Air Pollution from Road Traffic and Systemic Inflammation in Adults: A Cross-Sectional Analysis in the European ESCAPE Project.

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

Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study.

BACKGROUND: Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample. METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). RESULTS: Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals. CONCLUSION: Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.

Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample.

Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures >80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p<0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.

Circulating levels of p,p'-DDE are related to prevalent hypertension in the elderly.

BACKGROUND: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women. METHODS: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure ≥140mmHg or a diastolic blood pressure ≥90mmHg, and/or use of antihypertensive medication. RESULTS: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 1.35 for a 1 SD change, 95% CI 1.17-1.56, p<0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06-1.43, p=0.006). CONCLUSION: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure.

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).

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

Insurance data for research in companion animals: benefits and limitations.

The primary aim of this article is to review the use of animal health insurance data in the scientific literature, especially in regard to morbidity or mortality in companion animals and horses. Methods and results were compared among studies on similar health conditions from different nations and years. A further objective was to critically evaluate benefits and limitations of such databases, to suggest ways to maximize their utility and to discuss the future use of animal insurance data for research purposes. Examples of studies on morbidity, mortality and survival estimates in dogs and horses, as well as neoplasia in dogs, are discussed.We conclude that insurance data can and should be used for research purposes in companion animals and horses. Insurance data have been successfully used, e.g. to quantify certain features that may have been hitherto assumed, but unmeasured. Validation of insurance databases is necessary if they are to be used in research. This must include the description of the insured population and an evaluation of the extent to which it represents the source population. Data content and accuracy must be determined over time, including the accuracy/consistency of diagnostic information. Readers must be cautioned as to limitations of the databases and, as always, critically appraise findings and synthesize information with other research. Similar findings from different study designs provide stronger evidence than a sole report. Insurance data can highlight common, expensive and severe conditions that may not be evident from teaching hospital case loads but may be significant burdens on the health of a population.