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Maaike Steenhof,
Ian S Mudway,
Ilse Gosens,
Gerard Hoek,
Krystal J Godri,
Frank J Kelly,
Roy M Harrison,
Raymond H H Pieters,
Flemming R Cassee,
Erik Lebret,
Bert A Brunekreef, Maciej Strak,
Nicole A H Janssen
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ABSTRACT: OBJECTIVES: To investigate which air pollution characteristics are associated with biomarkers for acute nasal airway inflammation in healthy subjects. We hypothesised that associations would be strongest for oxidative potential (OP) of particles. METHODS: 31 volunteers were exposed to ambient air pollution at five sites in The Netherlands: two traffic sites, an underground train station, a farm and an urban background site. Each subject visited at least three sites between March and October 2009 and was exposed for 5 h per visit including exercise for 20 min every hour (h). Air pollution measurements during this 5-h-period included particulate matter (PM) mass concentration, elemental composition, elemental and organic carbon (OC), particle number concentration, OP, endotoxins, O(3) and NO(2). Pro-inflammatory biomarkers were measured before, 2 and 18 h postexposure, including cytokine IL-6 and IL-8, protein and lactoferrin in nasal lavage (NAL) as well as IL-6 in blood. One- and two-pollutant mixed models were used to analyse associations between exposure and changes in biomarkers. RESULTS: In two-pollutant models, cytokines in NAL were positively associated with OC, endotoxin and NO(2); protein was associated with NO(2); and lactoferrin was associated with all PM characteristics that were high at the underground site. In blood, associations with OC and endotoxin were negative. CONCLUSIONS: We observed no consistent effects in two-pollutant models for PM mass concentration and OP. Instead, we found consistent associations with nasal inflammatory markers for other PM characteristics, specifically OC, endotoxin and NO(2).
Occupational and environmental medicine 02/2013; · 3.64 Impact Factor
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Maciej Strak,
Gerard Hoek,
Maaike Steenhof,
Evren Kilinc,
Krystal J Godri,
Ilse Gosens,
Ian S Mudway,
René van Oerle,
Henri M H Spronk,
Flemming R Cassee,
Frank J Kelly,
Roy M Harrison,
Bert Brunekreef,
Erik Lebret,
Nicole A H Janssen
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ABSTRACT: OBJECTIVES: Increases in ambient particulate matter (PM) have been associated with an elevated risk of stroke, myocardial ischaemia and coronary heart disease, with activation of blood coagulation likely playing an important role. PM-mediated activation of two major activation pathways of coagulation provides a potential mechanism for the observed association between PM and cardiovascular disease. However, it remains unclear which specific characteristics and components of air pollution are responsible. METHODS: In order to investigate those characteristics and components, we semiexperimentally exposed healthy adult volunteers at five different locations with increased contrasts and reduced correlations among PM characteristics. Volunteers were exposed for 5 h, exercising intermittently, 3-7 times at different sites from March to October 2009. On site, we measured PM mass and number concentration, its oxidative potential (OP), content of elemental/organic carbon, trace metals, sulphate, nitrate and gaseous pollutants (ozone, nitrogen oxides). Before and 2 and 18 h after exposure we sampled blood from the participants and measured thrombin generation using the calibrated automated thrombogram. RESULTS: We found that thrombin generation increases in the intrinsic (FXII-mediated) blood coagulation pathway in relation to ambient air pollution exposure. The associations with NO(2), nitrate and sulphate were consistent and robust, insensitive to adjustment for other pollutants. The associations with tissue factor-mediated thrombogenicity were not very consistent. CONCLUSIONS: Ex vivo thrombin generation was associated with exposure to NO(2), nitrate and sulphate, but not PM mass, PM OP or other measured air pollutants.
Occupational and environmental medicine 02/2013; · 3.64 Impact Factor
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Maciej Strak,
Nicole A H Janssen,
Ilse Gosens,
Flemming R Cassee,
Erik Lebret,
Krystal J Godri,
Ian S Mudway,
Frank J Kelly,
Roy M Harrison,
Bert Brunekreef,
Maaike Steenhof,
Gerard Hoek
Environmental Health Perspectives 01/2013; 121(1):a11-2. · 7.04 Impact Factor
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Maciej Strak,
Gerard Hoek,
Krystal J Godri,
Ilse Gosens,
Ian S Mudway,
René van Oerle,
Henri M H Spronk,
Flemming R Cassee,
Erik Lebret,
Frank J Kelly,
Roy M Harrison,
Bert Brunekreef,
Maaike Steenhof,
Nicole A H Janssen
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ABSTRACT: Exposure to ambient particulate matter (PM) has been associated with adverse cardiovascular effects in epidemiological studies. Current knowledge of independent effects of individual PM characteristics remains limited.
Using a semi-experimental design we investigated which PM characteristics were consistently associated with blood biomarkers believed to be predictive of the risk of cardiovascular events. We exposed healthy adult volunteers at 5 different locations chosen to provide PM exposure contrasts with reduced correlations among PM characteristics. Each of the 31 volunteers was exposed for 5 h, exercising intermittently, 3-7 times at different sites from March to October 2009. Extensive on-site exposure characterization included measurements of PM mass and number concentration, elemental- (EC) and organic carbon (OC), trace metals, sulfate, nitrate, and PM oxidative potential (OP). Before and 2 h and 18 h after exposure we measured acute vascular blood biomarkers - C-reactive protein, fibrinogen, platelet counts, von Willebrand Factor, and tissue plasminogen activator/plasminogen activator inhibitor-1 complex. We used two-pollutant models to assess which PM characteristics were most consistently associated with the measured biomarkers.
We found OC, nitrate and sulfate to be most consistently associated with different biomarkers of acute cardiovascular risk. Associations with PM mass concentrations and OP were less consistent, whereas other measured components of the air pollution mixture, including PNC, EC, trace metals and NO2, were not associated with the biomarkers after adjusting for other pollutants.
PLoS ONE 01/2013; 8(3):e58944. · 4.09 Impact Factor
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Maciej Strak,
Nicole A H Janssen,
Krystal J Godri,
Ilse Gosens,
Ian S Mudway,
Flemming R Cassee,
Erik Lebret,
Frank J Kelly,
Roy M Harrison,
Bert Brunekreef,
Maaike Steenhof,
Gerard Hoek
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ABSTRACT: Background: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations among, and differential measurement errors of, individual components contribute to this uncertainty.Objectives: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers.Methods: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittently, three to seven times at different locations during March-October 2009. We measured PM10, PM2.5, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function [FEV1 (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF25-75 (forced expiratory flow at 25-75% of vital capacity), and PEF (peak expiratory flow)] and fractional exhaled nitric oxide (FENO) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression.Results: An interquartile increase in PNC (33,000 particles/cm3) was associated with an 11% [95% confidence interval (CI): 5, 17%] and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV1 with PNC, NO2 (nitrogen dioxide), and NOx (nitrogen oxides).Conclusions: Changes in PNC, NO2, and NOx were associated with evidence of acute airway inflammation (i.e., FENO) and impaired lung function. PM mass concentration and PM10 oxidative potential were not predictive of the observed acute responses.
Environmental Health Perspectives 05/2012; 120(8):1183-9. · 7.04 Impact Factor
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Maaike Steenhof,
Ilse Gosens, Maciej Strak,
Krystal J Godri,
Gerard Hoek,
Flemming R Cassee,
Ian S Mudway,
Frank J Kelly,
Roy M Harrison,
Erik Lebret,
Bert Brunekreef,
Nicole A H Janssen,
Raymond H H Pieters
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ABSTRACT: Ambient particulate matter (PM) exposure is associated with respiratory and cardiovascular morbidity and mortality. To what extent such effects are different for PM obtained from different sources or locations is still unclear. This study investigated the in vitro toxicity of ambient PM collected at different sites in the Netherlands in relation to PM composition and oxidative potential.
PM was sampled at eight sites: three traffic sites, an underground train station, as well as a harbor, farm, steelworks, and urban background location. Coarse (2.5-10 μm), fine (< 2.5 μm) and quasi ultrafine PM (qUF; < 0.18 μm) were sampled at each site. Murine macrophages (RAW 264.7 cells) were exposed to increasing concentrations of PM from these sites (6.25-12.5-25-50-100 μg/ml; corresponding to 3.68-58.8 μg/cm2). Following overnight incubation, MTT-reduction activity (a measure of metabolic activity) and the release of pro-inflammatory markers (Tumor Necrosis Factor-alpha, TNF-α; Interleukin-6, IL-6; Macrophage Inflammatory Protein-2, MIP-2) were measured. The oxidative potential and the endotoxin content of each PM sample were determined in a DTT- and LAL-assay respectively. Multiple linear regression was used to assess the relationship between the cellular responses and PM characteristics: concentration, site, size fraction, oxidative potential and endotoxin content.
Most PM samples induced a concentration-dependent decrease in MTT-reduction activity and an increase in pro-inflammatory markers with the exception of the urban background and stop & go traffic samples. Fine and qUF samples of traffic locations, characterized by a high concentration of elemental and organic carbon, induced the highest pro-inflammatory activity. The pro-inflammatory response to coarse samples was associated with the endotoxin level, which was found to increase dramatically during a three-day sample concentration procedure in the laboratory. The underground samples, characterized by a high content of transition metals, showed the largest decrease in MTT-reduction activity. PM size fraction was not related to MTT-reduction activity, whereas there was a statistically significant difference in pro-inflammatory activity between Fine and qUF PM. Furthermore, there was a statistically significant negative association between PM oxidative potential and MTT-reduction activity.
The response of RAW264.7 cells to ambient PM was markedly different using samples collected at various sites in the Netherlands that differed in their local PM emission sources. Our results are in support of other investigations showing that the chemical composition as well as oxidative potential are determinants of PM induced toxicity in vitro.
Particle and Fibre Toxicology 09/2011; 8:26. · 7.25 Impact Factor
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ABSTRACT: Monitoring studies have shown that commuters are exposed to high air pollution concentrations, but there is limited evidence of associated health effects. We carried out a study to investigate the acute respiratory health effects of air pollution related to commuting by bicycle.
Twelve healthy adults cycled a low- and a high-traffic intensity route during morning rush hour in Utrecht, The Netherlands. Exposure to traffic-related air pollution was characterised by measurements of PM(10), soot and particle number. Before, directly after and 6 h after cycling we measured lung function (FEV(1), FVC, PEF), exhaled NO (FE(NO)) and respiratory symptoms. The association between post- minus pre-exposure difference in health effects and exposure during cycling was evaluated with linear regression models.
The average particle number concentration was 59% higher, while the average soot concentration was 39% higher on the high-traffic route than on the low-traffic route. There was no difference for PM(10). Contrary to our hypothesis, associations between air pollution during cycling and lung function changes immediately after cycling were mostly positive. Six hours after cycling, associations between air pollution exposure and health were mostly negative for lung function changes and positive for changes in exhaled NO, although non-significant.
We found substantial differences in ultrafine particle number and soot exposure between two urban cycling routes. Exposure to ultrafine particles and soot during cycling was weakly associated with increased exhaled NO, indicative of airway inflammation, and decrements in lung function 6 h after exposure. A limitation of the study was the relatively small sample size.
Occupational and environmental medicine 09/2009; 67(2):118-24. · 3.64 Impact Factor
