Increases in air pollution, especially the particulate component, are associated with increased cardiovascular mortality, possibly through increases in thrombogenic mechanisms. The research presented in this thesis addresses the hypothesis that diesel exhaust particulates (DEP) increase thrombogenicity by impairing the release of tissue plasminogen activator (t-PA) from vascular endothelial cells, thus inhibiting the endogenous fibrinolytic mechanisms that promote thrombus breakdown. The initial aims of this work were to develop an in vivo model of thrombosis, to determine whether exposure to DEP did alter clotting. Initial attempts to develop the Folts’ model (which stimulates thrombus formation via arterial stenosis and mechanical injury), first in male C57/Bl6 mice and later in male Wistar rats, were unsuccessful. An alternative approach, using ferric chloride (FeCl3) to induce chemical injury to the rat carotid artery was found to produce reliable and reproducible thrombotic occlusion: this model was used for all subsequent experiments. The effects of DEP on thrombus formation were assessed in vivo by applying the FeCl3 model. DEP were administered via intratracheal instillation or tail vein injection 2, 6 or 24 hours prior to induction of thrombosis. The effects of DEP were compared with vehicle and suitable controls: carbon black (a clean carbon nanoparticle); quartz (a large non-carbon particle that causes well-characterised pulmonary inflammation). The time to thrombotic occlusion was significantly reduced 6h after intra-pulmonary instillation of DEP (0.5ml of a 1mg/ml suspension). In contrast, instillation of carbon black or quartz had no significant effect on thrombosis, despite causing greater pulmonary (increased neutrophils and levels of interleukin-6, tumour necrosis factor-α and C-reactive protein in bronchoalveolar lavage fluid) and systemic (C-reactive protein in plasma) inflammation than DEP. Direct administration of DEP (0.5mg/kg) to the blood stream resulted in an acute (2 hours after injection) increase in time to thrombotic occlusion in the absence of pulmonary inflammation. A similar (but less pronounced) effect was observed following administration of carbon black (0.5mg/kg). These data suggest that the DEP-mediated increase in thrombosis is independent of pulmonary and systemic inflammation. The mechanisms involved were addressed by measuring platelet-monocyte interactions (flow cytometry) and markers of the endogenous fibrinolytic system (ELISA). Exposure (either instillation of injection) to DEP significantly increased platelet-monocyte aggregation. Carbon black and quartz produced no such effect (but did increase platelet-platelet aggregation). t-PA antigen and activity were reduced, whilst PAI-1 and fibrinogen were increased, following either instillation or injection of DEP. The final aim was to develop a suitable dispersant for use in cell culture to determine whether DEP alter the expression (real-time polymerase chain reaction; rtPCR) and generation (enzyme-linked immunosorbent assay; ELISA) of t-PA and plasminogen activator inhibitor (PAI-1). Cell culture medium containing bovine serum albumin (0.5mg/ml; BSA) provided the best combination for DEP dispersal and maintenance of small particle size (<200nM), without detrimental effects on human umbilical endothelial cells (HUVECs). Exposure (6 and 24 hours) of HUVECs to DEP resulted in reduced basal and thrombin stimulated t-PA and PAI-1 expression. This was mirrored by reduced detection of t-PA and PAI-1 in culture medium. In conclusion, these investigations confirm that exposure to DEP is capable of increasing the rate of thrombus formation and that this is, in part, mediated by an alteration in the endogenous fibrinolytic system. These changes did not appear to be secondary to pulmonary or systemic inflammation. Whilst cell culture experiments suggested DEP could directly alter endogenous fibrinolytic activity in endothelial cells, there was no evidence from these experiments of DEP translocation into the systemic circulation. Thus, this work suggests that DEP is capable of increasing thrombus formation in vivo via several mechanisms. Similar changes may account for the increased thrombus formation in humans exposed to diesel exhaust in air pollution.

No description available.

Thesis (M. P. A.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Air pollution is a well known public health problem that involves both long-term and acute effects. An outcome associated with traffic-related air pollution is respiratory illness. Many studies have described the relationship between asthmatic symptoms and traffic-related air pollution; however, few have investigated the potential of air pollution to cause asthma itself, especially among adults. The overall aim of this thesis was to study the relationship between vehicle exhaust levels at home and the prevalence of self-reported annoyance and asthmatic symptoms, and the incidence of asthma and rhinitis. These relationships were evaluated using different indicators of exposure with a high spatial resolution. Three different data sets were used for the four papers included in this thesis. The first paper (paper I) is based on a questionnaire that was sent to a random selection of the adult population within three Swedish cities (Gothenburg, Uppsala, and Umeå) as part of the Swedish Environmental Protection Agency’s health-related environmental monitoring. The aim was to study the degree of self-reported annoyance and the prevalence of asthmatic symptoms in relation to the levels of vehicle exhaust outside the home. The level of exposure was described using modeled levels of nitrogen dioxide (NO2) as the exposure indicator. The second paper (paper II) is based on new asthma cases identified within the Obstructive Lung disease In Northern Sweden (OLIN) study, each with a matched referent. The aim of this study was to analyze if new cases of asthma had higher levels of vehicle exhaust outside the home compared to the population controls. Exposure was assessed using both measured levels of NO2 outside each home, and by summarizing the amount of traffic within a 200 metre buffer surrounding each participant’s home. Papers III and IV were based on the Respiratory Health in Northern Europe (RHINE) Cohort, a prospective cohort of adults included in 1990 and followed up with in 1999. The proportion of new cases of asthma (papers III and IV) and rhinitis (paper IV) were identified based on the answers from the initial and follow-up questionnaires. In paper III, exposure was assessed by using meteorological dispersion models to calculate the levels of NO2 outside each home as an indicator of the levels of vehicle exhaust. As an alternative indicator, the distance from each participant’s home to the nearest major road was calculated using geographical information system (GIS) tools. The exposure assessment in paper IV was also based on meteorological dispersion models, but expressed the levels of vehicle exhaust as particle mass concentration. The results show that the levels of vehicle exhaust outside the home are significantly correlated with the degree of self-reported annoyance and the prevalence of asthmatic symptoms, and also with the risk of developing asthma, but not rhinitis, among adults. The odds ratio (OR) for high annoyance to vehicle exhaust and reporting asthmatic symptoms was 1.14 (95% Confidence Interval, CI 1.11-1.18) and 1.04 (95% CI 1.01-1.07) per 1 µg/m3 increase in the NO2 level outside the home, respectively. Paper II showed there was a non-significant tendency for increased risk of developing asthma among those living with high levels of vehicle exhaust outside their home. This finding was then supported by papers III and IV, showing a significant relationship between the onset of asthma and the mean (winter) levels of NO2 outside the home (OR=1.46, 95% CI 1.07-1.99 per 10 µg/m3) and the levels of vehicle exhaust particles outside the home. In paper III, living close to a major road was significantly related to the risk of developing asthma. No significant results were shown between vehicle exhaust and rhinitis. In conclusion, vehicle exhaust outside the home is associated with the prevalence of annoyance and asthmatic symptoms, and with the risk of developing asthma, but not rhinitis, among adults.

Since 1970, vehicle’s exhaust pollutions have received increasing attention as a source of air pollution at both local (human health concerns) and global (global warming) scales. This study mainly discusses diesel and gasoline vehicles because, today, over 90% of vehicles on the road use gasoline and diesel fuels. The major concerns of gasoline exhaust contaminants are carbon monoxide (CO), hydrocarbon (HC), carbon dioxide (CO2) and polycyclic aromatic hydrocarbons (PAHs); the major concerns of diesel exhaust emissions contaminants are nitrogen oxides (NOX) and particulate matter (PM). The aim of this study is mainly to compare gasoline and diesel fuels, and to determine which fuel and its developed forms are less harmful to humans, and which are most suitable for the natural environment at both a local and global level. The results show that burning gasoline fuels will emit less PM and NOX emissions than burning diesel fuels, but it will generate about 50% more CO2 than diesel fuels, and it also emit about ten times more CO, PAHs and around five times more HC than diesel fuels; burning diesel fuels will produce less CO2 emissions than gasoline fuels, but will emit around ten times more NOX and PM than gasoline fuels. Consequently using a gasoline car in urban areas might help to reduce the human health effects; using a diesel car on motorways or in rural areas might help to reduce the greenhouse gas (GHG) emissions and minimize the global warming effects. Biofuels, biodiesel and ethanol, have the potential to minimize the vehicle exhaust emissions and adverse effects. Nonetheless, there are still many debatable issues around biodiesel, such as insufficient fuel supply and health concerns (especially, ultrafine particles (UFPs)). In the future, there remains a need to continue the further studies of vehicle exhaust emissions, and to improve the understanding of all vehicle exhaust emissions and all of their impacts, especially the vehicle exhaust health research.

The exhaust gas recirculation (EGR) system has been widely used to reduce nitrogen oxide (NOx) emission, improve fuel economy and suppress knock by using the characteristics of charge dilution. However, previous studies have shown that as the EGR rate at a given engine operating condition increases, the combustion instability increases. The combustion instability increases cyclic variations resulting in the deterioration of engine performance and increasing hydrocarbon emissions. Therefore, the optimum EGR rate should be carefully determined in order to obtain the better engine performance and emissions. A thermodynamic cycle simulation of the four-stroke spark-ignition engine was used to determine the effects of EGR on engine performance, emission characteristics and second law parameters, considering combustion instability issues as EGR level increases. A parameter, called 'Fuel Fraction Burned,' was introduced as a function of the EGR percentage and used in the simulation to incorporate the combustion instability effects. A comprehensive parametric investigation was conducted to examine the effects of variations in EGR, load and speed for a 5.7 liter spark-ignition automotive engine. Variations in the thermal efficiencies, brake specific NOx emissions, average combustion temperature, mean exhaust temperature, maximum temperature and relative heat transfer as functions of exhaust gas recycle were determined for both cooled and adiabatic EGR configurations. Also effects of variations in the load and speed on thermal efficiencies, relative heat transfers and destruction of availability due to combustion were determined for 0% EGR and 20% EGR cases with both cooled and adiabatic configurations. For both EGR configurations, thermal efficiencies first increase, reach a maximum at about 16% EGR and then decrease as the EGR level increases. Thermal efficiencies are slightly higher for cooled EGR configuration than that for adiabatic configuration. Concentration of nitric oxide emissions decreases from about 2950 ppm to 200 ppm as EGR level increases from 0% to 20% for cooled EGR configuration. The cooled EGR configuration results in lower nitric oxide emissions relative to the adiabatic EGR configuration. Also second law parameters show the expected trends as functions of EGR. Brake thermal efficiency is higher for the 20% EGR case than that for the no EGR case over the range of load (0 to WOT) and speed (600 rpm to 6000 rpm). Predictions made from the simulation were compared with some of the available experimental results. Predicted thermal efficiencies showed a similar trend when compared to the available experimental data. Also, percentage of unused fuel availability increases as the EGR level increases, and it can be seen as one of the effects of deteriorating combustion quality as the EGR level increases.

Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains xiv, 173 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 158-160).

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xviii, 144 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 106-113).

Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains xv, 164 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 154-156).

Thesis (M.S.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains xii, 114 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 101-103).