TY - JOUR AB - BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380. AU - Olsson, A.* AU - Bouaoun, L.* AU - Schüz, J.* AU - Vermeulen, R.* AU - Behrens, T.* AU - Ge, C.* AU - Kromhout, H.* AU - Siemiatycki, J.* AU - Gustavsson, P.* AU - Boffetta, P.* AU - Kendzia, B.* AU - Radoi, L.* AU - Barul, C.* AU - Karrasch, S. AU - Wichmann, H.-E. AU - Consonni, D.* AU - Landi, M.T.* AU - Caporaso, N.E.* AU - Merletti, F.* AU - Migliore, E.* AU - Richiardi, L.* AU - Jöckel, K.H.* AU - Ahrens, W.* AU - Pohlabeln, H.* AU - Fernández-Tardón, G.* AU - Zaridze, D.* AU - Field, J.K.* AU - Lissowska, J.* AU - Świątkowska, B.* AU - McLaughlin, J.R.* AU - Demers, P.A.* AU - Schejbalova, M.* AU - Foretova, L.* AU - Janout, V.* AU - Pándics, T.* AU - Fabianova, E.* AU - Mates, D.* AU - Forastiere, F.* AU - Straif, K.* AU - Brüning, T.* AU - Vlaanderen, J.* AU - Peters, S.* C1 - 69821 C2 - 55266 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Lung cancer risks associated with occupational exposure to pairs of five lung carcinogens: Results from a pooled analysis of case-control studies (SYNERGY). JO - Environ. Health Perspect. VL - 132 IS - 1 PB - Us Dept Health Human Sciences Public Health Science PY - 2024 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Although ambient temperature has been linked with injury incidence, there have been few nationwide studies to quantify the temperature-related risk and burden of cause-specific injury hospitalizations. Additionally, the impact of human-induced climate change to injury burden remains unknown. OBJECTIVES: Our objectives are to examine the associations between ambient temperature and injury hospitalizations from various causes and to quantify the contribution of human-induced warming to the heat-related burden. METHODS: We collected injury hospitalization data from a nationwide hospital-based registry in China during 2000-2019. Using a time-stratified case-crossover design, we investigated the associations between daily mean temperature (°C) and cause-specific injury hospitalizations. We also quantified the burden of heat-related injuries under the scenarios with and without anthropogenic forcing, using the Detection and Attribution Model Intercomparison Project to assess the contribution of human-induced warming. RESULTS: Our study included a total of 988,087 patients with hospitalization records for injuries. Overall, compared to the temperature at minimum risk of hospitalization (-12.1°C), the relative risk of hospitalization at extreme hot temperature (30.8°C, 97.5th percentile) was 1.18 [95% confidence interval (CI): 1.14, 1.22], with an approximately linear association between temperature and hospitalization. Vulnerability to heat-related injuries was more pronounced among males, young (<18 years of age) or middle-aged (45-64 years of age) individuals, and those living in the North. The heat-related attributable fraction increased from 23.2% in the 2000s to 23.6% in the 2010s, with a corresponding increase in the contribution of human-induced change over time. In the 2010s, the heat-related attributable fractions for specific causes of injury ranged from 12.4% to 54.4%, with human-induced change accounting for 6.7% to 10.6% of the burden. DISCUSSION: This nationwide study presents new evidence of significant associations between temperature and cause-specific injury hospitalizations in China and highlights the increasing contribution of human-induced warming to the injury burden. https://doi.org/10.1289/EHP14057. AU - Zhou, L.* AU - Liu, C.* AU - He, C. AU - Lei, J.* AU - Zhu, Y.* AU - Gao, Y.* AU - Xuan, J.* AU - Kan, H.* AU - Chen, R.* C1 - 70682 C2 - 55708 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Quantification of the heat-related risk and burden of hospitalizations for cause-specific injuries and contribution of human-induced climate change: A time-stratified case-crossover study in China. JO - Environ. Health Perspect. VL - 132 IS - 5 PB - Us Dept Health Human Sciences Public Health Science PY - 2024 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) 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 PM2.5 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 PM2.5 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-μg/m3 increase in PM2.5 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 PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141. AU - Chen, J.* AU - Braun, D.* AU - Christidis, T.* AU - Cork, M.J.* AU - Rodopoulou, S.* AU - Samoli, E.* AU - Stafoggia, M.* AU - Wolf, K. AU - Wu, X.* AU - Yuchi, W.* AU - Andersen, Z.J.* AU - Atkinson, R.* AU - Bauwelinck, M.* AU - de Hoogh, K.* AU - Janssen, N.A.H.* AU - Katsouyanni, K.* AU - Klompmaker, J.O.* AU - Kristoffersen, D.T.* AU - Lim, Y.H.* AU - Oftedal, B.* AU - Strak, M.* AU - Vienneau, D.* AU - Zhang, J.* AU - Burnett, R.T.* AU - Hoek, G.* AU - Dominici, F.* AU - Brauer, M.* AU - Brunekreef, B.* C1 - 68883 C2 - 53741 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Long-term exposure to low-level PM2.5 and mortality: Investigation of heterogeneity by harmonizing analyses in large cohort studies in Canada, United States, and Europe. JO - Environ. Health Perspect. VL - 131 IS - 12 PB - Us Dept Health Human Sciences Public Health Science PY - 2023 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Epidemiological evidence on the health risks of sulfur dioxide (SO2) is more limited compared with other pollutants, and doubts remain on several aspects, such as the form of the exposure-response relationship, the potential role of copollutants, as well as the actual risk at low concentrations and possible temporal variation in risks. OBJECTIVES: Our aim was to assess the short-term association between exposure to SO2 and daily mortality in a large multilocation data set, using advanced study designs and statistical techniques. METHODS: The analysis included 43,729,018 deaths that occurred in 399 cities within 23 countries between 1980 and 2018. A two-stage design was applied to assess the association between the daily concentration of SO2 and mortality counts, including first-stage time-series regressions and second-stage multilevel random-effect meta-analyses. Secondary analyses assessed the exposure-response shape and the lag structure using spline terms and distributed lag models, respectively, and temporal variations in risk using a longitudinal meta-regression. Bi-pollutant models were applied to examine confounding effects of particulate matter with an aerodynamic diameter of ≤10μm (PM10) and 2.5μm (PM2.5), ozone, nitrogen dioxide, and carbon monoxide. Associations were reported as relative risks (RRs) and fractions of excess deaths. RESULTS: The average daily concentration of SO2 across the 399 cities was 11.7 μg/m3, with 4.7% of days above the World Health Organization (WHO) guideline limit (40 μg/m3, 24-h average), although the exceedances occurred predominantly in specific locations. Exposure levels decreased considerably during the study period, from an average concentration of 19.0 μg/m3 in 1980-1989 to 6.3 μg/m3 in 2010-2018. For all locations combined, a 10-μg/m3 increase in daily SO2 was associated with an RR of mortality of 1.0045 [95% confidence interval (CI): 1.0019, 1.0070], with the risk being stable over time but with substantial between-country heterogeneity. Short-term exposure to SO2 was associated with an excess mortality fraction of 0.50% [95% empirical CI (eCI): 0.42%, 0.57%] in the 399 cities, although decreasing from 0.74% (0.61%, 0.85%) in 1980-1989 to 0.37% (0.27%, 0.47%) in 2010-2018. There was some evidence of nonlinearity, with a steep exposure-response relationship at low concentrations and the risk attenuating at higher levels. The relevant lag window was 0-3 d. Significant positive associations remained after controlling for other pollutants. DISCUSSION: The analysis revealed independent mortality risks associated with short-term exposure to SO2, with no evidence of a threshold. Levels below the current WHO guidelines for 24-h averages were still associated with substantial excess mortality, indicating the potential benefits of stricter air quality standards. https://doi.org/10.1289/EHP11112. AU - O'Brien, E.* AU - Masselot, P.* AU - Sera, F.* AU - Royé, D.* AU - Breitner-Busch, S. AU - Ng, C.F.S.* AU - de Sousa Zanotti Stagliorio Coélho, M.* AU - Madureira, J.* AU - Tobias, A.* AU - Vicedo-Cabrera, A.M.* AU - Bell, M.L.* AU - Lavigne, E.* AU - Kan, H.* AU - Gasparrini, A.* C1 - 67753 C2 - 54063 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Short-term association between sulfur dioxide and mortality: A multicountry analysis in 399 cities. JO - Environ. Health Perspect. VL - 131 IS - 3 PB - Us Dept Health Human Sciences Public Health Science PY - 2023 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Greenness, referring to a measurement of the density of vegetated land (e.g., gardens, parks, grasslands), has been linked with many human health outcomes. However, the evidence on greenness exposure and human microbiota remains limited, inconclusive, drawn from specific regions, and based on only modest sample size. OBJECTIVES: We aimed to study the association between greenness exposure and human microbial diversity and composition in a large sample across 34 countries and regions. METHODS: We explored associations between residential greenness and human microbial alpha-diversity, composition, and genus abundance using data from 34 countries. Greenness exposure was assessed using the normalized difference vegetation index and the enhanced vegetation index mean values in the month before sampling. We used linear regression models to estimate the association between greenness and microbial alpha-diversity and tested the effect modification of age, sex, climate zone, and pet ownership of participants. Differences in microbial composition were tested by permutational multivariate analysis of variance based on Bray-Curtis distance and differential taxa were detected using the DESeq2 R package between two greenness exposure groups split by median values of greenness. RESULTS: We found that higher greenness was significantly associated with greater richness levels in the palm and gut microbiota but decreased evenness in the gut microbiota. Pet ownership and climate zone modified some associations between greenness and alpha-diversity. Palm and gut microbial composition at the genus level also varied by greenness. Higher abundances of the genera Lactobacillus and Bifidobacterium, and lower abundances of the genera Anaerotruncus and Streptococcus, were observed in people with higher greenness levels. DISCUSSION: These findings suggest that residential greenness was associated with microbial richness and composition in the human skin and gut samples, collected across different geographic contexts. Future studies may validate the observed associations and determine whether they correspond to improvements in human health. https://doi.org/10.1289/EHP12186. AU - Zhang, Y.D.* AU - Fan, S.J.* AU - Zhang, Z.* AU - Li, J.X.* AU - Liu, X.X.* AU - Hu, L.X.* AU - Knibbs, L.D.* AU - Dadvand, P.* AU - Jalaludin, B.* AU - Browning, M.H.E.M.* AU - Zhao, T. AU - Heinrich, J.* AU - He, Z.* AU - Chen, C.Z.* AU - Zhou, Y.* AU - Dong, G.H.* AU - Yang, B.Y.* C1 - 67995 C2 - 54473 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Association between residential greenness and human microbiota: Evidence from multiple countries. JO - Environ. Health Perspect. VL - 131 IS - 8 PB - Us Dept Health Human Sciences Public Health Science PY - 2023 SN - 0091-6765 ER - TY - JOUR AU - Forastiere, F.* AU - Peters, A. C1 - 64637 C2 - 51970 TI - Response to "Comment on 'Invited perspective: The NO2 and mortality dilemma solved? Almost there!'". JO - Environ. Health Perspect. VL - 130 IS - 3 PY - 2022 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic (β-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). METHODS: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and β-pinene (SOAβPIN-SP) or naphthalene (SOANAP-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. RESULTS: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOANAP-SP compared with SOAβPIN-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOANAP-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. DISCUSSION: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with β-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413. AU - Offer, S. AU - Hartner, E. AU - Di Bucchianico, S. AU - Bisig, B. AU - Bauer, S. AU - Pantzke, J. AU - Zimmermann, E. AU - Cao, X. AU - Binder, S. AU - Kuhn, E. AU - Huber, A. AU - Jeong, S. AU - Käfer, U. AU - Martens, P.* AU - Mesceriakovas, A.* AU - Bendl, J. AU - Brejcha, R. AU - Buchholz, A.* AU - Gat, D.* AU - Hohaus, T.* AU - Rastak, N. AU - Jakobi, G. AU - Kalberer, M.* AU - Kanashova, T.* AU - Hu, Y. AU - Ogris, C. AU - Marsico, A. AU - Theis, F.J. AU - Pardo, M.* AU - Gröger, T.M. AU - Oeder, S. AU - Orasche, J. AU - Paul, A.* AU - Ziehm, T.* AU - Zhang, Z.H.* AU - Adam, T. AU - Sippula, O.* AU - Sklorz, M. AU - Schnelle-Kreis, J. AU - Czech, H. AU - Kiendler-Scharr, A.* AU - Rudich, Y.* AU - Zimmermann, R. C1 - 64249 C2 - 51883 TI - Effect of atmospheric aging on soot particle toxicity in lung cell models at the air-liquid interface: Differential toxicological impacts of biogenic and anthropogenic Secondary Organic Aerosols (SOAs). JO - Environ. Health Perspect. VL - 130 IS - 2 PY - 2022 SN - 0091-6765 ER - TY - JOUR AU - Vinceti, M.* AU - Balboni, E.* AU - Filippini, T.* AU - Wise, L.A.* AU - Nocetti, L.* AU - Eichmüller, M. AU - Zamboni, G.* AU - Chiari, A.* AU - Michalke, B. C1 - 66610 C2 - 53243 TI - Selenium species in cerebrospinal fluid and hippocampal volume among individuals with mild cognitive impairment. JO - Environ. Health Perspect. VL - 130 IS - 11 PY - 2022 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Inconsistent associations between long-term exposure to particles with an aerodynamic diameter ≤ 2.5   μ m [fine particulate matter ( PM 2.5 )] components and mortality have been reported, partly related to challenges in exposure assessment. OBJECTIVES: We investigated the associations between long-term exposure to PM 2.5 elemental components and mortality in a large pooled European cohort; to compare health effects of PM 2.5 components estimated with two exposure modeling approaches, namely, supervised linear regression (SLR) and random forest (RF) algorithms. METHODS: We pooled data from eight European cohorts with 323,782 participants, average age 49 y at baseline (1985-2005). Residential exposure to 2010 annual average concentration of eight PM 2.5 components [copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)] was estimated with Europe-wide SLR and RF models at a 100 × 100   m scale. We applied Cox proportional hazards models to investigate the associations between components and natural and cause-specific mortality. In addition, two-pollutant analyses were conducted by adjusting each component for PM 2.5 mass and nitrogen dioxide ( NO 2 ) separately. RESULTS: We observed 46,640 natural-cause deaths with 6,317,235 person-years and an average follow-up of 19.5 y. All SLR-modeled components were statistically significantly associated with natural-cause mortality in single-pollutant models with hazard ratios (HRs) from 1.05 to 1.27. Similar HRs were observed for RF-modeled Cu, Fe, K, S, V, and Zn with wider confidence intervals (CIs). HRs for SLR-modeled Ni, S, Si, V, and Zn remained above unity and (almost) significant after adjustment for both PM 2.5 and NO 2 . HRs only remained (almost) significant for RF-modeled K and V in two-pollutant models. The HRs for V were 1.03 (95% CI: 1.02, 1.05) and 1.06 (95% CI: 1.02, 1.10) for SLR- and RF-modeled exposures, respectively, per 2   ng / m 3 , adjusting for PM 2.5 mass. Associations with cause-specific mortality were less consistent in two-pollutant models. CONCLUSION: Long-term exposure to V in PM 2.5 was most consistently associated with increased mortality. Associations for the other components were weaker for exposure modeled with RF than SLR in two-pollutant models. https://doi.org/10.1289/EHP8368. AU - Chen, J.* AU - Rodopoulou, S.* AU - de Hoogh, K.* AU - Strak, M.* AU - Andersen, Z.J.* AU - Atkinson, R.* AU - Bauwelinck, M.* AU - Bellander, T.* AU - Brandt, J.* AU - Cesaroni, G.* AU - Concin, H.* AU - Fecht, D.* AU - Forastiere, F.* AU - Gulliver, J.* AU - Hertel, O.* AU - Hoffmann, B.* AU - Hvidtfeldt, U.A.* AU - Janssen, N.A.H.* AU - Jöckel, K.H.* AU - Jørgensen, J.* AU - Katsouyanni, K.* AU - Ketzel, M.* AU - Klompmaker, J.O.* AU - Lager, A.* AU - Leander, K.* AU - Liu, S.* AU - Ljungman, P.* AU - MacDonald, C.J.* AU - Magnusson, P.K.E.* AU - Mehta, A.* AU - Nagel, G.* AU - Oftedal, B.* AU - Pershagen, G.* AU - Peters, A. AU - Raaschou-Nielsen, O.* AU - Renzi, M.* AU - Rizzuto, D.* AU - Samoli, E.* AU - van der Schouw, Y.T.* AU - Schramm, S.* AU - Schwarze, P.* AU - Sigsgaard, T.* AU - Sørensen, M.* AU - Stafoggia, M.* AU - Tjønneland, A.* AU - Vienneau, D.* AU - Weinmayr, G.* AU - Wolf, K. AU - Brunekreef, B.* AU - Hoek, G.* C1 - 61781 C2 - 50174 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Long-term exposure to fine particle elemental components and natural and cause-specific mortality – a pooled analysis of eight European cohorts within the ELAPSE project. JO - Environ. Health Perspect. VL - 129 IS - 4 PB - Us Dept Health Human Sciences Public Health Science PY - 2021 SN - 0091-6765 ER - TY - JOUR AU - Forastiere, F.* AU - Peters, A. C1 - 63864 C2 - 51819 SP - 121304 TI - Invited perspective: The NO2 and mortality dilemma solved? Almost there! JO - Environ. Health Perspect. VL - 129 IS - 12 PY - 2021 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 ( LD 50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [ LD 50 ( LD 50 ≤ 50 mg / kg )], and nontoxic chemicals ( L D 50 > 2,000 mg / kg ). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495. AU - Mansouri, K.* AU - Karmaus, A.L.* AU - Fitzpatrick, J.* AU - Patlewicz, G.* AU - Pradeep, P.* AU - Alberga, D.* AU - Alepee, N.* AU - Allen, T.E.H.* AU - Allen, D.* AU - Alves, V.M.* AU - Andrade, C.H.* AU - Auernhammer, T.R.* AU - Ballabio, D.* AU - Bell, S.* AU - Benfenati, E.* AU - Bhattacharya, S.* AU - Bastos, J.V.* AU - Boyd, S.* AU - Brown, J.B.* AU - Capuzzi, S.J.* AU - Chushak, Y.* AU - Ciallella, H.* AU - Clark, A.M.* AU - Consonni, V.* AU - Daga, P.R.* AU - Ekins, S.* AU - Farag, S.* AU - Fedorov, M.* AU - Fourches, D.* AU - Gadaleta, D.* AU - Gao, F.* AU - Gearhart, J.M.* AU - Goh, G.* AU - Goodman, J.M.* AU - Grisoni, F.* AU - Grulke, C.M.* AU - Hartung, T.* AU - Hirn, M.* AU - Karpov, P. AU - Korotcov, A.* AU - Lavado, G.J.* AU - Lawless, M.* AU - Li, X.* AU - Luechtefeld, T.* AU - Lunghini, F.* AU - Mangiatordi, G.F.* AU - Marcou, G.* AU - Marsh, D.* AU - Martin, T.* AU - Mauri, A.* AU - Muratov, E.N.* AU - Myatt, G.J.* AU - Nguyen, D.T.* AU - Nicolotti, O.* AU - Note, R.* AU - Pande, P.* AU - Parks, A.K.* AU - Peryea, T.* AU - Polash, A.H.* AU - Rallo, R.* AU - Roncaglioni, A.* AU - Rowlands, C.J.* AU - Ruiz, P.* AU - Russo, D.P.* AU - Sayed, A.* AU - Sayre, R.* AU - Sheils, T.* AU - Siegel, C.* AU - Silva, A.C.* AU - Simeonov, A.* AU - Sosnin, S.* AU - Southall, N.* AU - Strickland, J.* AU - Tang, Y.* AU - Teppen, B.* AU - Tetko, I.V. AU - Thomas, D.* AU - Tkachenko, V.* AU - Todeschini, R.* AU - Toma, C.* AU - Tripodi, I.* AU - Trisciuzzi, D.* AU - Tropsha, A.* AU - Varnek, A.* AU - Vukovic, K.* AU - Wang, Z.* AU - Wang, L.* AU - Waters, K.M.* AU - Wedlake, A.J.* AU - Wijeyesakere, S.J.* AU - Wilson, D.* AU - Xiao, Z.* AU - Yang, H.* AU - Zahoranszky-Kohalmi, G.* AU - Zakharov, A.V.* AU - Zhang, F.F.* AU - Zhang, Z.* AU - Zhao, T.* AU - Zhu, H.* AU - Zorn, K.M.* AU - Casey, W.* AU - Kleinstreuer, N.C.* C1 - 61961 C2 - 50584 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - CATMoS: Collaborative acute toxicity modeling suite. JO - Environ. Health Perspect. VL - 129 IS - 4 PB - Us Dept Health Human Sciences Public Health Science PY - 2021 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Epidemiological evidence on the health effects of ultrafine particles (UFP) remains insufficient to infer a causal relationship that is largely due to different size ranges and exposure metrics examined across studies. Moreover, evidence regarding the association between UFP and cardiovascular disease at a sub-daily timescale is lacking.OBJECTIVE: We investigated the relationship between different particle metrics, including particle number (PNC), length (PLC), and surface area (PSC) concentrations, and myocardial infarction (MI) at an hourly timescale.METHODS: We collected hourly air pollution and meteorological data from fixed urban background monitoring sites and hourly nonfatal MI cases from a MI registry in Augsburg, Germany, during 2005-2015. We conducted a time-stratified case-crossover analysis with conditional logistic regression to estimate the association between hourly particle metrics and MI cases, adjusted for air temperature and relative humidity. We also examined the independent effects of a certain particle metric in two-pollutant models by adjusting for copollutants, including particulate matter (PM) with an aerodynamic diameter of >= 10 mu m or 2.5 mu m (PM10 and PM2.5, respectively), nitrogen dioxide, ozone, and black carbon.RESULTS: Overall, a total of 5,898 cases of nonfatal MI cases were recorded. Exploratory analyses showed similar associations across particle metrics in the first 6-12 h. For example, interquartile range increases in PNC within the size range of 10-100 nm, PLC, and PSC were associated with an increase of MI 6 h later by 3.27% [95% confidence interval (CI): 0.27, 6.37], 5.71% (95% CI: 1.79, 9.77), and 5.84% (95% CI: 1.04, 10.87), respectively. Positive, albeit imprecise, associations were observed for PNC within the size range of 10-30 nm and 100-500 nm. Effect estimates for PLC and PSC remained similar after adjustment for PM and gaseous pollutants.CONCLUSIONS: Transient exposure to particle number, length, and surface area concentrations or other potentially related exposures may trigger the onset of nonfatal myocardial infraction. AU - Chen, K. AU - Schneider, A.E. AU - Cyrys, J. AU - Wolf, K. AU - Meisinger, C. AU - Heier, M. AU - von Scheidt, W.* AU - Kuch, B.* AU - Pitz, M.* AU - Peters, A. AU - Breitner-Busch, S. C1 - 57836 C2 - 48098 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Hourly exposure to ultrafine particle metrics and the onset of myocardial infarction in Augsburg, Germany. JO - Environ. Health Perspect. VL - 128 IS - 1 PB - Us Dept Health Human Sciences Public Health Science PY - 2020 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Air pollution contributes to type 2 diabetes and cardiovascular diseases, but its relevance for other complications of diabetes, in partic-ular distal sensorimotor polyneuropathy (DSPN), is unclear. Recent studies have indicated that DSPN is also increasingly prevalent in obesity. OBJECTIVES: We aimed to assess associations of air pollutants with prevalent and incident DSPN in a population-based study of older individuals with high rates of type 2 diabetes and obesity. METHODS: Cross-sectional analyses on prevalent DSPN were based on 1,075 individuals 62–81 years of age from the German Cooperative Health Research in the Region of Augsburg (KORA) F4 survey (2006–2008). Analyses on incident DSPN included 424 individuals without DSPN at base-line (KORA F4), of whom 188 had developed DSPN by the KORA FF4 survey (2013–2014). Associations of annual average air pollutant concentrations at participants’ residences with prevalent and incident DSPN were estimated using Poisson regression models with a robust error variance adjusting for multiple confounders. RESULTS: Higher particle number concentrations (PNCs) were associated with higher prevalence [risk ratio (RR) per interquartile range (IQR) increase = 1:10 (95% CI: 1.01, 1.20)] and incidence [1.11 (95% CI: 0.99, 1.24)] of DSPN. In subgroup analyses, particulate (PNC, PM10,PMcoarse, PM2:5, and PM2:5abs ) and gaseous (NOx,NO2 ) pollutants were positively associated with prevalent DSPN in obese participants, whereas corresponding estimates for nonobese participants were close to the null [e.g., for an IQR increase in PNC, RR = 1:17 (95% CI: 1.05, 1.31) vs. 1.06 (95% CI: 0.95, 1.19); pinteraction =0:22]. With the exception of PM2:5abs, corresponding associations with incident DSPN were positive in obese participants but null or inverse for nonobese participants, with pinteraction ≤ 0:13 [e.g., for PNC, RR = 1:28 (95% CI: 1.08, 1.51) vs. 1.03 (95% CI: 0.90, 1.18); pinteraction =0:03]. DISCUSSION: Both particulate and gaseous air pollutants were positively associated with prevalent and incident DSPN in obese individuals. Obesity and air pollution may have synergistic effects on the development of DSPN. https://doi.org/10.1289/EHP7311. AU - Herder, C.* AU - Schneider, A.E. AU - Zhang, S. AU - Wolf, K. AU - Maalmi, H.* AU - Huth, C. AU - Pickford, R. AU - Laxy, M. AU - Bönhof, G.J.* AU - Koenig, W.* AU - Rathmann, W.* AU - Roden, M.* AU - Peters, A. AU - Thorand, B. AU - Ziegler, D.* C1 - 60911 C2 - 49622 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - Association of long-term air pollution with prevalence and incidence of distal sensorimotor polyneuropathy: Kora F4/FF4 study. JO - Environ. Health Perspect. VL - 128 IS - 12 PB - Us Dept Health Human Sciences Public Health Science PY - 2020 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment. AU - Mansouri, K.* AU - Kleinstreuer, N.* AU - Abdelaziz, A.M.* AU - Alberga, D.* AU - Alves, V.M.* AU - Andersson, P.L.* AU - Andrade, C.H.* AU - Bai, F.* AU - Balabiu, I.* AU - Ballabio, D.* AU - Benfenati, E.* AU - Bhhatarai, B.* AU - Boyer, S.* AU - Chen, J.* AU - Consonni, V.* AU - Farag, S.* AU - Fourches, D.* AU - Garcia-Sosa, A.T.* AU - Grulke, C.M.* AU - Hong, H.* AU - Horvath, D.* AU - Hu, X.* AU - Huang, R.* AU - Jeliazkova, N.* AU - Li, J.* AU - Li, X.* AU - Liu, H.* AU - Manganelli, S.* AU - Mangiatordi, G.F.* AU - Maran, U.* AU - Marcou, G.* AU - Martin, T.* AU - Muratov, E.* AU - Nguyen, D.T.* AU - Nicolotti, O.* AU - Nikolov, N.G.* AU - Norinder, U.* AU - Papa, E.* AU - Petitjean, M.* AU - Piir, G.* AU - Pogodin, P.* AU - Poroikov, V.* AU - Qiao, X.* AU - Richard, A.M.* AU - Roncaglioni, A.* AU - Ruiz, P.* AU - Rupakheti, C.* AU - Sakkiah, S.* AU - Sangion, A.* AU - Schramm, K.-W.* AU - Selvaraj, C.* AU - Shah, I.* AU - Sild, S.* AU - Sun, L.* AU - Taboureau, O.* AU - Tang, Y.* AU - Tetko, I.V. AU - Todeschini, R.* AU - Tong, W.* AU - Trisciuzzi, D.* AU - Tropsha, A.* AU - van den Driessche, G.* AU - Varnek, A.* AU - Wang, Z.* AU - Wedebye, E.B.* AU - Williams, A.J.* AU - Xie, H.* AU - Zakharo, V.* AU - Zheng, Z.* AU - Judson, R.S.* C1 - 58325 C2 - 48183 CY - Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, Nc 27709-2233 Usa TI - CoMPARA: Collaborative modeling project for androgen receptor activity. JO - Environ. Health Perspect. VL - 128 IS - 2 PB - Us Dept Health Human Sciences Public Health Science PY - 2020 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association. OBJECTIVES: Our main aim was to study the association between long-term air pollution exposure and DNA methylation. METHODS: We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide (NO 2 ) and particulate matter (PM 2.5 , fine particulate matter with aerodynamic diameter ≤2.5 lm; PM 10 , particulate matter with aerodynamic diameter ≤10 lm) and PM 2.5absorbance , indicator of elemental carbon content (estimated with land-use-regression models) with DNA methylation in whole blood (Illumina® HumanMethylation450K BeadChip). Replication of the top hits was attempted in two independent samples from the population-based Cooperative Health Research in the Region of Augsburg studies (KORA). RESULTS: Depending on the p-value threshold used, we found significant associations between NO 2 exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold p < 1.19 × 10 −7 ) or for 4,980 CpG sites (False Discovery Rate < 0.05). The top associated CpG site was annotated to the PSMB9 gene (i.e., cg04908668). None of the seven Bonferroni significant CpG-sites were significantly replicated in the two KORA-cohorts. No associations were found for PM exposure. CONCLUSIONS: Long-term NO 2 exposure was genome-wide significantly associated with DNA methylation in the identification cohort but not in the replication cohort. Future studies are needed to further elucidate the potential mechanisms underlying NO 2 -exposure–related respiratory disease. AU - de F C Lichtenfels, A.J.* AU - van der Plaat, D.A.* AU - de Jong, K.* AU - van Diemen, C.C.* AU - Postma, D.S.* AU - Nedeljkovic, I.* AU - van Duijn, C.M.* AU - Amin, N.* AU - la Bastide-van Gemert, S.* AU - de Vries, M.* AU - Ward-Caviness, C.K. AU - Wolf, K. AU - Waldenberger, M. AU - Peters, A. AU - Stolk, R.P.* AU - Brunekreef, B.* AU - Boezen, H.M.* AU - Vonk, J.M.* C1 - 52911 C2 - 44301 CY - Res Triangle Pk TI - Long-term air pollution exposure, genome-wide DNA methylation and lung function in the lifelines cohort study. JO - Environ. Health Perspect. VL - 126 IS - 2 PB - Us Dept Health Human Sciences Public Health Science PY - 2018 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: The role of tobacco smoke exposure in the development and persistence of asthma and rhinoconjunctivitis through childhood into adolescence is unclear. OBJECTIVES: We assessed the associations of parental smoking from fetal life through adolescence with asthma and rhinoconjunctivitis during childhood and adolescence. METHODS: We analyzed data for 10,860 participants of five European birth cohort studies from the Mechanisms of the Development of Allergy (MeDALL) consortium. Parental smoking habits and health outcomes (early transient, persistent, and adolescent-onset asthma and rhinoconjunctivitis) were based on questionnaires covering the period from pregnancy to 14-16 y of age. Data were combined and analyzed using a one-stage and two-stage individual participant data meta-analysis. RESULTS: Overall, any maternal smoking during pregnancy tended to be associated with an increased odds of prevalent asthma [adjusted odds ratio (aOR)=1.19 (95% CI: 0.98, 1.43)], but not prevalent rhinoconjunctivitis [aOR=1.05 (95% CI: 0.90, 1.22)], during childhood and adolescence. In analyses with phenotypes related to age of onset and persistence of disease, any maternal smoking during pregnancy was associated with early transient asthma [aOR=1.79 (95% CI: 1.14, 2.83)]. Maternal smoking of ≥10 cigarettes/day during pregnancy was associated with persistent asthma [aOR=1.66 (95% CI: 1.29, 2.15)] and persistent rhinoconjunctivitis [aOR=1.55 (95% CI, 1.09, 2.20)]. Tobacco smoke exposure during fetal life, infancy, childhood, and adolescence was not associated with adolescent-onset asthma or rhinoconjunctivitis. CONCLUSIONS: Findings from this combined analysis of five European birth cohorts strengthen evidence linking early exposure to tobacco smoke with asthma during childhood and adolescence. Children with high early-life exposure were more likely than unexposed children to have early transient and persistent asthma and persistent rhinoconjunctivitis. AU - Thacher, J.D.* AU - Gehring, U.* AU - Gruzieva, O.* AU - Standl, M. AU - Pershagen, G.* AU - Bauer, C.P.* AU - Berdel, D.* AU - Keller, T.* AU - Koletzko, S.* AU - Koppelman, G.H.* AU - Kull, I.* AU - Lau, S.* AU - Lehmann, I.* AU - Maier, D.* AU - Schikowski, T.* AU - Wahn, U.* AU - Wijga, A.H.* AU - Heinrich, J. AU - Bousquet, J.* AU - Antò, J.M.* AU - von Berg, A.* AU - Melén, E.* AU - Smit, H.A.* AU - Keil, T.* AU - Bergström, A.* C1 - 53414 C2 - 44561 TI - Maternal smoking during pregnancy and early childhood and development of asthma and rhinoconjunctivitis - a MeDALL project. JO - Environ. Health Perspect. VL - 126 IS - 4 PY - 2018 SN - 0091-6765 ER - TY - JOUR AB - Background: A rich literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), with strong support for an important role for ultrafine (nano-sized) particles. At present, relatively little human health or epidemiology data exists for engineered nanomaterials (NM) despite clear parallels in their physicochemical properties and biological actions in in vitro models. Objectives: NMs are available in a range of physicochemical characteristics which allow a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NM, while the study of NM provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. Methods: A workshop of experts systematically analysed the information available and identified 19 key Lessons that can facilitate knowledge exchange between these discipline areas. Discussion: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment, to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas where additional research prioritisation would facilitate both research fields simultaneously. Conclusion: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. AU - Stone, V.* AU - Miller, M.* AU - Clift, M.J.D.* AU - Elder, A.* AU - Mills, N.L.* AU - Møller, P.* AU - Schins, R.P.F.* AU - Vogel, U.* AU - Kreyling, W.G. AU - Jensen, K.A.* AU - Kuhlbusch, T.A.J.* AU - Schwarze, P.E.* AU - Hoet, P.* AU - Pietroiusti, A.* AU - de Vizcaya-Ruiz, A.* AU - Baeza-Squiban, A.* AU - Lang Tran, C.* AU - Cassee, F.R.* C1 - 50007 C2 - 41963 CY - Res Triangle Pk TI - Nanomaterials vs ambient ultrafine particles: An opportunity to exchange toxicology knowledge. JO - Environ. Health Perspect. VL - 125 IS - 10 PB - Us Dept Health Human Sciences Public Health Science PY - 2017 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. https://doi.org/10.1289/EHP424. AU - Stone, V.* AU - Miller, M.R.* AU - Clift, M.J.D.* AU - Elder, A.* AU - Mills, N.L.* AU - Møller, P.* AU - Schins, R.P.F.* AU - Vogel, U.* AU - Kreyling, W.G. AU - Alstrup Jensen, K.* AU - Kuhlbusch, T.A.J.* AU - Schwarze, P.E.* AU - Hoet, P.* AU - Pietroiusti, A.* AU - de Vizcaya-Ruiz, A.* AU - Baeza-Squiban, A.* AU - Teixeira, J.P.* AU - Tran, C.L.* AU - Cassee, F.R.* C1 - 55468 C2 - 46174 TI - Nanomaterials versus ambient ultrafine particles: An opportunity to exchange toxicology knowledge. JO - Environ. Health Perspect. VL - 125 IS - 10 PY - 2017 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Previous studies have observed associations between air pollution and heart disease. Susceptibility to air pollution effects has been examined mostly with a test of effect modification, but little evidence is available whether air pollution distorts cardiovascular risk factor distribution. OBJECTIVES: This paper aims to examine distributional and heterogeneous effects of air pollution on known cardiovascular biomarkers. METHODS: A total of 1,112 men from the Normative Aging Study and residents of the Boston Greater area with mean age of 69 years at baseline were included in this study during the period 1995-2013. We used quantile regression and random slope models to investigate distributional effects and heterogeneity in the traffic-related responses on blood pressure, heart rate variability, repolarization, lipids, and inflammation. We considered 28-day averaged exposure to particle number, PM2.5 black carbon, and PM2.5 mass concentrations (measured at a single monitor near the site of the study visits). RESULTS: We observed some evidence suggesting distributional effects of traffic-related pollutants on systolic blood pressure, heart rate variability, corrected QT interval, low density lipoprotein (LDL) cholesterol, triglyceride, and intercellular adhesion molecule-1 (ICAM-1). For example, among participants with LDL cholesterol below 80mg/dL, an interquartile range increase in PM2.5 black carbon exposure was associated with a 7mg/dL (95%CI: 5; 10) increase in LDL cholesterol while among subjects with LDL cholesterol levels close to 160mg/dL, the same exposure was related to a 16mg/dL (95%CI: 13; 20) increase in LDL cholesterol. We observed similar heterogeneous associations across low versus high percentiles of the LDL distribution for PM2.5 mass and particle number. CONCLUSIONS: These results suggest that air pollution distorts the distribution of cardiovascular risk factors, and that, for several outcomes, effects may be greatest among individuals who are already at high risk. AU - Bind, M.A.* AU - Peters, A. AU - Koutrakis, P.* AU - Coull, B.* AU - Vokonas, P.* AU - Schwartz, J.* C1 - 48089 C2 - 39897 CY - Res Triangle Pk SP - 1189-1198 TI - Quantile regression analysis of the distributional effects of air pollution on blood pressure, heart rate variability, blood lipids, and biomarkers of inflammation in elderly American men: The normative aging study. JO - Environ. Health Perspect. VL - 124 IS - 8 PB - Us Dept Health Human Sciences Public Health Science PY - 2016 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Urban populations are highly vulnerable to the adverse effects of heat, with heat-related mortality showing intra-urban variations that are likely due to differences in urban characteristics and socioeconomic status. OBJECTIVES: To investigate the influence of urban green and urban blue, i.e., urban vegetation and water bodies, on heat-related excess mortality in the elderly above 65 years in Lisbon, Portugal between 1998 and 2008. METHODS: We used remotely sensed data and geographic information to determine the amount of urban vegetation and the distance to water bodies (the Atlantic Ocean and the Tagus estuary). Poisson Generalized Additive Models were fitted, allowing for the interaction between equivalent temperature [Universal Thermal Climate Index (UTCI)] and quartiles of urban greenness [classified using the Normalized Differenced Vegetation Index (NDVI)] and proximity to water (≤ 4 km versus > 4 km), while adjusting for potential confounders. RESULTS: The association between mortality and a 1°C in UTCI above the 99th percentile (24.8°C) was stronger for areas in the lowest NDVI quartile (14.7% higher; 95% CI: 1.9, 17.5%) than areas in the highest quartile (3.0%; 95% CI: 2.0, 4.0%). In areas > 4km from water, a 1°C in UTCI above the 99th percentile was associated with a 7.1% increase in mortality (95% CI: 6.2, 8.1%), whereas in areas ≤ 4 km from water, the estimated increase in mortality was only 2.1% (95% CI: 1.2, 3.0%). CONCLUSIONS: Urban green and blue appeared to have a mitigating effect on heat-related mortality in the elderly population in Lisbon. Increasing the amount of vegetation may be a good strategy to counteract the adverse effects of heat in urban areas. Our findings also suggest potential benefits of urban blue that may be present several kilometers from a body of water. AU - Burkart, K.* AU - Meier, F.* AU - Schneider, A.E. AU - Breitner-Busch, S. AU - Canario, P.* AU - Alcoforado, M.J.* AU - Scherer, D.* AU - Endlicher, W.* C1 - 47463 C2 - 39348 CY - Res Triangle Pk SP - 927-934 TI - Modification of heat-related mortality in an elderly urban population by vegetation (urban green) and proximity to water (urban blue): Evidence from Lisbon, Portugal. JO - Environ. Health Perspect. VL - 124 IS - 7 PB - Us Dept Health Human Sciences Public Health Science PY - 2016 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the EPA Endocrine Disruptor Screening Program (EDSP). OBJECTIVES: Here, we describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. METHODS: CERAPP combined multiple models developed in collaboration among 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1677 chemical structures provided by US EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. RESULTS: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing. CONCLUSION: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other endpoints. AU - Mansouri, K.* AU - Abdelaziz, A. AU - Rybacka, A.* AU - Roncaglioni, A.* AU - Tropsha, A.* AU - Varnek, A.* AU - Zakharov, A.* AU - Worth, A.* AU - Richard, A.M.* AU - Grulke, C.M.* AU - Trisciuzzi, D.* AU - Fourches, D.* AU - Horvath, D.* AU - Benfenati, E.* AU - Muratov, E.* AU - Wedebye, E.B.* AU - Grisoni, F.* AU - Mangiatordi, G.F.* AU - Incisivo, G.M.* AU - Hong, H.* AU - Ng, H.W.* AU - Tetko, I.V. AU - Balabin, I.* AU - Kancherla, J.* AU - Shen, J.* AU - Burton, J.* AU - Nicklaus, M.* AU - Cassotti, M.* AU - Nikolov, N.G.* AU - Nicolotti, O.* AU - Andersson, P.L.* AU - Zang, Q.* AU - Politi, R.* AU - Beger, R.D.* AU - Todeschini, R.* AU - Huang, R.J.* AU - Farag, S.* AU - Rosenberg, S.A.* AU - Slavov, S.* AU - Hu, X.* AU - Judson, R.S.* C1 - 47973 C2 - 39808 CY - Res Triangle Pk SP - 1023-1033 TI - CERAPP: Collaborative estrogen receptor activity prediction project. JO - Environ. Health Perspect. VL - 124 IS - 7 PB - Us Dept Health Human Sciences Public Health Science PY - 2016 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer, respiratory, and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites. OBJECTIVES: To study the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data, and identify potential biological pathways for additional investigation. METHODS: We collected whole blood samples from three independent studies, KORA F3 (2004-05) and F4 (2006-08) from Germany and Normative Aging Study (1999-2007) from the US, and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results. RESULTS: Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (one for 2-day average, one for 7-day and ten for 28-day) at a genome-wide Bonferroni significance level (p<=7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I-squared statistics for homogeneity assessment across the studies, four of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p>0.05 and I(2)<0.5: the site from the 7-day average results and 3 for the 28-day average. Applying False Discovery Rate, p-value<0.05 was observed in 8 and 1819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively. CONCLUSION: The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient particulate matter exposure to adverse health effect through variations in DNA methylation. AU - Panni, T. AU - Mehta, A.J.* AU - Schwartz, J.D.* AU - Baccarelli, A.A.* AU - Just, A.C.* AU - Wolf, K. AU - Wahl, S. AU - Cyrys, J. AU - Kunze, S. AU - Strauch, K. AU - Waldenberger, M. AU - Peters, A. C1 - 47625 C2 - 40680 CY - Res Triangle Pk SP - 983-990 TI - A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. JO - Environ. Health Perspect. VL - 124 IS - 7 PB - Us Dept Health Human Sciences Public Health Science PY - 2016 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Epidemiological studies have identified associations between air pollution and green space access with type 2 diabetes in adults. However it remains unclear to what extent associations with greenness are attributable to air pollution exposure. OBJECTIVES: We aimed to investigate associations between long-term exposure to air pollution and satellite-derived greenness with insulin resistance in adolescents. METHODS: 837 participants of two German birth cohorts (LISAplus and GINIplus) were included in the analysis. Generalized additive models were used to determine the association of individual satellite-derived greenness defined by the Normalized Difference Vegetation Index (NDVI), long-term air pollution exposure estimated by land-use regression (LUR) models with insulin resistance (HOMA-IR) in 15 year-old adolescents. Models were adjusted for study area, cohort, socioeconomic, and individual characteristics such as BMI, physical activity, and smoking. RESULTS: 2-SD increases in nitrogen dioxide (NO2, 8.9 μg/m(3)) and particulate matter smaller than 10μm in diameter (PM10, 6.7 μg/m(3)) were significantly associated with 11.4% (95% CI: 4.4, 18.9) and 11.4% (95% CI: 0.4, 23.7) higher HOMA-IR. A 2-SD increase in NDVI in a 1000m buffer (0.2 units) was significantly associated with a lower HOMA-IR (-7.4% (95% CI: -13.3, -1.1)). Associations tended to be stronger in adolescents who spent more time outside and those with a lower socioeconomic status. In combined models including both air pollution and greenness, only NO2 remained significantly associated with HOMA-IR, while effect estimates for all other exposures attenuated after adjustment for NO2. CONCLUSIONS: NO2, often considered as a marker of traffic, was independently associated with insulin resistance. The observed association between higher greenness exposure and lower HOMA-IR in adolescents might thus be mainly due to the lower co-exposure to traffic-related air pollution. AU - Thiering, E. AU - Markevych, I. AU - Brüske, I. AU - Fuertes, E. AU - Kratzsch, J.* AU - Sugiri, D.* AU - Hoffmann, B.* AU - von Berg, A.* AU - Bauer, C.P.* AU - Koletzko, S.* AU - Berdel, D.* AU - Heinrich, J. C1 - 47880 C2 - 39698 CY - Res Triangle Pk SP - 1291-1298 TI - Associations of residential long-term air pollution exposures and satellite-derived greenness with insulin resistance in German adolescents. JO - Environ. Health Perspect. VL - 124 IS - 8 PB - Us Dept Health Human Sciences Public Health Science PY - 2016 SN - 0091-6765 ER - TY - JOUR AB - INTRODUCTION: Investigations in urban areas have just begun to explore how the indoor dust microbiome may affect the pathogenesis of asthma and allery. We aimed to investigate the early fungal and bacterial microbiome in house dust with allergic sensitization and wheezing later in childhood. METHODS: Individual dust samples from 189 homes of the LISAplus birth cohort study were collected shortly after birth from living room floors and profiled for fungal and bacterial microbiome. Fungal and bacterial diversity was assessed with terminal restriction fragment length polymorphism (tRFLP) and defined by the Simpson diversity index. Information on wheezing outcomes and co-variates until the age of 10 years was obtained by parental questionnaires. Information on specific allergic sensitization was available at 6 and 10 years. Logistic regression and General Estimation Equation (GEE) models were used to examine the relationship between microbial diversity and health outcomes. RESULTS: Logistic regression analyses revealed a significantly reduced risk of developing sensitization to aero-allergens at 6 years and ever wheezing until the age of 10 years for exposure to higher fungal diversity (adjusted Odds Ratio aOR (95%CI): 0.26 (0.10-0.70)), and 0.42 (0.18-0.96), respectively), in adjusted analyses. The associations were attenuated for the longitudinal analyses (GEE) until the age of 10 years. There was no association between higher exposure to bacterial diversity and the tested health outcomes. CONCLUSION: Higher early exposure to fungal diversity might help to prevent from developing sensitization to aero-allergens in early childhood, but the reasons for attenuated effects in later childhood require further prospective studies. AU - Tischer, C.G. AU - Weikl, F. AU - Probst, A.J.* AU - Standl, M. AU - Heinrich, J. AU - Pritsch, K. C1 - 48694 C2 - 41257 CY - Res Triangle Pk SP - 1919-1923 TI - Urban dust microbiome: Impact on later atopy and wheezing. JO - Environ. Health Perspect. VL - 124 IS - 12 PB - Us Dept Health Human Sciences Public Health Science PY - 2016 SN - 0091-6765 ER - TY - JOUR AB - 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 (Cu), Iron (Fe), Potassium (K), Nickel (Ni), Sulfur (S), Silicon (Si), Vanadium (V) and Zinc (Zn) 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 which 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 S (1.14; 95% CI: 1.06, 1.23 per 200 ng/m(3)). In a two-pollutant model, the association with PM2.5 S was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. CONCLUSIONS: Long-term exposure to PM2.5 S was associated with natural cause mortality. This association was robust to adjustment for other pollutants and PM2.5. AU - Beelen, R.* AU - Hoek, G.* AU - Raaschou-Nielsen, O.* AU - Stafoggia, M.* AU - Andersen, Z.J.* AU - Weinmayr, G.* AU - Hoffmann, B.* AU - Wolf, K. AU - Samoli, E.* AU - Fischer, P.H.* AU - Nieuwenhuijsen, M.J.* AU - Xun, W.W.* AU - Katsouyanni, K.* AU - Dimakopoulou, K.* AU - Marcon, A.* AU - Vartiainen, E.* AU - Lanki, T.* AU - Yli-Tuomi, T.* AU - Oftedal, B.* AU - Schwarze, P.E.* AU - Nafstad, P. AU - de Faire, U.* AU - Pedersen, N.L.* AU - Ostenson, C.G.* AU - Fratiglioni, L.* AU - Penell, J.* AU - Korek, M.* AU - Pershagen, G.* AU - Eriksen, K.T.* AU - Overvad, K.* AU - Sørensen, M.* AU - Eeftens, M.* AU - Peeters, P.H.* AU - Meliefste, K.* AU - Wang, M.* AU - Bueno-de-Mesquita, H.B.* AU - Sugiri, D.* AU - Krämer, U.* AU - Heinrich, J. AU - de Hoogh, K.* AU - Key, T.* AU - Peters, A. AU - Hampel, R. AU - Concin, H.* AU - Nagel, G.* AU - Jaensch, A.* AU - Ineichen, A.* AU - Tsai, M.Y.* AU - Schaffner, E.* AU - Probst-Hensch, N.M.* AU - Schindler, C.* AU - Ragettli, M.S.* AU - Vilier, A.* AU - Clavel-Chapelon, F.* AU - Declercq, C.* AU - Ricceri, F.* AU - Sacerdote, C.* AU - Galassi, C.* AU - Migliore, E.* AU - Ranzi, A.* AU - Cesaroni, G.* AU - Badaloni, C.* AU - Forastiere, F.* AU - Katsoulis, M.* AU - Trichopoulou, A.* AU - Keuken, M.* AU - Jedynska, A.* AU - Kooter, I.M.* AU - Kukkonen, J.V.K.* AU - Sokhi, R.S.* AU - Vineis, P.* AU - Brunekreef, B.* C1 - 44007 C2 - 36685 CY - Res Triangle Pk SP - 525-533 TI - Natural-cause mortality and long-term exposure to particle components: An analysis of 19 European cohorts within the multi-center ESCAPE project. JO - Environ. Health Perspect. VL - 123 IS - 6 PB - Us Dept Health Human Sciences Public Health Science PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Air pollution has been related to mean changes in outcomes, including DNA methylation. However, mean regression analyses may not capture associations that occur primarily in the tails of the outcome distribution. OBJECTIVES: This study examined whether the association between particulate air pollution and DNA methylation differs across quantiles of the methylation distribution. We focused on methylation of candidate genes related to coagulation and inflammation: coagulation factor III (F3), intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFN-γ), interleukin-6 (IL-6), and toll-like receptor 2 (TRL-2). METHODS: We measured gene-specific blood DNA methylation repeatedly in 777 elderly men participating in the Normative Aging Study (1999-2010). We fit quantile regressions for longitudinal data to investigate whether the associations of particle number, PM2.5 black carbon, and PM2.5 mass concentrations (4-weeks moving average) with DNA methylation [expressed as the percentage of methylated cytosines over the sum of methylated and unmethylated cytosines at position 5 (%5mC)] varied across deciles of the methylation distribution. We reported the quantile regression coefficients which corresponded to absolute differences in DNA methylation (expressed in %5mC) associated with an interquartile range increase in air pollution concentration. RESULTS: Interquartile range increases in particle number, PM2.5 black carbon, and PM2.5 mass concentrations were associated with significantly lower methylation in the lower tails of the IFN-γ and ICAM-1 methylation distributions. For instance, a 3.4 µg/m(3) increase in PM2.5 mass concentration was associated with a 0.18%5mC (95% CI: -0.30, -0.06) decrease on the 20th percentile of ICAM-1 methylation, but was not significantly related to the 80th percentile (Estimate: 0.07%5mC, 95% CI: -0.09, 0.24). CONCLUSIONS: In our study population of older men, air pollution exposures were associated with a left shift in the lower tails of the IFN-γ and ICAM-1 methylation distributions. AU - Bind, M.A.* AU - Coull, B.A.* AU - Peters, A. AU - Baccarelli, A.A.* AU - Tarantini, L.* AU - Cantone, L.* AU - Vokonas, P.S.* AU - Koutrakis, P.* AU - Schwartz, J.D.* C1 - 44447 C2 - 36846 SP - 759-765 TI - Beyond the mean: Quantile regression to explore the association of air pollution with gene-specific methylation in the normative aging study. JO - Environ. Health Perspect. VL - 123 IS - 8 PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - Background: Limited information is available regarding long-term effects of air pollution on blood pressure (BP) and hypertension. Objective: We studied whether 1-year exposures to particulate matter (PM) and nitrogen oxides (NOx) were correlated with BP and hypertension in the elderly. Methods: We analyzed cross-sectional data from 27,752 Taipei City residents > 65 years of age who participated in a health examination program in 2009. Land-use regression models were used to estimate participants’ 1-year exposures to particulate matter with aerodynamic diameter ≤ 10 μm (PM10), coarse particles (PM2.5–10), fine particles (≤ 2.5 μm; PM2.5), PM2.5absorbance, NOx, and nitrogen dioxide (NO2). Generalized linear regressions and logistic regressions were used to examine the association between air pollution and BP and hypertension, respectively. Results: Diastolic BP was associated with 1-year exposures to air pollution, with estimates of 0.73 [95% confidence interval (CI): 0.44, 1.03], 0.46 (95% CI: 0.30, 0.63), 0.62 (95% CI: 0.24, 0.99), 0.34 (95% CI: 0.19, 0.50), and 0.65 (95% CI: 0.44, 0.85) mmHg for PM10 (10 μg/m3), PM2.5–10 (5 μg/m3), PM2.5 absorbance (10–5/m), NOx (20 μg/m3), and NO2 (10 μg/m3), respectively. PM2.5 was not associated with diastolic BP, and none of the air pollutants was associated with systolic BP. Associations of diastolic BP with PM10 and PM2.5 absorbance were stronger among participants with hypertension, diabetes, or a body mass index ≥ 25 kg/m2 than among participants without these conditions. One-year air pollution exposures were not associated with hypertension. Conclusions: One-year exposures to PM10, PM2.5-10, PM2.5 absorbance, and NOx were associated with higher diastolic BP in elderly residents of Taipei. AU - Chen, S.Y.* AU - Wu, C.F.* AU - Lee, J.H.* AU - Hoffmann, B.* AU - Peters, A. AU - Brunekreef, B.* AU - Chu, D.C.* AU - Chan, C.C.* C1 - 46678 C2 - 37668 SP - 779-784 TI - Associations between long-term air pollutant exposures and blood pressure in elderly residents of Taipei city: A cross-sectional study. JO - Environ. Health Perspect. VL - 123 IS - 8 PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Short-term exposure to air pollution has adverse effects among patients with asthma, whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. OBJECTIVE: 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 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 on 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 NO2, (adjusted OR = 1.10; 95% CI: 0.99, 1.21 per 10 μg/m(3); p=0.10) and NOx (1.04; 95% CI: 0.99, 1.08 per 20 μg/m(3); p=0.08). Non-significant positive associations were estimated for PM10 (1.04; 95% CI: 0.88, 1.23 per 10 μg/m(3)), PM2.5 (1.04; 95% CI: 0.88, 1.23 per 5 μg/m(3)), PM2.5absorbance (1.06; 95% CI: 0.95, 1.19 per 10(-5)/m), traffic load (1.10; 95% CI: 0.93, 1.30 per four million vehicles x m/day on major roads in a 100m buffer) and traffic intensity (1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A non-significant negative association was estimated for PMcoarse (0.98; 95% CI: 0.87, 1.14 per 5 μg/m(3)). CONCLUSIONS: Results are suggestive of a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (versus residential exposure assessment only) and phenotypic characterization is needed. AU - Jacquemin, B.* AU - Siroux, V.* AU - Sanchez, M.* AU - Carsin, A.E.* AU - Schikowski, T.* AU - Adam, M.* AU - Bellisario, V.* AU - Buschka, A.* AU - Bono, R.* AU - Brunekreef, B.* AU - Cai, Y.* AU - Cirach, M.* AU - Clavel-Chapelon, F.* AU - Declercq, C.* AU - de Marco, R.* AU - de Nazelle, A.* AU - Ducret-Stich, R.E.* AU - Ferretti, V.V.* AU - Gerbase, M.W.* AU - Hardy, R.* AU - Heinrich, J. AU - Janson, C.* AU - Jarvis, D.* AU - Al Kanaani, Z.* AU - Keidel, D.* AU - Kuh, D.* AU - Le Moual, N.* AU - Nieuwenhuijsen, M.J.* AU - Marcon, A.* AU - Modig, L.* AU - Pin, I.* AU - Rochat, T.* AU - Schindler, C.* AU - Sugiri, D.* AU - Stempfelet, M.* AU - Temam, S.* AU - Tsai, M.Y.* AU - Varraso, R.* AU - Vienneau, D.* AU - Vierkötter, A.* AU - Hansell, A.L.* AU - Krämer, U.* AU - Probst-Hensch, N.M.* AU - Sunyer, J.* AU - Künzli, N.* AU - Kauffmann, F.* C1 - 44006 C2 - 36684 CY - Res Triangle Pk SP - 613-621 TI - Ambient air pollution and adult asthma incidence in six European cohorts (ESCAPE). JO - Environ. Health Perspect. VL - 123 IS - 6 PB - Us Dept Health Human Sciences Public Health Science PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Exposure to particulate matter air pollution (PM) has been associated with cardiovascular diseases. OBJECTIVES: This study 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-sensitive 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 to persons living in a quiet residential street with less than 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/m(3)), 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. AU - Lanki, T.* AU - Hampel, R. AU - Tiittanen, P.* AU - Andrich, S.* AU - Beelen, R.* AU - Brunekreef, B.* AU - Dratva, J.* AU - de Faire, U.* AU - Fuks, K.B.* AU - Hoffman, B.* AU - Imboden, M.* AU - Jousilahti, P.* AU - Koenig, W.* AU - Mahabadi, A.A.* AU - Künzli, N.* AU - Pedersen, N.L.* AU - Penell, J.* AU - Pershagen, G.* AU - Probst-Hensch, N.M.* AU - Schaffner, E.* AU - Schindler, C.* AU - Sugiri, D.* AU - Swart, W.J.* AU - Tsai, M.Y.* AU - Turunen, A.W.* AU - Weinmayr, G.* AU - Wolf, K. AU - Yli-Tuomi, T.* AU - Peters, A. C1 - 44380 C2 - 36809 SP - 785-791 TI - Air pollution from road traffic and systemic inflammation in adults: A cross-sectional analysis in the European ESCAPE project. JO - Environ. Health Perspect. VL - 123 IS - 8 PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth. OBJECTIVE: We examined whether such alterations are present from birth through adolescence. METHODS: We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n=132) and at birth, during childhood, and during adolescence in a replication cohort (n=447). RESULTS: In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p=3.3x10(-11)) and CNTNAP2 (cg25949550, p=4.0x10(-9)) to be differentially methylated between exposed and non-exposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed vs. non-exposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time-points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR and GFI1 observed in that study was also evident in our discovery cohort. CONCLUSIONS: Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years - at least until adolescence. AU - Lee, K.W.* AU - Richmond, R.* AU - Hu, P.* AU - French, L.* AU - Shin, J.T.* AU - Bourdon, C.* AU - Reischl, E. AU - Waldenberger, M. AU - Zeilinger, S. AU - Gaunt, T.R.* AU - McArdle, W.* AU - Ring, S.* AU - Woodward, G.* AU - Bouchard, L.* AU - Gaudet, D.* AU - Davey Smith, G.* AU - Relton, C.* AU - Paus, T.* AU - Pausova, Z.* C1 - 32594 C2 - 35148 CY - Res Triangle Pk SP - 193-199 TI - Prenatal exposure to maternal cigarette smoking and DNA methylation: Epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age. JO - Environ. Health Perspect. VL - 123 IS - 2 PB - Us Dept Health Human Sciences Public Health Science PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - 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 pre-clinical marker of atherosclerosis. METHODS: Individually assigned levels of NO2, NOx, 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 9183 individuals resulted in an estimated increase in CIMT (geometric mean) of 0.72% (95% Confidence Interval [CI]: -0.65%, 2.10%) per 5 µg/m(3) 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/m(3) contrast in PM2.5. CONCLUSIONS: Using a standardized exposure and analytical protocol in four European cohorts, 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. AU - Perez, L.* AU - Wolf, K. AU - Hennig, F.* AU - Penell, J.* AU - Basagana, X.* AU - Aguilera, I.* AU - Agis, D.* AU - Beelen, R.* AU - Brunekreef, B.* AU - Cyrys, J.* AU - Fuks, K.B.* AU - Adam, M.* AU - Baldassare, D.* AU - Cirach, M.* AU - Elosua, R.* AU - Dratva, J.* AU - Hampel, R. AU - Koenig, W.* AU - Marrugat, J.* AU - de Faire, U.* AU - Pershagen, G.* AU - Probst-Hensch, N.M.* AU - de Nazelle, A.* AU - Nieuwenhuijsen, M.J.* AU - Rathmann, W.* AU - Rivera, M.* AU - Seissler, J. AU - Schindler, C.* AU - Thierry, J.* AU - Hoffmann, B.* AU - Peters, A. AU - Künzli, N.* C1 - 43425 C2 - 36366 CY - Res Triangle Pk SP - 597-605 TI - Air pollution and atherosclerosis: A cross-sectional analysis of four European cohort studies in the ESCAPE study. JO - Environ. Health Perspect. VL - 123 IS - 6 PB - Us Dept Health Human Sciences Public Health Science PY - 2015 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Studies on the association between traffic noise and cardiovascular diseases rarely considered air pollution as a covariate in the analyses. Isolated systolic hypertension has not yet been in the focus of epidemiological noise research. METHODS: The association between traffic noise (road and rail) and the prevalence of hypertension was assessed in two study populations with a total of 4,166 participants aged 25-74 years. Traffic noise (weighted day-night average noise level LDN) at the facade of the dwellings was derived from noise maps. Annual average PM2.5 mass concentrations at residential addresses were estimated by land-use regression. Hypertension was assessed by blood pressure readings, self-reported doctor diagnosed hypertension, and antihypertensive drug intake. RESULTS: In the Greater Augsburg study population, traffic noise and air pollution were not associated with hypertension. In the City of Augsburg population (n = 1,893), where the exposure assessment was more detailed, the adjusted odds ratio (OR) for a 10-dB(A) increase in noise was 1.16 (95% CI: 1.00, 1.35), and 1.11 (95% CI: 0.94, 1.30) after additional adjustment for PM2.5. The adjusted OR for a 1-μg/m(3) increase in PM2.5 was 1.15 (95% CI: 1.02, 1.30), and 1.11 (95% CI: 0.98, 1.27) after additional adjustment for noise. For isolated systolic hypertension, the fully adjusted OR for noise was 1.43 (95% CI: 1.10, 1.86) and for PM2.5 was 1.08 (95% CI: 0.87, 1.34). CONCLUSIONS: Traffic noise and PM2.5 were both associated with a higher prevalence of hypertension. Mutually adjusted associations with hypertension were positive but no longer statistically significant. AU - Babisch, W.* AU - Wolf, K. AU - Petz, M.* AU - Heinrich, J. AU - Cyrys, J. AU - Peters, A. C1 - 30878 C2 - 33981 CY - Res Triangle Pk SP - 492-498 TI - Associations between traffic noise, particulate air pollution, hypertension, and isolated systolic hypertension in adults: The KORA study. JO - Environ. Health Perspect. VL - 122 IS - 5 PB - Us Dept Health Human Sciences Public Health Science PY - 2014 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Long-term exposure to air pollution is 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: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated 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, 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 non-medicated 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 for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled 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 non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent. AU - Fuks, K.* AU - Weinmayr, G.* AU - Foraster, M.* AU - Dratva, J.* AU - Hampel, R. AU - Houthuijs, D.* AU - Oftedal, B.* AU - Oudin, A.* AU - Panasevich, S.* AU - Penell, J.* AU - Sommar, J.N.* AU - Sørensen, M.* AU - Tiittanen, P.* AU - Wolf, K. AU - Xun, W.W.* AU - Aguilera, I.* AU - Basagana, X.* AU - Beelen, R.* AU - Bots, M.L.* AU - Brunekreef, B.* AU - Bueno-de-Mesquita, H.B.* AU - Caracciolo, B.* AU - Cirach, M.* AU - de Faire, U.* AU - de Nazelle, A.* AU - Eeftens, M.* AU - Elosua, R.* AU - Erbel, R.* AU - Forsberg, B.* AU - Fratiglioni, L.* AU - Gaspoz, J.M.* AU - Hilding, A.* AU - Jula, A.* AU - Korek, M.* AU - Krämer, U.* AU - Künzli, N.* AU - Lanki, T.* AU - Leander, K.* AU - Magnusson, P.K.* AU - Marrugat, J.* AU - Nieuwenhuijsen, M.J.* AU - Ostenson, C.G.* AU - Pedersen, N.L.* AU - Pershagen, G.* AU - Phuleria, H.C.* AU - Probst-Hensch, N.M.* AU - Raaschou-Nielsen, O.* AU - Schaffner, E.* AU - Schikowski, T.* AU - Schindler, C.* AU - Schwarze, P.E.* AU - Søgaard, A.J.* AU - Sugiri, D.* AU - Swart, W.J.* AU - Tsai, M.Y.* AU - Turunen, A.W.* AU - Vineis, P.* AU - Peters, A. AU - Hoffmann, B.* C1 - 31302 C2 - 34402 CY - Res Triangle Pk SP - 896-905 TI - 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). JO - Environ. Health Perspect. VL - 122 IS - 9 PB - Us Dept Health Human Sciences Public Health Science PY - 2014 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma. OBJECTIVE: 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 age 7-8 years (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution (NO2, 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/Ala(114)Val and rs1695/IIe(105)Val) 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 ≥1 GSTP1 rs1138272 minor allele were at increased risk of current asthma (OR=2.59; 95%CI: 1.43, 4.68 per 10 µg/m(3) 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-values 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma were OR=1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70) respectively, for minor allele carriers compared to OR=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. AU - MacIntyre, E.A. AU - Brauer, M.* AU - Melén, E.* AU - Bauer, C.P.* AU - Bauer, M.* AU - Berdel, D.* AU - Bergström, A.* AU - Brunekreef, B.* AU - Chan-Yeung, M.* AU - Klümper, C.* AU - Fuertes, E. AU - Gehring, U.* AU - Gref, A.* AU - Heinrich, J. AU - Herbarth, O.* AU - Kerkhof, M.* AU - Koppelman, G.H.* AU - Kozyrskyj, A.L.* AU - Pershagen, G.* AU - Postma, D.S.* AU - Thiering, E. AU - Tiesler, C.M. AU - Carlsten, C.* C1 - 30744 C2 - 33828 CY - Res Triangle Pk SP - 418-424 TI - GSTP1 and TNF gene variants and associations between air pollution and incident childhood asthma: The Traffic, Asthma and Genetics (TAG) study. JO - Environ. Health Perspect. VL - 122 IS - 4 PB - Us Dept Health Human Sciences Public Health Science PY - 2014 SN - 0091-6765 ER - TY - JOUR AB - 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. AU - MacIntyre, E.A. AU - Gehring, U.* AU - Mölter, A.* AU - Fuertes, E. AU - Klümper, C.* AU - Krämer, U.* AU - Quass, U.* AU - Hoffmann, B.* AU - Gascon, M.* AU - Brunekreef, B.* AU - Koppelman, G.H.* AU - Beelen, R.* AU - Hoek, G.* AU - Birk, M. AU - de Jongste, J.C.* AU - Smit, H.A.* AU - Cyrys, J. AU - Gruzieva, O.* AU - Korek, M.* AU - Bergström, A.* AU - Agius, R.M.* AU - de Vocht, F.* AU - Simpson, A.* AU - Porta, D.* AU - Forastiere, F.* AU - Badaloni, C.* AU - Cesaroni, G.* AU - Esplugues, A.* AU - Fernández-Somoano, A.* AU - Lerxundi, A.* AU - Sunyer, J.* AU - Cirach, M.* AU - Nieuwenhuijsen, M.J.* AU - Pershagen, G.* AU - Heinrich, J. C1 - 30726 C2 - 33797 CY - Res Triangle Pk SP - 107-113 TI - Air pollution and respiratory infections during early childhood: An analysis of 10 European birth cohorts within the ESCAPE project. JO - Environ. Health Perspect. VL - 122 IS - 1 PB - Us Dept Health Human Sciences Public Health Science PY - 2014 SN - 0091-6765 ER - TY - JOUR AB - 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] below 2.5 µm in diameter), coarse PM (PM between 2.5 and 10 µm), PM10 (PM below 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: 99,446 subjects were included, 3,086 of whom developed stroke. A 5-μg/m(3) increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke (hazard ratio [HR] = 1.19, 95% confidence interval [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 co-exposure. The association with PM2.5 was apparent among those aged 60+ years (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among subjects with PM2.5 exposure below 25 μg/m(3) (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. AU - Stafoggia, M.* AU - Cesaroni, G.* AU - Peters, A. AU - Andersen, Z.J.* AU - Badaloni, C.* AU - Beelen, R.* AU - Caracciolo, B.* AU - Cyrys, J. AU - de Faire, U.* AU - de Hoogh, K.* AU - Eriksen, K.T.* AU - Fratiglioni, L.* AU - Galassi, C.* AU - Gigante, B.* AU - Havulinna, A.S.* AU - Hennig, F.* AU - Hilding, A.* AU - Hoek, G.* AU - Hoffmann, B.* AU - Houthuijs, D.* AU - Korek, M.* AU - Lanki, T.* AU - Leander, K.* AU - Magnusson, P.K.* AU - Meisinger, C. AU - Migliore, E.* AU - Overvad, K.* AU - Ostenson, C.G.* AU - Pedersen, N.L.* AU - Pekkanen, J.* AU - Penell, J.* AU - Pershagen, G.* AU - Pundt, N.* AU - Pyko, A.* AU - Raaschou-Nielsen, O.* AU - Ranzi, A.* AU - Ricceri, F.* AU - Sacerdote, C.* AU - Swart, W.J.* AU - Turunen, A.W.* AU - Vineis, P.* AU - Weimar, C.* AU - Weinmayr, G.* AU - Wolf, K. AU - Brunekreef, B.* AU - Forastiere, F.* C1 - 31303 C2 - 34405 CY - Res Triangle Pk SP - 919-925 TI - Long-term exposure to ambient air pollution and incidence of cerebrovascular events: Results from 11 European cohorts within the ESCAPE project. JO - Environ. Health Perspect. VL - 122 IS - 9 PB - Us Dept Health Human Sciences Public Health Science PY - 2014 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Land use regression (LUR) models have mostly been developed to explain intra-urban 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: 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 (PM2.5, PM2.5 absorbance) by combining standardized measurement data from 17 (PM) and 23 (NO2) ESCAPE 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 R(2)s were only slightly lower than the model R(2) (NO2: 54%, PM2.5: 80%, 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 which were excluded from model building (median R(2): 59% NO2; 42% PM2.5; 67% PM2.5 absorbance). CONCLUSIONS: Using a large dataset 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. AU - Wang, M.* AU - Beelen, R.* AU - Bellander, T.* AU - Birk, M. AU - Cesaroni, G.* AU - Cirach, M.* AU - Cyrys, J. AU - de Hoogh, K.* AU - Declercq, C.* AU - Dimakopoulou, K.* AU - Eeftens, M.* AU - Eriksen, K.T.* AU - Forastiere, F.* AU - Galassi, C.* AU - Grivas, G.* AU - Heinrich, J. AU - Hoffmann, B.* AU - Ineichen, A.* AU - Korek, M.* AU - Lanki, T.* AU - Lindley, S.* AU - Modig, L.* AU - Mölter, A.* AU - Nafstad, P.* AU - Nieuwenhuijsen, M.J.* AU - Nystad, W.* AU - Olsson, D.* AU - Raaschou-Nielsen, O.* AU - Ragettli, M.* AU - Ranzi, A.* AU - Stempfelet, M.* AU - Sugiri, D.* AU - Tsai, M.Y.* AU - Udvardy, O.* AU - Varró, M.J.* AU - Vienneau, D.* AU - Weinmayr, G.* AU - Wolf, K. AU - Yli-Tuomi, T.* AU - Hoek, G.* AU - Brunekreef, B.* C1 - 31189 C2 - 34284 CY - Res Triangle Pk SP - 843-849 TI - Performance of multi-city land use regression models for nitrogen dioxide and fine particles. JO - Environ. Health Perspect. VL - 122 IS - 8 PB - Us Dept Health Human Sciences Public Health Science PY - 2014 SN - 0091-6765 ER - TY - JOUR AB - 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. AU - Gehring, U.* AU - Gruzieva, O.* AU - Agius, R.M.* AU - Beelen, R.* AU - Custovic, A.* AU - Cyrys, J. AU - Eeftens, M.* AU - Flexeder, C. AU - Fuertes, E. AU - Heinrich, J. AU - Hoffmann, B.* AU - de Jongste, J.C.* AU - Kerkhof, M.* AU - Klümper, C.* AU - Korek, M.* AU - Mölter, A.* AU - Schultz, E.S.* AU - Simpson, A.* AU - Sugiri, D.* AU - Svartengren, M.* AU - von Berg, A.* AU - Wijga, A.H.* AU - Pershagen, G.* AU - Brunekreef, B.* C1 - 28615 C2 - 33487 SP - 1357-1364 TI - Air pollution exposure and lung function in children: The ESCAPE project. JO - Environ. Health Perspect. VL - 121 IS - 11-12 PB - US Dept. Health Human Sci. PY - 2013 SN - 0091-6765 ER - TY - JOUR AB - Background: Epidemiological studies have demonstrated associations between noise exposure and cardiovascular events. However, there have been few studies of possible underlying mechanisms. Objectives: We examined the association between individual day-time noise exposure and heart rate variability (HRV). Methods: In a prospective panel study in Augsburg, Germany (March 2007-December 2008), 110 individuals participated in 326 electrocardiogram recordings with a mean duration of six hours. Five-minute averages of heart rate (HR) and HRV parameters were determined. Individual noise exposure was measured as A-weighted equivalent continuous sound pressure levels (Leq). Effects were estimated using additive mixed models adjusted for long- and short-term time trends and physical activity. Due to non-linear exposure-response functions we performed piecewise linear analyses with a cut-off point at 65 dB(A). Results: Concurrent increases of 5dB(A) in Leq<65dB(A) were associated with increases in HR (%-change of mean value: 1.48%; 95% CI: 1.37, 1.60%) and the ratio of low frequency (LF) to high frequency (HF) power (4.89%; 95% CI: 3.48, 6.32%), and with decreases in LF (-3.77%; 95% CI: -5.49, -2.02%) and HF (-8.56%; 95% CI: -10.31, -6.78%) power. Standard deviation of normal-to-normal intervals (SDNN) was positively associated with concurrent noise <65dB(A) (5.74%; 95% CI: 5.13, 6.36) but negatively associated with noise lagged by five- to 15-minutes (-0.53% to -0.69%). Associations with cardiac function were less pronounced for noise ≥65dB(A), with some in opposite directions from associations with noise <65dB(A). Concurrent associations were modified by sex and age. Conclusions: Individual day-time noise exposure was associated with immediate changes in HRV, suggesting a possible mechanism linking noise to cardiovascular risk. Noise at lower levels may have health consequences beyond those resulting from “fight-or-flight” responses to high levels of noise. AU - Kraus, U. AU - Schneider, A.E. AU - Breitner-Busch, S. AU - Hampel, R. AU - Rückerl, R. AU - Pitz, M.* AU - Geruschkat, U. AU - Belcredi, P. AU - Radon, K.* AU - Peters, A. C1 - 23662 C2 - 31225 SP - 607-612 TI - Individual day-time noise exposure during routine activities and heart rate variability in adults: A repeated measures study. JO - Environ. Health Perspect. VL - 121 IS - 5 PB - US Dept. Health Human Sciences Public Health Science PY - 2013 SN - 0091-6765 ER - TY - JOUR AB - Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms "radiation" AND "heart" AND "disease," OR "radiation" AND "stroke," OR "radiation" AND "circulatory" AND "disease." Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.Results: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.Conclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations). AU - Little, M.P.* AU - Azizova, T.V.* AU - Bazyka, D.* AU - Bouffler, S.D.* AU - Cardis, E.* AU - Chekin, S.* AU - Chumak, V.V.* AU - Cucinotta, F.A.* AU - de Vathaire, F.* AU - Hall, P.* AU - Harrison, J.D.* AU - Hildebrandt, G.* AU - Ivanov, V.* AU - Kashcheev, V.V.* AU - Klymenko, S.V.* AU - Kreuzer, M.* AU - Laurent, O.* AU - Ozasa, K.* AU - Schneider, T.* AU - Tapio, S. AU - Taylor, A.M.* AU - Tzoulaki, I.* AU - Vandoolaeghe, W.L.* AU - Wakeford, R.* AU - Zablotska, L.B.* AU - Zhang, W.* AU - Lipshultz, S.E.* C1 - 10849 C2 - 30391 SP - 1503-1511 TI - Systematic review and meta-analysis of circulatory disease from exposure to low-level ionizing radiation and estimates of potential population mortality risks. JO - Environ. Health Perspect. VL - 120 IS - 11 PB - National Institute of Environmental Health Sciences PY - 2012 SN - 0091-6765 ER - TY - JOUR AU - Schöllnberger, H. AU - Kaiser, J.C. C1 - 11348 C2 - 30630 SP - a452-a453 TI - Estimating risk of circulatory disease from exposure to low-level ionizing radiation. JO - Environ. Health Perspect. VL - 120 IS - 12 PB - National Institute of Environmental Health Sciences PY - 2012 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. OBJECTIVES: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. METHODS: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. CONCLUSION: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health. AU - Vrijheid, M.* AU - Casas, M.* AU - Bergström, A.* AU - Carmichael, A.* AU - Cordier, S.* AU - Eggesbø, M.* AU - Eller, E.* AU - Fantini, M.P.* AU - Fernández, M.F.* AU - Fernández-Somoano, A.* AU - Gehring, U.* AU - Grazuleviciene, R.* AU - Hohmann, C.* AU - Karvonen, A.M.* AU - Keil, T.* AU - Kogevinas, M.* AU - Koppen, G.* AU - Krämer, U.* AU - Kuehni, C.E.* AU - Magnus, P.* AU - Majewska, R.* AU - Andersen, A.M.* AU - Patelarou, E.* AU - Petersen, M.S.* AU - Pierik, F.H.* AU - Polanska, K.* AU - Porta, D.* AU - Richiardi, L.* AU - Santos, A.C.* AU - Slama, R.* AU - Sram, R.J.* AU - Thijs, C.* AU - Tischer, C.G. AU - Toft, G.* AU - Trnovec, T.* AU - Vandentorren, S.* AU - Vrijkotte, T.G.* AU - Wilhelm, M.* AU - Wright, J.* AU - Nieuwenhuijsen, M.* C1 - 7197 C2 - 29542 SP - 29-37 TI - European birth cohorts for environmental health research. JO - Environ. Health Perspect. VL - 120 IS - 1 PB - US Dept Health Human Sciences Public Health Science PY - 2012 SN - 0091-6765 ER - TY - JOUR AB - Increasing evidence suggests a proatherogenic role for lipoprotein-associated phospholipase A₂ (Lp-PLA2). A meta-analysis of published cohorts has shown that Lp-PLA2 is an independent predictor of coronary heart disease events and stroke. OBJECTIVE: In this study, we investigated whether the association between air pollution and cardiovascular disease might be partly explained by increased Lp-PLA2 mass in response to exposure. METHODS: A prospective longitudinal study of 200 patients who had had a myocardial infarction was performed in Augsburg, Germany. Up to six repeated clinical examinations were scheduled every 4-6 weeks between May 2003 and March 2004. Supplementary to the multicenter AIRGENE protocol, we assessed repeated plasma Lp-PLA2 concentrations. Air pollution data from a fixed monitoring site representing urban background concentrations were collected. We measured hourly means of particle mass [particulate matter (PM) < 10 µm (PM₁₀) and PM < 2.5 µm (PM(2.5)) in aerodynamic diameter] and particle number concentrations (PNCs), as well as the gaseous air pollutants carbon monoxide (CO), sulfur dioxide (SO₂), ozone (O₃), nitric oxide (NO), and nitrogen dioxide (NO₂). Data were analyzed using mixed models with random patient effects. RESULTS: Lp-PLA2 showed a positive association with PM₁₀, PM(2.5), and PNCs, as well as with CO, NO₂, NO, and SO₂ 4-5 days before blood withdrawal (lag 4-5). A positive association with O₃ was much more immediate (lag 0). However, inverse associations with some pollutants were evident at shorter time lags. CONCLUSION: These preliminary findings should be replicated in other study populations because they suggest that the accumulation of acute and subacute effects or the chronic exposure to ambient particulate and gaseous air pollution may result in the promotion of atherosclerosis, mediated, at least in part, by increased levels of Lp-PLA2. AU - Brüske, I. AU - Hampel, R. AU - Baumgärtner, Z.* AU - Rückerl, R. AU - Greven, S.* AU - Koenig, W.* AU - Peters, A. AU - Schneider, A.E. C1 - 6041 C2 - 28774 SP - 921-926 TI - Ambient air pollution and lipoprotein-associated phospholipase A2 in survivors of myocardial infarction. JO - Environ. Health Perspect. VL - 119 IS - 7 PB - US Dept. Health Human Sciences Public Health Science PY - 2011 SN - 0091-6765 ER - TY - JOUR AB - The link between concentrations of particulate matter (PM) and respiratory morbidity has been investigated in numerous studies. The aim of this study was to analyze the role of different particle size fractions with respect to respiratory health in Beijing, China. Data on particle size distributions from 3 nm to 1 µm; PM10 (PM ≤ 10 µm), nitrogen dioxide (NO(2)), and sulfur dioxide concentrations; and meteorologic variables were collected daily from March 2004 to December 2006. Concurrently, daily counts of emergency room visits (ERV) for respiratory diseases were obtained from the Peking University Third Hospital. We estimated pollutant effects in single- and two-pollutant generalized additive models, controlling for meteorologic and other time-varying covariates. Time-delayed associations were estimated using polynomial distributed lag, cumulative effects, and single lag models. Associations of respiratory ERV with NO(2) concentrations and 100-1,000 nm particle number or surface area concentrations were of similar magnitude-that is, approximately 5% increase in respiratory ERV with an interquartile range increase in air pollution concentration. In general, particles < 50 nm were not positively associated with ERV, whereas particles 50-100 nm were adversely associated with respiratory ERV, both being fractions of ultrafine particles. Effect estimates from two-pollutant models were most consistent for NO(2).Present levels of air pollution in Beijing were adversely associated with respiratory ERV. NO(2) concentrations seemed to be a better surrogate for evaluating overall respiratory health effects of ambient air pollution than PM(10) or particle number concentrations in Beijing. AU - Leitte, A.M.* AU - Schlink, U.* AU - Herbarth, O.* AU - Wiedensohler, A.* AU - Pan, XC.* AU - Hu, M.* AU - Richter, M.* AU - Wehner, B.* AU - Tuch, T.* AU - Wu, Z.* AU - Yang, M.* AU - Liu, L. AU - Breitner-Busch, S. AU - Cyrys, J. AU - Peters, A. AU - Wichmann, H.-E. AU - Franck, U. C1 - 6326 C2 - 28508 SP - 508-513 TI - Size-segregated particle number concentrations and respiratory emergency room visits in Beijing, China. JO - Environ. Health Perspect. VL - 119 IS - 4 PB - Research Triangle Park, N. C. National Institute of Environmental Health Sciences PY - 2011 SN - 0091-6765 ER - TY - JOUR AB - Exposure of humans to air pollutants such as ozone and particulate matter (PM) may result in airway and systemic inflammation and altered immune function. One putative mechanism may be through modification of cell-surface costimulatory molecules. We examined whether changes in expression of costimulatory molecules on circulating cells are associated with ambient levels of fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] in a susceptible population of diabetic individuals. Twenty subjects were studied for 4 consecutive days. Daily measurements of PM2.5 and meteorologic data were acquired on the rooftop of the exam site. Circulating cell-surface markers that mediate innate immune and inflammatory responses were assessed by flow cytometry on each day. Sensitivity analysis was conducted on glutathione S-transferase M1 (GSTM1) genotype, body mass index, and glycosylated hemoglobin A1c (HbA1c) levels to determine their role as effect modifiers. Data were analyzed using random effects models adjusting for season, weekday, and meteorology. RESULTS: We found significantly increased monocyte expression (mean fluorescent intensity) of CD80, CD40, CD86, HLA-DR, and CD23 per 10-μg/m3 increase in PM2.5 at 2- to 4-day lag times after exposure. These findings were significantly higher in obese individuals, in individuals with HbA1c > 7%, and in participants who were GSTM1 null. Exposure to PM2.5 can enhance antigen-presenting cell phenotypes on circulating cells, which may have consequences in the development of allergic or autoimmune diseases. These effects are amplified in diabetic individuals with characteristics that are associated with insulin resistance or with oxidative stress. AU - Schneider, A.E. AU - Alexis, N.E.* AU - Diaz-Sanchez, D.* AU - Neas, L.M.* AU - Harder, S.* AU - Herbst, M.C.* AU - Cascio, W.E.* AU - Buse, J.B.* AU - Peters, A. AU - Devlin, R.B.* C1 - 5446 C2 - 28768 CY - Research Triangle Park, N. C. SP - 778-783 TI - Ambient PM2.5 exposure up-regulates the expression of costimulatory receptors on circulating monocytes in diabetic individuals. JO - Environ. Health Perspect. VL - 119 IS - 6 PB - National Institute of Environmental Health Sciences PY - 2011 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: The mechanisms of action of many environmental agents commonly involve oxidative stress resulting from mitochondrial dysfunction. Zinc is a common environmental metallic contaminant that has been implicated in a variety of oxidant-dependent toxicological responses. Unlike ions of other transition metals such as iron, copper, and vanadium, Zn(2+) does not generate reactive oxygen species (ROS) through redox cycling. OBJECTIVE: To characterize the role of oxidative stress in zinc-induced toxicity. METHODS: We used an integrated imaging approach that employs the hydrogen peroxide (H2O2)-specific fluorophore Peroxy Green 1 (PG1), the mitochondrial potential sensor 5,5 ,6,6 -tetrachloro-1,1 ,3,3 -tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and the mitochondria-targeted form of the redox-sensitive genetically encoded fluorophore MTroGFP1 in living cells. RESULTS: Zinc treatment in the presence of the Zn(2+) ionophore pyrithione of A431 skin carcinoma cells preloaded with the H(2)O(2)-specific indicator PG1 resulted in a significant increase in H(2)O(2) production that could be significantly inhibited with the mitochondrial inhibitor carbonyl cyanide 3-chlorophenylhydrazone. Mitochondria were further implicated as the source of zinc-induced H(2)O(2) formation by the observation that exposure to zinc caused a loss of mitochondrial membrane potential. Using MTroGFP1, we showed that zinc exposure of A431 cells induces a rapid loss of reducing redox potential in mitochondria. We also demonstrated that zinc exposure results in rapid swelling of mitochondria isolated from mouse hearts. CONCLUSION: Taken together, these findings show a disruption of mitochondrial integrity, H(2)O(2) formation, and a shift toward positive redox potential in cells exposed to zinc. These data demonstrate the utility of real-time, live-cell imaging to study the role of oxidative stress in toxicological responses. AU - Cheng, W.Y.* AU - Tong, H.Y.* AU - Miller, E.W.* AU - Chang, C.J.* AU - Remington, J.* AU - Zucker, R.M.* AU - Bromberg, P.A.* AU - Samet, J.M.* AU - Hofer, T.P. C1 - 4813 C2 - 27571 SP - 902-908 TI - An integrated imaging approach to the study of oxidative stress generation by mitochondrial dysfunction in living cells. JO - Environ. Health Perspect. VL - 118 IS - 7 PB - US Dept Health Human Sciences Public Health Science PY - 2010 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Epidemiological studies have shown that ambient particulate matter (PM) and changes in air temperature are associated with increased cardiopulmonary events. OBJECTIVE: We hypothesized that patients with previous myocardial infarction (MI) experience changes in heart rate (HR) and repolarization parameters, such as Bazett-corrected QT interval (QTc), and T-wave amplitude (Tamp), in association with increases in air pollution and temperature changes. METHODS: Between May 2003 and February 2004, 67 MI survivors from the Augsburg KORA-MI registry repeatedly sent 16 sec electrocardiograms (ECGs) with a personal transmitter (Viapac) via telephone to the Philips Monitoring Center, where ECG parameters were immediately analyzed. Meteorological data and air pollutants were acquired from fixed monitoring sites on an hourly basis. Additive mixed models were used for analysis. Effect modification by patient characteristics was investigated. RESULTS: The analysis of the 1,745 ECGs revealed an increased HR associated with interquartile range (IQR) increases in PM levels among participants not using beta-adrenergic receptor blockers and among those with body mass index ≥ 30 kg/m². We observed a 24- to 47-hr lagged QTc prolongation [0.5% change (95% confidence interval, 0.0-1.0%)] in association with IQR increases in levels of PM ≤ 2.5 µm in aerodynamic diameter, especially in patients with one [0.6% (0.1-1.0%)] or two [1.2% (0.4-2.1%)] minor alleles of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) single-nucleotide polymorphism rs2364725. Positive immediate (0-23 hr) and inverse delayed (48-71 hr up to 96-119 hr) associations were evident between PM and Tamp. We detected an inverse U-shaped association between temperature and Tamp, with a maximum Tamp at 5°C. CONCLUSIONS: Increased air pollution levels and temperature changes may lead to changes in HR and repolarization parameters that may be precursors of cardiac problems. AU - Hampel, R. AU - Schneider, A. AU - Brüske, I. AU - Zareba, W.* AU - Cyrys, J. AU - Rückerl, R. AU - Breitner-Busch, S. AU - Korb, H.* AU - Sunyer, J.* AU - Wichmann, H.-E. AU - Peters, A.E. C1 - 5128 C2 - 27915 SP - 1755-1761 TI - Altered cardiac repolarization in association with air pollution and air temperature among myocardial infarction survivors. JO - Environ. Health Perspect. VL - 118 IS - 12 PB - Natl. Inst Health, Natl. Inst. Environmental Health Sciences PY - 2010 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear. OBJECTIVE: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally. METHODS: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal," "borderline," or "abnormal" according to the subscales "emotional symptoms," "conduct problems," "hyperactivity/inattention," "peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires. RESULTS: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age. CONCLUSIONS: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important. AU - Rückinger, S.* AU - Rzehak, P. AU - Chen, C.-M. AU - Sausenthaler, S. AU - Koletzko, S.* AU - Bauer, C.-P.* AU - Hoffmann, U.* AU - Krämer, U.* AU - Berdel, D.* AU - von Berg, A.* AU - Bayer, O.* AU - Wichmann, H.-E. AU - von Kries, R.* AU - Heinrich, J. C1 - 185 C2 - 27139 SP - 150-154 TI - Prenatal and postnatal tobacco exposure and behavioral problems in 10-year-old children: Results from the GINI-plus prospective birth cohort study. JO - Environ. Health Perspect. VL - 118 IS - 1 PB - US Dept. Health Human Sciences Pubilc. PY - 2010 SN - 0091-6765 ER - TY - JOUR AB - Numerous studies have shown associations between ambient air pollution and daily mortality. OBJECTIVES: Our goal was to investigate the association of ambient air pollution and daily mortality in Erfurt, Germany, over a 10.5-year period after the German unification, when air quality improved. METHODS: We obtained daily mortality counts and data on mass concentrations of particulate matter (PM) < 10 mu m in aerodynamic diameter (PM10), gaseous pollutants, and meteorology in Erfurt between October 1991 and March 2002. We obtained ultrafine particle number concentrations (UFP) and mass concentrations of PM < 2.5 mu m in aerodynamic diameter (PM2.5) from September 1995 to March 2002. We analyzed the data using semiparametric Poisson regression models adjusting for trend, seasonality, influenza epidemics, day of the week, and meteorology. We evaluated cumulative associations between air pollution and mortality using polynomial distributed lag (PDL) models and multiday moving averages of air pollutants. We evaluated changes in the associations over time in time-varying coefficient models. RESULTS: Air pollution concentrations decreased over the study period. Cumulative exposure to UFP was associated with increased mortality. An interquartile range (IQR) increase in the 15-day cumulative mean UFP of 7,649 cm(-3) was associated with a relative risk (RR) of 1.060 [95% confidence interval (CI), 1.008-1.114] for PDL models and an RR/IQR of 1.055 (95% CI, 1.011-1.101) for moving averages. RRs decreased from the mid-1990s to the late 1990s. CONCLUSION: Results indicate an elevated mortality risk from short-term exposure to UFP. They further suggest that RRs for short-term associations of air pollution decreased as pollution control measures were implemented in Eastern Germany. AU - Breitner-Busch, S. AU - Stölzel, M. AU - Cyrys, J. AU - Pitz, M.* AU - Wölke, G. AU - Kreyling, W.G. AU - Küchenhoff, H.* AU - Heinrich, J. AU - Wichmann, H.-E. AU - Peters, A. C1 - 1645 C2 - 26127 SP - 448-454 TI - Short-term mortality rates during a decade of improved air quality in Erfurt, Germany. JO - Environ. Health Perspect. VL - 117 IS - 3 PB - Us Dept Health Human Sciences Public Health Science PY - 2009 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Traffic-related air pollution is related with asthma, and this association may be modified by genetic factors. OBJECTIVES: We investigated the role of genetic polymorphisms potentially modifying the association between home outdoor levels of modeled nitrogen dioxide and asthma. METHODS: Adults from 13 cities of the second European Community Respiratory Health Survey (ECRHS II) were included (n = 2,920), for whom both DNA and outdoor NO(2) estimates were available. Home addresses were geocoded and linked to modeled outdoor NO(2) estimates, as a marker of local traffic-related pollution. We examined asthma prevalence and evaluated polymorphisms in genes involved in oxidative stress pathways [gluthatione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) and NAD(P)H:quinine oxidoreductase (NQO1)], inflammatory response [tumor necrosis factor alpha (TNFA)], immunologic response [Toll-like receptor 4 (TLR4)], and airway reactivity [adrenergic receptor beta2 (ADRB2)]. RESULTS: The association between modeled NO(2) and asthma prevalence was significant for carriers of the most common genotypes of NQO1 rs2917666 [odds ratio (OR) = 1.54; 95% confidence interval (CI), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new-onset asthma, the effect of NO(2) was significant for the most common genotype of NQO1 rs2917666 (OR = 1.52; 95% CI, 1.09-2.16). A significant interaction was found between NQO1 rs2917666 and NO(2) for asthma prevalence (p = 0.02) and new-onset asthma (p = 0.04). CONCLUSIONS: Genetic polymorphisms in the NQO1 gene are related to asthma susceptibility among persons exposed to local traffic-related air pollution. This points to the importance of antioxidant pathways in the protection against the effects of air pollution on asthma. AU - Castro-Giner, F.* AU - Künzli, N.* AU - Jacquemin, B.* AU - Forsberg, B.* AU - de Cid, R.* AU - Sunyer, J.* AU - Jarvis, D.* AU - Briggs, D.* AU - Vienneau, D.* AU - Norbäck, D.* AU - Gonzalez, J.R.* AU - Guerra, S.* AU - Janson, C.* AU - Antò, J.M.* AU - Wjst, M. AU - Heinrich, J. AU - Estivill, X.* AU - Kogevinas, M.* C1 - 1171 C2 - 26188 SP - 1919-1924 TI - Traffic-related air pollution, oxidative stress genes, and asthma (ECHRS). JO - Environ. Health Perspect. VL - 117 IS - 12 PB - Us Dept Health Human Sciences Public Health Science PY - 2009 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: It has been hypothesized that ambient particulate air pollution is able to modify the autonomic nervous control of the heart, measured as heart rate variability (HRV). Previously we reported heterogeneous associations between particulate matter with aerodynamic diameter < 2.5 mu m (PM2.5) and HRV across three study centers. OBJECTIVE: We evaluated whether exposure misclassification, effect modification by medication, or differences in particle composition could explain die inconsistencies. METHODS: Subjects with coronary heart disease visited clinics biweekly in Amsterdam, the Netherlands; Erfurt, Germany; and Helsinki, Finland for 6-8 months. The standard deviation (SD) of NN intervals on an electrocardiogram (ECG; SDNN) and high frequency (HF) power of HRV was measured with ambulatory ECG during paced breathing. Outdoor levels of PM2.5 were measured at a central site. In Amsterdam and Helsinki, indoor and personal PM2.5 were measured during the 24 hr preceding the clinic visit. PM2.5 was apportioned between sources using principal component analyses. We analyzed associations of indoor/personal PM2.5 elements of PM2.5 and source-specific PM2.5 With HRV using linear regression. RESULTS: Indoor and personal PM2.5 were not associated with HRV. Increased outdoor PM2.5 was associated with decreased SDNN and HF at lags of 2 and 3 days only among persons not using beta-blocker medication. Traffic-related PM2.5 was associated with decreased SDNN, and long-range transported PM2.5 with decreased SDNN and HF, most strongly among persons not using beta blockers. Indicators for PM2.5 from traffic and long-range transport were also associated with decreased HRV. CONCLUSIONS: Our results suggest that differences in the composition of particles, beta-blocker use, and obesity of study subjects may explain some inconsistencies among previous studies on HRV. AU - de Hartog, J.J.* AU - Lanki, T.* AU - Timonen, K.L.* AU - Hoek, G.* AU - Janssen, N.A.H.* AU - Ibald-Mulli, A. AU - Peters, A. AU - Heinrich, J. AU - Tarkiainen, T.H.* AU - van Grieken, R.* AU - van Wijnen, J.H.* AU - Brunekreef, B.* AU - Pekkanen, J.* C1 - 117 C2 - 26226 SP - 105-111 TI - Associations between PM2.5 and heart rate variability are modified by particle composition and beta-blocker use in patients with coronary heart disease. JO - Environ. Health Perspect. VL - 117 IS - 1 PB - Us Dept Health Human Sciences Public Health Science PY - 2009 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Evidence suggests that cardiovascular effects of air pollution are mediated by inflammation and that air pollution can induce genetic expression of the interleukin-6 gene (IL6). OBJECTIVES: We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients with cardiovascular disease. METHODS: We repeatedly determined plasma IL-6 in 955 myocardial infarction survivors from six European cities (n = 5,539). We conducted city-specific analyses using additive mixed models adjusting for patient characteristics, time trend, and weather to assess the impact of air pollutants on plasma IL-6. We pooled city-specific estimates using meta-analysis methodology. We selected three IL6 single-nucleotide polymorphisms (SNPs) and one SNP each from the fibrinogen alpha-chain gene (FGA) and beta-chain gene (FGB) for gene-environment analyses. RESULTS: We found the most consistent modifications for variants in IL6 rs2069832 and FBG rs1800790 after exposure to carbon monoxide (CO; 24-hr average; p-values for interaction, 0.034 and 0.019, respectively). Nitrogen dioxide effects were consistently modified, but p-values for interaction were larger (0.09 and 0.19, respectively). The strongest effects were seen 6-11 hr after exposure, when, for example, the overall effect of a 2.2% increase in IL-6 per 0.64 mg/m(3) CO was modified to a 10% (95% confidence interval, 4.6-16%) increase in IL-6 (p-value for interaction 0.002) for minor homozygotes of FGB rs1800790. CONCLUSIONS: The effect of gaseous traffic-related air pollution on inflammation may be stronger in genetic subpopulations with ischemic heart disease. This information could offer an opportunity to identify postinfarction patients who would benefit more than others from a cleaner environment and antiinflammatory treatment. AU - Ljungman, P.* AU - Bellander, T.* AU - Schneider, A.E. AU - Breitner-Busch, S. AU - Forastiere, F.* AU - Hampel, R. AU - Illig, T. AU - Jacquemin, B.* AU - Katsouyanni, K.* AU - von Klot, S. AU - Koenig, W.* AU - Lanki, T.* AU - Nyberg, F.* AU - Pekkanen, J.* AU - Pistelli, R.* AU - Pitsavos, C.* AU - Rosenqvist, M.* AU - Sunyer, J.* AU - Peters, A. C1 - 1298 C2 - 26487 SP - 1373-1379 TI - Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms. JO - Environ. Health Perspect. VL - 117 IS - 9 PB - Us Dept Health Human Sciences Public Health Science PY - 2009 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight. OBJECTIVE: Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth. METHODS: We recruited pregnant women in two French maternity hospitals in 2005-2006 as part of the EDEN mother-child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth. RESULTS: Median benzene exposure was 1.8 mu g/m(3) (5th, 95th percentiles, 0.5, 7.5 mu g/m(3)). Log-transformed benzene exposure was associated with a gestational age-adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), -135 to -1 g] and of 1.9 mm, in mean head circumference at birth (95% CI, -3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 turn in head circumference assessed during the third trimester (95% CL -4.0 to 0.3 mm) and of 1.5 turn in head circumference assessed at the end of the second trimester of pregnancy (95% Cl, -3.1 to 0 mm). CONCLUSIONS: Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants. AU - Slama, R.* AU - Thiebaugeorges, O.* AU - Goua, V.* AU - Aussel, L.* AU - Sacco, P.* AU - Bohet, A.* AU - Forhan, A.* AU - Ducot, B.* AU - Annesi-Maesano, I.* AU - Heinrich, J. AU - Magnin, G.* AU - Schweitzer, M.* AU - Kaminski, M.* AU - Charles, M.A.* C1 - 1191 C2 - 26565 SP - 1313-1321 TI - Maternal personal exposure to airborne benzene and intrauterine growth. JO - Environ. Health Perspect. VL - 117 IS - 8 PB - Us Dept Health Human Sciences Public Health Science PY - 2009 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: The inhalation of combustion-derived nanoparticles (CDNPs) is believed to cause an oxidative stress response, which in turn may lead to pulmonary or even systemic inflammation. OBJECTIVE AND METHODS: In this study we assessed whether the in vivo inflammatory response-which is generally referred to as particle toxicity-of mice to CDNPs can be predicted in vitro by a cell-free ascorbate test for the surface reactivity or, more precisely, oxidative potency (Ox(Pot),) of particles. RESULTS: For six types of CDNPs with widely varying particle diameter (10-50 nm), organic content (OC; 1-20%), and specific Brunauer, Emmett, and Teller (BET) surface area (43-800 m(2)/g), Ox(Pot) correlated strongly with the in vivo inflammatory response (pulmonary polymorphonuclear neutrophil influx 24 hr after intratracheal particle instillation). However, for CDNPs with high organic content, Ox(Pot) could not explain the observed inflammatory response, possibly due to shielding of the Ox(Pot) of the carbon core of CDNPs by an organic coating. On the other hand, a pathway-specific gene expression screen indicated that, for particles rich in polycyclic aromatic hydrocarbon (PAHs), cytochrome P450 1A1 (CYP1A1) enzyme-mediated biotransformation of bioavailable organics may generate oxidative stress and thus enhance the in vivo inflammatory response. CONCLUSION: The compensatory nature of both effects (shielding of carbon core and biotransformation of PAHs) results in a good correlation between inflammatory response and BET surface area for all CDNPs. Hence, the in vivo inflammatory response can either be predicted by BET surface area or by a simple quantitative model, based on in vitro Ox(Pot) and Cyp1a1 induction. AU - Stöger, T. AU - Takenaka, S. AU - Frankenberger, B. AU - Ritter, B. AU - Karg, E.W. AU - Maier, K.L. AU - Schulz, S. AU - Schmid, O. C1 - 1028 C2 - 26399 SP - 54-60 TI - Deducing in vivo toxicity of combustion-derived nanoparticles from a cell-free oxidative potency assay and metabolic activation of organic compounds. JO - Environ. Health Perspect. VL - 117 IS - 1 PB - Us Dept Health Human Sciences Public Health Science PY - 2009 SN - 0091-6765 ER - TY - JOUR AB - BACKGROUND: Exposure to fine airborne particulate matter [<= 2.5 mu m in aerodynamic diameter (PM2.5)] has been associated with cardiovascular and hematologic effects, especially in older people with cardiovascular disease. Some epidemiologic studies suggest that adults with diabetes also may be a particularly susceptible population. OBJECTIVES: The purpose of this study was to analyze the short-term effects of ambient PM2.5 on markers of endothelial function in diabetic volunteers.METHODS: We conducted a prospective panel study in 22 people with type 2 diabetes mellitus in Chapel Hill, North Carolina (USA), from November 2004 to December 2005. We acquired daily measurements of PM2.5 and meteorologic data at central monitoring sites. On 4 consecutive days, we measured endothelial function by brachial artery ultrasound in all participants and by pulsewave measurements in a subgroup. Data were analyzed using additive mixed models with a random participant effect and adjusted for season, day of the week, and meteorology. RESULTS: Flow-mediated dilatation decreased in association with PM2.5 during the first 24 hr, whereas small-artery elasticity index decreased with a delay of 1 and 3 days. These PM2.5-associated decrements in endothelial function were greater among participants with a high body mass index, high glycosylated hemoglobin Ale, low adiponectin, or the null polymorphism of glutathione S-transferase M1. However, high levels of myeloperoxidase on the examination day led to strongest effects on endothelial dysfunction. CONCLUSIONS: These data demonstrate that PM2.5 exposure may cause immediate endothelial dysfunction. Clinical characteristics associated with insulin resistance were associated with enhanced effects of PM on endothelial function. In addition, participants with greater oxidative potential seem to be more susceptible. AU - Schneider, A.E. AU - Neas, L.* AU - Herbst, M.C.* AU - Case, M.* AU - Williams, R.W.* AU - Cascio, W.* AU - Hinderliter, A.* AU - Holguin, F.* AU - Buse, J.B.* AU - Dungan, K.* AU - Styner, M.* AU - Peters, A. AU - Devlin, R.B.* C1 - 4376 C2 - 25842 SP - 1666-1674 TI - Endothelial Dysfunction: Associations with Exposure to Ambient Fine Particles in Diabetic Individuals. JO - Environ. Health Perspect. VL - 116 IS - 12 PB - National Institute of Environmental Health Sciences, Research Triangle Park PY - 2008 SN - 0091-6765 ER - TY - JOUR AB - There is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration. OBJECTIVES: The objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research. DISCUSSION: Participants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time-activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case-control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed. CONCLUSIONS: To make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies. AU - Slama, R. AU - Darrow, L.* AU - Parker, J.* AU - Woodruff, T.J.* AU - Strickland, M.* AU - Nieuwenhuijsen, M.* AU - Glinianaia, S.* AU - Hoggatt, K.J.* AU - Kannan, S.* AU - Hurley, F.* AU - Kalinka, J.* AU - Srám, R.* AU - Brauer, M.* AU - Wilhelm, M.* AU - Heinrich, J. AU - Ritz, B.* C1 - 4575 C2 - 25489 SP - 791-798 TI - Meeting report: Atmospheric pollution and human reproduction. JO - Environ. Health Perspect. VL - 116 IS - 6 PB - Research Triangle Park, NC [u.a.] PY - 2008 SN - 0091-6765 ER - TY - JOUR AB - Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation. Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles. A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004. We compared repeated measurements of interleukin 6 (IL-6) , fibrinogen, and C-reactive protein (CRP) with concurrent levels of air pollution. We collected hourly data on particle number concentrations (PNC) , mass concentrations of particulate matter (PM) < 10 µm (PM10) and < 2.5 µm (PM2.5) , gaseous pollutants, and meteorologic data at central monitoring sites in each city. City-specific confounder models were built for each blood marker separately, adjusting for meteorology and time-varying and time-invariant covariates. Data were analyzed with mixed-effects models. Pooled results show an increase in IL-6 when concentrations of PNC were elevated 12–17 hr before blood withdrawal [percent change of geometric mean, 2.7 ; 95% confidence interval (CI) , 1.0–4.6]. Five day cumulative exposure to PM10 was associated with increased fibrinogen concentrations (percent change of arithmetic mean, 0.6 ; 95% CI, 0.1–1.1) . Results remained stable for smokers, diabetics, and patients with heart failure. No consistent associations were found for CRP. Results indicate an immediate response to PNC on the IL-6 level, possibly leading to the production of acute-phase proteins, as seen in increased fibrinogen levels. This might provide a link between air pollution and adverse cardiac events. AU - Rückerl, R. AU - Greven, S. AU - Ljungman, P.* AU - Aalto, P.* AU - Antoniades, C.* AU - Bellander, T.* AU - Berglind, N.* AU - Chrysohoou, C.* AU - Forastiere, F.* AU - Jacquemin, B.* AU - von Klot, S. AU - Koenig, W.* AU - Küchenhoff, H.* AU - Lanki, T.* AU - Pekkanen, J.* AU - Perucci, CA.* AU - Schneider, A.E. AU - Sunyer, J.* AU - Peters, A. AU - AIRGENE Study Group (*) C1 - 3637 C2 - 24603 SP - 1072-1080 TI - Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors. JO - Environ. Health Perspect. VL - 115 IS - 7 PY - 2007 SN - 0091-6765 ER - TY - JOUR AB - Some studies have suggested that particulate matter (PM) levels during pregnancy may be associated with birth weight. Road traffic is a major source of fine PM (PM with aerodynamic diameter < 2.5 µm ; PM2.5) . We determined to characterize the influence of maternal exposure to atmospheric pollutants due to road traffic and urban activities on offspring term birth weight. Women from a birth cohort [the LISA (Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children) cohort] who delivered a non-premature baby with a birth weight > 2,500 g in Munich metropolitan area were included. We assessed PM2.5, PM2.5 absorbance (which depends on the blackness of PM2.5, a marker of traffic-related air pollution) , and nitrogen dioxide levels using a land-use regression model, taking into account the type and length of roads, population density, land coverage around the home address, and temporal variations in pollution during pregnancy. Using Poisson regression, we estimated prevalence ratios (PR) of birth weight < 3,000 g, adjusted for gestational duration, sex, maternal smoking, height, weight, and education. Exposure was defined for 1,016 births. Taking the lowest quartile of exposure during pregnancy as a reference, the PR of birth weight < 3,000 g associated with the highest quartile was 1.7 for PM2.5 [95% confidence interval (CI) , 1.2–2.7], 1.8 for PM2.5 absorbance (95% CI, 1.1–2.7) , and 1.2 for NO2 (95% CI, 0.7–1.7) . The PR associated with an increase of 1 µg/m3 in PM2.5 levels was 1.13 (95% CI, 1.00–1.29) . Increases in PM2.5 levels and PM2.5 absorbance were associated with decreases in term birth weight. Traffic-related air pollutants may have adverse effects on birth weight. AU - Slama, R. AU - Morgenstern, V. AU - Cyrys, J. AU - Zutavern, A. AU - Herbarth, O.* AU - Wichmann, H.-E. AU - Heinrich, J. C1 - 1415 C2 - 24586 SP - 1283-1292 TI - Traffic-related atmospheric pollutants levels during pregnancy and offspring's term birth weight: A study relying on a land-use regression exposure model. JO - Environ. Health Perspect. VL - 115 IS - 9 PY - 2007 SN - 0091-6765 ER - TY - JOUR AU - Stöger, T. AU - Schmid, O. AU - Takenaka, S. AU - Schulz, S. C1 - 4228 C2 - 24863 SP - 290-291 TI - Inflammatory Response to TiO2 and Carbonaceous Particles Scales Best with BET Surface Area. JO - Environ. Health Perspect. VL - 115 IS - 6 PY - 2007 SN - 0091-6765 ER - TY - JOUR AB - Little is known about the mechanisms involved in lung inflammation caused by the inhalation or instillation of nanoparticles. Current research focuses on identifying the particle parameter that can serve as a proper dose metric. OBJECTIVES: The purpose of this study was to review published dose-response data on acute lung inflammation in rats and mice after instillation of titanium dioxide particles or six types of carbon nanoparticles. I explored four types of dose metrics: the number of particles, the joint length--that is, the product of particle number and mean size--and the surface area defined in two different ways. FINDINGS: With the exception of the particle size-based surface area, all other parameters worked quite well as dose metrics, with the particle number tending to work best. The apparent mystery of three equally useful dose metrics could be explained. Linear dose-response relationships were identified at sufficiently low doses, with no evidence of a dose threshold below which nanoparticle instillation ceased to cause inflammation. In appropriately reduced form, the results for three different sets of response parameters agreed quite well, indicating internal consistency of the data. The reduced data revealed particle-specific differences in surface toxicity of the carbon nanoparticles, by up to a factor of four, with diesel soot being at the low end. CONCLUSIONS: The analysis suggests that the physical characterization of nanoparticles and the methods to determine surface toxicity have to be improved significantly before the appropriate dose metric for lung inflammation can be identified safely. There is also a need for refinements in quantifying response to exposure. AU - Wittmaack, K. C1 - 1813 C2 - 25053 SP - 187-194 TI - In search of the most relevant parameter for quantifying lung inflammatory response to nanoparticle exposure: Particle number, surface area, or what? JO - Environ. Health Perspect. VL - 115 IS - 2 PY - 2007 SN - 0091-6765 ER - TY - JOUR AB -   A response by K. Wittmaack to a letter to the editor about his article “In search of the most relevant parameter for quantifying lung inflammatory response to nanoparticle exposure: particle number, surface area,” which appeared in the vol. 115, 2007 issue is presented.   AU - Wittmaack, K. C1 - 3538 C2 - 25052 SP - 291-292 TI - Dose and response metrics in nanotoxicology: Wittmaack responds to Oberdoerster et al. and Stöger et al.. JO - Environ. Health Perspect. VL - 115 IS - 6 PY - 2007 SN - 0091-6765 ER - TY - JOUR AB - Background: Otitis media is one of the most common infections in young children. Although exposure to environmental tobacco smoke is a known risk factor associated with otitis media, little information is available regarding the potential association with air pollution. Objective: We set out to study the relationship between exposure to traffic-related air pollution and otitis media in two birth cohorts. Methods: Individual estimates of outdoor concentrations of traffic-related air pollutants - nitrogen dioxide, fine particles [particulate matter with aerodynamic diameters ≤ 2.5 μ (PM2.5)], and elemental carbon - were calculated for home addresses of approximately 3,700 and 650 infants from birth cohort studies in the Netherlands and Germany, respectively. Air pollution exposure was analyzed in relation to physician diagnosis of otitis media in the first 2 years of life. Results: Odds ratios (adjusted for known major risk factors) for otitis media indicated positive associations with traffic-related air pollutants. An increase in 3 μg/m3 PM2.5, 0.5 μg/m3 elemental carbon, and 10 μg/m3 NO2 was associated with odds ratios of 1.13 (95% confidence interval, 1.00-1.27), 1.10 (1.00-1.22), and 1.14 (1.03-1.27) in the Netherlands and 1.24 (0.84-1.83), 1.10 (0.86-1.41), and 1.14 (0.87-1.49) in Germany, respectively. Conclusions: These findings indicate an association between exposure to traffic-related air pollutants and the incidence of otitis media. Given the ubiquitous nature of air pollution exposure and the importance of otitis media to children's health, these findings have significant public health implications. AU - Brauer, M.* AU - Gehring, U. AU - Brunekreef, B.* AU - de Jongste, J.* AU - Gerritsen, J.* AU - Rovers, M.* AU - Wichmann, H.-E. AU - Wijga, A.* AU - Heinrich, J. C1 - 3861 C2 - 24048 SP - 1414-1418 TI - Traffic-related air pollution and otitis media. JO - Environ. Health Perspect. VL - 114 IS - 9 PY - 2006 SN - 0091-6765 ER - TY - JOUR AB - Introduction: Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. Design: With in a prospective birth cohort, we performed a case-control study; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides. Results: Eight organochlorine pesticides were measurable in all samples (medians; nanograms per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p′-DDE): 97.3/83.8; β-hexachlorocyclohexane (β-HCH): 13.6/12.3; hexachlorobenzene (HCB): 10.6/8.8; α-endosulfan: 7.0/6.7; oxychlordane: 4.5/4.1; 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p′-DDT): 4.6/4.0; dieldrin: 4.1/3.1; cis-heptachloroepoxide (cis-HE): 2.5/2.2. Five compounds [octachlorostyrene (OCS); pentachlorobenzene, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p′-DDD); o,p′-DDT; mirex] were measurable in most samples (detection rates 90.8-99.2%) but in lower concentrations. For methoxychlor, cis-chlordane, pentachloroanisole (PCA), γ-HCH, 1,1-dichloro-2-(2-chlorophenyl)-2,2(4-chlorophenyl)ethane, trans-chlordane, α-HCH, and o,p′-DDE, both concentrations and detection rates were low (26.5-71.5%). Heptachlor, HCH (δ, ε), aldrin, β-endosulfan and trans-heptachloroepoxide were detected at negligible concentrations and low detection rates and were not analyzed further. Seventeen of 21 organochlorine pesticides [p,p′-DDT, p,p′-DDE, p,p′-DDD, o,p′-DDT, HCH (α, β, γ), HCB, PCA, α-endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0.012), there were no significant differences between cryptorchid and healthy boys for individual chemicals. However, combined statistical analysis of the eight most abundant persistent pesticides showed that pesticide levels in breast milk were significantly higher in boys with cryptorchidism (p = 0.032). Conclusion: The association between congenital cryptorchidism and some persistent pesticides in breast milk as a proxy for maternal exposure suggests that testicular descent in the fetus may be adversely affected. AU - Damgaard, I.N.* AU - Skakkebaek, N.E.* AU - Toppari, J.* AU - Virtanen, H.E.* AU - Shen, H. AU - Schramm, K.-W. AU - Petersen, J.H.* AU - Jensen, T.K.* AU - Main, K.M.* C1 - 149 C2 - 23724 SP - 1133-1138 TI - Persistent pesticides in human breast milk and cryptorchidism. JO - Environ. Health Perspect. VL - 114 IS - 7 PY - 2006 SN - 0091-6765 ER - TY - JOUR AU - Geiser, M.* AU - Rothen-Rutishauser, B.* AU - Kapp, N.* AU - Gehr, P.* AU - Schürch, S.* AU - Kreyling, W.G. AU - Schulz, S. AU - Semmler, M. AU - Heyder, J. AU - Im Hof, V.* C1 - 3075 C2 - 23877 SP - 212-213 TI - Ultrafine particles. JO - Environ. Health Perspect. VL - 114 PY - 2006 SN - 0091-6765 ER - TY - JOUR AB - Objective: It has been proposed that the redox activity of particles may represent a major determinant of their toxicity. We measured the in vitro ability of ambient fine particles [particulate matter with aerodynamic diameters ≤ 2.5 μm (PM2.5)] to form hydroxyl radicals (•OH) in an oxidant environment, as well as to deplete physiologic antioxidants (ascorbic acid, glutathione) in the naturally reducing environment of the respiratory tract lining fluid (RTLF). The objective was to examine how these toxicologically relevant measures were related to other PM characteristics, such as total and elemental mass concentration and light absorbance. Design: Gravimetric PM2.5 samples (n = 716) collected over 1 year from 20 centers participating in the European Community Respiratory Health Survey were available. Light absorbance of these filters was measured with reflectometry. PM suspensions were recovered from filters by vortexing and sonication before dilution to a standard concentration. The oxidative activity of these particle suspensions was then assessed by measuring their ability to generate •OH in the presence of hydrogen peroxide, using electron spin resonance and 5,5-dimethyl-1-pyrroline-N-oxide as spin trap, or by establishing their capacity to deplete antioxidants from a synthetic model of the RTLF. Results and Conclusions: PM oxidative activity varied significantly among European sampling sites. Correlations between oxidative activity and all other characteristics of PM were low, both within centers (temporal correlation) and across communities (annual mean). Thus, no single surrogate measure of PM redox activity could be identified. Because these novel measures are suggested to reflect crucial biologic mechanisms of PM, their use may be pertinent in epidemiologic studies. Therefore, it is important to define the appropriate methods to determine oxidative activity of PM. AU - Künzli, N.* AU - Mudway, I.S.* AU - Götschi, T.* AU - Shi, T.* AU - Kelly, F.J.* AU - Cook, S.* AU - Burney, P.* AU - Forsberg, B.* AU - Gauderman, J.W.* AU - Hazenkamp, M.E.* AU - Heinrich, J. AU - Jarvis, D.* AU - Norbäck, D.* AU - Payo-Losa, F.* AU - Poli, A.* AU - Sunyer, J.* AU - Borm, P.J.* C1 - 4998 C2 - 23693 SP - 684-690 TI - Comparison of oxidative properties, light absorbance and total and elemental mass concentration of ambient PM2.5 collected at 20 European sites. JO - Environ. Health Perspect. VL - 114 IS - 5 PY - 2006 SN - 0091-6765 ER - TY - JOUR AB - Epidemiologic studies have shown that ambient particulate matter (PM) has adverse effects on cardiovascular health. Effective mitigation of the health effects requires identification of the most harmful PM sources. The objective of our study was to evaluate relative effects of fine PM [aero-dynamic diameter ≤ 2.5 μm (PM2.5)] from different sources on exercise-induced ischemia. We collected daily outdoor PM2.5 samples between autumn 1998 and spring 1999 in Helsinki, Finland. The mass of PM2.5 was apportioned between five sources. Forty-five elderly nonsmoking persons with stable coronary heart disease visited a clinic biweekly for submaximal exercise testing, during which the occurrence of ST segment depressions was recorded. Levels of PM2.5 originating from local traffic and long-range transport were associated with ST segment depressions > 0.1 mV, with odds ratios at 2-day lag of 1.53 [95% confidence interval (CI), 1.19-1.97] and 1.11 (95% CI, 1.02-1.20) per 1 μg/m3, respectively. In multipollutant models, where we used indicator elements for sources instead of source-specific PM2.5, only absorbance (elemental carbon), an indicator of local traffic and other combustion, was associated with ST segment depressions. Our results suggest that the PM fraction originating from combustion processes, notably traffic, exacerbates ischemic heart diseases associated with PM mass. AU - Lanki, T.* AU - de Hartog, J.J.* AU - Heinrich, J. AU - Hoek, G.* AU - Janssen, N.A.H.* AU - Peters, A. AU - Stölzel, M. AU - Timonen, K.L.* AU - Vallius, M.* AU - Vanninen, E.* AU - Pekkanen, J.* C1 - 4725 C2 - 23692 SP - 655-660 TI - Can we identify sources of fine particles responsible for exercise-induced ischemia on days with elevated air pollution? The ULTRA study. JO - Environ. Health Perspect. VL - 114 IS - 5 PY - 2006 SN - 0091-6765 ER - TY - JOUR AB - Increased levels of particulate air pollution are associated with increased respiratory and cardiovascular mortality and morbidity. Some epidemiologic and toxicologic research suggests ultrafine particles (UFPs) (< 100 nm) to be more harmful per unit mass than larger particles. Our study was aimed at a quantitative comparison of acute adverse effects of different types of carbonaceous UFPs at a dose range that causes a moderate inflammatory response in lungs. We used six different particle types (primary particle size 10-50 nm, specific surface area 30-800 m2/g, and organic content 1-20%): PrintexG, Printex90, flame soot particles with different organic content (SootL, SootH), spark-generated ultrafine carbon particles (ufCP), and the reference diesel exhaust particles (DEP) SRM1650a. Mice were instilled with 5, 20, and 50 μg of each particle type, and bronchoalveolar lavage was analyzed 24 hr after instillation for inflammatory cells and the level of proinflammatory cytokines. At respective mass-doses, particle-caused detrimental effects ranked in the following order: ufCP > SootL ≥ SootH > Printex90 > PrintexG > DEP. Relating the inflammatory effects to the particle characteristics - organic content, primary particle size, or specific surface area - demonstrates the most obvious dose response for particle surface area. Our study suggests that the surface area measurement developed by Brunauer, Emmett, and Teller is a valuable reference unit for the assessment of causative health effects for carbonaceous UFPs. Additionally, we demonstrated the existence of a threshold for the particle surface area at an instilled dose of approximately 20 cm2, below which no acute proinflammatory responses could be detected in mice. AU - Stöger, T. AU - Reinhard, C. AU - Takenaka, S. AU - Schröppel, A. AU - Karg, E.W. AU - Ritter, B. AU - Heyder, J. AU - Schulz, S. C1 - 4044 C2 - 23533 SP - 328-333 TI - Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. JO - Environ. Health Perspect. VL - 114 IS - 3 PY - 2006 SN - 0091-6765 ER - TY - JOUR AB - Stochastic modeling was used to predict nitrogen dioxide and fine particles [particles collected with an upper 50% cut point of 2.5 μm aerodynamic diameter (PM2.5)] levels at 1,669 addresses of the participants of two ongoing birth cohort studies conducted in Munich, Germany. Alternatively, the Gaussian multisource dispersion model IMMISnet/em was used to estimate the annual mean values for NO2 and total suspended particles (TSP) for the 40 measurement sites and for all study subjects. The aim of this study was to compare the measured NO2 and PM2.5 levels with the levels predicted by the two modeling approaches (for the 40 measurement sites) and to compare the results of the stochastic and dispersion modeling for all study infants (1,669 sites). NO2 and PM2.5 concentrations obtained by the stochastic models were in the same range as the measured concentrations, whereas the NO2 and TSP levels estimated by dispersion modeling were higher than the measured values. However, the correlation between stochastic- and dispersion-modeled concentrations was strong for both pollutants: At the 40 measurement sites, for NO2, r = 0.83, and for PM, r = 0.79; at the 1,669 cohort sites, for NO2, r = 0.83 and for PM, r = 0.79. Both models yield similar results regarding exposure estimate of the study cohort to traffic-related air pollution, when classified into tertiles; that is, 70% of the study subjects were classified into the same category. In conclusion, despite different assumptions and procedures used for the stochastic and dispersion modeling, both models yield similar results regarding exposure estimation of the study cohort to traffic-related air pollutants. AU - Cyrys, J. AU - Hochadel, M. AU - Gehring, G. AU - Hoek, G.* AU - Diegmann, V.* AU - Brunekreef, B.* AU - Heinrich, J. C1 - 2824 C2 - 23131 SP - 987-992 TI - GIS-based estimation of exposure to particulate matter and NO2 in an urban area: Stochastic versus dispersion modeling. JO - Environ. Health Perspect. VL - 113 IS - 8 PY - 2005 SN - 0091-6765 ER - TY - JOUR AB - High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPS; particles < 0.1 μm). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 μm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential. AU - Geiser, M.* AU - Rothen-Rutishauser, B.* AU - Kapp, N.* AU - Schürch, S.* AU - Kreyling, W.G. AU - Schulz, S. AU - Semmler, M. AU - Im Hof, V.* AU - Heyder, J. AU - Gehr, P.* C1 - 663 C2 - 22977 SP - 1555-1560 TI - Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. JO - Environ. Health Perspect. VL - 113 IS - 11 PY - 2005 SN - 0091-6765 ER - TY - JOUR AB - Epidemiologic studies report associations between particulate air pollution and cardiovascular morbidity and mortality, but the underlying pathophysiologic mechanisms are still unclear. We tested the hypothesis that patients with preexisting coronary heart disease experience changes in the repolarization parameters in association with rising concentrations of air pollution. A prospective panel study was conducted in Erfurt, East Germany, with 12 repeated electrocardiogram (ECG) recordings in 56 males with ischemic heart disease. Hourly particulate and gaseous air pollution and meteorologic data were acquired. The following ECG parameters reflecting myocardial substrate and vulnerability were measured: QT duration, T-wave amplitude, T-wave complexity, and variability of T-wave complexity. Fixed effect regression analysis was used adjusting for subject, trend, weekday, and meteorology. The analysis showed a significant increase in QT duration in response to exposure to organic carbon; a significant decrease in T-wave amplitude with exposure to ultrafine, accumulation mode, and PM2.5 particles (particles < 2.5 μm in aerodynamic diameter); and a corresponding significant increase of T-wave complexity in association with PM2.5 particles for the 24 hr before ECG recordings. Variability of T-wave complexity showed a significant increase with organic and elemental carbon in the same time interval. This study provides evidence suggesting an immediate effect of air pollution on repolarization duration, morphology, and variability representing myocardial substrate and vulnerability, key factors in the mechanisms of cardiac death. AU - Henneberger, A.* AU - Zareba, W.* AU - Ibald-Mulli, A. AU - Rückerl, R. AU - Cyrys, J. AU - Couderc, J.-P.* AU - Mykins, B.* AU - Woelke, G. AU - Wichmann, H.-E. AU - Peters, A. C1 - 3897 C2 - 22683 SP - 440-446 TI - Repolarization changes induced by air pollution in ischemic heart disease patients. JO - Environ. Health Perspect. VL - 113 IS - 4 PY - 2005 SN - 0091-6765 ER - TY - JOUR AU - Thurston, G.D.* AU - Stölzel, M. C1 - 4055 C2 - 23271 SP - 1768-1774 TI - Workshop report: Workshop on source apportionment of particulate matter health effects­intercomparison of results and implications. JO - Environ. Health Perspect. VL - 113 IS - 12 PY - 2005 SN - 0091-6765 ER - TY - JOUR AU - Gehring, U. AU - Triche, E.* AU - van Strien, R.T.* AU - Belanger, K.* AU - Holford, T.* AU - Gold, D.R.* AU - Jankun, T.* AU - Ren, P.* AU - McSharry, J.-E.* AU - Beckett, W.S.* AU - Platts-Mills, T.A.E.* C1 - 444 C2 - 22050 SP - 834-839 TI - Prediction of residential pet and cockroach allergen levels using questionnaire information. JO - Environ. Health Perspect. VL - 112 IS - 8 PY - 2004 SN - 0091-6765 ER - TY - JOUR AB - Given the hypothesis that air pollution is associated with elevated blood pressure and heart rate, the effect of daily concentrations of air pollution on blood pressure and heart rate was assessed in 131 adults with coronary heart disease in Helsinki, Finland; Erfurt, Germany; and Amsterdam, the Netherlands. Blood pressure was measured by a digital monitor, and heart rate was calculated as beats per minute from an electrocardiogram recording with the patient in supine position. Particle concentrations were measured at central measuring sites. Linear regression was used to model the association between 24-hr mean concentrations of particles and blood pressure and heart rate. Estimates were adjusted for trend, day of week, temperature, barometric pressure, relative humidity, and medication use. Pooled effect estimates showed a small significant decrease in diastolic and systolic blood pressure in association with particulate air pollution; a slight decrease in heart rate was found. Of the three centers, Erfurt revealed the most consistent particle effects. The results do not support findings from previous studies that had shown an increase in blood pressure and heart rate in healthy individuals in association with particles. However, particle effects might differ in cardiac patients because of medication intake and disease status, both affecting the autonomic control of the heart. AU - Ibald-Mulli, A. AU - Timonen, K.L.* AU - Peters, A. AU - Heinrich, J. AU - Wölke, G. AU - Buzorius, G.* AU - Kreyling, W.G. AU - de Hartog, J.* AU - Hoek, G.* AU - ten Brink, H.M.* AU - Pekkanen, J.* C1 - 10219 C2 - 37001 SP - 369-377 TI - Effects of Particulate Air Pollution on Blood Pressure and Heart Rate in Subjects with Cardiovascular Disease : A Multe-Centre Approach. JO - Environ. Health Perspect. VL - 112 IS - 3 PY - 2004 SN - 0091-6765 ER - TY - JOUR AU - Frye, C. AU - Hoelscher, B. AU - Cyrys, J. AU - Wjst, M. AU - Wichmann, H.-E. AU - Heinrich, J. C1 - 10217 C2 - 21514 SP - 383-387 TI - Association of Lung Function with Declining Ambient Air Pollution. JO - Environ. Health Perspect. VL - 111 IS - 3 PY - 2003 SN - 0091-6765 ER - TY - JOUR AU - Gavett, S.H.* AU - Haykal-Coates, N.* AU - Copeland, L.B.* AU - Heinrich, J. AU - Gilmour, M.I.* C1 - 10216 C2 - 21361 SP - 1471-1478 TI - Metal Composition of Ambient PM2.5 Influences Severity of Allergic Airways Disease in Mice. JO - Environ. Health Perspect. VL - 111 IS - 12 PY - 2003 SN - 0091-6765 ER - TY - JOUR AU - Lippmann, M.* AU - Frampton, M.* AU - Schwartz, J.* AU - Dockery, D.* AU - Schlesinger, R.* AU - Koutrakis, P.* AU - Froines, J.* AU - Nel, A.* AU - Finkelstein, J.* AU - Godleski, J.* AU - Kaufman, J.* AU - Koenig, J.* AU - Larson, T.* C1 - 10218 C2 - 21633 SP - 1074-1092 TI - The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program : A Midcourse Report of Status, Progress and Plans. JO - Environ. Health Perspect. VL - 111 IS - 8 PY - 2003 SN - 0091-6765 ER - TY - JOUR AB - Evidence that indoor dampness and mold growth are associated with respiratory health has been accumulating, but few studies have been able to examine health risks in relation to measured levels of indoor mold exposure. In particular, little is known about the contribution of indoor molds to the development of allergic sensitization. As a part of an ongoing study examining the effects of ambient air pollutants on respiratory health and atopic diseases in German school children, we examined the relation between viable mold levels indoors and allergic sensitization in 272 children. We examined whether allergic sensitization in children is associated with higher fungal spore count in settled house dust sampled from living room floors. Adjusting for age, sex, parental education, region of residency, and parental history of atopy, we found that mold spore counts for Cladosporium and Aspergillus were associated with an increased risk of allergic sensitization. Sensitized children exposed to high levels of mold spores (> 90th percentile) were more likely to suffer from symptoms of rhinoconjunctivitis. We conclude that elevated indoor concentrations of molds in wintertime might play a role in increasing the risk of developing atopic symptoms and allergic sensitization not only to molds but also to other common, inhaled allergens. These effects were strongest in the group of children who had lived in the same home since birth. AU - Jacob, B. AU - Ritz, B.* AU - Gehring, U. AU - Koch, A.* AU - Bischof, W.* AU - Wichmann, H.-E. AU - Heinrich, J. AU - INGA Study Group (*) C1 - 22059 C2 - 20692 SP - 647-653 TI - Indoor Exposure to Molds and Allergic Sensitization. JO - Environ. Health Perspect. VL - 110 IS - 7 PY - 2002 SN - 0091-6765 ER - TY - JOUR AB - Agglomerates of ultrafine particles (AUFPs) may cause adverse health effects because of their large surface area. To evaluate physiologic responses of immune cells, we studied whether agglomerates of 77-nm elemental carbon [(EC); specific surface area 750 m2/g] and 21 nm titanium dioxide (TiO(2) particles (specific surface area 50 m(2)/g) affect the release of lipid mediators by alveolar macrophages (AMs). After 60-min incubation with 1 microg/mL AUFP-EC (corresponding to 7.5 cm(2) particle surface area), canine AMs (1 x 10(6) cells/mL) released arachidonic acid (AA) and the cyclooxygenase (COX) products prostaglandin E(2) (PGE(2), thromboxane B(2), and 12-hydroxyheptadecatrienoic acid but not 5-lipoxygenase (5-LO) products. AUFP-TiO(2) with a 10-fold higher mass (10 microg/mL) than AUFP-EC, but a similar particle surface area (5 cm(2) also induced AMs to release AA and COX products. Agglomerates of 250 nm TiO(2) particles (specific surface area 6.5 m(2)/g) at 100 microg/mL mass concentration (particle surface area 6.5 cm(2) showed the same response. Interestingly, 75 cm(2)/mL surface area of AUFP-EC and 16 cm(2)/mL surface area of AUFP-TiO(2) additionally induced the release of the 5-LO products leukotriene B(4) and 5-hydroxyeicosatetraenoic acid. Respiratory burst activity of stimulated canine neutrophils was partially suppressed by supernatants of AMs treated with various mass concentrations of the three types of particles. Inhibition of neutrophil activity was abolished by supernatants of AMs treated with COX inhibitors prior to AUFP-incubation. This indicates that anti-inflammatory properties of PGE(2) dominate the overall response of lipid mediators released by AUFP-affected AMs. In conclusion, our data indicate that surface area rather than mass concentration determines the effect of AUFPs, and that activation of phospholipase A(subscript)2(/subscript) and COX pathway occurs at a lower particle surface area than that of 5-LO-pathway. We hypothesize a protective role of PGE(2) in downregulating potential inflammatory reactions induced by ultrafine particles. AU - Beck-Speier, I. AU - Dayal, E. AU - Karg, E.W. AU - Maier, K.L. AU - Roth, C. AU - Ziesenis, A. AU - Heyder, J. C1 - 9538 C2 - 20224 SP - 613-618 TI - Agglomerates of Ultrafine Particles of Elemental Carbon and TiO2 Induce Generation of Lipid Mediators in Alveolar Macrophages. JO - Environ. Health Perspect. VL - 109 PY - 2001 SN - 0091-6765 ER - TY - JOUR AB - beta(1-->3)-Glucans are potent proinflammatory agents that have been suggested to play a role in indoor-related respiratory health effects. The aim of this study was to assess whether beta(1-->3)-glucan concentrations in house dust are correlated with levels of endotoxins, allergens, and culturable mold spore counts in house dust. Further, the associations of beta(1-->3)-glucan with housing characteristics and occupant behavior were assessed. beta(1-->3)-Glucan was measured in settled house dust from living room floors of 395 homes of two German cities, Erfurt and Hamburg, with a specific enzyme immunoassay. Concentrations ranged from below the limit of detection to 19,013 microg/m(2) (22,588 microg/g dust). Concentrations per square meter were found to be correlated with endotoxins, mite and cat allergens, and culturable mold spores. Correlations were weaker when concentrations were expressed per gram of dust, indicating that variance in concentrations of all factors is largely determined by the amount of dust sampled. Associations between beta(1-->3)-glucan, housing characteristics, and occupant behavior were found for concentrations per square meter but not for concentrations per gram of dust. The following characteristics were associated with a significant increase in beta(1-->3)-glucan levels: carpets in the living room [means ratio (MR) = 1.9-2.1], keeping a dog inside (MR = 1.4), use of the home by four or more persons (MR = 1.4), use of the living room for > 180 hr/week (MR = 2.1), lower frequency of vacuum cleaning (MR = 1.6-3.0) and dust cleaning (MR = 1.2 and 1.4, respectively), and presence of mold spots during the past 12 months (MR = 1.4). We conclude that that the amount of dust sampled can be used as a proxy for hygiene and that beta(1-->3)-glucan concentrations per square meter are related to the amount of dust sampled. AU - Gehring, U. AU - Douwes, J.* AU - Doekes, G.* AU - Koch, A.* AU - Bischof, W.* AU - Fahlbusch, B.* AU - Richter, K.* AU - Wichmann, H.-E. AU - Heinrich, J. C1 - 21685 C2 - 19869 SP - 139-144 TI - ß(1-3)-Glucan in House Dust of German Homes : Housing Characteristics, Occupant Behavior and Relations with Endotoxins, Allergens and Molds. JO - Environ. Health Perspect. VL - 109 IS - 2 PY - 2001 SN - 0091-6765 ER - TY - JOUR AB - The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways. AU - Takenaka, S. AU - Karg, E.W. AU - Roth, C. AU - Schulz, S. AU - Ziesenis, A. AU - Heinzmann, U. AU - Schramel, P. AU - Heyder, J. C1 - 10220 C2 - 22563 SP - 547-551 TI - Pulmonary and systematic distribution of inhaled ultrafine silver particles in rats. JO - Environ. Health Perspect. VL - 109 PY - 2001 SN - 0091-6765 ER - TY - JOUR AB - Increased mortality has been observed in association with elevated concentrations of air pollutants in European cities and in the United States. We reassessed the effects of particulate matter in Central Europe. Mortality and air pollution data were obtained for a highly polluted region of the Czech Republic and a rural region in Germany. Poisson regression analyses were conducted considering trend, season, meteorology, and influenza epidemics as confounders in both a parametric and a nonparametric approach. The Czech Republic had a 3.8% increase in mortality [95% confidence interval (CI), 0.8-6.9%] in association with 100 microg/m(3) total suspended particles (TSP) (lagged 2 days) for the time period 1982-1994. During the last 2 years of study, 68% of the TSP consisted of particulate matter [less than/equal to] 10 microm in aerodynamic diameter (PM(10)). An increase of 100 microg/m(3) TSP (lagged 1 day) was associated with a 9.5% increase in mortality (CI, 1.2-18.5%) and 100 microg/m(3) PM(10 )(lagged 1 day) showed a 9.8% increase in mortality (CI, 0.7-19.7%). We found no evidence for an association between mortality and particulate matter in the rural area in Germany at the Czech border. Data from the coal basin in the Czech Republic suggested an increase in mortality associated with the concentration of particulate matter in a highly polluted setting in Central Europe that is consistent with the associations observed in other western European cities and in the United States. AU - Peters, A. AU - Skorkovsky, J.* AU - Kotesovec, F.* AU - Brynda, J.* AU - Spix, C. AU - Wichmann, H.-E. AU - Heinrich, J. C1 - 21375 C2 - 19492 SP - 283-287 TI - Associations between Mortality and Air Pollution in Central Europe. JO - Environ. Health Perspect. VL - 108 IS - 4 PY - 2000 SN - 0091-6765 ER - TY - JOUR AB - Numerous investigations have been carried out on the possible impact of the Chernobyl accident on the prevalence of anomalies at birth and on perinatal mortality. In many cases the studies were aimed at the detection of differences of pregnancy outcome measurements between regions or time periods. Most authors conclude that there is no evidence of a detrimental physical effect on congenital anomalies or other outcomes of pregnancy following the accident. In this paper, we report on statistical analyses of time trends of perinatal mortality in Germany. Our main intention is to investigate whether perinatal mortality, as reflected in official records, was increased in 1987 as a possible effect of the Chernobyl accident. We show chat, in Germany as a whole, there was a significantly elevated perinatal mortality proportion in 1987 as compared to the trend function. The increase is 4.8% (p = 0.0046) of the expected perinatal death proportion for 1987. Even more pronounced levels of 8.2% (p = 0.0458) and 8.5% (p = 0.0702) may be found in the higher contaminated areas of the former German Democratic Republic (GDR), including West Berlin, and of Bavaria, respectively. To investigate the impact of statistical models on results, we applied three standard regression techniques. The observed significant increase in 1987 is independent of the statistical model used. Stillbirth proportions show essentially the same behavior as perinatal death proportions, but the results for all of Germany are nonsignificant due to the smaller numbers involved. Analysis of the association of stillbirth proportions with the Cs-137 deposition on a district level in Bavaria discloses a significant relationship. Our results are in contrast to those of many analyses of the health consequences of the Chernobyl accident and contradict the present radiobiologic knowledge. As we are dealing with highly aggregated data, other causes or artifacts may explain the observed effects. Hence, the findings should be interpreted with caution, and further independent evidence should be sought. AU - Scherb, H. AU - Weigelt, E. AU - Brüske, I. C1 - 10221 C2 - 19346 SP - 159-164 TI - Regression Analysis of Time Trends in Perinatal Mortality in Germany, 1980-1993. JO - Environ. Health Perspect. VL - 108 IS - 2 PB - NC [u.a.] PY - 2000 SN - 0091-6765 ER - TY - JOUR AU - Brüske, I. C1 - 20909 C2 - 18954 SP - 253-258 TI - Occupational cancer in Germany. JO - Environ. Health Perspect. VL - 107 (Suppl.2) PY - 1999 SN - 0091-6765 ER - TY - JOUR AB - This cross-sectional epidemiological study collected health data for 2,470 school children between 5 and 14 years of age (89% of eligible children) who had lived most of their lives in either one of two counties strongly impacted by industrial pollution (Bitterfeld and Hettstedt) or in a neighboring county without any sources of industrial pollution (Zerbst). The objective of the study was to examine whether regional differences--with respect to the occurrence of childhood respiratory diseases and symptoms or allergies--exist and, if such differences are found, whether they persist when we adjust for the effects of known risk factors such as medical and sociodemographic factors or factors related to the indoor environment. Controlling for medical, sociodemographic, and indoor factors, according to parental reports, children residing in Hettstedt have about a 50% increased lifetime prevalence for physician-diagnosed allergies, eczema, and bronchitis compared to children from Zerbst and about twice the number of respiratory symptoms such as wheeze, shortness of breath, and cough without cold. Sensitization to common aeroallergens according to skin prick tests [odds ratio (OR) = 1.38; 95% confidence interval (CI), 1.02-1.86] and specific IgE levels (OR = 1.75; CI, 1.31-2.33) was more common for children from Hettstedt than children from the nonpolluted county. Bitterfeld children, on the other hand, more often received a diagnosis of asthma and eczema than children residing in Zerbst and also showed slightly increased sensitization rates. In conclusion, industrial pollution related to mining and smelting operations in the county of Hettstedt were associated with a higher lifetime prevalence of respiratory disorders and an increased rate of allergic sensitization in children between the ages of 5 and 14 years. Further studies are needed to determine what role the high dust content of heavy metals plays in Hettstedt. AU - Heinrich, J. AU - Hoelscher, B. AU - Wjst, M. AU - Ritz, B.* AU - Cyrys, J. AU - Wichmann, H.-E. C1 - 20925 C2 - 18970 SP - 53-62 TI - Respiratory diseases and allergies in two polluted areas in East Germany. JO - Environ. Health Perspect. VL - 107 IS - 1 PY - 1999 SN - 0091-6765 ER - TY - JOUR AB - comments on S. Patandin et al. : Dietary exposure to polychlorinated biphenyls and dioxins from infancy until adulthood: a comparison between breast-feeding, toddler, and long-term exposure. Environ Health Perspect 107:45-51 (1999). AU - LaKind, J.S.* AU - Filser, J.G. C1 - 23993 C2 - 31431 SP - A495-A497 TI - Dietary exposure to PCBs and dioxins. JO - Environ. Health Perspect. VL - 107 IS - 10 PB - US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PY - 1999 SN - 0091-6765 ER - TY - JOUR AB - The lung's response to deposited particles may depend upon the physical-chemical properties of the particles, the amount initially deposited, and the persistence of the particles. Clearance involves mucociliary transport as well as the action of phagocytic cells in nonciliated regions of the lung. Depending on the animal species studied, particle type, and particle load, inorganic materials are ingested by macrophages on alveolar surfaces with half-times of 0.6 to 7 hr. Particle-laden macrophages may migrate to airways, but we believe that an important mechanism of clearance is the dissolution of particles within alveolar macrophages and the subsequent translocation of dissolved materials to the blood. Particle dissolution in situ has long been recognized but was often thought to be carried out extracellularly in the alveolar lining layer, airway mucus, or interstitial fluid. However, many particles such as cobalt oxide or iron oxide which dissolve very little in simulated lung fluid, are solubilized more rapidly within alveolar macrophages. Clearance of particles from the lungs can be followed by a number of techniques, both invasive and noninvasive. The approaches vary in expense and resolution, and can be directed toward quantifying mechanical removal of particles versus their intracellular dissolution. Noninvasive methods permit repeated measurements of particle retention in the lungs of the same animal or human and thus allow replications and serial measurements. Greater precision with respect to the sites of retention and redistribution is achieved with quantitative morphometric methods that utilize fixation followed by physically dividing the respiratory tract into individual pieces. AU - Brain, J.D. AU - Godleski, J.J. AU - Kreyling, W.G. C1 - 20601 C2 - 13812 SP - 119-125 TI - In vivo evaluation of chemical biopersistence of nonfibrous inorganic particles. JO - Environ. Health Perspect. VL - 102 IS - 5 PY - 1994 SN - 0091-6765 ER - TY - JOUR AB - The effect of 2-aminofluorene (2-AF) on the toxicity of 2-aminoanthracene (2-AA) and 1,6-dinitropyrene (1,6-DNP) was studied in N-acetyltransferase-proficient V79-NHr1A2 cells genetically engineered for the expression of cytochrome P4501A2, and in wild-type V79-NH cells. 2-AA inhibited the growth of V79-NHr1A2 cells and induced the formation of micronuclei at concentrations of 0.1 to 1.0 μM, but was virtually without toxic effects at a concentration of 10 μM. Addition of 2-AF protected against the cytotoxic and genotoxic effects elicited by low concentrations of 2-AA. Half-maximum protection was observed at 0.2 to 0.5 μM 2-AF. The arylamine also prevented the cytotoxicity caused by 1,6-DNP in V79-NH cells and completely suppressed the formation of 1-acetylamino-6-nitropyrene from 1,6-DNP in these cells. The results indicate that arylamines and related N-hydroxyarylamines are substrates for the same acetyltransferase in V79-NH cells. In consequence, arylamines are capable of suppressing the activation of their proximate cytotoxic and genotoxic products in these cells and, presumably, in vivo. AU - Kiefer, F. AU - Cumpelik, O. AU - Reen, R.K. AU - Doehmer, J. AU - Wiebel, F.J. C1 - 40047 C2 - 38933 SP - 95-97 TI - Arylamines suppress their own activation and that of nitroarenes in V79 Chinese hamster cells by competing for acetyltransferases. JO - Environ. Health Perspect. VL - 102 IS - SUPPL. 6 PY - 1994 SN - 0091-6765 ER - TY - JOUR AU - Adler, I.-D. AU - Parry, J.M. C1 - 19827 C2 - 12976 SP - 5-9 TI - Development of Screening Tests for Aneuploidy Induction by Environmental Pollutants. JO - Environ. Health Perspect. VL - 101 PY - 1993 SN - 0091-6765 ER - TY - JOUR AB - When legally required mutagenicity testing of chemicals is undertaken, the important genetic end point of aneuploidy is not included because validated test methods are lacking. Therefore, the Commission of the European Communities (CEC) has funded a research program to develop and validate tests for aneuploidy induction. Ten chemicals, selected on the basis of their ability to interact with cell organelles relevant for aneuploidy induction, were tested in 11 laboratories. The assays ranged from in vitro tubulin assembly studies to in vivo germ-cell tests. The results allow several conclusions: a) Fungal aneuploidy tests are not capable of detecting inhibitors of mammalian tubulin polymerization such as colchicine and vinblastine. Therefore, they will not play a role in screening for aneuploidy but are of value for studying the relationship between induced aneuploidy and recombination. b) Chemicals that induce aneuploidy in mammalian germ cells are readily detected in the in vitro mammalian cell systems. Some chemicals such as thiabendazole and thimerosal induce aneuploidy in vitro but do not appear to be very effective in vivo. c) Cell division aberrations induced in mammalian cells in vitro seem to be predictive for aneuploidy induction in the same cell type. Likewise, c-mitotic effects and cell cycle delay in vivo in mitotic and meiotic cells correlate with aneuploidy induction in the respective tissue. A second CEC Aneuploidy Program has started recently to refine the most promising test protocols, to provide understanding of the variety of mechanisms by which chemicals induce aneuploidy, and to establish a data base for aneugens among environmental pollutants. AU - Adler, I.-D. AU - Parry, J.M. C1 - 40322 C2 - 40643 SP - 5-9 TI - Development of screening tests for aneuploidy induction by environmental pollutants. JO - Environ. Health Perspect. VL - 101 PY - 1993 SN - 0091-6765 ER - TY - JOUR AB - Mammalian germ cell stages exhibit differences in DNA synthesis activity, capability to repair DNA damage, and chromosome-associated proteins. The sensitivity to mutation induction may be influenced by such factors as the accessibility of DNA to chemical mutagens, the interval between DNA damage induction and the next round of DNA replication, and the repair of DNA damage. Such qualitative and quantitative differences indicate the complexities of mutation induction in vivo and emphasize that no single in vitro test system can adequately represent the in vivo situation. Therefore, germ-cell mutagenesis in humans can most adequately be represented by an vivo mammalian germ-cell test system. Information regarding the mechanisms of mutation induction in germ cells of the mouse, appropriate mutation test systems available in the mouse, as well as principles of chemical mutagenesis in the mouse and their implications for an adequate human genetic risk estimation will be discussed. AU - Favor, J.B. C1 - 33948 C2 - 37479 SP - 263-267 TI - Genetic effects from exposure to hazardous agents. JO - Environ. Health Perspect. VL - 101 IS - SUPPL. 3 PY - 1993 SN - 0091-6765 ER - TY - JOUR AB - Intracellular dissolution of inhaled inorganic particles is an important clearance mechanism of the lung and occurs in phagolysosomal vacuoles of phagocytes. Flow cytometric measurements of intraphagolysosomal pH in alveolar macrophages (AM) obtained from beagle dogs, Wistar rats, and from a baboon were made using fluorescein isothiocyanate-labeled amorphous silica particles (FSP). AM were obtained by bronchoalveolar lavage. FSP were phagocytized by AM in cell suspensions incubated in full media for 24 hr up to 6 days. Dual laser flow cytometry was performed and six-parameter list mode data were recorded from forward scatter, side scatter, and fluorescence intensities at 530 nm excited at 457 nm and 488 nm as well as logarithmic fluorescence intensity at wavelengths 630 nm excited at 488 nm. In this way it was possible to discriminate viable AM with phagocytized FSP from lysing AM with phagocytized FSP and from cells without FSP and from free FSP. Viable cells were distinguished from lysing cells by staining with propidium iodide immediately before the flow cytometric measurement. A calibration curve for the pH value was determined from FSP suspended in buffered media at pH values ranging from 3.5 to 7.5. First flow cytometrical results indicated that after an incubation time of 24 hr, the mean intraphagolysosomal pH of viable AM was 4.7 ± 0.3 for dogs and 5.1 ± 0.5 for rats. The intraphagolysosomal pH of the baboon AM was 4.5. AU - Heilmann, P. AU - Beisker, W. AU - Miaskowski, U. AU - Camner, P. AU - Kreyling, W.G. C1 - 40673 C2 - 34268 SP - 115-120 TI - Intraphagolysosomal pH in canine and rat alveolar macrophages: Flow cytometric measurements. JO - Environ. Health Perspect. VL - 97 PY - 1992 SN - 0091-6765 ER - TY - JOUR AU - Kreyling, W.G. AU - Covelli, V. AU - Metivier, H. AU - Morgan, A. AU - Patrick, G. C1 - 19103 C2 - 12159 TI - International Symposium on the Role of the Alveolar Macrophage in the Clearance of Inhaled Particles, 19-21 September 1990, Oxford University, UK. JO - Environ. Health Perspect. PY - 1990 SN - 0091-6765 ER - TY - JOUR AB - Studies were conducted on inhalation pharmacokinetics of 1,3-butadiene and of its primary reactive metabolic intermediate 1,2-epoxybutene-3 in rats (Sprague-Dawley) and mice (B6C3F1). Investigations of inhalation pharmacokinetics of 1,3-butadiene revealed saturation kinetics of 1,3-butadiene metabolism in both species. For rats and mice linear pharmacokinetics apply at exposure concentrations below 1000 ppm 1,3-butadiene; saturation of 1,3-butadiene metabolism is observed at atmospheric concentrations of about 2000 ppm. The estimated maximal metabolic elimination rates were 400 mumole/hr/kg for mice and 200 mumole/hr/kg for rats. This shows that 1,3-butadiene is metabolized by mice at about twice the rate of rats. Investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 revealed major differences in metabolism of this compound between both species. No indication of saturation kinetics of 1,2-epoxybutene-3 metabolism could be observed in rats up to exposure concentrations of 5000 ppm, whereas in mice the saturation of epoxybutene metabolism became apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate for 1,2-epoxybutene-3 was 350 mumole/hr/kg in mice and greater than 2600 mumole/hr/kg in rats. When the animals are exposed to high concentrations of 1,3-butadiene, 1,2-epoxybutene-3 is exhaled by rats and mice. For rats 1,2-epoxybutene-3 concentration in the gas phase of the system reaches a plateau at about 4 ppm. For mice, 1,2-epoxybutene-3 concentration increases with exposure time until, at about 10 ppm, signs of acute toxicity are observed. Under these conditions hepatic nonprotein sulfhydryl compounds are virtually depleted in mice but not in rats. AU - Laib, R.J. AU - Filser, J.G. AU - Kreiling, R. AU - Vangala, R.R. AU - Bolt, H.M. C1 - 18330 C2 - 11520 SP - 57-63 TI - Inhalation Pharmacokinetics of 1,3-butadiene and 1,2-epoxybutene-3 in Rats and Mice. JO - Environ. Health Perspect. VL - 86 PY - 1990 SN - 0091-6765 ER - TY - JOUR AB - Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 mumole/hr/kg for rats and 400 mumole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 mumole/hr/kg for rats and 0.4 mumole/hr/kg for mice. Our data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound. AU - Peter, H. AU - Wiegand, H.-J. AU - Filser, J.G. AU - Bolt, H.M. AU - Laib, R.J. C1 - 18327 C2 - 11517 SP - 89-92 TI - Inhalation Pharmacokinetics of Isoprene in Rats and Mice. JO - Environ. Health Perspect. VL - 86 PY - 1990 SN - 0091-6765 ER -