Outdoor air pollution as a risk factor for testing positive for SARS-CoV-2: A nationwide test-negative case-control study in the Netherlands.

Air pollution is a known risk factor for several diseases, but the extent to which it influences COVID-19 compared to other respiratory diseases remains unclear. We performed a test-negative case-control study among people with COVID-19-compatible symptoms who were tested for SARS-CoV-2 infection, to assess whether their long- and short-term exposure to ambient air pollution (AAP) was associated with testing positive (vs. negative) for SARS-CoV-2. We used individual-level data for all adult residents in the Netherlands who were tested for SARS-CoV-2 between June and November 2020, when only symptomatic people were tested, and modeled ambient concentrations of PM10, PM2.5, NO2 and O3 at geocoded residential addresses. In long-term exposure analysis, we selected individuals who did not change residential address in 2017-2019 (1.7 million tests) and considered the average concentrations of PM10, PM2.5 and NO2 in that period, and different sources of PM (industry, livestock, other agricultural activities, road traffic, other Dutch sources, foreign sources). In short-term exposure analysis, individuals not changing residential address in the two weeks before testing day (2.7 million tests) were included in the analyses, thus considering 1- and 2-week average concentrations of PM10, PM2.5, NO2 and O3 before testing day as exposure. Mixed-effects logistic regression analysis with adjustment for several confounders, including municipality and testing week to account for spatiotemporal variation in viral circulation, was used. Overall, there was no statistically significant effect of long-term exposure to the studied pollutants on the odds of testing positive vs. negative for SARS-CoV-2. However, significant positive associations of long-term exposure to PM10 and PM2.5 from specifically foreign and livestock sources, and to PM10 from other agricultural sources, were observed. Short-term exposure to PM10 (adjusting for NO2) and PM2.5 were also positively associated with increased odds of testing positive for SARS-CoV-2. While these exposures seemed to increase COVID-19 risk relative to other respiratory diseases, the underlying biological mechanisms remain unclear. This study reinforces the need to continue to strive for better air quality to support public health.

Effects of long-term exposure to outdoor air pollution on COVID-19 incidence: A population-based cohort study accounting for SARS-CoV-2 exposure levels in the Netherlands.

Several studies have linked air pollution to COVID-19 morbidity and severity. However, these studies do not account for exposure levels to SARS-CoV-2, nor for different sources of air pollution. We analyzed individual-level data for 8.3 million adults in the Netherlands to assess associations between long-term exposure to ambient air pollution and SARS-CoV-2 infection (i.e., positive test) and COVID-19 hospitalisation risks, accounting for spatiotemporal variation in SARS-CoV-2 exposure levels during the first two major epidemic waves (February 2020-February 2021). We estimated average annual concentrations of PM10, PM2.5 and NO2 at residential addresses, overall and by PM source (road traffic, industry, livestock, other agricultural sources, foreign sources, other Dutch sources), at 1 × 1 km resolution, and weekly SARS-CoV-2 exposure at municipal level. Using generalized additive models, we performed interval-censored survival analyses to assess associations between individuals' average exposure to PM10, PM2.5 and NO2 in the three years before the pandemic (2017-2019) and COVID-19-outcomes, adjusting for SARS-CoV-2 exposure, individual and area-specific confounders. In single-pollutant models, per interquartile (IQR) increase in exposure, PM10 was associated with 7% increased infection risk and 16% increased hospitalisation risk, PM2.5 with 8% increased infection risk and 18% increased hospitalisation risk, and NO2 with 3% increased infection risk and 11% increased hospitalisation risk. Bi-pollutant models suggested that effects were mainly driven by PM. Associations for PM were confirmed when stratifying by urbanization degree, epidemic wave and testing policy. All emission sources of PM, except industry, showed adverse effects on both outcomes. Livestock showed the most detrimental effects per unit exposure, whereas road traffic affected severity (hospitalisation) more than infection risk. This study shows that long-term exposure to air pollution increases both SARS-CoV-2 infection and COVID-19 hospitalisation risks, even after controlling for SARS-CoV-2 exposure levels, and that PM may have differential effects on these COVID-19 outcomes depending on the emission source.

Airway contraction and cytokine release in isolated rat lungs induced by wear particles from the road and tire interface and road vehicle brakes.

The dominant road traffic particle sources are wear particles from the road and tire interface, and from vehicle brake pads. The aim of this work was to investigate the effect of road and brake wear particles on pulmonary function and biomarkers in isolated perfused rat lungs. Particles were sampled from the studded tire wear of three road pavements containing different rock materials in a road simulator; and from the wear of two brake pad materials using a pin-on-disk machine. Isolated rat lungs inhaled the coarse and fine fractions of the sampled particles resulting in an estimated total particle lung dose of 50 µg. The tidal volume (TV) was measured during the particle exposure and the following 50 min. Perfusate and BALF were analyzed for the cytokines TNF, CXCL1 and CCL3. The TV of lungs exposed to rock materials was significantly reduced after 25 min of exposure compared to the controls, for quartzite already after 4 min. The particles of the heavy-duty brake pads had no effect on the TV. Brake particles resulted in a significant elevation of CXCL1 in the perfusate. Brake particles showed significant elevations of all three measured cytokines, and quartzite showed a significant elevation of TNF in BALF. The study shows that the toxic effect on lungs exposed to airborne particles can be investigated using measurements of tidal volume. Furthermore, the study shows that the choice of rock material in road pavements has the potential to affect the toxicity of road wear PM10.

Comparative toxicity of ultrafine particles around a major airport in human bronchial epithelial (Calu-3) cell model at the air-liquid interface.

Relatively high concentrations of ultrafine particles (UFPs) have been observed around airports, in which aviation and road traffic emissions are the major sources. This raises concerns about the potential health impacts of airport UFPs, particularly in comparison to those emitted by road traffic. UFPs mainly derived from aviation or road traffic emissions were collected from a location near a major international airport, Amsterdam-Schiphol airport (AMS), depending on the wind direction, along with UFPs from an aircraft turbine engine at low and full thrust. Human bronchial epithelial cells (Calu-3) model in combination with an air-liquid interface (ALI) cloud system was used for the in vitro exposure to UFPs at low doses ranging from 0.09 to 2.07 µg/cm2. Particle size distribution was measured. Cell viability, cytotoxicity and inflammatory potential (interleukin (IL) 6 and 8 secretion) on Calu-3 cells were assessed after exposure for 24 h. The biological measurements on Calu-3 cells confirm that pro-inflammatory responses still can be activated at the high cell viability (> 80%) and low cytotoxicity. By the Benchmark Dose (BMD) analysis, Airport and Non-Airport (road traffic) UFPs as well as UFPs samples from a turbine engine have similar toxic properties. Our results suggest that UFPs from aviation and road traffic in airport surroundings may have similar adverse effects on public health.

Ex vivo innate responses to particulate matter from livestock farms in asthma patients and healthy individuals.

BACKGROUND: Asthma patients suffer from periodic acute worsening of symptoms (i.e. loss of asthma control or exacerbations), triggered by a variety of exogenous stimuli. With the growing awareness that air pollutants impact respiratory diseases, we investigated whether particulate matter (PM) derived from various livestock farms (BioPM) differentially affected innate and oxidative stress responses in asthma and health. METHODS: Peripheral blood mononuclear cells (PBMCs), collected from patients sequentially before and during loss of asthma control and from healthy individuals, were exposed to BioPM collected from chicken, goat and pig farms (1 and 5 µg/ml), with or without pre-treatment with antioxidants. Cytokine release and oxidative stress were assessed. RESULTS: PBMCs produced IFNγ, IL-1ß, IL-10 and TNFα upon stimulation with BioPM, with that from pig farms inducing the highest cytokine levels. Overall, cytokine production was irrespective of the presence or state of disease. However, PBMCs from stable asthma patients upon exposure to the three BioPM showed more extreme TNFα responses than those from healthy subjects. Furthermore, PBMCs obtained during loss of asthma control that were exposed to BioPM from pig farms showed enhanced IFNγ release as well as decreased oxidative stress levels upon pre-treatment with N-acetylcysteine (NAC) compared to stable disease. NAC, but not superoxide dismutase and catalase, also counteracted BioPM-induced cytokine release, indicating the importance of intracellular reactive oxygen species in the production of cytokines. CONCLUSIONS: BioPM triggered enhanced pro-inflammatory responses by PBMCs from both healthy subjects and asthma patients, with those from patients during loss of asthma control showing increased susceptibility to BioPM from pig farms in particular.

Airborne particulate matter from goat farm increases acute allergic airway responses in mice.

Background: Inhalation exposure to biological particulate matter (BioPM) from livestock farms may provoke exacerbations in subjects suffering from allergy and asthma. The aim of this study was to use a murine model of allergic asthma to determine the effect of BioPM derived from goat farm on airway allergic responses.Methods: Fine (<2.5 µm) BioPM was collected from an indoor goat stable. Female BALB/c mice were ovalbumin (OVA) sensitized and challenged with OVA or saline as control. The OVA and saline groups were divided in sub-groups and exposed intranasally to different concentrations (0, 0.9, 3, or 9 µg) of goat farm BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected.Results: In saline-challenged mice, goat farm BioPM induced 1) a dose-dependent increase in neutrophils in BALF and 2) production of macrophage inflammatory protein-3a. In OVA-challenged mice, BioPM induced 1) inflammatory cells in BALF, 2) OVA-specific Immunoglobulin (Ig)G1, 3) airway mucus secretion-specific gene expression. RNAseq analysis of lungs indicates that neutrophil chemotaxis and oxidation-reduction processes were the representative genomic pathways in saline and OVA-challenged mice, respectively.Conclusions: A single exposure to goat farm BioPM enhanced airway inflammation in both saline and OVA-challenged allergic mice, with neutrophilic response as Th17 disorder and eosinophilic response as Th2 disorder indicative of the severity of allergic responses. Identification of the mode of action by which farm PM interacts with airway allergic pathways will be useful to design potential therapeutic approaches.

Livestock farm particulate matter enhances airway inflammation in mice with or without allergic airway disease.

Effects of airborne biological particulate matter (BioPM; from livestock farms) on the pulmonary airways are not well studied. The aim of the present study was to investigate whether fine (<2.5 µm) BioPM derived from indoor animal stables (two chicken and two pig farms) could modify airway allergic responses by using a mouse model of allergic airway disease (allergic asthma). After intraperitoneal ovalbumin (OVA) sensitization mice were either intranasally challenged with OVA (allergic mice) or saline (non-allergic controls). Mice were also intranasally treated with farm-derived BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected one day after intranasal exposure. BioPM from all the farms caused an acute neutrophilic inflammatory response in non-allergic mice. In allergic mice, BioPM derived from pig farm 2 induced a larger cellular inflammatory response than other farm-derived BioPM. All farm BioPM elicited Th17 cytokine (Interleukin (IL)-23) production except chicken farm 2, whereas Th2 cytokine (IL-5) increase was only induced by BioPM collected from chicken farm 2. These results indicate the exposure of BioPM from chicken and pig farms may cause the enhancement of airway allergic response in mice following exposure to OVA. More variation in the responses between farms was observed in allergic than non-allergic mice. Understanding the source and doses of BioPM that may affect the airway allergic response could help susceptible individuals to avoid worsening their respiratory diseases.

Microbiome composition of airborne particulate matter from livestock farms and their effect on innate immune receptors and cells.

Patients with respiratory diseases in rural areas have been reported to have enhanced responsiveness to ambient particulate matter (PM). In addition to the physical and chemical components, ambient PM can contain microorganisms or parts thereof, referred here as BioPM, that can also contribute to the adverse health effects. This study aimed to characterize the microbial composition of BioPM originating from livestock, and to investigate whether these BioPM can trigger the activation of innate receptors and cells. Coarse (PM2.5-10 µm) and fine (PM<2.5 µm) BioPM samples were collected from indoor chicken, pig and goat farms using the versatile aerosol concentration enrichment system (VACES) connected to a Biosampler. The fungal and bacterial communities were assessed with an amplicon based approach using Next Generation Sequencing (NGS). In parallel, HEK-Blue cells expressing different pattern recognition receptors (Toll like receptors (TLR) 2, 3, 4, 5, 7, 8, 9 and NOD 1, 2) and a human monocytic cell line (MM6) were exposed to BioPM samples from these sites. Distinct airborne microbiota profiles associated with the corresponding animal farm were observed. Moreover, the various BioPM contained mainly ligands for TLR2 and TLR4 resulting in a concentration-dependent increase of pro-inflammatory cytokine secreted by MM6 cells. In addition, we show for the first time that only the pig-derived BioPM induced TLR5 activation. These findings suggest that animal farm specific BioPM trigger distinct inflammatory responses, which may contribute to airway diseases in humans.

Pro-inflammatory responses to PM0.25 from airport and urban traffic emissions.

Air traffic is rapidly growing, raising concerns about the air pollution in the surroundings of airports and its impact on public health. However, little is known about the impact of air pollution sources on air quality and health in the vicinity of airports. In this study, the sources and adverse health effects of airport-related particulate matter (PM) were investigated and compared to those of urban traffic emissions. Ambient PM0.25 were collected at the Los Angeles International Airport (LAX) and at a central Los Angeles site (USC campus), along with PM2.5 collected directly from turbine and diesel engines. The particle chemical composition, oxidative potential (OP) (ascorbic acid (AA), and electron spin resonance (ESR) assay) as well as their reactive oxygen species (ROS) activity, inflammatory potential (interleukin (IL) 6 and 8 and tumor necrosis factor (TNF)-α) and cytotoxicity on human bronchial epithelial (16HBE) cells were assessed. Chemical composition measurements confirmed that aircraft emissions were the major source to LAX PM0.25, while the sources of the USC samples were more complex, including traffic emissions, suspended road and soil dust, and secondary aerosols. The traffic-related transition metals (Fe and Cu) in LAX and USC samples mainly affected OP values of particles, while multiple factors such as composition, size distribution and internalized amount of particles contributed to the promotion of ROS generation in 16HBE cells during 4 h exposure. Internalized particles in cells might also play an important role in activating inflammatory responses during cell recovery period, with LAX particles being more potent. Our results demonstrated considerable toxicity of airport-related particles, even at low exposure concentrations, suggesting that airport emission as source of PM0.25 may also contribute to the adverse effects on public health attributable to PM. The potency of such particles is in the same range as those collected at a site in urban area impacted heavily by traffic emissions.

Diesel engine exhaust accelerates plaque formation in a mouse model of Alzheimer's disease.

BACKGROUND: Increasing evidence from toxicological and epidemiological studies indicates that the central nervous system is an important target for ambient air pollutants. We have investigated whether long-term inhalation exposure to diesel engine exhaust (DEE), a dominant contributor to particulate air pollution in urban environments, can aggravate Alzheimer's Disease (AD)-like effects in female 5X Familial AD (5XFAD) mice and their wild-type female littermates. Following 3 and 13 weeks exposures to diluted DEE (0.95 mg/m3, 6 h/day, 5 days/week) or clean air (controls) behaviour tests were performed and amyloid-ß (Aß) plaque formation, pulmonary histopathology and systemic inflammation were evaluated. RESULTS: In a string suspension task, assessing for grip strength and motor coordination, 13 weeks exposed 5XFAD mice performed significantly less than the 5XFAD controls. Spatial working memory deficits, assessed by Y-maze and X-maze tasks, were not observed in association with the DEE exposures. Brains of the 3 weeks DEE-exposed 5XFAD mice showed significantly higher cortical Aß plaque load and higher whole brain homogenate Aß42 levels than the clean air-exposed 5XFAD littermate controls. After the 13 weeks exposures, with increasing age and progression of the AD-phenotype of the 5XFAD mice, DEE-related differences in amyloid pathology were no longer present. Immunohistochemical evaluation of lungs of the mice revealed no obvious genetic background-related differences in tissue structure, and the DEE exposure did not cause histopathological changes in the mice of both backgrounds. Luminex analysis of plasma cytokines demonstrated absence of sustained systemic inflammation upon DEE exposure. CONCLUSIONS: Inhalation exposure to DEE causes accelerated plaque formation and motor function impairment in 5XFAD transgenic mice. Our study provides further support that the brain is a relevant target for the effects of inhaled DEE and suggests that long-term exposure to this ubiquitous air pollution mixture may promote the development of Alzheimer's disease.

Oxidative potential of particulate matter collected at sites with different source characteristics.

BACKGROUND: The oxidative potential (OP) of particulate matter (PM) has been proposed as a more health relevant metric than PM mass. Different assays exist for measuring OP and little is known about how the different assays compare. AIM: To assess the OP of PM collected at different site types and to evaluate differences between locations, size fractions and correlation with PM mass and PM composition for different measurement methods for OP. METHODS: PM2.5 and PM10 was sampled at 5 sites: an underground station, a farm, 2 traffic sites and an urban background site. Three a-cellular assays; dithiothreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbate depletion (OP(AA)) were used to characterize the OP of PM. RESULTS: The highest OP was observed at the underground, where OP of PM10 was 30 (OP(DTT)) to >600 (OP(ESR)) times higher compared to the urban background when expressed as OP/m(3) and 2-40 times when expressed as OP/µg. For the outdoor sites, samples from the farm showed significantly lower OP(ESR) and OP(AA), whereas samples from the continuous traffic site showed the highest OP for all assays. Contrasts in OP between sites were generally larger than for PM mass and were lower for OP(DTT) compared to OP(ESR) and OP(AA). Furthermore, OP(DTT)/µg was significantly higher in PM2.5 compared to PM10, whereas the reverse was the case for OP(ESR). OP(ESR) and OP(AA) were highly correlated with traffic-related PM components (i.e. EC, Fe, Cu, PAHs), whereas OP(DTT) showed the highest correlation with PM mass and OC. CONCLUSIONS: Contrasts in OP between sites, differences in size fractions and correlation with PM composition depended on the specific OP assay used, with OP(ESR) and OP(AA) showing the most similar results. This suggests that either OP(ESR) or OP(AA) and OP(DTT) can complement each other in providing information regarding the oxidative properties of PM, which can subsequently be used to study its health effects.

Particulate matter beyond mass: recent health evidence on the role of fractions, chemical constituents and sources of emission.

Particulate matter (PM) is regulated in various parts of the world based on specific size cut offs, often expressed as 10 or 2.5 µm mass median aerodynamic diameter. This pollutant is deemed one of the most dangerous to health and moreover, problems persist with high ambient concentrations. Continuing pressure to re-evaluate ambient air quality standards stems from research that not only has identified effects at low levels of PM but which also has revealed that reductions in certain components, sources and size fractions may best protect public health. Considerable amount of published information have emerged from toxicological research in recent years. Accumulating evidence has identified additional air quality metrics (e.g. black carbon, secondary organic and inorganic aerosols) that may be valuable in evaluating the health risks of, for example, primary combustion particles from traffic emissions, which are not fully taken into account with PM2.5 mass. Most of the evidence accumulated so far is for an adverse effect on health of carbonaceous material from traffic. Traffic-generated dust, including road, brake and tire wear, also contribute to the adverse effects on health. Exposure durations from a few minutes up to a year have been linked with adverse effects. The new evidence collected supports the scientific conclusions of the World Health Organization Air Quality Guidelines and also provides scientific arguments for taking decisive actions to improve air quality and reduce the global burden of disease associated with air pollution.

Cell toxicity and oxidative potential of engine exhaust particles: impact of using particulate filter or biodiesel fuel blend.

The link between emissions of vehicular particulate matter (PM) and adverse health effects is well established. However, the influence of new emission control technologies and fuel types on both PM emissions and health effects has been less well investigated. We examined the health impact of PM emissions from two vehicles equipped with or without a diesel particulate filter (DPF). Both vehicles were powered either with diesel (B0) or a 50% v/v biodiesel blend (B50). The DPF effectively decreased PM mass emissions (∼85%), whereas the fuel B50 without DPF lead to less reduction (∼50%). The hazard of PM per unit distance driven was decreased for the DPF-equipped vehicle as indicated by a reduced cytotoxicity, oxidative, and pro-inflammatory potential. This was not evident and even led to an increase when the hazard was expressed on a per unit of mass basis. In general, the PM oxidative potential was similar or reduced for the B50 compared to the B0 powered vehicle. However, the use of B50 resulted in increased cytotoxicity and IL-6 release in BEAS-2B cells irrespective of the expression metric. This study shows that PM mass reduction achieved by the use of B50 will not necessarily decrease the hazard of engine emissions, while the application of a DPF has a beneficial effect on both PM mass emission and PM hazard.

Physicochemical characterization of airborne particulate matter at a mainline underground railway station.

Underground railway stations are known to have elevated particulate matter (PM) loads compared to ambient air. As these particles are derived from metal-rich sources and transition metals may pose a risk to health by virtue of their ability to catalyze generation of reactive oxygen species (ROS), their potential enrichment in underground environments is a source of concern. Compared to coarse (PM10) and fine (PM2.5) particulate fractions of underground railway airborne PM, little is known about the chemistry of the ultrafine (PM0.1) fraction that may contribute significantly to particulate number and surface area concentrations. This study uses inductively coupled plasma mass spectrometry and ion chromatography to compare the elemental composition of size-fractionated underground PM with woodstove, roadwear generator, and road tunnel PM. Underground PM is notably rich in Fe, accounting for greater than 40% by mass of each fraction, and several other transition metals (Cu, Cr, Mn, and Zn) compared to PM from other sources. Importantly, ultrafine underground PM shows similar metal-rich concentrations as the coarse and fine fractions. Scanning electron microscopy revealed that a component of the coarse fraction of underground PM has a morphology indicative of generation by abrasion, absent for fine and ultrafine particulates, which may be derived from high-temperature processes. Furthermore, underground PM generated ROS in a concentration- and size-dependent manner. This study suggests that the potential health effects of exposure to the ultrafine fraction of underground PM warrant further investigation as a consequence of its greater surface area/volume ratio and high metal content.

The policy relevance of wear emissions from road transport, now and in the future--an international workshop report and consensus statement.

UNLABELLED: Road transport emissions are a major contributor to ambient particulate matter concentrations and have been associated with adverse health effects. Therefore, these emissions are targeted through increasingly stringent European emission standards. These policies succeed in reducing exhaust emissions, but do not address "nonexhaust" emissions from brake wear, tire wear, road wear and suspension in air of road dust. Is this a problem? To what extent do nonexhaust emissions contribute to ambient concentrations of PM10 or PM2.5? In the near future, wear emissions may dominate the remaining traffic-related PM10 emissions in Europe, mostly due to the steep decrease in PM exhaust emissions. This underlines the need to determine the relevance of the wear emissions as a contribution to the existing ambient PM concentrations, and the need to assess the health risks related to wear particles, which has not yet received much attention. During a workshop in 2011, available knowledge was reported and evaluated so as to draw conclusions on the relevance of traffic-related wear emissions for air quality policy development. On the basis of available evidence, which is briefly presented in this paper it was concluded that nonexhaust emissions and in particular suspension in air of road dust are major contributors to exceedances at street locations of the PM10 air quality standards in various European cities. Furthermore, wear-related PM emissions that contain high concentrations of metals may (despite their limited contribution to the mass of nonexhaust emissions) cause significant health risks for the population, especially those living near intensely trafficked locations. To quantify the existing health risks, targeted research is required on wear emissions, their dispersion in urban areas, population exposure, and its effects on health. Such information will be crucial for environmental policymakers as an input for discussions on the need to develop control strategies. IMPLICATIONS: Road transport particulate matter (PM) emissions are associated with adverse health effects. Stringent policies succeed in reducing the exhaust PM emissions, but do not address "nonexhaust" emissions from brake wear, tire wear, road wear, and suspension in air of road dust. In the near future the nonexhaust emissions will dominate the road transport PM emissions. Based on the limited available evidence, it is argued that dedicated research is required on nonexhaust emissions and dispersion to urban areas from both an air quality and a public health perspective. The implicated message to regulators and policy makers is that road transport emissions continue to be an issue for health and air quality, despite the encouraging rapid decrease of tailpipe exhaust emissions.

Health effects of black carbon

Black carbon is a good indicator of combustion-related air pollution and was only recently recognized as a short-lived climate-forcer, which contributes to warming the Earth’s atmosphere. This report presents the results of a systematic review of evidence of the health effects of black carbon in ambient air. Epidemiological studies provide sufficient evidence of the association of cardiopulmonary morbidity and mortality with exposure to black carbon. Toxicological studies suggest that black carbon may operate as a universal carrier of a wide variety of chemicals of varying toxicity to the human body. Although black carbon may not be a major, directly toxic component of fine particulate matter, reducing people’s exposure to particulate matter containing black carbon should reduce its effects on their health, as well as helping to mitigate climate change. This review is of particular interest to environmental health professionals concerned with assessing and reducing the health effects of air pollution, as well as to those who use scientific evidence in support of climate change mitigation policies.

Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men.

BACKGROUND: In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men. METHODS AND RESULTS: Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 µg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release. CONCLUSIONS: Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

Oxidative stress and DNA damage responses in rat and mouse lung to inhaled carbon nanoparticles.

We have investigated whether short-term nose-only inhalation exposure to electric spark discharge-generated carbon nanoparticles (∼60 nm) causes oxidative stress and DNA damage responses in the lungs of rats (152 µg/m(3); 4 h) and mice (142 µg/m(3); 4 h, or three times 4 h). In both species, no pulmonary inflammation and toxicity were detected by bronchoalveolar lavage or mRNA expression analyses. Oxidative DNA damage (measured by fpg-comet assay), was also not increased in mouse whole lung tissue or isolated lung epithelial cells from rat. In addition, the mRNA expressions of the DNA base excision repair genes OGG1, DNA Polß and XRCC1 were not altered. However, in the lung epithelial cells isolated from the nanoparticle-exposed rats a small but significant increase in APE-1 mRNA expression was measured. Thus, short-term inhalation of carbon nanoparticles under the applied exposure regimen, does not cause oxidative stress and DNA damage in the lungs of healthy mice and rats.

Pulmonary and cardiovascular effects of traffic-related particulate matter: 4-week exposure of rats to roadside and diesel engine exhaust particles.

Traffic-related particulate matter (PM) may play an important role in the development of adverse health effects, as documented extensively in acute toxicity studies. However, rather little is known about the impacts of prolonged exposure to PM. We hypothesized that long-term exposure to PM from traffic adversely affects the pulmonary and cardiovascular system through exacerbation of an inflammatory response. To examine this hypothesis, Fisher F344 rats, with a mild pulmonary inflammation at the onset of exposure, were exposed for 4 weeks, 5 days/week for 6 h a day to: (a) diluted diesel engine exhaust (PM(DEE)), or: (b) near roadside PM (PM(2.5)). Ultrafine particulates, which are largely present in diesel soot, may enter the systemic circulation and directly or indirectly trigger cardiovascular effects. Hence, we assessed the effects of traffic-related PM on pulmonary inflammation and activity of procoagulants, vascular function in arteries, and cytokine levels in the heart 24 h after termination of the exposures. No major adverse health effects of prolonged exposure to traffic-related PM were detected. However, some systemic effects due to PM(DEE) exposure occurred including decreased numbers of white blood cells and reduced von Willebrand factor protein in the circulation. In addition, lung tissue factor activity is reduced in conjunction with reduced lung tissue thrombin generation. To what extent these alterations contribute to thrombotic effects and vascular diseases remains to be established. In conclusion, prolonged exposure to traffic-related PM in healthy animals may not be detrimental due to various biological adaptive response mechanisms.

Diesel engine exhaust initiates a sequence of pulmonary and cardiovascular effects in rats.

This study was designed to determine the sequence of events leading to cardiopulmonary effects following acute inhalation of diesel engine exhaust in rats. Rats were exposed for 2 h to diesel engine exhaust (1.9 mg/m(3)), and biological parameters related to antioxidant defense, inflammation, and procoagulation were examined after 4, 18, 24, 48, and 72 h. This in vivo inhalation study showed a pulmonary anti-oxidant response (an increased activity of the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase and an increase in heme oxygenase-1 protein, heme oxygenase activity, and uric acid) which precedes the inflammatory response (an increase in IL-6 and TNF-α). In addition, increased plasma thrombogenicity and immediate anti-oxidant defense gene expression in aorta tissue shortly after the exposure might suggest direct translocation of diesel engine exhaust components to the vasculature but mediation by other pathways cannot be ruled out. This study therefore shows that different stages in oxidative stress are not only affected by dose increments but are also time dependent.