Exposure Assessment for Atmospheric Ultrafine Particles (UFPs) and Implications in Epidemiologic Research

Epidemiologic research has shown increases in adverse cardiovascular and respiratory outcomes in relation to mass concentrations of particulate matter (PM) ≤2.5 or ≤10 μm in diameter (PM(2.5), PM(10), respectively). In a companion article [Delfino RJ, Sioutas C, Malik S. 2005. Environ Health Perspect 113(8):934–946]), we discuss epidemiologic evidence pointing to underlying components linked to fossil fuel combustion. The causal components driving the PM associations remain to be identified, but emerging evidence on particle size and chemistry has led to some clues. There is sufficient reason to believe that ultrafine particles < 0.1 μm (UFPs) are important because when compared with larger particles, they have order of magnitudes higher particle number concentration and surface area, and larger concentrations of adsorbed or condensed toxic air pollutants (oxidant gases, organic compounds, transition metals) per unit mass. This is supported by evidence of significantly higher in vitro redox activity by UFPs than by larger PM. Although epidemiologic research is needed, exposure assessment issues for UFPs are complex and need to be considered before undertaking investigations of UFP health effects. These issues include high spatial variability, indoor sources, variable infiltration of UFPs from a variety of outside sources, and meteorologic factors leading to high seasonal variability in concentration and composition, including volatility. To address these issues, investigators need to develop as well as validate the analytic technologies required to characterize the physical/chemical nature of UFPs in various environments. In the present review, we provide a detailed discussion of key characteristics of UFPs, their sources and formation mechanisms, and methodologic approaches to assessing population exposures

Potential Role of Ultrafine Particles in Associations between Airborne Particle Mass and Cardiovascular Health

Numerous epidemiologic time-series studies have shown generally consistent associations of cardiovascular hospital admissions and mortality with outdoor air pollution, particularly mass concentrations of particulate matter (PM) ≤2.5 or ≤10 μm in diameter (PM(2.5), PM(10)). Panel studies with repeated measures have supported the time-series results showing associations between PM and risk of cardiac ischemia and arrhythmias, increased blood pressure, decreased heart rate variability, and increased circulating markers of inflammation and thrombosis. The causal components driving the PM associations remain to be identified. Epidemiologic data using pollutant gases and particle characteristics such as particle number concentration and elemental carbon have provided indirect evidence that products of fossil fuel combustion are important. Ultrafine particles < 0.1 μm (UFPs) dominate particle number concentrations and surface area and are therefore capable of carrying large concentrations of adsorbed or condensed toxic air pollutants. It is likely that redox-active components in UFPs from fossil fuel combustion reach cardiovascular target sites. High UFP exposures may lead to systemic inflammation through oxidative stress responses to reactive oxygen species and thereby promote the progression of atherosclerosis and precipitate acute cardiovascular responses ranging from increased blood pressure to myocardial infarction. The next steps in epidemiologic research are to identify more clearly the putative PM casual components and size fractions linked to their sources. To advance this, we discuss in a companion article (Sioutas C, Delfino RJ, Singh M. 2005. Environ Health Perspect 113:947–955) the need for and methods of UFP exposure assessment

Repolarization Changes Induced by Air Pollution in Ischemic Heart Disease Patients

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 PM(2.5) particles (particles < 2.5 μm in aerodynamic diameter); and a corresponding significant increase of T-wave complexity in association with PM(2.5) 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

Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.

The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria

Kritik an Population Attributable Fraction bei genauerem Hinsehen nicht gerechtfertigt

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Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freibur

Size-Segregated Particle Number Concentrations and Respiratory Emergency Room Visits in Beijing, China

BACKGROUND: The link between concentrations of particulate matter (PM) and respiratory morbidity has been investigated in numerous studies. OBJECTIVES: The aim of this study was to analyze the role of different particle size fractions with respect to respiratory health in Beijing, China. METHODS: Data on particle size distributions from 3 nm to 1 mu m; PM10 (PM &lt;= 10 mu m), nitrogen dioxide (NO2), 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. RESULTS: Associations of respiratory ERV with NO2 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 &lt;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 NO2. CONCLUSIONS: Present levels of air pollution in Beijing were adversely associated with respiratory ERV. NO2 concentrations seemed to be a better surrogate for evaluating overall respiratory health effects of ambient air pollution than PM10 or particle number concentrations in Beijing.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000289065900032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Environmental SciencesPublic, Environmental &amp; Occupational HealthToxicologySCI(E)37ARTICLE4508-51311

Human serum metabolic profiles are age dependent

Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32–81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10−04 to 7.8 × 10−42, αcorr = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging