.11 (-30.30; -26.04), women, %: -0.28 (-0.47; -0.09)/mmol/mol: -0.28 (-0.47; -0.09))., Interpretation: Air pollution may be associated with higher HbA1c levels in newly diagnosed type 2 diabetes patients. Further studies are warranted to examine this association.

Background: Evidence on the long-term effects of air pollution exposure on childhood allergy is limited., Objective: We investigated the association between air pollution exposure and allergic sensitization to common allergens in children followed prospectively during the first 10 years of life., Methods: Five European birth cohorts participating in the European Study of Cohorts for Air Pollution Effects project were included: BAMSE (Sweden), LISAplus and GINIplus (Germany), MAAS (Great Britain), and PIAMA (The Netherlands). Land-use regression models were applied to assess the individual residential outdoor levels of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5), the mass concentration of particles between 2.5 and 10 μm in size, and levels of particulate matter with an aerodynamic diameter of less than 10 μm (PM10), as well as measurement of the blackness of PM2.5 filters and nitrogen dioxide and nitrogen oxide levels. Blood samples drawn at 4 to 6 years of age, 8 to 10 years of age, or both from more than 6500 children were analyzed for allergen-specific serum IgE against common allergens. Associations were assessed by using multiple logistic regression and subsequent meta-analysis., Results: The prevalence of sensitization to any common allergen within the 5 cohorts ranged between 24.1% and 40.4% at the age of 4 to 6 years and between 34.8% and 47.9% at the age of 8 to 10 years. Overall, air pollution exposure was not associated with sensitization to any common allergen, with odds ratios ranging from 0.94 (95% CI, 0.63-1.40) for a 1 × 10(-5) ∙ m(-1) increase in measurement of the blackness of PM2.5 filters to 1.26 (95% CI, 0.90-1.77) for a 5 μg/m(3) increase in PM2.5 exposure at birth address. Further analyses did not provide consistent evidence for a modification of the air pollution effects by sex, family history of atopy, or moving status., Conclusion: No clear associations between air pollution exposure and development of allergic sensitization in children up to 10 years of age were revealed., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

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: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood., Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts--BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)--and to derive combined effect estimates using meta-analysis., Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter≤2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5-10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates., Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR=1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR=1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR=1.09; 95% CI: 1.02, 1.16 per 10-μg/m3)., Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media.

Background: Environmental and lifestyle factors regulate the expression and release of immune mediators. It has been hypothesised that ambient air pollution may be such an external factor and that the association between air pollution and impaired glucose metabolism may be attributable to inflammatory processes. Therefore, we assessed the associations between air pollution, circulating immune mediators and impaired glucose metabolism., Methods: We analysed concentrations of 14 pro- and anti-inflammatory immune mediators as well as fasting glucose and insulin levels in plasma of 363 women from the Study on the influence of Air pollution on Lung function, Inflammation and Aging (SALIA, Germany). Exposure data for a group of pollutants such as nitrogen oxides (NO2, NOx) and different fractions of particulate matter were available for the participants' residences. We calculated the association between the pollutants and impaired glucose metabolism by multiple regression models., Results: The study participants had a mean age of 74.1 (SD 2.6) years and 48% showed impaired glucose metabolism based on impaired fasting glucose or previously diagnosed type 2 diabetes. Only long-term exposure NO2 and NOx concentrations showed positive associations (NO2: OR 1.465, 95% CI 1.049-2.046, NOx: OR 1.409, 95% CI 1.010-1.967) per increased interquartile range of NO2 (14.65 µg/m(3)) or NOx (43.16 µg/m(3)), respectively, but statistical significance was lost after correction for multiple comparisons. Additional adjustment for circulating immune mediators or the use of anti-inflammatory medication had hardly any impact on the observed ORs., Conclusions: Our results suggest that exposure to nitrogen oxides may contribute to impaired glucose metabolism, but the associations did not reach statistical significance so that further studies with larger sample sizes are required to substantiate our findings. Our data do not preclude a role of inflammatory mechanisms in adipose or other tissues which may not be reflected by immune mediators in plasma.

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.)

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.

The causes of adult-onset asthma are poorly established, and the asthmogenic role of air pollution has been investigated primarily in children. This review assesses the current evidence of the association between air pollution and asthma incidence among subjects free of asthma at least until late childhood. Seven publications from five study populations fulfilled the inclusion criteria (one case-control and six cohort studies). All but one used markers of local traffic-related air pollution to characterize long-term exposure. Those studies reported similar associations with traffic-related air pollution. However, protocols, definitions of asthma, and exposure assignment were rather heterogeneous, and three publications relied on the same study; thus we abstain from meta-analytic summaries. Reported patterns of effect modification (e.g., by sex, atopy, or smoking) were inconsistent. Overall, the role of traffic-related air pollution in adult-onset asthma is less conclusive than in childhood asthma. Larger studies with more consistent definitions of phenotypes and exposure assessment for local traffic-related pollutants (e.g., ultrafine particles) are needed. Pooling existing cohorts such as in the ongoing European ESCAPE and TRANSPHORM consortia are promising steps. There is, however, a need for large-scale megacohorts to investigate these effects in standardized ways and to identify the most susceptible populations., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Cross-sectional and ecological studies indicate that air pollution may be a risk factor for type 2 diabetes, but prospective data are lacking., Objective: We examined the association between traffic-related air pollution and incident type 2 diabetes., Design: Between 1985 and 1994, cross-sectional surveys were performed in the highly industrialized Ruhr district (West Germany); a follow-up investigation was conducted in 2006 using data from the Study on the Influence of Air Pollution on Lung, Inflammation and Aging (SALIA) cohort., Participants: 1,775 nondiabetic women who were 54-55 years old at baseline participated in both baseline and follow-up investigations and had complete information available., Materials and Methods: Using questionnaires, we assessed 16-year incidence (1990-2006) of type 2 diabetes and information about covariates. Complement factor C3c as marker for subclinical inflammation was measured at baseline. Individual exposure to traffic-related particulate matter (PM) and nitrogen dioxide was determined at different spatial scales., Results: Between 1990 and 2006, 87 (10.5%) new cases of diabetes were reported among the SALIA cohort members. The hazards for diabetes were increased by 15-42% per interquartile range of PM or traffic-related exposure. The associations persisted when different spatial scales were used to assess exposure and remained robust after adjusting for age, body mass index, socioeconomic status, and exposure to several non-traffic-related sources of air pollution. C3c was associated with PM pollution at baseline and was a strong independent predictor of incident diabetes. Exploratory analyses indicated that women with high C3c blood levels were more susceptible for PM-related excess risk of diabetes than were women with low C3c levels., Conclusions: Traffic-related air pollution is associated with incident type 2 diabetes among elderly women. Subclinical inflammation may be a mechanism linking air pollution with type 2 diabetes., Relevance to Clinical Practice: Our study identifies traffic-related air pollution as a novel and potentially modifiable risk factor of type 2 diabetes.

Background: While adverse effects of exposure to air pollutants on respiratory health are well studied, little is known about the effect of a reduction in air pollutants on chronic respiratory symptoms and diseases. We investigated whether different declines in air pollution levels in industrialised and rural areas in Germany were associated with changes in respiratory health over a period of about 20 years., Methods: We used data from the SALIA cohort study in Germany (Study on the influence of Air pollution on Lung function, Inflammation and Aging) to assess the association between the prevalence of chronic obstructive pulmonary disease (COPD) and chronic respiratory symptoms and the decline in air pollution exposure. In 1985-1994, 4874 women aged 55-years took part in the baseline investigation. Of these, 2116 participated in a questionnaire follow-up in 2006 and in a subgroup of 402 women lung function was tested in 2008-2009. Generalized estimating equation (GEE) models were used to estimate the effect of a reduction in air pollution on respiratory symptoms and diseases., Results: Ambient air concentrations of particulate matter with aerodynamic size < 10 microm (PM10) declined in average by 20 microg/m3. Prevalence of chronic cough with phlegm production and mild COPD at baseline investigation compared to follow-up was 9.5% vs. 13.3% and 8.6% vs. 18.2%, respectively. A steeper decline of PM10 was observed in the industrialized areas in comparison to the rural area, this was associated with a weaker increase in prevalence of respiratory symptoms and COPD. Among women who never smoked, the prevalence of chronic cough with phlegm and mild COPD was estimated at 21.4% and 39.5%, respectively, if no air pollution reduction was assumed, and at 13.3% and 17.5%, respectively, if air pollution reduction was assumed., Conclusion: We concluded that parallel to the decline of ambient air pollution over the last 20 years in the Ruhr area the age-related increase in chronic respiratory diseases and symptoms appears to attenuate in the population of elderly women.

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.

Background: Traffic-related air pollution (TAP) impairs respiratory health and could influence the development of allergies, as was demonstrated in urban areas with relatively high pollution. Whether eczema is affected by TAP was rarely investigated., Objective: To investigate whether exposure to TAP affects eczema and respiratory allergies also in small-town areas with lower concentrations of pollution., Methods: Between 1995 and 1999, we recruited 3390 newborns from small-town areas. Diagnoses and symptoms of eczema and respiratory allergies were recorded by annual questionnaires. Seventy-seven percent of families participated until the child's 6th birthday, when a clinical test for eczema and IgE-sensitization was performed. Individual exposure to traffic-related soot and NO(2) at the children's home addresses was determined by land-use-regression. We used Cox-regression/log-binomial-regression to determine its confounder-adjusted association with incidence and prevalence of eczema and respiratory allergies., Results: The prevalence of eczema at age 6 was significantly higher in children who resided in areas where TAP was higher. The adjusted relative risk for doctor diagnosed eczema for instance was 1.69 (95% confidence interval 1.04-2.75) per 90%-range of soot concentration. Current eczema at the 6 year clinical investigation was likewise associated, children with parental allergies showed significantly stronger effects (p<0.05). Incidence of eczema was not affected. No associations between TAP and asthma, hay fever, or allergic sensitization emerged., Conclusion: Eczema was sensitive to TAP, effects emerged even in lower polluted small-town areas of Germany. They could be seen for prevalence but not incidence of eczema. This is equivalent to a longer duration of eczema in exposed children.

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

Background: Socio-economic status, smoking, and exposure to increased levels of environmental air pollution are associated with adverse effects on respiratory health. We assessed the contribution of occupational exposures, smoking and outdoor air pollution as competing factors for the association between socio-economic status and respiratory health indicators in a cohort of women from the Ruhr area aged 55 at the time of investigation between 1985 and 1990., Methods: Data of 1251 women with spirometry and complete questionnaire information about respiratory diseases, smoking and potential confounders were used in the analyses. Exposure to large-scale air pollution was assessed with data from monitoring stations. Exposure to small-scale air pollution was assessed as traffic-related exposure by distance to the nearest major road. Socio-economic status was defined by educational level. Multiple regression models were used to estimate the contribution of occupational exposures, smoking and outdoor air pollution to social differences in respiratory health., Results: Women with less than 10 years of school education in comparison to more than 10 years of school education were more often occupationally exposed (16.4% vs. 10.1%), smoked more often (20.3% vs. 13.9%), and lived more often close to major roads (26.0% vs. 22.9%). Long-term exposure to increased levels of PM10 was significantly associated with lower school education. Women with low school education were more likely to suffer from respiratory symptoms and had reduced lung function. In the multivariate analysis the associations between education and respiratory health attenuated after adjusting for occupational exposure, smoking and outdoor air pollution. The crude odds ratio for the association between the lung function indicator FEV1 less than 80% of predicted value and educational level (<10 years vs. >10 years of school education) was 1.83 (95% CI: 1.22-2.74). This changed to 1.56 (95% CI: 1.03-2.37) after adjusting for occupational exposure, smoking and outdoor air pollution., Conclusion: We found an association between socio-economic status and respiratory health. This can partly be explained by living conditions indicated by occupational exposure, smoking behaviour and ambient air pollution. A relevant part of the social differences in respiratory health, however, remained unexplained.

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/methods: Current air pollution levels pose a threat to the health of children starting from conception. The scientific evidence is presented for mortality, morbidity, and sub-clinical effects. The first section deals with exposure data, the following sections with the evidence of health effects from epidemiology and toxicology leading to recommendations., Results: Improved air quality reduces the number of infants' deaths as well as disease and pain., Conclusions: Medical doctors have a responsibility to know the facts and to advise their patients. Doctors when visiting their patients' homes should be aware of the possibly grave impact of the indoor environment for the respiratory health of their patients. They should recognize and advise the parents on problems associated with environmental tobacco smoke, poor ventilation, mould growth, and maintenance of heating installations. With regard to outdoor air pollution, doctors could serve as role models and also advise their patients and parents on environmentally friendly behaviour. Such behaviour not only calls for personal commitment but also for the right infrastructure to be provided (e.g. public transport, district heating). Doctors should be proactive in the community and in their country as advocates for a healthier environment for our children.

The aim of this study was to investigate the relationship between different levels of air pollution and IgG antibody titers against tetanus toxoid in sera of 6 year old children (n = 354). Additionally, other parameters of the humoral immune response (immunoglobulins G, A, M, total IgE, complement component C3c, C-reactive protein (CRP)) were analysed. The index areas were Leipzig, Magdeburg (Saxony/Saxe-Anhalt), and Duisburg, Dortmund (Ruhr region). The control areas were Osterburg and Borken. IgG antibodies against tetanus toxoid were measured by ELISA in sera of children vaccinated three times DPT in early childhood. The other humoral parameters were measured by nephelometry. In comparison to the control area Borken the sera of children living in the index areas Duisburg and Dortmund showed a lower antibody titer. There were no differences between the index areas (Leipzig, Magdeburg) and the control area Osterburg. It has to be taken into account that the choice of Osterburg as a control area is problematic because of the lack of data on air pollution. Statistically, there was no relationship between antibody titer against tetanus toxoid and the additionally measured parameters of the humoral immune response.

A number of air pollutants is known to affect the immune system resulting in alterations of the complement activity in serum. We determined the levels of C3c, one of the activation products of the component C3, in serum samples obtained from various population groups living in areas with different levels of air pollution in Northrhine-Westphalia (FRG). The results show that the serum C3c levels tend to be increased in subjects living in areas with elevated levels of air pollution. By applying a linear regression model it can be demonstrated that a significant part of the variance of the C3c concentrations is explained by the residence area factor after making allowance for the effect of various confounders. The increase of the serum C3c concentrations appears to result from an increased activation of the complement component C3. The underlying mechanisms as well as the pathophysiological significance of these findings are unknown.

Measurements of carboxyhemoglobin (COHb)-content from about 13,000 inhabitants of various sites in western North Rhine-Westphalia are presented. Analyses were part of surveys on the effects of air pollution conducted between 1975 and 1980 in five designated, polluted areas. Determinations were executed in the Medical Institute for Environmental Hygiene, Duesseldorf, on behalf of the Ministry of Labour, Health and Social Administration. Analysis of blood samples for CO-content was performed by gas chromatography. Carboxyhemoglobin levels were calculated by reference to the individual hemoglobin levels. Our surveys have been conducted during several years and included different seasons. Before 1977, fifty years old men were investigated. Until 1978, sixty years old men were studied. In 1979 and 1980, sixty years old women and ten years old children were additionally incorporated into the survey. Statistical analysis of data included variables which influence personal CO-burden such as smoking, and in the case of non-smokers indoor air exposure through passive smoking, use of gas facilities and heating in the flat, as well as occupational exposure. Besides, the influence of age, sex and location was considered. The average COHb-level of the populations under study was expressed as the median of the distribution. The distribution-free Mann-Whitney U-test served for assessment of differences between groups. As a further parameter, the percentage of the measurements greater than 2,5% COHb was chosen, because it was thought to be more relevant to risk populations, i.e. people suffering from Angina pectoris. As expected, tobacco smoking exerted the greatest influence on COHb-level. In non-smokers a trend, indicating a relationship between indoor air pollution and COHb-content could be observed. If high CO gas such as coke gas was used in flats with gas facilities COHb-levels were significantly raised. Surveys performed in 1979 and in 1980 showed a sex-dependent difference between median COHb saturations, women having lower values than men. The difference of these figures between adults and children is statistically significant. Comparisons between adult nonsmokers from various sites prompted a significant difference only in the case of the Oberbergischer Kreis (County), having the lowest median COHb-value. The highest COHb-levels by far were encountered in the city of Duisburg in January 1979, when very unfavourable meterological conditions (Smog alarm, degree 1) were present. The median COHb saturations reached on this occasion were very near to the limits considered to be critical for populations at special risk.

Klaus Unfried,1,* Ursula Krämer,1,* Ulrich Sydlik,1 Andrea Autengruber,1 Andreas Bilstein,2 Sabine Stolz,1 Alessandra Marini,1 Tamara Schikowski,1 Stefanie Keymel,3 Jean Krutmann1 1IUF Leibniz Research Institute of Environmental Medicine, 2bitop AG, Witten, 3Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany *These authors contributed equally to this work Background: Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial.Objective: The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin® inhalation solution) leads to a reduction of neutrophilic cells and interleukin-8 (IL-8) levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution.Methods: A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined.Results: While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite) were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence interval 0.45–0.93). Extended analyses considering period effects revealed that the percentage of neutrophils in sputum was significantly lower after ectoine inhalation than in the placebo group (P=0.035) even after the washout phase.Conclusion: The current study is the first human trial in which the effects of inhaled ectoine on neutrophilic lung inflammation were investigated. Besides demonstrating beneficial effects on inflammatory sputum parameters, the study proves the feasibility of the therapeutic approach in an aged study group. Keywords: osmolytes, extremolytes, molecular prevention, neutrophil apoptosis, SALIA cohort, air pollution

The prevalence of atopic diseases has increased dramatically during recent decades; the reasons are not known. Among various plausible hypotheses the so-called hygiene hypothesis (jungle hypothesis) has gained public interest recently. According to this hypothesis improved hygiene leading to a decreased stimulation of the immune system by infections, parasites, vaccinations or contact with immunostimulating agents has led to an immunodeviation with T helper (Th)2-enhancing effects followed by increased occurrence of IgE-mediated allergies.The hygiene hypothesis is not defined precisely, and some questions remain open: the influence of actual infectious disease or specific vaccinations, the nature of infectious agents (virus, bacteria, fungi, parasites), the definition of the term‘hygiene’, the nature of other immunostimulating agents and the effects upon different atopic diseases. As arguments in favour of the hygiene hypothesis, the following study results are quoted: children of farmers have less allergies; children from academic parents show an increased risk of atopic diseases; children from anthroposophic families have decreased allergy prevalence rates; effects of endotoxin and CD14 gene polymorphism; and the protective influence of gut flora with high amounts of lactobacilli. The following findings argue against the hygiene hypotheses: parasite infections are associated with an increased risk of urticaria and atopic eczema; some microorganisms e.g. respiratory syncytial virus (RSV),Bordetella pertussisenhance IgE production; patients with active tuberculosis have high Th2 reactions; pertussis vaccination has a protective effect; high allergy prevalences in very poor regions (inner city slums in the United States, Africa, Southern America); germfree conditions prevent the spontaneous outbreak of atopic eczema in certain mouse strains, many other influences (e.g. traffic exhaust exposure) are associated with allergy and sensitization. Comparing the prevalence of atopic diseases and sensitization in East and West German children after reunification there was a striking difference with regard to higher prevalence rates of respiratory atopic diseases in West German children compared to the East, which was not seen for atopic eczema. No single factor has been established to explain this East–West German difference. When differences in pertussis vaccination strategy (in West Germany in the 1980s only about 50% of the children were vaccinated, while in East Germany this was obligatory for everyone) were included in the analysis, it became obvious that 20% of West German children were suffering from pertussis infection compared to 0.5% of East German children and pertussis infection increased the risk for atopic respiratory disease, although not for eczema and sensitization. When pertussis vaccination and infection was included among the confounders to be adjusted for in the multivariate logistic regression, the East–West German difference disappeared for asthma and wheezing, so it can be concluded that pertussis vaccination does prevent pertussis infection and thereby prevents asthma and wheezing independent of atopic sensitization. Furthermore, it has become clear that pollens are not only allergen carriers but also produce proinflammatory mediators of eicosanoid-like activity. These pollen-associated lipid mediators (PALMs) − among them pollotrienes − are able to attract neutrophils and activate the innate immune system. They should be regarded together with pollutants and allergens as modulating factors in the determination of allergic disease development.From a critical evaluation of the evidence it is concluded that the hygiene hypothesis represents an attractive theory and stimulus for further research, particularly the more precise aspect of the jungle hypothesis, with an inverse relationship between parasite infestation and respiratory atopy. It seems that the hygiene hypothesis fits only for atopic respiratory but not for atopic skin disease. Regarding the partly controversial data it is too early to give practical recommendations for allergy prevention based on this hypothesis. There is no rationale to recommend avoidance of vaccinations or adequate body cleaning measures. Effective programmes for primary prevention will be possible only after increased research efforts have elucidated the true causes of increased allergy prevalence. [ABSTRACT FROM AUTHOR]

Background: East-West comparison studies in Europe find higher prevalences of infectious airway diseases and lower prevalences of allergies in eastern areas. Pollution from sulphur dioxide (SO2) or total suspended particles (TSP) are discussed as causes of this difference.Methods: In four differently polluted areas of East Germany where pollution decreased dramatically between 1989 and 1995 cross-sectional studies in about 7-year-old children were repeated every year between 1991 and 1995. In two differently polluted areas of West Germany studies with the same design were done in 1991 and 1994. In all, 19090 children participated in the study. Thirteen different questions about airway diseases and allergies were evaluated. Logistic regression was used to adjust for confounding.Results: With the exception of pneumonia, all infectious airway diseases and irritations of the airways show a steeper temporal decrease in East than in West Germany or are positively associated with either SO2 or TSP in East Germany. For allergies and related symptoms no differences in time trends could be detected or no association with SO2 or TSP could be seen in East Germany.Conclusion: Most airway diseases were more frequent in East than in West Germany in 1991 and were associated with SO2 or TSP. The decrease in these pollutants between 1991 and 1995 has already had a favourable effect. An effect of SO2 or TSP pollution on allergies and related symptoms could not be detected. This pollution does not protect against the development of allergies. [ABSTRACT FROM AUTHOR]

The effects of long term influence of air pollution especially of particles on morbidity are still under debate. Some of the larger studies which have been conducted to clarify the subject include the Harvard Six-City study, the North American study on health effects of acid aerosols, the Swiss studies SCARPOL and SAPALDIA, studies in East and West Germany and the Southern Californian UCLA study. Retrospective cohort studies in Europe are ongoing. The impossibility to monitor personal exposure during long periods of time (years) or retrospectively is one of the major methodological difficulties in these studies. Outdoor measurements from fixed stations are often used instead and individuals are recruited from areas around these stations. Two different problems have to be considered when determining the association between air pollution and health by regression models in this type of study namely spatial clustering and ecological exposure definition.Despite apparent similarities very different methods are used in the above mentioned studies to deal with these problems: (1) Regression models treating individuals as independent, (2)ecological regression, (3)random effect models with a two stage estimation procedure or (4)closed estimation procedures as well as models including area specific covariates.In the above mentioned studies the problems of spatial clustering and of ecological exposure definition were not distinguished, because it is the area where clustering could occur and it is also the area for which air pollution concentrations are defined. But, there can be spatial clustering combined with personal exposure definition and no spatial clustering with ecological exposure definition. Spatial clustering can be caused by random area specific variation or by systematic area specific deviations from the regression: Ecological regression does not solve the problem of spatial clustering for the individuals. Multilevel models can adequately account for spatial clustering. Estimation procedures for multilevel models are now commonly available in standard statistical packages. Two types of variables are used in this type of analysis. The first are defined for individuals, the second for areas. Hierarchical two-level analysis is adequate. Second level variables should be included to account for systematic deviations between regression residuals within areas. Additional area specific random variables can be included to account for additional random fluctuation between areas. But, it has to be taken into account that random effect models alone can not account for unmeasured covariates on an ecological level.Main purpose of the studies is to draw inferences about individuals. Therefore in the analysis of this type of study the higher level area effects should be viewed as nuisance parameter which must be taken into account in order to correctly estimate parameter estimates for the individual. The authors, whose methods have been reviewed, do not agree in their judgement whether the one air pollution measurement in the area is a measurement of an area property (unit of observation is the area), or whether it is a proxy for unavailable individual level data (unit of observation is the individual). [ABSTRACT FROM AUTHOR]

Introduction In the brain, estrogen plays an important role in neural plasticity and its decline during menopause might result in cognitive impairment and predispose to the development of dementia. Two estrogen receptors – α and ß – mediate estrogen actions either as ligand-activated dimeric transcription factors or as membrane-embedded ER monomers. Objective To analyze ERß-variants and ApoE-genotype in the population-based SALIA cohort of 834 non-demented, elderly women. Aims We aimed to explore, whether ERß variants may impact on cognitive performance in interaction with air pollution and APOE. Methods DNA was isolated from lymphocytes. ApoE-epsilon-variants and ERß SNPs rs944045, rs1256062, rs10144225 and rs2274705 were determined by LCG /KBioscience (Hoddesdon, UK). All participants were assessed for cognitive impairment by the CERAD-Plus test battery. Subtests were merged to a total z-score, that corrected for gender, age and time of education. Long-term exposure to air pollution was backextrapolated from data collected by monitoring stations using a geographic information system. Results SNP analysis revealed that 3 ERß variants (rs1256062, rs10144225 and rs2274705) were significantly correlated with lower CERAD z total scores and especially with decline in episodic memory. These effects were strengthened in APOE-epsilon-E4 carriers. Air pollution (NO 2 , PM2,5) did not worsen the CERAD z total score of the women, but interacting with the ERß variants PM2,5 affected their visuoconstructive practice and NO 2 their semantic memory. Conclusion In this population-based, prospective study a gene-gene interaction effect of ApoE and ERß on cognitive performance appeared. Moreover, significant gene-environment interactions on cognition were found for air pollution. [ABSTRACT FROM AUTHOR]