Coarse particulate matter (PM2.5-10) in Los Angeles Basin air induces expression of inflammation and cancer biomarkers in rat brains.
ABSTRACT: Air pollution is linked to brain inflammation, which accelerates tumorigenesis and neurodegeneration. The molecular mechanisms that connect air pollution with brain pathology are largely unknown but seem to depend on the chemical composition of airborne particulate matter (PM). We sourced ambient PM from Riverside, California, and selectively exposed rats to coarse (PM2.5-10: 2.5-10?µm), fine (PM<2.5: <2.5?µm), or ultrafine particles (UFPM: <0.15?µm). We characterized each PM type via atomic emission spectroscopy and detected nickel, cobalt and zinc within them. We then exposed rats separately to each PM type for short (2 weeks), intermediate (1-3 months) and long durations (1 year). All three metals accumulated in rat brains during intermediate-length PM exposures. Via RNAseq analysis we then determined that intermediate-length PM2.5-10 exposures triggered the expression of the early growth response gene 2 (EGR2), genes encoding inflammatory cytokine pathways (IL13-R?1 and IL-16) and the oncogene RAC1. Gene upregulation occurred only in brains of rats exposed to PM2.5-10 and correlated with cerebral nickel accumulation. We hypothesize that the expression of inflammation and oncogenesis-related genes is triggered by the combinatorial exposure to certain metals and toxins in Los Angeles Basin PM2.5-10.
Project description:Previous studies on air pollutants and birth outcomes have reported inconsistent results. Chemical components of particulate matter ? 2.5 µm (PM2.5) composition are spatially -heterogeneous, which might contribute to discrepancies across PM2.5 studies.We explored whether birth weight at term is affected by PM2.5, PM10 (PM ? 10 µm), and gaseous pollutants.We calculated exposures during gestation and each trimester for PM2.5 chemical components, PM10, PM2.5, carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide for births in 2000-2007 for states in the northeastern and mid-Atlantic United States. Associations between exposures and risk of low birth weight (LBW) were adjusted by family and individual characteristics and region. Interaction terms were used to investigate whether risk differs by race or sex.Several PM2.5 chemical components were associated with LBW. Risk increased 4.9% (95% CI: 3.4, 6.5%), 4.7% (3.2, 6.2%), 5.7% (2.7, 8.8%), and 5.0% (3.1, 7.0%) per interquartile range increase of PM2.5 aluminum, elemental carbon, nickel, and titanium, respectively. Other PM2.5 chemical components and gaseous pollutants showed associations, but were not statistically significant in multipollutant models. The trimester associated with the highest relative risk differed among pollutants. Effect estimates for PM2.5 elemental carbon and nickel were higher for infants of white mothers than for those of African-American mothers, and for males than females.Most exposure levels in our study area were in compliance with U.S. Environmental Protection Agency air pollution standards; however, we identified associations between PM2.5 components and LBW. Findings suggest that some PM2.5 components may be more harmful than others, and that some groups may be particularly susceptible.
Project description:AIMS: The aim of this study was to determine (i) whether long-term exposure to air pollution was associated with all-cause mortality using the Myocardial Ischaemia National Audit Project (MINAP) data for England and Wales, and (ii) the extent to which exposure to air pollution contributed to socioeconomic inequalities in prognosis. METHODS AND RESULTS: Records of patients admitted to hospital with acute coronary syndrome (ACS) in MINAP collected under the National Institute for Cardiovascular Outcomes Research were linked to modelled annual average air pollution concentrations for 2004-10. Hazard ratios for mortality starting 28 days after admission were estimated using Cox proportional hazards models. Among the 154 204 patients included in the cohort, the average follow-up was 3.7 years and there were 39 863 deaths. Mortality rates were higher for individuals exposed to higher levels of particles with a diameter of ?2.5 µm (PM2.5; PM, particulate matter): the fully adjusted hazard ratio for a 10 µg/m(3) increase in PM2.5 was 1.20 (95% CI 1.04-1.38). No associations were observed for larger particles or oxides of nitrogen. Air pollution explained socioeconomic inequalities in survival to only a small extent. CONCLUSION: Mortality from all causes was higher among individuals with greater exposure to PM2.5 in survivors of hospital admission for ACS in England and Wales. Despite higher exposure to PM2.5 among those from more deprived areas, such exposure was a minor contribution to the socioeconomic inequalities in prognosis following ACS. Our findings add to the evidence of mortality associated with long-term exposure to fine particles.
Project description:BACKGROUND: The prevalence of asthma in children is a significant phenomenon in the Caribbean. Among the etiologic factors aggravating asthma in children, environmental pollution is one of the main causes. In Guadeloupe, pollution is primarily transported by Saharan dust including inhalable particles. METHODS: This study assesses, over one year (2011), the short-term effects of pollutants referred to as PM10 (PM10: particulate matter <10 µm) and PM2.5-10 (PM2.5-10: particulate matter >2.5 µm and <10 µm) contained in Saharan dust, on the visits of children aged between 5 and 15 years for asthma in the health emergency department of the main medical facility of the archipelago of Guadeloupe. A time-stratified case-crossover model was applied and the data were analysed by a conditional logistic regression for all of the children but also for sub-groups corresponding to different age classes and genders. RESULTS: The visits for asthma concerned 836 children including 514 boys and 322 girls. The Saharan dust has affected 15% of the days of the study (337 days) and involved an increase in the average daily concentrations of PM10 (49.7 µg/m3 vs. 19.2 µg/m3) and PM 2.5-10 (36.2 µg/m3 vs. 10.3 µg/m3) compared to days without dust. The excess risk percentages (IR%) for visits related to asthma in children aged between 5 and 15 years on days with dust compared to days without dust were, for PM10, ((IR %: 9.1% (CI95%, 7.1%-11.1%) versus 1.1%(CI95%, -5.9%-4.6%)) and for PM2.5-10 (IR%: 4.5%(CI95%, 2.5%-6.5%) versus 1.6% (CI95%, -1.1%-3.4%). There was no statistical difference in the IR% for periods with Saharan dust among different age group of children and between boys and girls for PM10 and PM2.5-10. CONCLUSION: The PM10 and PM2.5-10 pollutants contained in the Saharan dust increased the risk of visiting the health emergency department for children with asthma in Guadeloupe during the study period.
Project description:Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality.Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter.Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ? 2.5 ?m (PM2.5) and ? 10 ?m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis.The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced.Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
Project description:BACKGROUND: Emerging evidence, mainly from Europe and Asia, indicates that venous thromboembolism (VTE) occurs most often in winter. Factors implicated in such seasonality are low temperature-mediated exacerbation of coagulation and high levels of particulate matter (PM) air pollution. However, in contrast to most European and Asian cities, particulate matter pollution peaks in the summer in many North American cities. OBJECTIVES: We aimed to exploit this geographical difference and examine the temporal distribution of VTE in a cold-weather, North American city, Detroit, with a summer PM peak. Our goal was thereby to resolve the influence of temperature and PM levels on VTE. METHODS: Our retrospective, analytical semi-ecological study used chart review to confirm 1,907 acute, ambulatory VTE cases, divided them by location (Detroit versus suburban), and plotted monthly VTE frequency distributions. We used Environmental Protection Agency data to determine the temporal distribution of PM pollution components in Detroit. Suburban PM air pollution is presumed negligible and therefore not monitored. RESULTS: Acute VTE cases in Detroit (1,490) exhibited a summer peak (June 24(th)) and differed from both a uniform distribution (P<0.01) and also that of 1,123 no-VTE cases (P<0.02). Levels of 10 µm diameter PM and coarse particle (2.5 to 10 µm) PM also exhibited summer peaks versus a winter peak for 2.5 µm diameter PM. Contrary to their urban counterparts, suburban cases of acute VTE (417) showed no monthly variation. CONCLUSIONS: The summer peak of acute VTE in Detroit indicates that low temperature is not a major factor in VTE pathogenesis. In contrast, concordance of the 10 µm diameter PM, coarse particle, and the Detroit VTE monthly distributions, combined with no monthly suburban VTE variation, is consistent with a role for PM pollution. Furthermore, divergence of the VTE and 2.5 µm PM distributions suggests that particle size may play a role.
Project description:BACKGROUND: Dozens of studies link acute exposure to particulate matter (PM) air pollution with premature mortality and morbidity, but questions remain about which species and sources in the vast PM mixture are responsible for the observed health effects. Although a few studies exist on the effects of species and sources in U.S. cities, European cities-which have a higher proportion of diesel engines and denser urban populations-have not been well characterized. Information on the effects of specific sources could aid in targeting pollution control and in articulating the biological mechanisms of PM. OBJECTIVES: Our study examined the effects of various PM sources on daily mortality for 2003 through 2007 in Barcelona, a densely populated city in the northeast corner of Spain. METHODS: Source apportionment for PM ? 2.5 ?m and ? 10 µm in aerodynamic diameter (PM2.5 and PM10) using positive matrix factorization identified eight different factors. Case-crossover regression analysis was used to estimate the effects of each factor. RESULTS: Several sources of PM2.5, including vehicle exhaust, fuel oil combustion, secondary nitrate/organics, minerals, secondary sulfate/organics, and road dust, had statistically significant associations (p < 0.05) with all-cause and cardiovascular mortality. Also, in some cases relative risks for a respective interquartile range increase in concentration were higher for specific sources than for total PM2.5 mass. CONCLUSIONS: These results along with those from our multisource models suggest that traffic, sulfate from shipping and long-range transport, and construction dust are important contributors to the adverse health effects linked to PM.
Project description:Exposure to air pollution particulate matter (PM) and tuberculosis (TB) are two of the leading global public health challenges affecting low and middle income countries. An estimated 4.26 million premature deaths are attributable to household air pollution and an additional 4.1 million to outdoor air pollution annually. Mycobacterium tuberculosis (M.tb) infects a large proportion of the world's population with the risk for TB development increasing during immunosuppressing conditions. There is strong evidence that such immunosuppressive conditions develop during household air pollution exposure, which increases rates of TB development. Exposure to urban air pollution has been shown to alter the outcome of TB therapy. Here we examined whether in vitro exposure to urban air pollution PM alters human immune responses to M.tb. PM2.5 and PM10 (aerodynamic diameters <2.5?m, <10?m) were collected monthly from rainy, cold-dry and warm-dry seasons in Iztapalapa, a highly populated TB-endemic municipality of Mexico City with elevated outdoor air pollution levels. We evaluated the effects of seasonality and size of PM on cytotoxicity and antimycobacterial host immunity in human peripheral blood mononuclear cells (PBMC) from interferon gamma (IFN-?) release assay (IGRA)+ and IGRA- healthy study subjects. PM10 from cold-dry and warm-dry seasons induced the highest cytotoxicity in PBMC. With the exception of PM2.5 from the cold-dry season, pre-exposure to all seasonal PM reduced M.tb phagocytosis by PBMC. Furthermore, M.tb-induced IFN-? production was suppressed in PM2.5 and PM10-pre-exposed PBMC from IGRA+ subjects. This observation coincides with the reduced expression of M.tb-induced T-bet, a transcription factor regulating IFN-? expression in T cells. Pre-exposure to PM10 compared to PM2.5 led to greater loss of M.tb growth control. Exposure to PM2.5 and PM10 collected in different seasons differentially impairs M.tb-induced human host immunity, suggesting biological mechanisms underlying altered M.tb infection and TB treatment outcomes during air pollution exposures.
Project description:BACKGROUND: Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic. OBJECTIVES: The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers. METHODS: Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ? 2.5 µm in aerodynamic diameter (PM2.5), PM ? 10 µm in diameter (PM10), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters. RESULTS: We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated. CONCLUSIONS: Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.
Project description:Few studies have investigated effects of air pollution on the incidence of cerebrovascular events.We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts.Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) ? 2.5 ?m in diameter], coarse PM (PM between 2.5 and 10 ?m), PM10 (PM ? 10 ?m), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation.A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-?g/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those ? 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 ?g/m3 (HR = 1.33, 95% CI: 1.01, 1.77).We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value.
Project description:Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ?2.5, ?10, and 2.5-10 ?m in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89-3.14 per 10-5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38-2.71 per 10-5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors.We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.