Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers.
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ABSTRACT:
SUBMITTER: Madden MC
PROVIDER: S-EPMC4354281 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
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Project description:BackgroundOver one-third of the U.S. population is exposed to unsafe levels of ozone (O3). Dietary supplementation with fish oil (FO) or olive oil (OO) has shown protection against other air pollutants. This study evaluates potential cardiopulmonary benefits of FO or OO supplementation against acute O3 exposure in young healthy adults.MethodsForty-three participants (26 ± 4 years old; 47% female) were randomized to receive 3 g/day of FO, 3 g/day OO, or no supplementation (CTL) for 4 weeks prior to undergoing 2-hour exposures to filtered air and 300 ppb O3 with intermittent exercise on two consecutive days. Outcome measurements included spirometry, sputum neutrophil percentage, blood markers of inflammation, tissue injury and coagulation, vascular function, and heart rate variability. The effects of dietary supplementation and O3 on these outcomes were evaluated with linear mixed-effect models.ResultsCompared with filtered air, O3 exposure decreased FVC, FEV1, and FEV1/FVC immediately post exposure regardless of supplementation status. Relative to that in the CTL group, the lung function response to O3 exposure in the FO group was blunted, as evidenced by O3-induced decreases in FEV1 (Normalized CTL -0.40 ± 0.34 L, Normalized FO -0.21 ± 0.27 L) and FEV1/FVC (Normalized CTL -4.67 ± 5.0 %, Normalized FO -1.4 ± 3.18 %) values that were on average 48% and 70% smaller, respectively. Inflammatory responses measured in the sputum immediately post O3 exposure were not different among the three supplementation groups. Systolic blood pressure elevations 20-h post O3 exposure were blunted by OO supplementation.ConclusionFO supplementation appears to offer protective effects against lung function decrements caused by acute O3 exposure in healthy adults.
| S-EPMC9378480 | biostudies-literature
Project description:Exposure to diesel exhaust emissions (DEE) is strongly linked to innate immune injury and lung injury, but the role of macrophage chemoattractant CXCL17 in the lung damage caused by DEE exposure remains unclear. In this study, whole-body plethysmography (WBP), inflammatory cell differential count, and histopathological analysis were performed to assess respiratory parameters, airway inflammation, and airway injury in C57BL/6 male mice exposed to DEE for 3 months. qRT-PCR, IHC (immunohistochemistry), and ELISA were performed to measure the CXCL17 expression in airway epithelium or BALF (bronchoalveolar lavage fluid) following DEE/Diesel exhaust particle (DEP) exposure. Respiratory parameters, airway inflammation, and airway injury were assessed in CXCL17-overexpressing mice through adeno-associated virus vector Type 5 (AAV5) infection. Additionally, an in vitro THP-1 and HBE co-culture system was constructed. Transwell assay was carried out to evaluate the effect of rh-CXCL17 (recombinant human protein-CXCL17) on THP-1 cell migration. Flow cytometry and qRT-PCR were conducted to assess the impacts of rh-CXCL17 on apoptosis and inflammation/remodeling of HBE cells. We found that the mice exposed to DEE showed abnormal respiratory parameters, accompanied by airway injury and remodeling (ciliary injury in airway epithelium, airway smooth muscle hyperplasia, and increased collagen deposition). Carbon content in airway macrophages (CCAM), but not the number of macrophages in BALF, increased significantly. CXCL17 expression significantly decreased in mice airways and HBE after DEE/DEP exposure. AAV5-CXCL17 enhanced macrophage recruitment and clearance of DEE in the lungs of mice, and it improved respiratory parameters, airway injury, and airway remodeling. In the THP-1/HBE co-culture system, rh-CXCL17 increased THP-1 cell migration while attenuating HBE cell apoptosis and inflammation/remodeling. Therefore, CXCL17 might attenuate DEE-induced lung damage by recruiting and activating pulmonary macrophages, which is expected to be a novel therapeutic target for DEE-associated lung diseases.
| S-EPMC10459829 | biostudies-literature
Project description:BackgroundInteractions between acute exposures to environmental chemical contaminants and psychological stress may be important in situations where they are likely to co-occur, ranging in intensity from daily urban living to participation in war. Modification of symptomatic responses by stress may play a role in medically unexplained symptoms attributed to low-level chemical exposures.ObjectivesWe hypothesized that the combination of exposure to diesel exhaust (DE) and acute psychological stress would cause sickness responses in healthy volunteers. Moreover, these responses would be greater in individuals with self-reported prior chemical odor intolerance.MethodsOne hundred adult subjects underwent 1-hr exposures to diluted DE and clean air control. Half of the subjects performed a public-speaking stressor task during the exposures. Subjects completed questionnaires to determine their Chemical Odor Intolerance Index score. Plasma cortisol, end-tidal carbon dioxide, and the severity of 35 symptoms were measured at time points before and after the exposures.ResultsSubjects exposed to DE demonstrated small but statistically significant increases in severity for several symptom categories, including sickness response and upper respiratory, central nervous system, and total symptoms. The psychological stressor did not increase symptom severity independently or via interaction with DE. Subjects with prior self-reported chemical intolerance had more severe sickness response symptoms from DE.ConclusionsThese results suggest that exposure to DE can cause acute sickness response symptoms and that these symptoms are also associated with increased levels of self-reported chemical intolerance. The results did not confirm our hypothesis that an acute stressor would increase sickness response symptom severity during the exposure.
| S-EPMC3223003 | biostudies-literature
Project description:Recently, we reported that diesel exhaust particles (DEPs) disrupt tight junctions (TJs) in alveolar epithelial cells (AECs) via an increase in reactive oxygen species (ROS). In this study, we investigated the role of protein kinase C (PKC)-? activation in DEP-induced lung injury. C57/bl6 mice were instilled intratracheally with 50 ?l of saline containing 100 ?g of DEPs or titanium dioxide (TiO2). Twenty-four hours later, bronchoalveolar lavage was performed to assess neutrophil counts and protein concentrations. In addition, in vitro experiments were performed in primary rat and human AECs exposed to DEPs (50 ?g/cm(2)) for 3 hours. Transepithelial electrical conductance was measured, and TJ protein association was analyzed by immunoprecipitation. To determine whether the overexpression of antioxidants prevented DEP-induced lung injury, AECs and mice were infected with adenoviruses containing catalase and manganese superoxide dismutase (MnSOD) plasmids. In vivo, the overexpression of catalase and MnSOD prevented DEP-induced neutrophil recruitment. The inhibition of PKC-? activation also prevented DEP-induced neutrophil recruitment in vivo. In vitro, DEPs activated PKC-? in AECs, but not in alveolar macrophages. Using a specific myristolated PKC-? pseudosubstrate pepetide (PKC-? ps), we showed that PKC-? mediated the DEP-induced dissociation of occludin and zonula occludin-1 (ZO1) in rat and human AECs. In addition, the overexpression of constitutively active PKC-? induced the dissociation of occludin and ZO1 in AECs. DEP-induced TJ disruption occurs via PKC-?. TJ disruption seems to be in part responsible for DEP-induced lung injury.
| S-EPMC3604088 | biostudies-other
Project description:Background: Diesel exhaust (DE) is the primary source of urban fine particulate matter, which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix® platform (GeneChip® Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 µg/m³ of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes. Keywords: time course
2008-01-03 | GSE7462 | GEO
Project description:BackgroundMost studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure-response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders.MethodsWe conducted a nested case-control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density-sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided.ResultsWe observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 μg/m(3)-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 μg/m(3)-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P (interaction) = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other.ConclusionOur findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.
| S-EPMC3369553 | biostudies-literature
Project description:Particulate matter (PM) air pollution is associated with alterations in cardiac conductance and sudden cardiac death in epidemiological studies. Traffic-related air pollutants, including diesel exhaust (DE) may be at least partly responsible for these effects. In this experimental study we assessed whether short-term exposure to DE would result in alterations in heart rate variability (HRV), a non-invasive measure of autonomic control of the heart.In a double-blind, crossover, controlled-exposure study, 16 adult volunteers were exposed (at rest) in randomized order to filtered air (FA) and two levels of diluted DE (100 or 200 microg/m(3) of fine particulate matter) in 2-h sessions. Before, and at four time points after each exposure we assessed HRV. HRV parameters assessed included both time domain statistics (standard deviation of N-N intervals (SDNN), and the square root of the mean of the sum of squared differences between successive N-N intervals (RMSSD)) and frequency domain statistics (high-frequency (HF) power, low-frequency (LF) power, and the LF/HF ratio).We observed an effect at 3-h after initiation of DE inhalation on the frequency domain statistics of HRV. DE at 200 microg/m(3) elicited an increase in HF power compared to FA (Delta=0.33; 95% CI: 0.01-0.7) and a decrease in LF/HF ratio (Delta=-0.74; 95% CI: -1.2 to -0.2). The effect of DE on HF power was not consistent among study participants. There was no DE effect on time domain statistics and no significant DE effect on HRV in later time points.We did not observe a consistent DE effect on the autonomic control of the heart in a controlled-exposure experiment in young participants. Efforts are warranted to understand discrepancies between epidemiological and experimental studies of air pollution's impact on HRV.
| S-EPMC2518070 | biostudies-literature
Project description:Background: Diesel exhaust (DE) is the primary source of urban fine particulate matter, which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix® platform (GeneChip® Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 µg/m³ of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes. Experiment Overall Design: We conducted a crossover, double-blind experiment, randomized to order of DE and filtered-air (FA) exposure with each participant exposed on four different days to each of four conditions: FA and DE calibrated to 50µg/m3 (DE50), 100µg/m3 (DE100), and 200µg/m3 (DE200) of fine particulate matter (PM2.5- particles with aerodynamic diameter 2.5µm or less). Exposure sessions were conducted at least 2 weeks apart.
2008-06-15 | E-GEOD-7462 | biostudies-arrayexpress
Project description:BackgroundExposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.MethodsThirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.ResultsThe standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.ConclusionsA cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.
| S-EPMC4007775 | biostudies-literature
Project description:Diesel exhaust enhances allergic inflammation, and pollutants are associated with heightened susceptibility to viral respiratory infections. The effects of combined diesel and virus exposure in humans are unknown.Test whether acute exposure to diesel modifies inflammatory responses to influenza virus in normal humans and those with allergies.We conducted a double-blind, randomized, placebo-controlled study of nasal responses to live attenuated influenza virus in normal volunteers and those with allergic rhinitis exposed to diesel (100 ?g/m(3)) or clean air for 2 hours, followed by standard dose of virus and serial nasal lavages. Endpoints were inflammatory mediators (ELISA) and virus quantity (quantitative reverse-transcriptase polymerase chain reaction). To test for exposure effect, we used multiple regression with exposure group (diesel vs. air) as the main explanatory variable and allergic status as an additional factor.Baseline levels of mediators did not differ among groups. For most postvirus nasal cytokine responses, there was no significant diesel effect, and no significant interaction with allergy. However, diesel was associated with significantly increased IFN-? responses (P = 0.02), with no interaction with allergy in the regression model. Eotaxin-1 (P = 0.01), eosinophil cationic protein (P < 0.01), and influenza RNA sequences in nasal cells (P = 0.03) were significantly increased with diesel exposure, linked to allergy.Short-term exposure to diesel exhaust leads to increased eosinophil activation and increased virus quantity after virus inoculation in those with allergic rhinitis. This is consistent with previous literature suggesting a diesel "adjuvant" effect promoting allergic inflammation, and our data further suggest this change may be associated with reduced virus clearance.Clinical trial registered with www.clinicaltrials.gov (NCT00617110).
| S-EPMC3297091 | biostudies-literature