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1.  Air Pollution and Atherosclerosis: A Cross-Sectional Analysis of Four European Cohort Studies in the ESCAPE Study 
Environmental Health Perspectives  2015;123(6):597-605.
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.
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.
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.
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.
Perez L, Wolf K, Hennig F, Penell J, Basagaña X, Foraster M, Aguilera I, Agis D, Beelen R, Brunekreef B, Cyrys J, Fuks KB, Adam M, Baldassarre D, Cirach M, Elosua R, Dratva J, Hampel R, Koenig W, Marrugat J, de Faire U, Pershagen G, Probst-Hensch NM, de Nazelle A, Nieuwenhuijsen MJ, Rathmann W, Rivera M, Seissler J, Schindler C, Thiery J, Hoffmann B, Peters A, Künzli N. 2015. Air pollution and atherosclerosis: a cross-sectional analysis of four European cohort studies in the ESCAPE Study. Environ Health Perspect 123:597–605;
PMCID: PMC4455580  PMID: 25625785
2.  Natural-Cause Mortality and Long-Term Exposure to Particle Components: An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project 
Beelen, Rob | Hoek, Gerard | Raaschou-Nielsen, Ole | Stafoggia, Massimo | Andersen, Zorana Jovanovic | Weinmayr, Gudrun | Hoffmann, Barbara | Wolf, Kathrin | Samoli, Evangelia | Fischer, Paul H. | Nieuwenhuijsen, Mark J. | Xun, Wei W. | Katsouyanni, Klea | Dimakopoulou, Konstantina | Marcon, Alessandro | Vartiainen, Erkki | Lanki, Timo | Yli-Tuomi, Tarja | Oftedal, Bente | Schwarze, Per E. | Nafstad, Per | De Faire, Ulf | Pedersen, Nancy L. | Östenson, Claes-Göran | Fratiglioni, Laura | Penell, Johanna | Korek, Michal | Pershagen, Göran | Eriksen, Kirsten Thorup | Overvad, Kim | Sørensen, Mette | Eeftens, Marloes | Peeters, Petra H. | Meliefste, Kees | Wang, Meng | Bueno-de-Mesquita, H. Bas | Sugiri, Dorothea | Krämer, Ursula | Heinrich, Joachim | de Hoogh, Kees | Key, Timothy | Peters, Annette | Hampel, Regina | Concin, Hans | Nagel, Gabriele | Jaensch, Andrea | Ineichen, Alex | Tsai, Ming-Yi | Schaffner, Emmanuel | Probst-Hensch, Nicole M. | Schindler, Christian | Ragettli, Martina S. | Vilier, Alice | Clavel-Chapelon, Françoise | Declercq, Christophe | Ricceri, Fulvio | Sacerdote, Carlotta | Galassi, Claudia | Migliore, Enrica | Ranzi, Andrea | Cesaroni, Giulia | Badaloni, Chiara | Forastiere, Francesco | Katsoulis, Michail | Trichopoulou, Antonia | Keuken, Menno | Jedynska, Aleksandra | Kooter, Ingeborg M. | Kukkonen, Jaakko | Sokhi, Ranjeet S. | Vineis, Paolo | Brunekreef, Bert
Environmental Health Perspectives  2015;123(6):525-533.
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.
Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter.
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.
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.
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.
Beelen R, Hoek G, Raaschou-Nielsen O, Stafoggia M, Andersen ZJ, Weinmayr G, Hoffmann B, Wolf K, Samoli E, Fischer PH, Nieuwenhuijsen MJ, Xun WW, Katsouyanni K, Dimakopoulou K, Marcon A, Vartiainen E, Lanki T, Yli-Tuomi T, Oftedal B, Schwarze PE, Nafstad P, De Faire U, Pedersen NL, Östenson C-G, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Overvad K, Sørensen M, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita HB, Sugiri D, Krämer U, Heinrich J, de Hoogh K, Key T, Peters A, Hampel R, Concin H, Nagel G, Jaensch A, Ineichen A, Tsai MY, Schaffner E, Probst-Hensch NM, Schindler C, Ragettli MS, Vilier A, Clavel-Chapelon F, Declercq C, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Katsoulis M, Trichopoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Sokhi RS, Vineis P, Brunekreef B. 2015. Natural-cause mortality and long-term exposure to particle components: an analysis of 19 European cohorts within the Multi-Center ESCAPE Project. Environ Health Perspect 123:525–533;
PMCID: PMC4455583  PMID: 25712504
3.  Ambient Air Pollution and Adult Asthma Incidence in Six European Cohorts (ESCAPE) 
Environmental Health Perspectives  2015;123(6):613-621.
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.
We aimed to investigate the association between air pollution and adult onset asthma.
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.
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).
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.
Jacquemin B, Siroux V, Sanchez M, Carsin AE, Schikowski T, Adam M, Bellisario V, Buschka A, Bono R, Brunekreef B, Cai Y, Cirach M, Clavel-Chapelon F, Declercq C, de Marco R, de Nazelle A, Ducret-Stich RE, Ferretti VV, Gerbase MW, Hardy R, Heinrich J, Janson C, Jarvis D, Al Kanaani Z, Keidel D, Kuh D, Le Moual N, Nieuwenhuijsen MJ, Marcon A, Modig L, Pin I, Rochat T, Schindler C, Sugiri D, Stempfelet M, Temam S, Tsai MY, Varraso R, Vienneau D, Vierkötter A, Hansell AL, Krämer U, Probst-Hensch NM, Sunyer J, Künzli N, Kauffmann F. 2015. Ambient air pollution and adult asthma incidence in six European cohorts (ESCAPE). Environ Health Perspect 123:613–621;
PMCID: PMC4455584  PMID: 25712593
4.  Quantifying the health impacts of ambient air pollutants: recommendations of a WHO/Europe project 
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).
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.
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.
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.
Electronic supplementary material
The online version of this article (doi:10.1007/s00038-015-0690-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4480843  PMID: 26024815
Air pollutants; Health impact assessment; Cost–benefit analysis; Particulate matter; Ozone; Nitrogen dioxide
5.  BMI, waist circumference at 8 and 12 years of age and FVC and FEV1 at 12 years of age; the PIAMA birth cohort study 
In adults, overweight is associated with reduced lung function, in children evidence on this association is conflicting. We examined the association of body mass index (BMI) and waist circumference (WC) at age 12, and of persistently (at ages 8 and 12 years) high BMI and large WC, with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at age 12.
Height, weight, WC and FVC and FEV1 were measured during a medical examination in 1288 12-year-olds participating in the PIAMA birth cohort study. 1090 children also had BMI and WC measured at age 8. The associations between BMI and WC and FVC, FEV1, and FEV1/FVC ratio were studied using local and linear regression analyses, separately for girls and boys. The regression models were adjusted for age, height, and pubertal development and maternal educational level.
High BMI and large WC (sd-score >90th percentile) were associated with higher FVC; in girls these associations were statistically significant (4.6% (95% CI: 1.5, 7.9) and 3.6% (95% CI: 0.6, 6.8) respectively in adjusted models). Similar associations were observed for persistently high BMI or large WC: girls with a high BMI or large WC at both 8 and 12 years had statistically significantly higher FVC at age 12 years (BMI: 4.9% (95% CI 0.9, 9.1), WC: 5.0% (95% CI 0.7, 9.6)) than girls with normal BMI or WC at both ages. No statistically significant associations were observed between (persistently) high BMI or large WC and FEV1. The FEV1/FVC ratio was statistically significantly lower in children with a high BMI or large WC than in children with a normal BMI or WC. Girls and boys with a persistently high BMI or large WC status had statistically significantly lower FEV1/FVC ratios.
At 12 years of age, a persistently high BMI or large WC is not yet associated with lower FVC and FEV1, suggesting that this association, that is commonly observed in adults, develops at a later age.
Electronic supplementary material
The online version of this article (doi:10.1186/s12890-015-0032-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4409985  PMID: 25896340
Birth cohort; Lung volume; Overweight
6.  Change in HbA1c Levels between the Age of 8 Years and the Age of 12 Years in Dutch Children without Diabetes: The PIAMA Birth Cohort Study 
PLoS ONE  2015;10(4):e0119615.
HbA1c is associated with cardiovascular risk in persons without diabetes and cardiovascular risk accumulates over the life course. Therefore, insight in factors determining HbA1c from childhood onwards is important. We investigated (lifestyle) determinants of HbA1c at age 12 years and the effects of growth on change in HbA1c and the tracking of HbA1c between the age of 8 and 12 years.
Study Design and Methods
Anthropometric measurements were taken and HbA1c levels were assessed in 955 children without diabetes aged around 12 years participating in the PIAMA birth cohort study. In 363 of these children HbA1c was also measured at age 8 years. Data on parents and children were collected prospectively by questionnaires.
We found no significant association between known risk factors for diabetes and HbA1c at age 12 years. Mean(SD) change in HbA1c between ages 8 and 12 years was 0.6(0.7) mmol/mol per year (or 0.1(0.1) %/yr). Anthropometric measures at age 8 and their change between age 8 and 12 years were not associated with the change in HbA1c. 68.9% of the children remained in the same quintile or had an HbA1c one quintile higher or lower at age 8 years compared to age 12 years.
The lack of association between known risk factors for diabetes and HbA1c suggest that HbA1c in children without diabetes is relatively unaffected by factors associated with glycaemia. HbA1c at age 8 years is by far the most important predictor of HbA1c at age 12. Therefore, the ranking of HbA1c levels appear to be fairly stable over time.
PMCID: PMC4395421  PMID: 25875773
7.  Determinants of the Spatial Distributions of Elemental Carbon and Particulate Matter in Eight Southern Californian Communities 
Emerging evidence indicates that near-roadway pollution (NRP) in ambient air has adverse health effects. However, specific components of the NRP mixture responsible for these effects have not been established. A major limitation for health studies is the lack of exposure models that estimate NRP components observed in epidemiological studies over fine spatial scale of tens to hundreds of meters. In this study, exposure models were developed for fine-scale variation in biologically relevant elemental carbon (EC). Measurements of particulate matter (PM) and EC less than 2.5 μm in aerodynamic diameter (EC2.5) and of PM and EC of nanoscale size less than 0.2 μm were made at up to 29 locations in each of eight Southern California Children's Health Study communities. Regression-based prediction models were developed using a guided forward selection process to identify traffic variables and other pollutant sources, community physical characteristics and land use as predictors of PM and EC variation in each community. A combined eight-community model including only CALINE4 near-roadway dispersion-estimated vehicular emissions accounting for distance, distance-weighted traffic volume, and meteorology, explained 51% of the EC0.2 variability. Community-specific models identified additional predictors in some communities; however, in most communities the correlation between predicted concentrations from the eight-community model and observed concentrations stratified by community were similar to those for the community-specific models. EC2.5 could be predicted as well as EC0.2. EC2.5 estimated from CALINE4 and population density explained 53% of the within-community variation. Exposure prediction was further improved after accounting for between-community heterogeneity of CALINE4 effects associated with average distance to Pacific Ocean shoreline (to 61% for EC0.2) and for regional NOx pollution (to 57% for EC2.5). PM fine spatial scale variation was poorly predicted in both size fractions. In conclusion, models of exposure that include traffic measures such as CALINE4 can provide useful estimates for EC0.2 and EC2.5 on a spatial scale appropriate for health studies of NRP in selected Southern California communities.
PMCID: PMC4192647  PMID: 25313293
8.  A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 
Lim, Stephen S | Vos, Theo | Flaxman, Abraham D | Danaei, Goodarz | Shibuya, Kenji | Adair-Rohani, Heather | Amann, Markus | Anderson, H Ross | Andrews, Kathryn G | Aryee, Martin | Atkinson, Charles | Bacchus, Loraine J | Bahalim, Adil N | Balakrishnan, Kalpana | Balmes, John | Barker-Collo, Suzanne | Baxter, Amanda | Bell, Michelle L | Blore, Jed D | Blyth, Fiona | Bonner, Carissa | Borges, Guilherme | Bourne, Rupert | Boussinesq, Michel | Brauer, Michael | Brooks, Peter | Bruce, Nigel G | Brunekreef, Bert | Bryan-Hancock, Claire | Bucello, Chiara | Buchbinder, Rachelle | Bull, Fiona | Burnett, Richard T | Byers, Tim E | Calabria, Bianca | Carapetis, Jonathan | Carnahan, Emily | Chafe, Zoe | Charlson, Fiona | Chen, Honglei | Chen, Jian Shen | Cheng, Andrew Tai-Ann | Child, Jennifer Christine | Cohen, Aaron | Colson, K Ellicott | Cowie, Benjamin C | Darby, Sarah | Darling, Susan | Davis, Adrian | Degenhardt, Louisa | Dentener, Frank | Des Jarlais, Don C | Devries, Karen | Dherani, Mukesh | Ding, Eric L | Dorsey, E Ray | Driscoll, Tim | Edmond, Karen | Ali, Suad Eltahir | Engell, Rebecca E | Erwin, Patricia J | Fahimi, Saman | Falder, Gail | Farzadfar, Farshad | Ferrari, Alize | Finucane, Mariel M | Flaxman, Seth | Fowkes, Francis Gerry R | Freedman, Greg | Freeman, Michael K | Gakidou, Emmanuela | Ghosh, Santu | Giovannucci, Edward | Gmel, Gerhard | Graham, Kathryn | Grainger, Rebecca | Grant, Bridget | Gunnell, David | Gutierrez, Hialy R | Hall, Wayne | Hoek, Hans W | Hogan, Anthony | Hosgood, H Dean | Hoy, Damian | Hu, Howard | Hubbell, Bryan J | Hutchings, Sally J | Ibeanusi, Sydney E | Jacklyn, Gemma L | Jasrasaria, Rashmi | Jonas, Jost B | Kan, Haidong | Kanis, John A | Kassebaum, Nicholas | Kawakami, Norito | Khang, Young-Ho | Khatibzadeh, Shahab | Khoo, Jon-Paul | Kok, Cindy | Laden, Francine | Lalloo, Ratilal | Lan, Qing | Lathlean, Tim | Leasher, Janet L | Leigh, James | Li, Yang | Lin, John Kent | Lipshultz, Steven E | London, Stephanie | Lozano, Rafael | Lu, Yuan | Mak, Joelle | Malekzadeh, Reza | Mallinger, Leslie | Marcenes, Wagner | March, Lyn | Marks, Robin | Martin, Randall | McGale, Paul | McGrath, John | Mehta, Sumi | Mensah, George A | Merriman, Tony R | Micha, Renata | Michaud, Catherine | Mishra, Vinod | Hanafiah, Khayriyyah Mohd | Mokdad, Ali A | Morawska, Lidia | Mozaff arian, Dariush | Murphy, Tasha | Naghavi, Mohsen | Neal, Bruce | Nelson, Paul K | Nolla, Joan Miquel | Norman, Rosana | Olives, Casey | Omer, Saad B | Orchard, Jessica | Osborne, Richard | Ostro, Bart | Page, Andrew | Pandey, Kiran D | Parry, Charles D H | Passmore, Erin | Patra, Jayadeep | Pearce, Neil | Pelizzari, Pamela M | Petzold, Max | Phillips, Michael R | Pope, Dan | Pope III, C Arden | Powles, John | Rao, Mayuree | Razavi, Homie | Rehfuess, Eva A | Rehm, Jürgen T | Ritz, Beate | Rivara, Frederick P | Roberts, Thomas | Robinson, Carolyn | Rodriguez-Portales, Jose A | Romieu, Isabelle | Room, Robin | Rosenfeld, Lisa C | Roy, Ananya | Rushton, Lesley | Salomon, Joshua A | Sampson, Uchechukwu | Sanchez-Riera, Lidia | Sanman, Ella | Sapkota, Amir | Seedat, Soraya | Shi, Peilin | Shield, Kevin | Shivakoti, Rupak | Singh, Gitanjali M | Sleet, David A | Smith, Emma | Smith, Kirk R | Stapelberg, Nicolas J C | Steenland, Kyle | Stöckl, Heidi | Stovner, Lars Jacob | Straif, Kurt | Straney, Lahn | Thurston, George D | Tran, Jimmy H | Van Dingenen, Rita | van Donkelaar, Aaron | Veerman, J Lennert | Vijayakumar, Lakshmi | Weintraub, Robert | Weissman, Myrna M | White, Richard A | Whiteford, Harvey | Wiersma, Steven T | Wilkinson, James D | Williams, Hywel C | Williams, Warwick | Wilson, Nicholas | Woolf, Anthony D | Yip, Paul | Zielinski, Jan M | Lopez, Alan D | Murray, Christopher J L | Ezzati, Majid
Lancet  2012;380(9859):2224-2260.
Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time.
We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden.
In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania.
Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.
Bill & Melinda Gates Foundation.
PMCID: PMC4156511  PMID: 23245609
9.  Long-Term Exposure to Ambient Air Pollution and Incidence of Cerebrovascular Events: Results from 11 European Cohorts within the ESCAPE Project 
Environmental Health Perspectives  2014;122(9):919-925.
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.
Citation: Stafoggia M, Cesaroni G, Peters A, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, Cyrys J, de Faire U, de Hoogh K, Eriksen KT, Fratiglioni L, Galassi C, Gigante B, Havulinna AS, Hennig F, Hilding A, Hoek G, Hoffmann B, Houthuijs D, Korek M, Lanki T, Leander K, Magnusson PK, Meisinger C, Migliore E, Overvad K, Östenson CG, Pedersen NL, Pekkanen J, Penell J, Pershagen G, Pundt N, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Swart WJ, Turunen AW, Vineis P, Weimar C, Weinmayr G, Wolf K, Brunekreef B, Forastiere F. 2014. Long-term exposure to ambient air pollution and incidence of cerebrovascular events: results from 11 European cohorts within the ESCAPE project. Environ Health Perspect 122:919–925;
PMCID: PMC4153743  PMID: 24835336
10.  Arterial Blood Pressure and Long-Term Exposure to Traffic-Related Air Pollution: An Analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE) 
Environmental Health Perspectives  2014;122(9):896-905.
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.
Citation: Fuks KB, Weinmayr G, Foraster M, Dratva J, Hampel R, Houthuijs D, Oftedal B, Oudin A, Panasevich S, Penell J, Sommar JN, Sørensen M, Tittanen P, Wolf K, Xun WW, Aguilera I, Basagaña X, Beelen R, Bots ML, Brunekreef B, Bueno-de-Mesquita HB, Caracciolo B, Cirach M, de Faire U, de Nazelle A, Eeftens M, Elosua R, Erbel R, Forsberg B, Fratiglioni L, Gaspoz JM, Hilding A, Jula A, Korek M, Krämer U, Künzli N, Lanki T, Leander K, Magnusson PK, Marrugat J, Nieuwenhuijsen MJ, Östenson CG, Pedersen NL, Pershagen G, Phuleria HC, Probst-Hensch NM, Raaschou-Nielsen O, Schaffner E, Schikowski T, Schindler C, Schwarze PE, Søgaard AJ, Sugiri D, Swart WJ, Tsai MY, Turunen AW, Vineis P, Peters A, Hoffmann B. 2014. Arterial blood pressure and long-term exposure to traffic-related air pollution: an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Environ Health Perspect 122:896–905;
PMCID: PMC4154218  PMID: 24835507
11.  Performance of Multi-City Land Use Regression Models for Nitrogen Dioxide and Fine Particles 
Environmental Health Perspectives  2014;122(8):843-849.
Background: Land use regression (LUR) models have been developed mostly to explain intraurban variations in air pollution based on often small local monitoring campaigns. Transferability of LUR models from city to city has been investigated, but little is known about the performance of models based on large numbers of monitoring sites covering a large area.
Objectives: We aimed to develop European and regional LUR models and to examine their transferability to areas not used for model development.
Methods: We evaluated LUR models for nitrogen dioxide (NO2) and particulate matter (PM; PM2.5, PM2.5 absorbance) by combining standardized measurement data from 17 (PM) and 23 (NO2) ESCAPE (European Study of Cohorts for Air Pollution Effects) study areas across 14 European countries for PM and NO2. Models were evaluated with cross-validation (CV) and hold-out validation (HV). We investigated the transferability of the models by successively excluding each study area from model building.
Results: The European model explained 56% of the concentration variability across all sites for NO2, 86% for PM2.5, and 70% for PM2.5 absorbance. The HV R2s were only slightly lower than the model R2 (NO2, 54%; PM2.5, 80%; PM2.5 absorbance, 70%). The European NO2, PM2.5, and PM2.5 absorbance models explained a median of 59%, 48%, and 70% of within-area variability in individual areas. The transferred models predicted a modest-to-large fraction of variability in areas that were excluded from model building (median R2: NO2, 59%; PM2.5, 42%; PM2.5 absorbance, 67%).
Conclusions: Using a large data set from 23 European study areas, we were able to develop LUR models for NO2 and PM metrics that predicted measurements made at independent sites and areas reasonably well. This finding is useful for assessing exposure in health studies conducted in areas where no measurements were conducted.
Citation: Wang M, Beelen R, Bellander T, Birk M, Cesaroni G, Cirach M, Cyrys J, de Hoogh K, Declercq C, Dimakopoulou K, Eeftens M, Eriksen KT, Forastiere F, Galassi C, Grivas G, Heinrich J, Hoffmann B, Ineichen A, Korek M, Lanki T, Lindley S, Modig L, Mölter A, Nafstad P, Nieuwenhuijsen MJ, Nystad W, Olsson D, Raaschou-Nielsen O, Ragettli M, Ranzi A, Stempfelet M, Sugiri D, Tsai MY, Udvardy O, Varró MJ, Vienneau D, Weinmayr G, Wolf K, Yli-Tuomi T, Hoek G, Brunekreef B. 2014. Performance of multi-city land use regression models for nitrogen dioxide and fine particles. Environ Health Perspect 122:843–849;
PMCID: PMC4123024  PMID: 24787034
12.  GSTP1 and TNF Gene Variants and Associations between Air Pollution and Incident Childhood Asthma: The Traffic, Asthma and Genetics (TAG) Study 
Environmental Health Perspectives  2014;122(4):418-424.
Background: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma.
Objective: Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma.
Methods: Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7–8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, ozone] were assigned to each child’s birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated.
Results: Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 μg/m3 NO2] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype.
Conclusions: Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution.
Citation: MacIntyre EA, Brauer M, Melén E, Bauer CP, Bauer M, Berdel D, Bergström A, Brunekreef B, Chan-Yeung M, Klümper C, Fuertes E, Gehring U, Gref A, Heinrich J, Herbarth O, Kerkhof M, Koppelman GH, Kozyrskyj AL, Pershagen G, Postma DS, Thiering E, Tiesler CM, Carlsten C, TAG Study Group. 2014. GSTP1 and TNF gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) Study. Environ Health Perspect 122:418–424;
PMCID: PMC3984232  PMID: 24465030
14.  Air Pollution and Respiratory Infections during Early Childhood: An Analysis of 10 European Birth Cohorts within the ESCAPE Project 
Environmental Health Perspectives  2013;122(1):107-113.
Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood.
Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts—BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)—and to derive combined effect estimates using meta-analysis.
Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5–10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates.
Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR = 1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR = 1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR = 1.09; 95% CI: 1.02, 1.16 per 10-μg/m3).
Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media.
Citation: MacIntyre EA, Gehring U, Mölter A, Fuertes E, Klümper C, Krämer U, Quass U, Hoffmann B, Gascon M, Brunekreef B, Koppelman GH, Beelen R, Hoek G, Birk M, de Jongste JC, Smit HA, Cyrys J, Gruzieva O, Korek M, Bergström A, Agius RM, de Vocht F, Simpson A, Porta D, Forastiere F, Badaloni C, Cesaroni G, Esplugues A, Fernández-Somoano A, Lerxundi A, Sunyer J, Cirach M, Nieuwenhuijsen MJ, Pershagen G, Heinrich J. 2014. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE project. Environ Health Perspect 122:107–113;
PMCID: PMC3888562  PMID: 24149084
15.  A ventilation intervention study in classrooms to improve indoor air quality: the FRESH study 
Environmental Health  2013;12:110.
Classroom ventilation rates often do not meet building standards, although it is considered to be important to improve indoor air quality. Poor indoor air quality is thought to influence both children’s health and performance. Poor ventilation in The Netherlands most often occurs in the heating season. To improve classroom ventilation a tailor made mechanical ventilation device was developed to improve outdoor air supply. This paper studies the effect of this intervention.
The FRESH study (Forced-ventilation Related Environmental School Health) was designed to investigate the effect of a CO2 controlled mechanical ventilation intervention on classroom CO2 levels using a longitudinal cross-over design. Target CO2 concentrations were 800 and 1200 parts per million (ppm), respectively. The study included 18 classrooms from 17 schools from the north-eastern part of The Netherlands, 12 experimental classrooms and 6 control classrooms. Data on indoor levels of CO2, temperature and relative humidity were collected during three consecutive weeks per school during the heating seasons of 2010–2012. Associations between the intervention and weekly average indoor CO2 levels, classroom temperature and relative humidity were assessed by means of mixed models with random school-effects.
At baseline, mean CO2 concentration for all schools was 1335 ppm (range: 763–2000 ppm). The intervention was able to significantly decrease CO2 levels in the intervention classrooms (F (2,10) = 17.59, p < 0.001), with a mean decrease of 491 ppm. With the target set at 800 ppm, mean CO2 was 841 ppm (range: 743–925 ppm); with the target set at 1200 ppm, mean CO2 was 975 ppm (range: 887–1077 ppm).
Although the device was not capable of precisely achieving the two predefined levels of CO2, our study showed that classroom CO2 levels can be reduced by intervening on classroom ventilation using a CO2 controlled mechanical ventilation system.
PMCID: PMC3893609  PMID: 24345039
Ventilation; Schools; Carbon dioxide; Indoor air quality; Intervention
16.  Air Pollution Exposure and Lung Function in Children: The ESCAPE Project 
Environmental Health Perspectives  2013;121(11-12):1357-1364.
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.
Citation: Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klümper C, Korek M, Mölter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B. 2013. Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364;
PMCID: PMC3855518  PMID: 24076757
17.  Ambient Air Pollution and Preeclampsia: A Spatiotemporal Analysis 
Environmental Health Perspectives  2013;121(11-12):1365-1371.
Background: Available evidence concerning the association between air pollution and preeclampsia is limited, and specific associations with early- and late-onset preeclampsia have not been assessed.
Objectives: We investigated the association, if any, between preeclampsia (all, early-, and late-onset) and exposure to nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5; fine particles), ≤ 10 μm, and 2.5–10 μm, and PM2.5 light absorption (a proxy for elemental carbon) during the entire pregnancy and during the first, second, and third trimesters.
Methods: This study was based on 8,398 pregnancies (including 103 cases of preeclampsia) among women residing in Barcelona, Spain (2000–2005). We applied a spatiotemporal exposure assessment framework using land use regression models to predict ambient pollutant levels during each week of pregnancy at the geocoded residence address of each woman at the time of birth. Logistic and conditional logistic regression models were used to estimate unadjusted and adjusted associations.
Results: We found positive associations for most of our evaluated outcome–exposure pairs, with the strongest associations observed for preeclampsia and late-onset preeclampsia in relation to the third-trimester exposure to fine particulate pollutants, and for early-onset preeclampsia in relation to the first-trimester exposure to fine particulate pollutants. Among our investigated associations, those of first- and third-trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia attained statistical significance.
Conclusion: We observed increased risk of preeclampsia associated with exposure to fine particulate air pollution. Our findings, in combination with previous evidence suggesting distinct pathogenic mechanisms for early- and late-onset preeclampsia, support additional research on this topic.
Citation: Dadvand P, Figueras F, Basagaña X, Beelen R, Martinez D, Cirach M, Schembari A, Hoek G, Brunekreef B, Nieuwenhuijsen MJ. 2013. Ambient air pollution and preeclampsia: a spatiotemporal analysis. Environ Health Perspect 121:1365–1371;
PMCID: PMC3855505  PMID: 24021707
18.  Long-term air pollution exposure and cardio- respiratory mortality: a review 
Environmental Health  2013;12:43.
Current day concentrations of ambient air pollution have been associated with a range of adverse health effects, particularly mortality and morbidity due to cardiovascular and respiratory diseases. In this review, we summarize the evidence from epidemiological studies on long-term exposure to fine and coarse particles, nitrogen dioxide (NO2) and elemental carbon on mortality from all-causes, cardiovascular disease and respiratory disease. We also summarize the findings on potentially susceptible subgroups across studies. We identified studies through a search in the databases Medline and Scopus and previous reviews until January 2013 and performed a meta-analysis if more than five studies were available for the same exposure metric.
There is a significant number of new studies on long-term air pollution exposure, covering a wider geographic area, including Asia. These recent studies support associations found in previous cohort studies on PM2.5. The pooled effect estimate expressed as excess risk per 10 μg/m3 increase in PM2.5 exposure was 6% (95% CI 4, 8%) for all-cause and 11% (95% CI 5, 16%) for cardiovascular mortality. Long-term exposure to PM2.5 was more associated with mortality from cardiovascular disease (particularly ischemic heart disease) than from non-malignant respiratory diseases (pooled estimate 3% (95% CI −6, 13%)). Significant heterogeneity in PM2.5 effect estimates was found across studies, likely related to differences in particle composition, infiltration of particles indoors, population characteristics and methodological differences in exposure assessment and confounder control. All-cause mortality was significantly associated with elemental carbon (pooled estimate per 1 μg/m3 6% (95% CI 5, 7%)) and NO2 (pooled estimate per 10 μg/m3 5% (95% CI 3, 8%)), both markers of combustion sources. There was little evidence for an association between long term coarse particulate matter exposure and mortality, possibly due to the small number of studies and limitations in exposure assessment. Across studies, there was little evidence for a stronger association among women compared to men. In subjects with lower education and obese subjects a larger effect estimate for mortality related to fine PM was found, though the evidence for differences related to education has been weakened in more recent studies.
PMCID: PMC3679821  PMID: 23714370
Air pollution; Mortality; Motorized traffic; Cardiovascular; Respiratory; Particles
19.  Composition of PM Affects Acute Vascular Inflammatory and Coagulative Markers - The RAPTES Project 
PLoS ONE  2013;8(3):e58944.
Exposure to ambient particulate matter (PM) has been associated with adverse cardiovascular effects in epidemiological studies. Current knowledge of independent effects of individual PM characteristics remains limited.
Using a semi-experimental design we investigated which PM characteristics were consistently associated with blood biomarkers believed to be predictive of the risk of cardiovascular events. We exposed healthy adult volunteers at 5 different locations chosen to provide PM exposure contrasts with reduced correlations among PM characteristics. Each of the 31 volunteers was exposed for 5 h, exercising intermittently, 3–7 times at different sites from March to October 2009. Extensive on-site exposure characterization included measurements of PM mass and number concentration, elemental- (EC) and organic carbon (OC), trace metals, sulfate, nitrate, and PM oxidative potential (OP). Before and 2 h and 18 h after exposure we measured acute vascular blood biomarkers - C-reactive protein, fibrinogen, platelet counts, von Willebrand Factor, and tissue plasminogen activator/plasminogen activator inhibitor-1 complex. We used two-pollutant models to assess which PM characteristics were most consistently associated with the measured biomarkers.
Results and Conclusion
We found OC, nitrate and sulfate to be most consistently associated with different biomarkers of acute cardiovascular risk. Associations with PM mass concentrations and OP were less consistent, whereas other measured components of the air pollution mixture, including PNC, EC, trace metals and NO2, were not associated with the biomarkers after adjusting for other pollutants.
PMCID: PMC3596332  PMID: 23516583
20.  Environmental exposure assessment in European birth cohorts: results from the ENRIECO project 
Environmental Health  2013;12:8.
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.
PMCID: PMC3564791  PMID: 23343014
Environment; Europe; Exposure assessment; Birth cohort; Review
22.  BMI and Waist Circumference; Cross-Sectional and Prospective Associations with Blood Pressure and Cholesterol in 12-Year-Olds 
PLoS ONE  2012;7(12):e51801.
Childhood and adolescent overweight, defined by body mass index (BMI) are associated with an increased risk of cardiovascular disease in later life. Abdominal adiposity may be more important in associations with cardiovascular diseases but waist circumference (WC) has been rarely studied in children. We studied associations between BMI and WC and blood pressure (BP) and cholesterol in 12-year-old children and prospectively changes in BMI or WC status between age 8 and 12 years and BP and cholesterol at age 12.
Study Design
Weight, height, WC, BP and cholesterol concentrations were measured in 1432 children at age 12 years. Linear regression was used to study the associations between high BMI and large WC (>90th percentile) and BP and cholesterol.
Systolic BP was 4.9 mmHg higher (95% (CI 2.5, 7.2) in girls and 4.2 mmHg (95%CI 1.9, 6.5) in boys with a high BMI. Large WC was also associated with higher systolic BP in girls (3.7 mmHg (95%CI 1.3, 6.1)) and boys (3.5 mmHg (95%CI 1.2, 5.8)). Diastolic BP and cholesterol concentrations were significantly positively (HDL cholesterol negatively) associated with high BMI and large WC, too. Normal weight children with a history of overweight did not have higher blood pressure levels or adverse cholesterol concentrations than children that were normal weight at both ages.
A high BMI and large WC were associated with higher BP levels and adverse cholesterol concentrations. WC should be taken into account when examining cardiovascular risk factors in children.
PMCID: PMC3522600  PMID: 23251628
23.  Satellite-based Estimates of Ambient Air Pollution and Global Variations in Childhood Asthma Prevalence 
Environmental Health Perspectives  2012;120(9):1333-1339.
Background: The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear.
Objectives: Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2), and modelled estimates of ozone.
Methods: We assigned satellite-based estimates of PM2.5 and NO2 at a spatial resolution of 0.1° × 0.1° and modeled estimates of ozone at a resolution of 1° × 1° to 183 ISAAC centers. We used center-level prevalence of severe asthma as the outcome and multilevel models to adjust for gross national income (GNI) and center- and country-level sex, climate, and population density. We examined associations (adjusting for GNI) between air pollution and asthma prevalence over time in centers with data from ISAAC Phase One (mid-1900s) and Phase Three (2001–2003).
Results: For the 13- to 14-year age group (128 centers in 28 countries), the estimated average within-country change in center-level asthma prevalence per 100 children per 10% increase in center-level PM2.5 and NO2 was –0.043 [95% confidence interval (CI): –0.139, 0.053] and 0.017 (95% CI: –0.030, 0.064) respectively. For ozone the estimated change in prevalence per parts per billion by volume was –0.116 (95% CI: –0.234, 0.001). Equivalent results for the 6- to 7-year age group (83 centers in 20 countries), though slightly different, were not significantly positive. For the 13- to 14-year age group, change in center-level asthma prevalence over time per 100 children per 10% increase in PM2.5 from Phase One to Phase Three was –0.139 (95% CI: –0.347, 0.068). The corresponding association with ozone (per ppbV) was –0.171 (95% CI: –0.275, –0.067).
Conclusion: In contrast to reports from within-community studies of individuals exposed to traffic pollution, we did not find evidence of a positive association between ambient air pollution and asthma prevalence as measured at the community level.
PMCID: PMC3440118  PMID: 22548921
air pollution; asthma prevalence; children; epidemiology; global; nitrogen dioxide; ozone; particulate matter; satellite observations
24.  Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts 
PLoS ONE  2012;7(8):e43214.
To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years.
Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s.
Exposure definition
Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life.
Outcome definition
Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age.
Data synthesis
Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.
We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.
Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.
PMCID: PMC3430634  PMID: 22952649
25.  Respiratory Health Effects of Airborne Particulate Matter: The Role of Particle Size, Composition, and Oxidative Potential—The RAPTES Project 
Environmental Health Perspectives  2012;120(8):1183-1189.
Background: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations among, and differential measurement errors of, individual components contribute to this uncertainty.
Objectives: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers.
Methods: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittently, three to seven times at different locations during March–October 2009. We measured PM10, PM2.5, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function [FEV1 (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF25–75 (forced expiratory flow at 25–75% of vital capacity), and PEF (peak expiratory flow)] and fractional exhaled nitric oxide (FENO) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression.
Results: An interquartile increase in PNC (33,000 particles/cm3) was associated with an 11% [95% confidence interval (CI): 5, 17%] and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV1 with PNC, NO2 (nitrogen dioxide), and NOx (nitrogen oxides).
Conclusions: Changes in PNC, NO2, and NOx were associated with evidence of acute airway inflammation (i.e., FENO) and impaired lung function. PM mass concentration and PM10 oxidative potential were not predictive of the observed acute responses.
PMCID: PMC3440077  PMID: 22552951
air pollution; experimental exposure; FENO; FEV1; FVC; oxidative potential; PM; ultrafine particles

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