Search

The comparison of endotoxin levels between study populations and countries is limited as a result of differences in sampling, extraction, and storage procedures. The objective of this study is to assess the levels and determinants of endotoxin in mattress and living room floor dust samples from three European countries, namely, Germany, the Netherlands, and Sweden, using a standardized sampling, storage, and analysis protocol. The mattress and living room floor dust was collected from the homes of 1065 German, Dutch, and Swedish (pre-)school children. All the samples were collected in the cool season and analyzed for endotoxin in a central laboratory. The determinants were assessed by a standardized questionnaire. The endotoxin concentrations in mattress and living room floor dust were found to be the highest in German homes and lowest in the Swedish ones. Differences between the geometric means were small (factor 1.1–1.7). Most of the associations between endotoxin concentrations and potential determinants were not statistically significant and heterogeneous across countries. However, keeping pets and having more than four persons living in the home were consistently associated with up to 1.7-fold higher endotoxin concentrations in mattress and floor dust. Furthermore, having carpets or rugs, and opening the windows frequently was associated with up to 3.4-fold and 1.3-fold higher endotoxin concentrations in living room floor dust, respectively. The proportion of variance explained by the questionnaire variables was generally low. In conclusion, the data on housing characteristics did not accurately predict the endotoxin concentrations in house dust, and could only partly explain the differences between countries. Practical Implications The differences between the endotoxin concentrations in German, Dutch, and Swedish homes are small. House dust endotoxin concentrations are associated with a number of housing factors, such as pet-ownership, floor cover, number of persons living in the home, and ventilation. The variability of the endotoxin levels between homes and countries can only be partly explained by these factors. [ABSTRACT FROM AUTHOR]

Background: Low sensitization rates to common allergens have been observed in farm children, which might be due to high exposure to microbial agents. It is not known how microbial agents modify the association between specific allergen exposure and sensitization. Objective: To examine the relations between house dust mite allergen exposure and mite sensitization in farm and nonfarm children and to assess the effects of microbial agents levels on this association. Methods: Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1), endotoxin, β(1,3)-glucans and fungal extracellular polysaccharides were measured in mattress dust of 402 children participating in a cross-sectional study in five European countries. Mite allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut-offs 1.4 and 10.4 μg/g. Sensitization was assessed by measurement of allergen-specific immunoglobulin E against house dust mite. Results: Prevalence ratios of mite sensitization for medium and high when compared with low mite allergen levels were 3.1 [1.7–5.7] and 1.4 [0.7–2.8] respectively. Highest mite sensitization rates at intermediate exposure levels were consistently observed across country (except for Sweden) and in both farm and nonfarm children. The shape of the dose–response curve was similar for above and below median mattress microbial agent levels, but the ‘sensitization peak’ appeared to be lower for above median levels. Conclusions: Our data suggest a bell-shaped dose–response relationship between mite allergen exposure and sensitization to mite allergens. In populations with high microbial agent levels and low sensitization rates, the curve is shifted down. [ABSTRACT FROM AUTHOR]

Provides information on the Pollution Effects on Asthmatic Children in Europe (PEACE), a study designed to examine the relationship between short-term changes in air pollution and lung function, respiratory symptoms and medication use. Goals of the PEACE study; Determination of the elemental composition of particles.

Background The Th1/Th 2 concept is a model to understand the pathophysiology of certain diseases. Atopic diseases (asthma, eczema and hayfever) are characterized by a chronic inflammatory reaction that is dominated by Th 2 cells, and type 1 diabetes mellitus (DM) is Th1 cell dominated. Because it is known that Th1 and Th 2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th 2-mediated disease is lower in patients with Th1-mediated disease. Objective To compare the prevalence of atopic diseases between children with DM and age-matched controls. Methods Parents of children with DM were requested by Dutch paediatricians to complete the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire on the prevalence of atopic diseases. A control group was derived from a Dutch cross-sectional survey (the ISAAC2 study). Results We received 555 completed questionnaires, which is estimated to be 25% of the total number of Dutch children with DM. The control group consisted of 777 children. After age-matching, the questionnaires of 188 DM patients were used. Symptoms of asthma, hayfever and eczema were reported less in the group of children with DM compared with the control group (wheeze last year, OR 0.796, 95% CI 0.408–1.554; hayfever symptoms last year, OR 0.642, 95% CI 0.369–1.118; eczema symptoms last year, OR 0.693, 95% CI 0.430–1.115). Conclusion The lower prevalence of astma, hayfever and eczema symptoms in DM patients compared with age-matched controls, although not statistically significant, is consistent with the Th1/Th 2 concept. [ABSTRACT FROM AUTHOR]

Background: Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts.Methods: Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood.Results: A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 μg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 μg/m(3) increase in NO2).Conclusions: Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood. [ABSTRACT FROM AUTHOR]

End-stage kidney disease (ESKD) poses a high burden on patients and health systems. While numerous studies indicate an association between air pollution and chronic kidney disease, studies on ESKD are rare. We investigated the association of long-term exposure to nitrogen dioxide (NO₂), fine particulate matter (PM 2.5 ), black carbon (BC) and ozone (O 3 ) with ESKD incidence in two large population-based European cohorts. We followed individuals in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP) and the Italian Rome Longitudinal Study (RoLS) using dialysis and kidney transplant registries. Long-term exposure to pollutants was estimated at the home address using Europe-wide land use regression models at 100x100m scale. Hazard ratios (HR) were determined from Cox-proportional hazard models adjusted for individual and neighbourhood level confounders. We observed 501 events among 136,823 individuals in VHM&PP (mean age 42.1 years; crude incidence rate (IR) 0.14 per 1000 person-years) and 3231 events among 1,939,461 individuals in RoLS (mean age 52.4 years; IR 0.22 per 1000 person-years). In VHM&PP, there was no evidence of an association between PM 2.5 or O 3 and ESKD. There were elevated HRs but with large confidence intervals for BC (HR 1.17 [95 % confidence interval (CI): 0.98, 1.39] for 0.5*10 -5 /m), and for NO₂ (HR 1.14 [95%CI: 0.96, 1.35] for 10 μg/m 3 ). In RoLS, ESKD was associated with PM 2.5 (HR 1.37 [95 % CI: 1.06, 1.76] for an increase of 5 μg/m 3 ), while there was no evidence of association with BC, NO 2 , or O 3 exposure. Our study suggests an association of air pollution with ESKD incidence, which differed between the two cohorts and may possibly be influenced by respective air pollution mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite the known link between air pollution and cause-specific mortality, its relation to chronic kidney disease (CKD)-associated mortality is understudied. Therefore, we investigated the association between long-term exposure to air pollution and CKD-related mortality in a large multicentre population-based European cohort. Cohort data were linked to local mortality registry data. CKD-death was defined as ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at participant's home address was determined with fine spatial resolution exposure models for nitrogen dioxide (NO 2 ), black carbon (BC), ozone (O 3 ), particulate matter ≤2.5 μm (PM 2.5 ) and several elemental constituents of PM 2.5 . Cox regression models were adjusted for age, sex, cohort, calendar year of recruitment, smoking status, marital status, employment status and neighbourhood mean income. Over a mean follow-up time of 20.4 years, 313 of 289,564 persons died from CKD. Associations were positive for PM 2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5 μg/m 3 , BC (1.26 (1.03-1.53) per 0.5 × 10 - 5 /m), NO 2 (1.13 (0.93-1.38) per 10 μg/m 3 ) and inverse for O 3 (0.71 (0.54-0.93) per 10 μg/m 3 ). Results were robust to further covariate adjustment. Exclusion of the largest sub-cohort contributing 226 cases, led to null associations. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different sources including traffic, biomass and oil burning and secondary pollutants, were associated with CKD-related mortality. In conclusion, our results suggest an association between air pollution from different sources and CKD-related mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM 2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible., Methods: We harmonized the study populations to individuals 65 + years of age, applied the same satellite-derived PM 2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF)., Results: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5 - μ g / m 3 increase in PM 2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM 2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141.

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), black carbon (BC), ozone (O 3 ), and 8 PM 2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO 2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m 3 ), PM 2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m 3 ), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10 -5 /m) with psychiatric disorders mortality, as well as with suicide (NO 2 : HR = 1.13 [95 % CI: 0.92, 1.38]; PM 2.5 : HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O 3 and 8 PM 2.5 components with any of the three mortality outcomes. Long-term exposure to NO 2 , PM 2.5 , and BC may lead to premature mortality from psychiatric disorders and suicide., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited., Methods: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM 2.5 ), nitrogen dioxide (NO 2 ), black carbon (BC), warm season ozone (O 3 ) and eight elemental components of PM 2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level., Results: The participants were followed from baseline (1985-2005) to 2011-2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5-95%) exposure levels of NO 2 , PM 2.5 , BC and O 3 were 24.1 μg/m 3 (12.8-39.2), 15.3 μg/m 3 (8.6-19.2), 1.6 10 -5  m -1 (0.7-2.1), and 87.0 μg/m 3 (70.3-97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 μg/m³ NO 2 , 1.04 (95% CI: 0.88, 1.21) per 5 μg/m³ PM 2.5 , 0.99 (95% CI: 0.89, 1.11) per 0.5 10 -5  m -1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 μg/m³ O 3 . We did not find associations between any of the elemental components of PM 2.5 and cancer of the kidney parenchyma., Conclusion: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Evidence for the association between long-term exposure to ambient particulate matter components and mortality from natural causes is sparse and inconsistent. We evaluated this association in six large administrative cohorts in the framework of the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) project. We analyzed data from country-wide administrative cohorts in Norway, Denmark, the Netherlands, Belgium, Switzerland and in Rome (Italy). Annual 2010 mean concentrations of copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V) and zinc (Zn) in fine particulate matter (PM 2.5 ) were estimated using 100 × 100 m Europe-wide hybrid land use regression models assigned to the participants' residential addresses. We applied cohort-specific Cox proportional hazard models controlling for area- and individual-level covariates to evaluate associations with natural mortality. Two pollutant models adjusting for PM 2.5 total mass or nitrogen dioxide (NO 2 ) were also applied. We pooled cohort-specific estimates using a random effects meta-analysis. We included almost 27 million participants contributing more than 240 million person-years. All components except Zn were significantly associated with natural mortality [pooled Hazard Ratios (HRs) (95% CI): 1.037 (1.014, 1.060) per 5 ng/m 3 Cu; 1.069 (1.031, 1.108) per 100 ng/m 3 Fe; 1.039 (1.018, 1.062) per 50 ng/m 3 K; 1.024 (1.006, 1.043) per 1 ng/m 3 Ni; 1.036 (1.016, 1.057) per 200 ng/m 3 S; 1.152 (1.048, 1.266) per 100 ng/m 3 Si; 1.020 (1.006, 1.034) per 2 ng/m 3 V]. Only K and Si were robust to PM 2.5 or NO 2 adjustment [pooled HRs (95% CI) per 50 ng/m 3 in K: 1.025 (1.008, 1.044), 1.020 (0.999, 1.042) and per 100 ng/m 3 in Si: 1.121 (1.039, 1.209), 1.068 (1.022, 1.117) adjusted for PM 2.5 and NO 2 correspondingly]. Our findings indicate an association of natural mortality with most components, which was reduced after adjustment for PM 2.5 and especially NO 2 ., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE)., Methods: In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000-11; follow-up until 2011-17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM 2·5 ), nitrogen dioxide (NO 2 ), black carbon, and tropospheric warm-season ozone (O 3 ) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis., Findings: We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM 2·5 , NO 2 , and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021-1·085) per 5 μg/m 3 increment in PM 2·5 , 1·044 (1·019-1·069) per 10 μg/m 3 NO 2 , and 1·039 (1·018-1·059) per 0·5 × 10 -5 /m black carbon. Associations with PM 2·5 , NO 2 , and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O 3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM 2·5 (10 μg/m 3 ) and NO 2 (40 μg/m 3 ) were 1·078 (1·046-1·111) per 5 μg/m 3 PM 2·5 and 1·049 (1·024-1·075) per 10 μg/m 3 NO 2 . Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032-1·092) for exposure lower than 1·5× 10 -5 /m, and 1·081 (0·966-1·210) for exposure lower than 1·0× 10 -5 /m., Interpretation: Long-term exposure to concentrations of PM 2·5 and NO 2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions., Funding: Health Effects Institute., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO 2 ), particulate matter with diameter <2.5 μm (PM 2.5 ), black carbon (BC), warm-season ozone (O 3 ), and eight elemental components of PM 2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO 2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 μg/m 3 ), PM 2.5 (1.12, 0.92-1.36 per 5 μg/m 3 ), and BC (1.15, 1.00-1.33 per 0.5 10 -5 /m) and liver cancer incidence. Associations with NO 2 and BC persisted in two-pollutant models with PM 2.5 . Most components of PM 2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM 2.5 or NO 2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 µm (PM 2.5 ), nitrogen dioxide (NO 2 ) and black carbon (BC) with asthma incidence in adults., Methods: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders., Results: Of 98 326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 μg·m -3 for PM 2.5 , 1.17 (95% CI 1.10-1.25) per 10 µg·m -3 for NO 2 and 1.15 (95% CI 1.08-1.23) per 0.5×10 -5  m -1 for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM 2.5 and NO 2 . NO 2 and BC estimates remained unchanged in two-pollutant models with PM 2.5 , whereas PM 2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold., Conclusions: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values., Competing Interests: Conflict of interest: S. Liu has nothing to disclose. Conflict of interest: J.T. Jørgensen has nothing to disclose. Conflict of interest: P. Ljungman has nothing to disclose. Conflict of interest: G. Pershagen has nothing to disclose. Conflict of interest: T. Bellander has nothing to disclose. Conflict of interest: K. Leander has nothing to disclose. Conflict of interest: P.K.E. Magnusson has nothing to disclose. Conflict of interest: D. Rizzuto has nothing to disclose. Conflict of interest: U.A. Hvidtfeldt has nothing to disclose. Conflict of interest: O. Raaschou-Nielsen has nothing to disclose. Conflict of interest: K. Wolf has nothing to disclose. Conflict of interest: B. Hoffmann has nothing to disclose. Conflict of interest: B. Brunekreef has nothing to disclose. Conflict of interest: M. Strak has nothing to disclose. Conflict of interest: J. Chen has nothing to disclose. Conflict of interest: A. Mehta has nothing to disclose. Conflict of interest: R.W. Atkinson has nothing to disclose. Conflict of interest: M. Bauwelinck has nothing to disclose. Conflict of interest: R. Varraso has nothing to disclose. Conflict of interest: M-C. Boutron-Ruault has nothing to disclose. Conflict of interest: J. Brandt has nothing to disclose. Conflict of interest: G. Cesaroni has nothing to disclose. Conflict of interest: F. Forastiere has nothing to disclose. Conflict of interest: D. Fecht has nothing to disclose. Conflict of interest: J. Gulliver has nothing to disclose. Conflict of interest: O. Hertel has nothing to disclose. Conflict of interest: K. de Hoogh has nothing to disclose. Conflict of interest: N.A.H. Janssen has nothing to disclose. Conflict of interest: K. Katsouyanni has nothing to disclose. Conflict of interest: M. Ketzel has nothing to disclose. Conflict of interest: J.O. Klompmaker has nothing to disclose. Conflict of interest: G. Nagel has nothing to disclose. Conflict of interest: B. Oftedal has nothing to disclose. Conflict of interest: A. Peters has nothing to disclose. Conflict of interest: A. Tjønneland has nothing to disclose. Conflict of interest: S.P. Rodopoulou has nothing to disclose. Conflict of interest: E Samoli has nothing to disclose. Conflict of interest: D.T. Kristoffersen has nothing to disclose. Conflict of interest: T. Sigsgaard has nothing to disclose. Conflict of interest: M. Stafoggia has nothing to disclose. Conflict of interest: D. Vienneau has nothing to disclose. Conflict of interest: G. Weinmayr has nothing to disclose. Conflict of interest: G. Hoek has nothing to disclose. Conflict of interest: Z.J. Andersen has nothing to disclose., (Copyright ©ERS 2021.)

Background: An association between long-term exposure to fine particulate matter (PM 2.5 ) and lung cancer has been established in previous studies. PM 2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the "Effects of Low-level Air Pollution: A Study in Europe" (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM 2.5 and lung cancer incidence., Methods: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM 2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status)., Results: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m 3 PM 2.5  K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m 3 PM 2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m 3 PM 2.5  S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m 3 PM 2.5  V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO 2 ). After adjustment for PM 2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative., Conclusions: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM 2.5 components may prove helpful in future lung cancer prevention strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD), but evidence is sparse and inconsistent., Objectives: We examined the association between long-term exposure to low-level air pollution and COPD incidence., Methods: Within the 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE) study, we pooled data from three cohorts, from Denmark and Sweden, with information on COPD hospital discharge diagnoses. Hybrid land use regression models were used to estimate annual mean concentrations of particulate matter with a diameter < 2.5 µm (PM 2.5 ), nitrogen dioxide (NO 2 ), and black carbon (BC) in 2010 at participants' baseline residential addresses, which were analysed in relation to COPD incidence using Cox proportional hazards models., Results: Of 98,058 participants, 4,928 developed COPD during 16.6 years mean follow-up. The adjusted hazard ratios (HRs) and 95% confidence intervals for associations with COPD incidence were 1.17 (1.06, 1.29) per 5 µg/m 3 for PM 2.5 , 1.11 (1.06, 1.16) per 10 µg/m 3 for NO 2 , and 1.11 (1.06, 1.15) per 0.5 10 -5 m -1 for BC. Associations persisted in subset participants with PM 2.5 or NO 2 levels below current EU and US limit values and WHO guidelines, with no evidence for a threshold. HRs for NO 2 and BC remained unchanged in two-pollutant models with PM 2.5 , whereas the HR for PM 2.5 was attenuated to unity with NO 2 or BC., Conclusions: Long-term exposure to low-level air pollution is associated with the development of COPD, even below current EU and US limit values and possibly WHO guidelines. Traffic-related pollutants NO 2 and BC may be the most relevant., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence., Methods: The "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 ), black carbon (BC), and ozone (O 3 ) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines., Results: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO 2 , PM 2.5 , BC and O 3 (warm season) were 24.2 µg/m 3 (19.5, 29.7), 15.4 µg/m 3 (12.8, 17.3), 1.6 10 -5 m -1 (1.3, 1.8), and 86.6 µg/m 3 (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM 2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m 3 ). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m 3 . We did not observe associations between NO 2 , BC or O 3 and lung cancer incidence., Conclusions: Long-term ambient PM 2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We developed Europe-wide models of long-term exposure to eight elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in particulate matter with diameter <2.5 μm (PM 2.5 ) using standardized measurements for one-year periods between October 2008 and April 2011 in 19 study areas across Europe, with supervised linear regression (SLR) and random forest (RF) algorithms. Potential predictor variables were obtained from satellites, chemical transport models, land-use, traffic, and industrial point source databases to represent different sources. Overall model performance across Europe was moderate to good for all elements with hold-out-validation R -squared ranging from 0.41 to 0.90. RF consistently outperformed SLR. Models explained within-area variation much less than the overall variation, with similar performance for RF and SLR. Maps proved a useful additional model evaluation tool. Models differed substantially between elements regarding major predictor variables, broadly reflecting known sources. Agreement between the two algorithm predictions was generally high at the overall European level and varied substantially at the national level. Applying the two models in epidemiological studies could lead to different associations with health. If both between- and within-area exposure variability are exploited, RF may be preferred. If only within-area variability is used, both methods should be interpreted equally.

Empirical spatial air pollution models have been applied extensively to assess exposure in epidemiological studies with increasingly sophisticated and complex statistical algorithms beyond ordinary linear regression. However, different algorithms have rarely been compared in terms of their predictive ability. This study compared 16 algorithms to predict annual average fine particle (PM 2.5 ) and nitrogen dioxide (NO 2 ) concentrations across Europe. The evaluated algorithms included linear stepwise regression, regularization techniques and machine learning methods. Air pollution models were developed based on the 2010 routine monitoring data from the AIRBASE dataset maintained by the European Environmental Agency (543 sites for PM 2.5 and 2399 sites for NO 2 ), using satellite observations, dispersion model estimates and land use variables as predictors. We compared the models by performing five-fold cross-validation (CV) and by external validation (EV) using annual average concentrations measured at 416 (PM 2.5 ) and 1396 sites (NO 2 ) from the ESCAPE study. We further assessed the correlations between predictions by each pair of algorithms at the ESCAPE sites. For PM 2.5 , the models performed similarly across algorithms with a mean CV R 2 of 0.59 and a mean EV R 2 of 0.53. Generalized boosted machine, random forest and bagging performed best (CV R 2 ~0.63; EV R 2 0.58-0.61), while backward stepwise linear regression, support vector regression and artificial neural network performed less well (CV R 2 0.48-0.57; EV R 2 0.39-0.46). Most of the PM 2.5 model predictions at ESCAPE sites were highly correlated (R 2  > 0.85, with the exception of predictions from the artificial neural network). For NO 2 , the models performed even more similarly across different algorithms, with CV R 2 s ranging from 0.57 to 0.62, and EV R 2 s ranging from 0.49 to 0.51. The predicted concentrations from all algorithms at ESCAPE sites were highly correlated (R 2  > 0.9). For both pollutants, biases were low for all models except the artificial neural network. Dispersion model estimates and satellite observations were two of the most important predictors for PM 2.5 models whilst dispersion model estimates and traffic variables were most important for NO 2 models in all algorithms that allow assessment of the importance of variables. Different statistical algorithms performed similarly when modelling spatial variation in annual average air pollution concentrations using a large number of training sites., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 μm (PM 2.5 ) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM 2.5 and PM 10 and gastric and UADT cancer incidence in European adults., Methods: Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses., Results: Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m 3 of PM 2.5 &#95;S was 1.92 (95%-confidence interval (95%-CI) 1.13;3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I 2  = 0%), and 1.63 (95%-CI 0.88;3.01) for PM 2.5 &#95;Zn (I 2  = 70%). For the other elements in PM 2.5 and all elements in PM 10 including PM 10 &#95;S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM 2.5 &#95;S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM 2.5 decreased whereas that for PM 2.5 &#95;S was robust., Conclusion: This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM 2.5 &#95;S but not PM 10 &#95;S, suggesting that S in PM 2.5 or correlated air pollutants may contribute to the risk of gastric cancer., (Copyright © 2018. Published by Elsevier Ltd.)

Background: In order to investigate associations between air pollution and adverse health effects consistent fine spatial air pollution surfaces are needed across large areas to provide cohorts with comparable exposures. The aim of this paper is to develop and evaluate fine spatial scale land use regression models for four major health relevant air pollutants (PM 2.5 , NO 2 , BC, O 3 ) across Europe., Methods: We developed West-European land use regression models (LUR) for 2010 estimating annual mean PM 2.5 , NO 2 , BC and O 3 concentrations (including cold and warm season estimates for O 3 ). The models were based on AirBase routine monitoring data (PM 2.5 , NO 2 and O 3 ) and ESCAPE monitoring data (BC), and incorporated satellite observations, dispersion model estimates, land use and traffic data. Kriging was performed on the residual spatial variation from the LUR models and added to the exposure estimates. One model was developed using all sites (100%). Robustness of the models was evaluated by performing a five-fold hold-out validation and for PM 2.5 and NO 2 additionally with independent comparison at ESCAPE measurements. To evaluate the stability of each model's spatial structure over time, separate models were developed for different years (NO 2 and O 3 : 2000 and 2005; PM 2.5 : 2013)., Results: The PM 2.5 , BC, NO 2 , O 3 annual, O 3 warm season and O 3 cold season models explained respectively 72%, 54%, 59%, 65%, 69% and 83% of spatial variation in the measured concentrations. Kriging proved an efficient technique to explain a part of residual spatial variation for the pollutants with a strong regional component explaining respectively 10%, 24% and 16% of the R 2 in the PM 2.5 , O 3 warm and O 3 cold models. Explained variance at fully independent sites vs the internal hold-out validation was slightly lower for PM 2.5 (65% vs 66%) and lower for NO 2 (49% vs 57%). Predictions from the 2010 model correlated highly with models developed in other years at the overall European scale., Conclusions: We developed robust PM 2.5 , NO 2 , O 3 and BC hybrid LUR models. At the West-European scale models were robust in time, becoming less robust at smaller spatial scales. Models were applied to 100 × 100 m surfaces across Western Europe to allow for exposure assignment for 35 million participants from 18 European cohorts participating in the ELAPSE study., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancers of the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient air pollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-use regression models for particulate matter (PM) below 10 µm (PM 10 ), below 2.5 µm (PM 2.5 ), between 2.5 and 10 µm (PM coarse ), PM 2.5 absorbance and nitrogen oxides (NO 2 and NO X ) as well as approximated by traffic indicators. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. During average follow-up of 14.1 years of 305,551 individuals, 744 incident cases of gastric cancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5 µg/m 3 of PM 2.5 was 1.38 (95% CI 0.99; 1.92) for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures considered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influence markedly the effect estimate for PM 2.5 and gastric cancer. Higher estimated risks of gastric cancer associated with PM 2.5 was found in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study shows an association between long-term exposure to PM 2.5 and gastric cancer, but not UADT cancers, suggesting that air pollution may contribute to gastric cancer risk., (© 2018 UICC.)

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: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent., Methods: In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5-10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses., Results: Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89-3.14 per 10-5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38-2.71 per 10-5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors., Conclusion: We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Ambient air pollution contains low concentrations of carcinogens implicated in the etiology of urinary bladder cancer (BC). Little is known about whether exposure to air pollution influences BC in the general population., Objective: To evaluate the association between long-term exposure to ambient air pollution and BC incidence., Design, Setting, and Participants: We obtained data from 15 population-based cohorts enrolled between 1985 and 2005 in eight European countries (N=303431; mean follow-up 14.1 yr). We estimated exposure to nitrogen oxides (NO 2 and NO x ), particulate matter (PM) with diameter <10μm (PM 10 ), <2.5μm (PM 2.5 ), between 2.5 and 10μm (PM 2.5-10 ), PM 2.5 absorbance (soot), elemental constituents of PM, organic carbon, and traffic density at baseline home addresses using standardized land-use regression models from the European Study of Cohorts for Air Pollution Effects project., Outcome Measurements and Statistical Analysis: We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and meta-analyses to estimate summary hazard ratios (HRs) for BC incidence., Results and Limitations: During follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of the exposures were associated with BC risk. The summary HRs associated with a 10-μg/m 3 increase in NO 2 and 5-μg/m 3 increase in PM 2.5 were 0.98 (95% confidence interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations include the lack of information about lifetime exposure., Conclusions: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC., Patient Summary: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study population to date and extensive assessment of exposure and comprehensive data on personal risk factors such as smoking. We found no association between the levels of outdoor air pollution at place of residence and bladder cancer risk., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to particulate matter air pollution (PM) has been associated with cardiovascular diseases., Objectives: In this study we evaluated whether annual exposure to ambient air pollution is associated with systemic inflammation, which is hypothesized to be an intermediate step to cardiovascular disease., Methods: Six cohorts of adults from Central and Northern Europe were used in this cross-sectional study as part of the larger ESCAPE project (European Study of Cohorts for Air Pollution Effects). Data on levels of blood markers for systemic inflammation-high-sensitivity C-reactive protein (CRP) and fibrinogen-were available for 22,561 and 17,428 persons, respectively. Land use regression models were used to estimate cohort participants' long-term exposure to various size fractions of PM, soot, and nitrogen oxides (NOx). In addition, traffic intensity on the closest street and traffic load within 100 m from home were used as indicators of traffic air pollution exposure., Results: Particulate air pollution was not associated with systemic inflammation. However, cohort participants living on a busy (> 10,000 vehicles/day) road had elevated CRP values (10.2%; 95% CI: 2.4, 18.8%, compared with persons living on a quiet residential street with < 1,000 vehicles/day). Annual NOx concentration was also positively associated with levels of CRP (3.2%; 95% CI: 0.3, 6.1 per 20 μg/m3), but the effect estimate was more sensitive to model adjustments. For fibrinogen, no consistent associations were observed., Conclusions: Living close to busy traffic was associated with increased CRP concentrations, a known risk factor for cardiovascular diseases. However, it remains unclear which specific air pollutants are responsible for the association.

Objective: Quantitative estimates of air pollution health impacts have become an increasingly critical input to policy decisions. The WHO project "Health risks of air pollution in Europe--HRAPIE" was implemented to provide the evidence-based concentration-response functions for quantifying air pollution health impacts to support the 2013 revision of the air quality policy for the European Union (EU)., Methods: A group of experts convened by WHO Regional Office for Europe reviewed the accumulated primary research evidence together with some commissioned reviews and recommended concentration-response functions for air pollutant-health outcome pairs for which there was sufficient evidence for a causal association., Results: The concentration-response functions link several indicators of mortality and morbidity with short- and long-term exposure to particulate matter, ozone and nitrogen dioxide. The project also provides guidance on the use of these functions and associated baseline health information in the cost-benefit analysis., Conclusions: The project results provide the scientific basis for formulating policy actions to improve air quality and thereby reduce the burden of disease associated with air pollution in Europe.

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.

Background: In four European cohorts, we investigated the cross-sectional association between long-term exposure to air pollution and intima-media thickness of the common carotid artery (CIMT), a preclinical marker of atherosclerosis., Methods: Individually assigned levels of nitrogen dioxide, nitrogen oxides, particulate matter ≤ 2.5 μm (PM2.5), absorbance of PM2.5 (PM2.5abs), PM10, PMcoarse, and two indicators of residential proximity to highly trafficked roads were obtained under a standard exposure protocol (European Study of Cohorts for Air Pollution Effects-ESCAPE study) in the Stockholm area (Sweden), the Ausburg and Ruhr area (Germany), and the Girona area (Spain). We used linear regression and meta-analyses to examine the association between long-term exposure to air pollution and CIMT., Results: The meta-analysis with 9,183 individuals resulted in an estimated increase in CIMT (geometric mean) of 0.72% (95% CI: -0.65%, 2.10%) per 5-μg/m3 increase in PM2.5 and 0.42% (95% CI: -0.46%, 1.30%) per 10-5/m increase in PM2.5abs. Living in proximity to high traffic was also positively but not significantly associated with CIMT. Meta-analytic estimates for other pollutants were inconsistent. Results were similar across different adjustment sets and sensitivity analyses. In an extended meta-analysis for PM2.5 with three other previously published studies, a 0.78% (95% CI: -0.18%, 1.75%) increase in CIMT was estimated for a 5-μg/m3 contrast in PM2.5., Conclusions: Using a standardized exposure and analytical protocol in four European cohorts, we found that cross-sectional associations between CIMT and the eight ESCAPE markers of long-term residential air pollution exposure did not reach statistical significance. The additional meta-analysis of CIMT and PM2.5 across all published studies also was positive but not significant.

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.

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: 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: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events., Objectives: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts., Methods: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) ≤ 2.5 μm in diameter], coarse PM (PM between 2.5 and 10 μm), PM10 (PM ≤ 10 μm), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation., Results: A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-μg/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those ≥ 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 μg/m3 (HR = 1.33, 95% CI: 1.01, 1.77)., Conclusions: We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value.

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: 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.

Epidemiological studies often use nitrogen dioxide (NO2) or proximity to roads to characterize exposure to more health-relevant pollutants (e.g., fine particles or black carbon aerosol) in vehicle exhaust. Due to the introduction of diesel-soot filters, particle-to-NO2 ratios may have decreased, but little information is available about these ratios over time. Our study aim was to evaluate the change in particle-to-NO2 ratios between 1999 and 2009. We compared data collected during measurement campaigns in 1999 and 2009 from Munich, the Netherlands, and Stockholm. Traffic-impacted and urban and regional background sites were studied during each campaign. The same pollutants were measured in each campaign (mass concentration of particles ≤ 2.5 microns in diameter (PM2.5), PM2.5 absorbance (a marker for black carbon), and NO2) using the same methods except for NO2: Palmes tubes were used in 1999 and Ogawa badges in 2009. Both NO2 methods were validated against side-by-side chemiluminescence measurements. The levels of PM2.5 absorbance and PM2.5 were significantly lower (p<0.05) in 2009 at traffic and urban background sites in Stockholm, but only slightly lower in Munich and the Netherlands. In contrast, NO2 levels were not significantly different in the three areas in 2009 compared to 1999. Statistically-significant decreases between 1999 and 2009 pollutant ratios in the Netherlands (PM2.5 absorbance/NO2 and PM2.5/NO2) and in Stockholm (PM2.5 absorbance/NO2 and PM2.5 absorbance/PM2.5) were observed. Smaller decreases in these ratios were observed in Munich. The contrast between traffic and urban background locations was larger in 2009 than 1999 for NO2, whereas it was smaller for PM2.5 absorbance and PM2.5. The lower PM2.5 absorbance/NO2 and PM2.5/NO2 ratios in 2009 is likely explained by the introduction of oxidative particle filters for diesel vehicles that reduce particles but produce NO2. The changed contrasts may affect estimates of health effects related to NO2 as a marker of proximity to roads., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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: 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.)

Objectives: To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE)., Design: Prospective cohort studies and meta-analysis of the results., Setting: Cohorts in Finland, Sweden, Denmark, Germany, and Italy., Participants: 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline., Main Outcome Measures: Modelled concentrations of particulate matter <2.5 μm (PM2.5), 2.5-10 μm (PMcoarse), and <10 μm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios., Results: 5157 participants experienced incident events. A 5 μg/m(3) increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 μg/m(3) increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 μg/m(3) for PM2.5 (1.18, 1.01 to 1.39, for 5 μg/m(3) increase in PM2.5) and below 40 μg/m(3) for PM10 (1.12, 1.00 to 1.27, for 10 μg/m(3) increase in PM10). Positive but non-significant associations were found with other pollutants., Conclusions: Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.

Background: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies., Objectives: We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol., Methods: As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6-8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5-10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis., Results: Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from -0.86% (95% CI: -1.48, -0.24%) for a 20-μg/m3 increase in NOx to -1.77% (95% CI: -3.34, -0.18%) for a 5-μg/m3 increase in PM2.5., Conclusions: Exposure to air pollution may result in reduced lung function in schoolchildren.

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: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations., Methods: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses., Findings: The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day)., Interpretation: Particulate matter air pollution contributes to lung cancer incidence in Europe., Funding: European Community's Seventh Framework Programme., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Land Use Regression (LUR) models have been used to describe and model spatial variability of annual mean concentrations of traffic related pollutants such as nitrogen dioxide (NO2), nitrogen oxides (NOx) and particulate matter (PM). No models have yet been published of elemental composition. As part of the ESCAPE project, we measured the elemental composition in both the PM10 and PM2.5 fraction sizes at 20 sites in each of 20 study areas across Europe. LUR models for eight a priori selected elements (copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)) were developed. Good models were developed for Cu, Fe, and Zn in both fractions (PM10 and PM2.5) explaining on average between 67 and 79% of the concentration variance (R(2)) with a large variability between areas. Traffic variables were the dominant predictors, reflecting nontailpipe emissions. Models for V and S in the PM10 and PM2.5 fractions and Si, Ni, and K in the PM10 fraction performed moderately with R(2) ranging from 50 to 61%. Si, NI, and K models for PM2.5 performed poorest with R(2) under 50%. The LUR models are used to estimate exposures to elemental composition in the health studies involved in ESCAPE.

Land use regression models (LUR) frequently use leave-one-out-cross-validation (LOOCV) to assess model fit, but recent studies suggested that this may overestimate predictive ability in independent data sets. Our aim was to evaluate LUR models for nitrogen dioxide (NO2) and particulate matter (PM) components exploiting the high correlation between concentrations of PM metrics and NO2. LUR models have been developed for NO2, PM2.5 absorbance, and copper (Cu) in PM10 based on 20 sites in each of the 20 study areas of the ESCAPE project. Models were evaluated with LOOCV and "hold-out evaluation (HEV)" using the correlation of predicted NO2 or PM concentrations with measured NO2 concentrations at the 20 additional NO2 sites in each area. For NO2, PM2.5 absorbance and PM10 Cu, the median LOOCV R(2)s were 0.83, 0.81, and 0.76 whereas the median HEV R(2) were 0.52, 0.44, and 0.40. There was a positive association between the LOOCV R(2) and HEV R(2) for PM2.5 absorbance and PM10 Cu. Our results confirm that the predictive ability of LUR models based on relatively small training sets is overestimated by the LOOCV R(2)s. Nevertheless, in most areas LUR models still explained a substantial fraction of the variation of concentrations measured at independent sites.

Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.