Diluted Diesel Exhaust Research Articles

Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease

Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease

Air pollution: the new cardiovascular risk factor

Air pollution: the new cardiovascular risk factor

Diesel exhaust inhalation increases thrombus formation in man

Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men. In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust inhalation increased thrombus formation under low- and high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels. Diesel exhaust also increased platelet-neutrophil and platelet-monocyte aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air. Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.

Exposure to diesel exhaust induces changes in EEG in human volunteers

BackgroundAmbient particulate matter and nanoparticles have been shown to translocate to the brain, and potentially influence the central nervous system. No data are available whether this may lead to functional changes in the brain.MethodsWe exposed 10 human volunteers to dilute diesel exhaust (DE, 300 μg/m3) as a model for ambient PM exposure and filtered air for one hour using a double blind randomized crossover design. Brain activity was monitored during and for one hour following each exposure using quantitative electroencephalography (QEEG) at 8 different sites on the scalp. The frequency spectrum of the EEG signals was used to calculate the median power frequency (MPF) and specific frequency bands of the QEEG.ResultsOur data demonstrate a significant increase in MPF in response to DE in the frontal cortex within 30 min into exposure. The increase in MPF is primarily caused by an increase in fast wave activity (β2) and continues to rise during the 1 hour post-exposure interval.ConclusionThis study is the first to show a functional effect of DE exposure in the human brain, indicating a general cortical stress response. Further studies are required to determine whether this effect is mediated by the nanoparticles in DE and to define the precise pathways involved.

Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease

BackgroundExposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.ObjectivesWe conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction.MethodsTwelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures.ResultsParticulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m3) were higher than ambient levels (31 ± 8 μg/m3) and levels in filtered air (0.5 ± 0.4 μg/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group.ConclusionsDespite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.

Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease

Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease

Abstract 803: Diesel Exhaust Inhalation Enhances Thrombus Formation In Man

Background: Transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction although the mechanism is unclear. The aim of this study was to investigate the effect of diesel exhaust inhalation on thrombus formation in man using an ex vivo model of thrombosis. Methods and Results: In a double-blind randomized cross-over study, 20 healthy volunteers were exposed to diluted diesel exhaust (300 μg/m3) or filtered air during intermittent exercise for 1 or 2 hours. Thrombus formation, coagulation, platelet activation and inflammatory markers were measured at 2 and 6 hours after exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber at low (212 /s) and high (1,690 /s) shear rates with porcine aortic tunica media as the thrombogenic substrate. Specimens were fixed, stained and thrombus area measured using computerized planimetry. Compared to filtered air, diesel exhaust increased thrombus formation in the low and high shear chambers by 24.2% (p&lt;0.001) and 19.1% (p&lt;0.001) respectively. This increased thrombogenicity was seen at two and six hours, and using two different types of diesel exposure. Although there were no effects on coagulation variables, diesel exhaust inhalation increased platelet-neutrophil (6.5% to 9.2%; P&lt;0.05) and platelet-monocyte (21.0% to 25.0%; P&lt;0.05) aggregates 2 hours following exposure. Conclusions: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes platelet activation in man. These findings provide a potential mechanism that links exposure to traffic-derived air pollution with acute atherothrombotic events including acute myocardial infarction.

Air Pollution and Mortality: Are We Closer to Understanding the How?

Air Pollution and Mortality: Are We Closer to Understanding the How?

Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease

Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function. In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions. During both exposure sessions, the heart rate increased with exercise (P<0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P=0.67). Exercise-induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22+/-4 vs. -8+/-6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve). Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events. (ClinicalTrials.gov number, NCT00437138 [ClinicalTrials.gov].).

Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis

Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%). At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.

Effect of organic compounds on nanoparticle formation in diluted diesel exhaust

Abstract. The nucleation of nanoparticles in the exhaust of a modern light-duty diesel vehicle was investigated on a chassis dynamometer. This laboratory study is focused on the influence of volatile organic compounds (VOCs) on nucleation of volatile nanoparticles. Different organic compounds were added to the dilution air of the particle sampling under different sampling conditions. Sample temperature and relative sample humidity were varied in a wide range. The number size distribution of the particles was measured with a scanning mobility particle sizer (SMPS) and showed significant differences in response to the added organic compounds. While the nucleation mode particles showed a large variation in concentration, the accumulation mode particles remained unchanged for all compounds. Depending on the functional group, organic compounds were capable of initiating and increasing (alcohols and toluene) or decreasing (acetone, aniline, and methyl tert-butyl ether (MTBE)) nucleation mode particles. Short volatile aliphatic hydrocarbons (hexane and cyclohexane) turned out to be without effect on nucleation of nanoparticles. Possible reasons for the differences are discussed.

Systemic immunotoxicity in AJ mice following 6-month whole body inhalation exposure to diesel exhaust

The purpose of these studies was to determine the effects of subchronic diesel exposure on indicators of systemic immunity in mice. AJ mice were exposed daily for 6 months (6 h/day) to atmospheres containing one of four concentrations (30, 100, 300, and 1000 μg/m 3) of diluted diesel exhaust (DE) in whole body exposure chambers. The effects of DE were compared to chamber exposure controls receiving fresh air. DE was assessed for effects on systemic immunity by measuring the proliferative response of spleen cells following stimulation with T cell (phytohemagglutinin, or PHA) or B cell (lipopolysaccharide, or LPS) mitogens. The results showed that DE at all exposure levels suppressed the proliferative response of T cells. B cell proliferation was increased at 30 μg/m 3 and was unaffected at the 100, 300, and 1000 μg/m 3 exposures. Polycyclic aromatic hydrocarbons (PAHs) are known to suppress spleen cell mitogenic responses, and it has been hypothesized by several groups that PAHs and perhaps benzo(a)pyrene (BaP)-quinones (BPQs) may be responsible for the effects of DE or diesel exhaust particles (DEP). Therefore, a second purpose of these studies was to determine the effects of in vitro BPQs on AJ mouse spleen cell mitogenic responses and compare to DE in preliminary studies. Unlike DE, BPQs were found to increase T cell proliferation. In addition, analysis of chamber atmospheres showed that there was little if any PAH and BPQs in DE. Therefore, these results demonstrate that because of the absence of BPQs in DE, they are likely not responsible for the immunosuppressive effect of DE on murine spleen cell responses.

Measurement of particulate matter from diesel engine exhaust using a tapered element oscillating microbalance

Acquisition of real-time particulate matter (PM) data is proposed by the use of a Rupprecht and Patashnick Company, Inc. Series 110 diesel particulate monitor tapered element oscillating microbalance (TEOM) mass measuring device. The objectives of using a TEOM diesel particulate analyser were to validate its collection capability and evaluate its real-time transient characteristics. Conventional PM measured using dilute diesel exhaust filtration was used as the base line for evaluating the TEOM collection capability. Real-time mass rate data were separated into positive and negative values, then integrated over the duration of the test. The integrated positive mass was divided by the integrated negative mass to create a ratio that is indicative of real PM collected versus moisture released from the filter. Tests were performed on heavy-duty diesel engines on a stationary dynamometer using the US Heavy Duty Federal Test Procedure speed and load cycle. TEOM sample tube temperatures at 35°C yielded the best TEOM-conventional PM filtration mass ratio. However, as sample path temperatures decreased, a decrease in the positive-negative mass ratio occurred. A compromise between conventional filter agreement and real-time data was made in selecting the temperature set point of 40°C as the most desirable sampling temperature. The sample flowrate was varied from one to four litres per minute. A comparison of the TEOM with a conventional filter decreased as the TEOM flow increased. The 1 l/min set point provided the best TEOM-conventional filtration ratio. The positive-negative mass ratio increased as flow decreased. The flow-rate of 3 l/min was chosen to be a compromise between the TEOM-conventional filtration mass ratio and real-time results. The best TEOM-conventional filtration ratio measured was 0.97. The best set of test results was a three-test averaged TEOM-conventional filtration ratio of 0.92 with a coefficient of variance of 0.15 per cent.

Toxicity of diesel engine exhausts in an in vitro model of lung slices in biphasic organotypic culture: induction of a proinflammatory and apoptotic response.

Precision-cut rat lung slices in organotypic culture placed in a biphasic air/liquid system were used for this study. This model allowed pathological as well as cellular and molecular biology investigations to be carried out. Slices were exposed to a continuous flow of diluted diesel exhaust, with a pO2 adjusted to 20% to avoid hypoxia-induced effects. The exposure system allowed five exhaust concentrations from the same diesel engine to be studied concomitantly, and also allowed the impact of removing the particulate matter using a filter cap on the exposure vials to be evaluated. Lung slices were exposed for 3 or 6 h to whole or filtered diesel exhaust. DNA integrity was characterized by two different techniques: (1) an ELISA for the determination of nucleosomes, and (2) the histochemical TUNEL method. By the TUNEL method, apoptotic cells were detected after a 6-h exposure followed by an incubation period of 18 h in a controlled atmosphere comprising 5% CO2/95% O2. Under these conditions, apoptotic nuclei were more frequent in slices exposed to diesel exhaust than in control slices. Cytokine production (tumor necrosis factor alpha, interleukin-1beta) in the culture medium was measured using an ELISA technique. After a 3-h exposure only TNF-alpha was detected and increased in the culture medium of lung slices exposed to diesel exhaust. Under the same conditions, nucleosome levels in the slices increases in a dose-dependent way. In conclusion, whole diesel exhaust induced an inflammatory response and DNA alterations which were reduced by filtration, thus indicating the important role of the particulate matter in diesel exhaust.

Pollution and the immune response: atopic diseases--are we too dirty or too clean?

The effect of pollutants on the immune system has filled tomes and is almost always controversial whether the topic is disinfectants in drinking water or particulates and lung cancer. Even whether outdoor and indoor air quality is improving or declining has been a source of considerable investigation, consultation and often litigation. Few areas, however, yield so much uncertainty and debate as the role of airborne pollutants in atopy. Atopy is defined as an immunoglobulin E- (IgE) mediated allergic response to environmental antigens and can be manifested as rhinitis, asthma or atopic dermatitis. While there is some debate over whether there has been a real increase in atopy over the last decades, it is indisputable that there has been a dramatic change over the last 200 years. While isolated cases of anaphylaxis had been noted before, allergies were unheard of until the early 19th century. Only 54 years after the first description of hay fever in England in 1819, it was considered an epidemic and a clear association with urbanization had been reported.1 What aspect of urbanization is involved has been much debated. There has been much discussion amongst both experimental immunologists and epidemiologists over whether pollutants are responsible for increased allergic sensitization and/or severity.2,3 In the last few years new studies have supported an alternative explanation, namely the decline in infectious diseases in industrialized countries.4,5 Does this ‘hygiene theory’ toll the death knell for the ‘pollution theory’? In this review I will argue that there is a compelling case to be made for both theories and that even this is not the entire picture.

Bronchoalveolar inflammation after exposure to diesel exhaust: comparison between unfiltered and particle trap filtered exhaust.

OBJECTIVES: Air pollution particulates have been identified as having adverse effects on respiratory health. The present study was undertaken to further clarify the effects of diesel exhaust on bronchoalveolar cells...

Efficiency of automotive cabin air filters to reduce acute health effects of diesel exhaust in human subjects.

OBJECTIVES: To evaluate the efficiency of different automotive cabin air filters to prevent penetration of components of diesel exhaust and thereby reduce biomedical effects in human subjects. Filtered air and...

Nasal Cavity Lining Fluid Ascorbic Acid Concentration Increases in Healthy Human Volunteers Following Short Term Exposure to Diesel Exhaust

To determine if diesel exhaust (DE) exposure modifies the antioxidant defense network within the respiratory tract lining fluids, a randomized, single blinded, crossover control study using nasal lavage and flexible video bronchoscopy with bronchial and broncho-alveolar lavage was performed. Fifteen healthy, nonsmoking, asymptomatic subjects were exposed to filtered air or diluted diesel exhaust (300mg m-3 partic-ulates, l.6ppm nitrogen dioxide) for one hour on 2 separate occasions, at least three weeks apart. To examine the kinetics of any DE-induced antioxidant reactions, nasal lavage fluid and blood samples were collected prior to, immediately after, and 51/2 hours post exposure. Bronchoscopy was performed 6 hours after the end of DE exposure. Ascorbic acid, uric acid and reduced glutathone (GSH) concentrations were determined in nasal, bronchial, bronchoalveolar lavage and plasma samples. Malondialdehyde (MDA) and protein carbonyl concentrations were determined in plasma and bronchoalveolar lavage samples. Nasal lavage ascorbic acid concentration increased 10-fold during DE exposure [1.02 (0.26–2.09) Vs 7.13 (4.66–10.79) μmol/L-1, but returned to basal levels 5.5 hours post-exposure [0.75 (0.26–1.51) μmol/L-']. There was no significant effect of DE exposure on nasal lavage uric acid or GSH concentration. DE exposure did not influence plasma, bronchial wash, or bronchoalveolar lavage antioxidant concentrations and no change in MDA or protein carbonyl concentrations were found. The physiological response to acute DE exposure is an increase in the level of ascorbic acid in the nasal cavity. This response appears to be sufficient to prevent further oxidant stress in the respiratory tract of normal individuals.

Four-Week Exposure to Disel Exhaust Includes Nasal Muscosal Hyperresponsiveness to Histamine in Guinea Pigs

The increasing prevalence of allergic rhinitis in many countries is becoming a social problem. It is important to determine whether air pollutants are related to the increase in the prevalence rate of allergic rhinitis or not. In this respect, it is necessary to elucidate whether exposure to air pollutants affects the nasal mucosa and causes nasal mucosal hyperresponsiveness to chemical mediators released by antigen-antibody reactions. A previous study revealed that diesel exhaust particulates are potent in augmenting increases in nasal congestion and nasal secretion induced by histamine (T. Kobayashi and T. Ito, 1995, Fundam. Appl. Toxicol. 27, 195-202). In the present study, using a rhinitis model of guinea pigs, we investigated whether short-term (3-hr) exposure to diesel exhaust induces nasal mucosal hyperresponsiveness to histamine. Guinea pigs of each group were exposed to filtered air or to a low or high concentration of diesel exhaust (1 and 3.2 mg/m3 particulates in diluted diesel exhaust, respectively) for 3 hr. After diesel exhaust exposure, sneezing frequency, nasal secretion from the nostril, and intranasal airway resistance induced by histamine were measured as indices of sneezing response, rhinorrhea, and nasal congestion, respectively. Short-term exposure to a low or high concentration of diesel exhaust itself did not induce sneezing, nasal secretion, or nasal congestion. However, short-term exposure to a high concentration of diesel exhaust augmented sneezing and nasal secretion, but not nasal congestion, induced by histamine. In conclusion, short-term exposure to diesel exhaust potently induces nasal mucosal hyperresponsiveness.

Short-term exposure to diesel exhaust induces nasal mucosal hyperresponsiveness to histamine in guinea pigs.

The increasing prevalence of allergic rhinitis in many countries is becoming a social problem. It is important to determine whether air pollutants are related to the increase in the prevalence rate of allergic rhinitis or not. In this respect, it is necessary to elucidate whether exposure to air pollutants affects the nasal mucosa and causes nasal mucosal hyperresponsiveness to chemical mediators released by antigen-antibody reactions. A previous study revealed that diesel exhaust particulates are potent in augmenting increases in nasal congestion and nasal secretion induced by histamine (T. Kobayashi and T. Ito, 1995, Fundam. Appl. Toxicol. 27, 195-202). In the present study, using a rhinitis model of guinea pigs, we investigated whether short-term (3-hr) exposure to diesel exhaust induces nasal mucosal hyperresponsiveness to histamine. Guinea pigs of each group were exposed to filtered air or to a low or high concentration of diesel exhaust (1 and 3.2 mg/m3 particulates in diluted diesel exhaust, respectively) for 3 hr. After diesel exhaust exposure, sneezing frequency, nasal secretion from the nostril, and intranasal airway resistance induced by histamine were measured as indices of sneezing response, rhinorrhea, and nasal congestion, respectively. Short-term exposure to a low or high concentration of diesel exhaust itself did not induce sneezing, nasal secretion, or nasal congestion. However, short-term exposure to a high concentration of diesel exhaust augmented sneezing and nasal secretion, but not nasal congestion, induced by histamine. In conclusion, short-term exposure to diesel exhaust potently induces nasal mucosal hyperresponsiveness.