Effect Of Diesel Exhaust Exposure Research Articles

Effect of Diesel Exhaust Exposure on Railroad Worker Health and Mortality

Hazardous work conditions expose employees to health and safety risks, and employers to potentially higher expenses including the possibility of a prolonged series of expensive litigation. Indeed, recognition of this in individual and organized (collective) bargaining over higher pay and health benefit coverage, and of course, government regulation involving improved safety measures and equipment design is common. It is easier for all to deal with such risks when they are recognized, and the extent of that risk known. Often, though, risks may appear uncertain, with contradictory evidence supporting opposing views. Such is the case for the exposure of railroad workers to diesel exhaust, a subject that has been investigated for decades with considerable disagreement. This paper contains a focused survey of published studies in the past thirty-five years using observational data and epidemiology (laboratory studies on animals) to review the extent to which disagreement has or not been abated.

Effects of Short-Term Exposure to Diesel Exhaust on the Ecophysiology, Growth, and Fecundity of Soybean (Glycine max (L.) Merr.) and Chicory (Cichorium intybus L.)

Plants growing along roadways are often exposed to vehicle exhaust containing both particulate matter (PM) and various gases that could affect gas exchange and thus plant reproduction. To investigate effects of diesel exhaust exposure on plant ecophysiology, growth, and fecundity, individuals of soybean (Glycine max (L.) Merr.) and chicory (Cichorium intybus L.) were exposed to either exhaust from a diesel generator or ambient air. Exposure occurred daily over a 5-day period (beginning 18 June 2013) using open-top chambers in an agricultural field in southwestern Ohio, United States. Plants were evaluated at 3 times (before, directly after exposure, and following a 5.5-week post-treatment recovery period) for photosynthetic rate (A), stomatal conductance (g), water use efficiency (WUE), stomatal clogging due to PM deposition, and number of nodes. Aboveground biomass, fruit number, mean seed number, and seed mass were measured for soybean after the recovery period. In soybean, A minimally decreased with exposure to diesel exhaust (compared to the control), but an increase in g and a decrease in WUE were detected after the exhaust treatment. Chicory exhibited a relatively low increase in A after the treatment, but there were no clear differences in g or WUE. Growth and fecundity were similar among all soybean plants directly after treatment, but after 5.5 weeks plants exposed to diesel exhaust had increased vegetative biomass while exhibiting no difference in fecundity. These plant species reacted differently to short-term diesel exhaust exposure, suggesting that the impact of diesel exhaust will depend on both the plant species and its physiology.

Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.

Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact P-value of P = 2.44 × 10−4 (i.e. 2/213). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (C5orf63; 7-CpGs) and unc-45 myosin chaperone A gene (UNC45A; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.

Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin

BackgroundWhile exposure to diesel exhaust particles has been linked to aberrant immune responses in allergic diseases such as asthma, little attention has been paid to their effects on the airway epithelial barrier. In this study, we sought to determine the effect of diesel exhaust exposure on airway epithelial barrier function and composition using in vitro and in vivo model systems.Methods16HBE14o- human bronchial epithelial cells were grown on collagen coated Transwell inserts and exposed to 5 to 50 μg/cm2 SRM 2975 diesel particulate matter (DEP) suspended in cell culture medium or vehicle controls. Changes in barrier function were assessed by measuring transepithelial electrical resistance (TEER) and permeability to 4 kDa FITC Dextran. Neonatal BALB/c mice were exposed to aerosolized DEP (255 ± 89 μg/m3; 2 h per day for 5 days) and changes in the tight junction protein Tricellulin were assessed 2 weeks post exposure.ResultsA six-hour incubation of epithelial cells with diesel exhaust particles caused a significant concentration-dependent reduction in epithelial barrier integrity as measured by decreased TEER and increased permeability to 4 kDa FITC-Dextran. This reduction in epithelial barrier integrity corresponded to a significant reduction in expression of the tight junction protein Tricellulin. siRNA mediated knockdown of Tricellulin recapitulated changes in barrier function caused by DEP exposure. Neonatal exposure to aerosolized DEP caused a significant reduction in lung Tricellulin 2 weeks post exposure at both the protein and mRNA level.ConclusionShort term exposure to DEP causes a significant reduction in epithelial barrier integrity through a reduction in the tight junction protein Tricellulin. Neonatal exposure to aerosolized DEP caused a significant and sustained reduction in Tricellulin protein and mRNA in the lung, suggesting that early life exposure to inhaled DEP may cause lasting changes in airway epithelial barrier function.

A historical job-exposure matrix for occupational exposure to diesel exhaust using elemental carbon as an indicator of exposure

Any study of the long-term health effects of diesel exhaust exposure requires past exposure to be assessed. Few historical measurements of occupational exposure to elemental carbon (EC) are available, so past exposure must be assessed using models and judgments based on indirect data. A job-exposure matrix (JEM) for historical occupational exposure to diesel exhaust based on EC is presented. Past exposure to EC in occupations with a high exposure to diesel exhaust was assessed using an eight-step process. The assessments were based on technical specific data and NO2-exposure data, and a current EC-exposure measurement program. Finally, group assessment was carried out by consensus. Temporal variations in exposure were assessed for different groups. The matrix was constructed to assess annual average EC exposure for 72 occupations between 1950 and 2004. EC exposure between 1950 and 2004 varied between 1 and 247 µg/m3, for farmers in 2000 and miners in 1975 respectively, and was generally highest in the 1970s. The JEM allows lifetime diesel exhaust exposure intensity in 72 occupations to be assessed and used in epidemiological studies.

Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone.

Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice. Mice were exposed for 6h to DE at a PM2.5 concentration of 250-300μg/m3, followed by assessment of adult neurogenesis in the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and olfactory bulb (OB). DE impaired cellular proliferation in the SGZ and SVZ in males, but not females. DE reduced adult neurogenesis, with male mice showing fewer new neurons in the SGZ, SVZ, and OB, and females showing fewer new neurons only in the OB. To assess whether blocking microglial activation protected against DE-induced suppression of adult hippocampal neurogenesis, male mice were pre-treated with pioglitazone (PGZ) prior to DE exposure. The effects of DE exposure on microglia, as well as neuroinflammation and oxidative stress, were reduced by PGZ. PGZ also antagonized DE-induced suppression of neurogenesis in the SGZ. These results suggest that DE exposure impairs adult neurogenesis in a sex-dependent manner, by a mechanism likely to involve microglia activation and neuroinflammation.

Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet

Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease, and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol accumulation, but many daily diets are deficient in this nutrient. Therefore, the effect of DE exposure in mice fed n-3 PUFA–deficient diet was investigated. Mice were fed control chow or n-3 PUFA–deficient diet for 4 weeks, then exposed to clean air or DE by inhalation for further 4 weeks. Liver histology, plasma parameters, and expression of fatty acid synthesis-related genes were evaluated. N-3 PUFA–deficient diet increased hepatic lipid droplets accumulation and expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE further increased the plasma leptin and the expression of fatty acid synthesis-related genes: Acacb, Fasn, and Scd1. N-3 PUFA–deficient diet and DE exposure potentially enhanced hepatic fatty acid synthesis and subsequently accumulation of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA–deficient diet may be an additional risk factor for the incidence of non-alcoholic fatty liver disease. The present study suggests an important mechanism for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs in the diet.

Effects of Antioxidant Treatment in a Randomized Control Study of Diesel Exhaust Inhalation

Exposure to traffic-related air pollution is associated with increased cardiovascular morbidity and mortality. Though the mechanisms between exposure and outcome are unclear, previous findings suggest that oxidative stress plays a role in more than one proposed pathway. Diesel exhaust, the dominant source of urban air pollution, comprises a mixture of components that, when inhaled, may directly or indirectly increase reactive oxygen species, decrease antioxidant capacity, and alter redox signaling. Based on the hypothesis that antioxidant levels reflect this response, we investigated the effect of diesel exhaust exposure on blood levels of the major cellular antioxidant glutathione in human subjects, and whether this response could be blunted by antioxidant pre-treatment. Seventeen healthy, nonsmoking adults, age 18-49, participated in a double-blind, crossover controlled exposure study. Subjects completed 120-minute exposures, randomized to order, to filtered air and 200 ug/m3 diesel exhaust, each with and without prior antioxidant treatment (ascorbate + N-acetylcysteine or placebo). Total and oxidized glutathione was measured in whole blood, drawn prior to and two hours after exposure. We further examined effect modification by genotype for the glutamate cysteine ligase catalytic subunit (GCLc). Compared with filtered air, the ratio of reduced to oxidized glutathione was significantly lower with exposure to diesel exhaust (-328; CI:-545, -111; p=0.003). Antioxidant treatment and genotype did not significantly modify this effect. Diesel exhaust inhalation was associated with a decrease in the ratio of reduced to oxidized glutathione in healthy adults, an effect that was not significantly attenuated by antioxidant treatment. This finding supports the theory that oxidative stress is one mechanism involved in the adverse effects associated with acute exposures to air pollution. Decreased antioxidant status may also exacerbate susceptibility to other oxidative insult.

Brain suppression of AP-1 by inhaled diesel exhaust and reversal by cerium oxide nanoparticles

One of the uses of cerium oxide nanoparticles (nanoceria, CeO2) is as a diesel fuel additive to improve fuel efficiency. Gene/environment interactions are important determinants in the etiology of age-related disorders. Thus, it is possible that individuals on high-fat diet and genetic predisposition to vascular disease may be more vulnerable to the adverse health effects of particle exposure. The aim of this pilot study was to test the hypothesis that inhalation of diesel exhaust (DE) or diesel exhaust-containing cerium oxide nanoparticles (DCeE) induces stress in the brain of a susceptible animal model. Atherosclerotic prone, apolipoprotein E knockout (ApoE−/−) mice fed a high-fat diet, were exposed by inhalation to purified air (control), DE or DCeE. The stress-responsive transcription factor, activator protein-1 (AP-1), was significantly decreased in the cortical and subcortical fraction of the brain after DE exposure. The addition of nanoceria to the diesel fuel reversed this effect. The activation of another stress-related transcription factor (NF-κB) was not inhibited. AP-1 is composed of complexes of the Jun and/or Fos family of proteins. Exposure to DCeE caused c-Jun activation and this may be a mechanism by which addition of nanoceria to the fuel reversed the effect of DE exposure on AP-1 activation. This pilot study demonstrates that exposure to DE does impact the brain and addition of nanoceria may be protective. However, more extensive studies are necessary to determine how DE induced reduction of AP-1 activity and compensation by nanoceria impacts normal function of the brain.

Route of exposure alters inflammation and lung function responses to diesel exhaust

Context: Mice are commonly used in studies investigating the effects of diesel exhaust exposure on respiratory health. A plethora of studies in this field has resulted in a range of exposure protocols, from inhalation of diesel exhaust, to the administration (via various routes) of diesel exhaust particles in solution.Objective: In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel exhaust particles suspended in solution and delivered intranasally.Materials and methods: Adult BALB/c mice were exposed to diesel exhaust via inhalation for 2 hours per day for 8 days. A representative, simultaneous sample of particles was collected and a second group of mice then exposed to them suspended in saline. A low and a high-dose were studied, with these matched based on respiratory parameters. Six and twenty-four hours after the last exposure we measured bronchoalveolar inflammation, lung volume, lung function and the amount of elemental carbon in alveolar macrophages.Results: Exposure via either route elicited pulmonary inflammation and changes in lung function. We identified significant differences in response between the two routes of exposure, with mice exposed via inhalation generally displaying more realistic dose-response relationships. Mice exposed via intranasal instillation responded more variably, with little influence of dose.Conclusions: Our results suggest that selection of the route of exposure is of critical importance in studies such as this. Further, inhalation exposure, while more methodologically difficult, resulted in responses more akin to those seen in humans.

The effect of diesel exhaust exposure on blood–brain barrier integrity and function in a murine model

Epidemiological studies indicate that exposure to diesel exhaust (DE) is associated with vascular-based disorders. To investigate the effect of DE on blood-brain barrier (BBB) function and integrity, 8-week-old BALB/c mice were randomized to DE in a cyclical treatment regimen over a 2-week period. Functional integrity of BBB was determined by considering brain parenchymal abundance of IgG within the hippocampal formation and cortex at 6 h and 24 h intervals following final exposure treatment. Neurovascular inflammation was expressed as the abundance of glial fibrillar acidic protein. Two doses of DE were studied and compared to air-only treated mice. Mice exposed to DE had substantially greater abundance of parenchymal IgG compared to control mice not exposed to DE. Increased parenchymal glial fibrillar acidic protein at 24 h post-DE exposure suggested heightened neurovascular inflammation. Our findings are proof-of-concept that inhalation of DE can compromise BBB function and support the broader contention that DE exposure may contribute to neurovascular disease risk.

Gene Expression Changes in the Olfactory Bulb of Mice Induced by Exposure to Diesel Exhaust Are Dependent on Animal Rearing Environment

There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 µg/m3, 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust.

Abstract 19334: Exposure to Diesel Exhaust Emissions Markedly Induce Systemic Lipid Peroxidation and the Development of Dysfunctional Prooxidative and Proinflammatory HDL

Rationale: Exposure to ambient particulate matter is associated with increased cardiovascular ischemic events and enhanced atherosclerosis, likely due in part to the promotion of systemic pro-oxidant and pro-inflammatory effects. Objective: The purpose of this study was to test our hypothesis that air pollutants may induce oxidative modifications of plasma lipoproteins resulting in alteration of the anti-oxidant and anti-inflammatory properties of high-density lipoproteins (HDL). Methods and Results: We exposed ApoE-/- and C57BL/6 wild-type male mice to diesel exhaust (DE) emissions at 200-300 µg PM2.5/m3 for two weeks, filtered air (FA) for two weeks or DE for two weeks, followed by FA for one week (DE+FA). HDL anti-oxidant capacity was assessed by a DCF-based cell fluorescence assay that evaluate the ability of HDL to inhibit LDL oxidation, determined by the level of fluorescence intensity. In the ApoE-/- background, DE and DE+FA mice significantly impaired the HDL anti-oxidant capacity in comparison with FA mice (p<0.001), as judged by almost a doubling in the level of DCF fluorescence and by a promotion rather than inhibition of oxidation. Decreased HDL anti-oxidant properties was accompanied by reduced anti-inflammatory capacity, as determined by a monocyte chemotaxis assay. The HDL anti-oxidant dysfunction correlated with decreased paraoxonase enzymatic activity, increased levels of plasma 8-isoprostanes, 12-HETE, and 13-HODE as well as liver malondialdehyde and 5-HETE levels (p< 0.05), with subsequent up-regulation of hepatic anti-oxidant genes, activation of unfolded protein response and the 5-lipoxygenase pathway. Moreover, while DE led to enhanced lipid peroxidation in the bronchoalveolar lavage fluid of both ApoE-/- and C57BL/6J mice, there were no effects of DE exposure on systemic lipid peroxidation or HDL functionality in the latter. Conclusions: DE emissions induced systemic pro-oxidant effects that led to the development of dysfunctional HDL in hyperlipidemic ApoE-/- mice, which might be one of the mechanisms how air pollution contributes to enhanced atherosclerosis.

Re: The Diesel Exhaust in Miners Study: A Nested Case–Control Study of Lung Cancer and Diesel Exhaust and a Cohort Mortality Study With Emphasis on Lung Cancer

some of the results support the hypothesis that diesel exhaust (DE) exposure increases the risk of lung cancer, some aspects of the results and potential limitations in the DEMS should be taken into consideration in the interpretation of the evidence. In the analysis of continuous exposure variables (1), the hazard ratio for one unit of cumulative DE exposure (one µg/m 3 -y respirable elemental carbon [REC]) was 1.001 among underground miners and 1.02 (ie, 20-fold higher) among surface miners. Corresponding HRs for one logtransformed unit of average REC intensity were 1.26 and 2.60, respectively. The authors interpret these results as indicating a stronger carcinogenic potential of “aged” DE. In the corresponding analysis of the nested case–control study, however, the risk of lung cancer among surface miners was not consistently increased [Table 4 in (2): a nonstatistically significant dose-dependent decrease in risk was shown for two of the variables]. The DEMS authors interpret these results in the light of the small number of lung cancer cases and the low levels of DE exposure in this group. The reader, however, remains uncertain as to whether surface miners, compared with underground miners, have between twofold and 20-fold higher DE-related risk or no increased risk at all. These results cast doubts on the validity of exposure assessment in the DEMS (3). The anomalous result of a higher overall standardized mortality ratio (SMR) among surface miners than among underground miners in the cohort analysis is attributed to confounding by smoking. No clear evidence, however, is provided to support this interpretation. In the nested case– control study, the distribution of controls by smoking habit [Table 2 in (2)] suggests a lower amount of smoking in surface vs underground miners. Although controls are not representative samples of the two groups of miners, this finding contradicts the hypothesis of tobacco smoking being a stronger confounder for surface miners than for underground miners. More importantly, the odds ratios for tobacco smoking were different in the two groups of miners; whereas the odds ratios in surface workers were consistent with previous studies (4), those in underground miners were much lower. The latter result is hardly credible and puts in question the way information on tobacco smoking was collected and analyzed in the DEMS. The DEMS authors quote a number of previous studies of DE-exposed workers as supporting evidence of their results (5–11). However, the results of some of these studies only weakly support the hypothesis of a causal association [eg, (7)], and several welldesigned studies that did not support the authors’ conclusions were not quoted [see (12) for a detailed review]. More importantly, these previous studies included drivers, machine operators, and railroad workers whose circumstances of DE exposure were closer to those of surface miners than to those of underground miners in the DEMS, for whom there was no clear evidence of an effect of DE exposure. The results reported in the two articles do not match the plan of the statistical analysis outlined in the DEMS protocol (13). One particularly striking example concerns the use of lag in exposure–response analyses. In the study protocol, only a brief mention of lagged analyses is made: “In addition, lagged estimates of exposure will be explored to account for the latent period relating to lung cancer development” [(13), page 21], whereas strong emphasis is given to results of lagged analyses in both articles. The exclusion of miners with less than 5 years of employment and the exclusion of the category at highest exposure in dose– response analyses were not mentioned in the protocol, but the key results of the study are based on these exclusions. This is not to say that data-driven analyses should not be conducted and reported. When a study protocol is prepared, typically on the basis of limited data from a pilot study, it is impossible to figure out all the nuances and complexities of the final data, but to ignore systematically the plans outlined in the protocol is not good practice and may open the door to an arbitrary selection of results. At a minimum, the reports should have distinguished between a priori and a posteriori analyses. The DEMS authors state (2) that exposure to REC in the range of 2–6 μg/m 3

Controlled human exposures to diesel exhaust

Diesel exhaust is a complex mixture of gaseous and particulate compounds resulting from an incomplete combustion of diesel fuel. Controlled human exposures to diesel exhaust and diesel exhaust particles (DEP) have contributed to understanding health effects. Such acute exposure studies of healthy subjects to diesel exhaust and DEP demonstrate a pro-inflammatory effect in the lung and systemically but only at higher concentrations (with a threshold dose approximating 300 µg/m3). Unexpectedly, there appears to be a lack of an inflammatory response to diesel exhaust and DEP in asthmatic individuals. Controlled human exposure studies of cardiovascular effects show that, comparable to other particle-associated exposures, diesel exhaust has a capacity to precipitate coronary artery disease. In addition, there is a relationship between diesel exhaust and DEP exposure and vascular endpoints; these effects in diesel exhaust may be diminished with removal of DEP. Many extra-pulmonary health effects of diesel exhaust exposure, including systemic inflammation, pro-thrombotic changes, and cardiovascular disease, are considered consequent to pro-inflammatory events and inflammation in the lung. Future research will focus on the relative importance of diesel exhaust components, potential interactions between components and other pollutants, effects in sensitive individuals, and effects of longer or repeated exposures.

Experimental exposure to diesel exhaust increases arterial stiffness in man

IntroductionExposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness.MethodsIn a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 μg/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated.ResultsBlood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure.ConclusionAcute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution.

Diesel Exhaust Enhanced Susceptibility to Influenza Infection is Associated with Decreased Surfactant Protein Expression

We have previously shown that exposure of respiratory epithelial cells to diesel exhaust (DE) enhances susceptibility to influenza infection and increases the production of interleukin (IL)-6 and interferon (IFN)-β. The purpose of this study was to confirm and expand upon these in vitro results by assessing the effects of DE exposure on the progression of influenza infection and on development of associated pulmonary immune and inflammatory responses in vivo. BALB/c mice were exposed to air or to DE containing particulate matter at concentrations of 0.5 or 2 mg/m3 for 4 h/day for 5 days and subsequently instilled with influenza A/Bangkok/1/79 virus. Exposure to 0.5 mg/m3 (but not the higher 2-mg/m3 dose) of DE increased susceptibility to influenza infection as demonstrated by a significant increase in hemagglutinin (HA) mRNA levels, a marker of influenza copies, and greater immunohistochemical staining for influenza virus protein in the lung. The enhanced susceptibility to infection observed in mice exposed to 0.5 mg/m3 of DE was associated with a significant increase in the expression of IL-6, while antiviral lung IFN levels were unaffected. Analysis of the expression and production of surfactant proteins A and D, which are components of the interferon-independent antiviral defenses, showed that these factors were decreased following exposure to 0.5 mg/m3 of DE but not to the higher 2-mg/m3 concentration. Taken together, the results demonstrate that exposure to DE enhances the susceptibility to respiratory viral infections by reducing the expression and production of antimicrobial surfactant proteins.

Effects of Diesel Exhaust Exposure on C-Reactive Protein and Serum Amyloid A

Effects of Diesel Exhaust Exposure on C-Reactive Protein and Serum Amyloid A

Cardiovascular Effects of Inhaled Diesel Exhaust in Spontaneously Hypertensive Rats

Particulate matter air pollution is associated with increased cardiovascular mortality. The present study examined the cardiac effects of diesel exhaust exposure in spontaneously hypertensive rats. These rats (4 mo old, n = 6 males and 4-6 females/concentration) were exposed to one of five diesel exhaust levels (0, 30, 100, 300, and 1000 micrograms particles/m3) for 6 h per day for 7 d. Electrocardiographic measurements were obtained by radiotelemetry beginning 3 d prior to exposure and ending 4 d after exposure cessation. Control rats displayed a reduced daytime heart rate from the beginning of the protocol, whereas exposed rats maintained a significantly elevated heart rate throughout the exposure. Daytime heart rate values for male control rats averaged 265 +/- 5 beats/min (mean +/- standard error [SE]), whereas values for exposed rats averaged 290 +/- 7 beats/min. This difference persisted during the evenings of the exposure period but was not observed at any time during the preexposure or postexposure periods. The PQ interval, an index of atrioventricular node sensitivity, was significantly prolonged among exposed animals in a concentration-dependent manner. Increased heart rate with prolongation of the PQ interval may represent a substrate for ventricular arrhythmias. These results concur with previous reports suggesting that realistic exposure concentrations of air pollution affect the pacemaking system of rats.

Health effects of diesel exhaust emissions.

Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components. Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function. There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response. Much of the research on adverse effects of diesel exhaust, both in vivo and in vitro, has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.