Andrea Polidori

Circulating Biomarkers of Inflammation, Antioxidant Activity, and Platelet Activation Are Associated with Primary Combustion Aerosols in Subjects with Coronary Artery Disease

Background Biomarkers of systemic inflammation have been associated with risk of cardiovascular morbidity and mortality. Objectives We aimed to clarify associations of particulate matter (PM) air pollution with systemic inflammation using models based on size-fractionated PM mass and markers of primary and secondary aerosols. Methods We followed a panel of 29 nonsmoking elderly subjects with a history of coronary artery disease (CAD) living in retirement communities in the Los Angeles, California, air basin. Blood plasma biomarkers were measured weekly over 12 weeks and included C-reactive protein (CRP), fibrinogen, tumor necrosis factor-α (TNF-α) and its soluble receptor-II (sTNF-RII), interleukin-6 (IL-6) and its soluble receptor (IL-6sR), fibrin D-dimer, soluble platelet selectin (sP-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), intracellular adhesion molecule-1 (sICAM-1), and myeloperoxidase (MPO). To assess changes in antioxidant capacity, we assayed erythrocyte lysates for glutathione peroxidase-1 (GPx-1) and copper-zinc superoxide dismutase (Cu,Zn-SOD) activities. We measured indoor and outdoor home daily size-fractionated PM mass, and hourly pollutant gases, total particle number (PN), fine PM elemental carbon (EC) and organic carbon (OC), estimated secondary organic aerosol (SOA) and primary OC (OCpri) from total OC, and black carbon (BC). We analyzed data with mixed models controlling for temperature and excluding weeks with infections. Results We found significant positive associations for CRP, IL-6, sTNF-RII, and sP-selectin with outdoor and/or indoor concentrations of quasi-ultrafine PM ≤ 0.25 μm in diameter, EC, OCpri, BC, PN, carbon monoxide, and nitrogen dioxide from the current-day and multiday averages. We found consistent positive but largely nonsignificant coefficients for TNF-α, sVCAM-1, and sICAM-1, but not fibrinogen, IL-6sR, or D-dimer. We found inverse associations for erythrocyte Cu,Zn-SOD with these pollutants and other PM size fractions (0.25–2.5 and 2.5–10 μm). Inverse associations of GPx-1 and MPO with pollutants were largely nonsignificant. Indoor associations were often stronger for estimated indoor EC, OCpri, and PN of outdoor origin than for uncharacterized indoor measurements. There was no evidence for positive associations with SOA. Conclusions Results suggest that traffic emission sources of OCpri and quasi-ultrafine particles lead to increased systemic inflammation and platelet activation and decreased antioxidant enzyme activity in elderly people with CAD.

Air Pollution Exposures and Circulating Biomarkers of Effect in a Susceptible Population: Clues to Potential Causal Component mixtures and mechanisms

Background Mechanisms involving oxidative stress and inflammation have been proposed to explain associations of ambient air pollution with cardiovascular morbidity and mortality. Experimental evidence suggests that organic components and ultrafine particles (UFP) are important. Methods We conducted a panel study of 60 elderly subjects with coronary artery disease living in retirement communities within the Los Angeles, California, air basin. Weekly biomarkers of inflammation included plasma interleukin-6, tumor necrosis factor-α soluble receptor II (sTNF-RII), soluble platelet selectin (sP-selectin), and C-reactive protein (CRP). Biomarkers of erythrocyte antioxidant activity included glutathione peroxidase-1 and superoxide dismutase. Exposures included outdoor home daily particle mass [particulate matter < 0.25, 0.25–2.5, and 2.5–10 μm in aerodynamic diameter (PM0.25, PM0.25–2.5, PM2.5–10)], and hourly elemental and black carbon (EC–BC), estimated primary and secondary organic carbon (OCpri, SOC), particle number (PN), carbon monoxide (CO), and nitrogen oxides–nitrogen dioxide (NOx–NO2). We analyzed the relation of biomarkers to exposures with mixed effects models adjusted for potential confounders. Results Primary combustion markers (EC–BC, OCpri, CO, NOx–NO2), but not SOC, were positively associated with inflammatory biomarkers and inversely associated with erythrocyte anti-oxidant enzymes (n = 578). PN and PM0.25 were more strongly associated with biomarkers than PM0.25–2.5. Associations for all exposures were stronger during cooler periods when only OCpri, PN, and NOx were higher. We found weaker associations with statin (sTNF-RII, CRP) and clopidogrel use (sP-selectin). Conclusions Traffic-related air pollutants are associated with increased systemic inflammation, increased platelet activation, and decreased erythrocyte antioxidant enzyme activity, which may be partly behind air pollutant–related increases in systemic inflammation. Differences in association by particle size, OC fraction, and seasonal period suggest components carried by UFP are important.

Estimating the Secondary Organic Aerosol Contribution to PM2.5 Using the EC Tracer Method Special Issue of Aerosol Science and Technology on Findings from the Fine Particulate Matter Supersites Program

The EC tracer method is applied to a series of measurements by different carbonaceous aerosol samplers in the Pittsburgh Air Quality Study (PAQS) in order to estimate the concentration of secondary organic aerosol. High-resolution measurements (2–6 h) and daily averaged concentrations were collected during the summer 2001 intensive (1 July to 4 August 2001) and are used for the analysis. The various samplers used during PAQS show differences in the measured concentrations of OC and EC due to the different sampling artifacts and sampling periods. A systematic approach for the separation of periods where SOA contributes significantly to the ambient OC levels from the periods where organic and elemental carbon concentrations are dominated by primary emissions is proposed. Ozone is used as an indicator of photochemical activity to identify periods of probable secondary organic aerosol production in the area. Gaseous tracers of combustion sources (CO, NO, and NO x ) are used to identify periods where most of the OC is primary. Periods dominated by primary emissions are used to establish the relationship between primary OC and EC, a tracer for primary combustion-generated carbon for the different sets of measurements for July 2001. Around 35% of the organic carbon concentration in Western Pennsylvania during July of 2001 is estimated to be secondary in origin.

Traffic-related air pollution and blood pressure in elderly subjects with coronary artery disease.

Background: Associations between blood pressure (BP) and ambient air pollution have been inconsistent. No studies have used ambulatory BP monitoring and outdoor home air-pollutant measurements with time-activity-location data. We address these gaps in a study of 64 elderly subjects with coronary artery disease, living in retirement communities in the Los Angeles basin. Methods: Subjects were followed up for 10 days with hourly waking ambulatory BP monitoring (n = 6539 total measurements), hourly electronic diaries for perceived exertion and location, and real-time activity monitors (actigraphs). We measured hourly outdoor home pollutant gases, particle number, PM2.5, organic carbon, and black carbon. Data were analyzed with mixed models controlling for temperature, posture, actigraph activity, hour, community, and season. Results: We found positive associations of systolic and diastolic BP with air pollutants. The strongest associations were with organic carbon (especially its estimated fossil-fuel- combustion fraction), multiday average exposures, and time periods when subjects were at home. An interquartile increase in 5-day average organic carbon (5.2 &mgr;g/m3) was associated with 8.2 mm Hg higher mean systolic BP (95% confidence interval = 3.0–13.4) and 5.8 mm Hg higher mean diastolic BP (3.0–8.6). Associations of BP with 1–8 hour average air pollution were stronger with reports of moderate to strenuous physical exertion but not with higher actigraph motion. Associations were also stronger among 12 obese subjects. Conclusions: Exposure to primary organic components of fossil fuel combustion near the home were strongly associated with increased ambulatory BP in a population at potential risk of heart attack. Low fitness or obesity may increase the effects of pollutants.

Associations of primary and secondary organic aerosols with airway and systemic inflammation in an elderly panel cohort.

Background: Exposure-response information about particulate air-pollution constituents is needed to protect sensitive populations. Particulate matter <2.5 mm (PM2.5) components may induce oxidative stress through reactive-oxygen-species generation, including primary organics from combustion sources and secondary organics from photochemically oxidized volatile organic compounds. We evaluated differences in airway versus systemic inflammatory responses to primary versus secondary organic particle components, particle size fractions, and the potential of particles to induce cellular production of reactive oxygen species. Methods: A total of 60 elderly subjects contributed up to 12 weekly measurements of fractional exhaled nitric oxide (NO; airway inflammation biomarker), and plasma interleukin-6 (IL-6; systemic inflammation biomarker). PM2.5 mass fractions were PM0.25 (<0.25 &mgr;m) and PM0.25–2.5 (0.25–2.5 &mgr;m). Primary organic markers included PM2.5 primary organic carbon, and PM0.25 polycyclic aromatic hydrocarbons and hopanes. Secondary organic markers included PM2.5 secondary organic carbon, and PM0.25 water soluble organic carbon and n-alkanoic acids. Gaseous pollutants included carbon monoxide (CO) and nitrogen oxides (NOx; combustion emissions markers), and ozone (O3; photochemistry marker). To assess PM oxidative potential, we exposed rat alveolar macrophages in vitro to aqueous extracts of PM0.25 filters and measured reactive-oxygen-species production. Biomarker associations with exposures were evaluated with mixed-effects models. Results: Secondary organic markers, PM0.25–2.5, and O3 were positively associated with exhaled NO. Primary organic markers, PM0.25, CO, and NOx were positively associated with IL-6. Reactive oxygen species were associated with both outcomes. Conclusions: Particle effects on airway versus systemic inflammation differ by composition, but overall particle potential to induce generation of cellular reactive oxygen species is related to both outcomes.

Association of Biomarkers of Systemic Inflammation with Organic Components and Source Tracers in Quasi-Ultrafine Particles

Background Evidence is needed regarding the air pollutant components and their sources responsible for associations between particle mass concentrations and human cardiovascular outcomes. We previously found associations between circulating biomarkers of inflammation and mass concentrations of quasi-ultrafine particles ≤ 0.25 μm in aerodynamic diameter (PM0.25) in a panel cohort study of 60 elderly subjects with coronary artery disease living in the Los Angeles Basin. Objectives We reassessed biomarker associations with PM0.25 using new particle composition data. Methods Weekly biomarkers of inflammation were plasma interleukin-6 (IL-6) and soluble tumor necrosis factor-α receptor II (sTNF-RII) (n = 578). Exposures included indoor and outdoor community organic PM0.25 constituents [polycyclic aromatic hydrocarbons (PAHs), hopanes, n-alkanes, organic acids, water-soluble organic carbon, and transition metals]. We analyzed the relation between biomarkers and exposures with mixed-effects models adjusted for potential confounders. Results Indoor and outdoor PAHs (low-, medium-, and high-molecular-weight PAHs), followed by hopanes (vehicle emissions tracer), were positively associated with biomarkers, but other organic components and transition metals were not. sTNF-RII increased by 135 pg/mL [95% confidence interval (CI), 45–225 pg/mL], and IL-6 increased by 0.27 pg/mL (95% CI, 0.10–0.44 pg/mL) per interquartile range increase of 0.56 ng/m3 outdoor total PAHs. Two-pollutant models of PM0.25 with PAHs showed that nominal associations of IL-6 and sTNF-RII with PM0.25 mass were completely confounded by PAHs. Vehicular emission sources estimated from chemical mass balance models were strongly correlated with PAHs (R = 0.71). Conclusions Traffic emission sources of organic chemicals represented by PAHs are associated with increased systemic inflammation and explain associations with quasi-ultrafine particle mass.

Local and Regional Secondary Organic Aerosol: Insights from a Year of Semi-Continuous Carbon Measurements at Pittsburgh

During the Pittsburgh Air Quality Study (PAQS) an automated semi-continuous thermal-optical transmittance (TOT) carbon analyzer was used to measure 2–4 h average particulate organic (OC) and elemental carbon (EC) concentrations from July 1, 2001 to August 13, 2002. To minimize the adsorption of vapor-phase organics, the sample air was drawn through a multi-channel parallel-plate diffusion denuder placed upstream of the carbon analyzer. Particulate OC and EC in the sample air were then collected on a quartz fiber filter (QFF) mounted inside the carbon analyzer, and analyzed immediately after collection. To account for any remaining organic vapors not retained by the denuder and collected on the sampling filter (positive artifact) a dynamic blank was run every two weeks. An upper-bound estimate of volatilization induced by the presence of the denuder upstream of the sampling filter (negative artifact) was also made. A detailed description of the operating protocol and quality assurance measurements is provided. The contributions of primary and secondary organic aerosol (SOA) to particulate OC were calculated using an “EC tracer method,” which is codified herein. Annual average SOA accounted for 33% of particulate OC. SOA accounted for 30–40% of monthly average OC from June to November in Pittsburgh, similar to previous summertime estimates for Atlanta (Lim and Turpin 2002) and much larger than previous estimates of SOA in the Los Angeles Basin (Turpin and Huntzicke 1995). Examination of concentration dynamics suggests that multi-day formation and regional transport is an important contributor to the higher SOA contributions to OC in Pittsburgh and suggests that SOA is likely to be a particularly important contributor to particulate OC in locations that are recipients of long distance transport, such as the eastern United States. †Currently at: Department of Environmental Engineering, Kyungpook National University, Korea. ††Currently at: Department of Chemical Engineering, Tecnológico de Monterrey, Monterrey, Mexico. †††Currently at: Department of Civil and Environmental Engineering, University of Illinois, Urbana-Champaign, IL. ††††Currently at: Department of Chemical Engineering, University of Patras, Patras, Greece.

Organic PM2.5 : Fractionation by Polarity, FTIR Spectroscopy, and OM/OC Ratio for the Pittsburgh Aerosol

A polarity-based extraction/fractionation method validated with standard compounds was used to characterize organic aerosol samples collected during the Pittsburgh Air Quality Study (PAQS). Organic extracts were separated into 5 polarity classes by sequential elution with hexane, dichloromethane, ethyl acetate, acetone, and methanol. Organic mass (OM) and carbon mass (OC) were measured in samples, their extracts, and their corresponding fractions yielding OM/OC ratios and the contribution of each polarity fraction to total OM. The study average OM/OC ratio for each fraction [(OM/OC)fraction] varied from 1.37 for the hexane fraction to 2.25 for the methanol fraction. OM/OC ratios for “non-extractable” organics ((OM/OC)N-E) were also predicted; the study average (OM/OC)N - E was 2.54, consistent with ratios of 2.1–3.2 for water-soluble organic aerosol species. Annual average ratios with and without the contributions of the “non-extractable” material [(OM/OC)total and (OM/OC)extract, respectively] were 2.05 ± 0.18(1σ) and 1.91 ± 0.24(1σ), similar to OM/OC of atmospherically relevant oligomers and aged aerosols measured elsewhere. Ratios were somewhat higher during summer/winter than spring/fall, probably because of a greater contribution of oxidized species such as dicarboxylic acids (summer), levoglucosan (winter and/or summer), and humic-like-substances (HULIS; winter and/or summer). We hypothesize that the OM/OC of atmospheric aerosols approaches a value of 1.9–2.1 as it ages and oligomerizes in the atmosphere. The annual-average contributions of each fraction to the total collected OM mass were, 16.8, 14.0, 11.7, 11.5, 19.3, and 26.7% for the hexane-, dichloromethane-, ethyl acetate-, acetone-, methanol-, and “non-extractable” fractions, respectively. Thus non-polar and very polar species dominated the OM mass throughout the year. Fourier transformed infrared (FTIR) spectroscopy was used to further characterize the composition of extracts and fractions. This method can be used to fractionate organic PM for toxicological studies as well as organic aerosol characterization.

Indoor/Outdoor Relationships, Trends, and Carbonaceous Content of Fine Particulate Matter in Retirement Homes of the Los Angeles Basin

Abstract Hourly indoor and outdoor fine particulate matter (PM2.5), organic and elemental carbon (OC and EC, respectively), particle number (PN), ozone (O3), carbon monoxide (CO), and nitrogen oxide (NOx) concentrations were measured at two different retirement communities in the Los Angeles, CA, area as part of the Cardiovascular Health and Air Pollution Study. Site A (group 1 [G1]) was operated from July 6 to August 20, 2005 (phase 1 [P1]) and from October 19 to December 10, 2005 (P2), whereas site B (group 2 [G2]) was operated from August 24 to October 15, 2005 (P1), and from January 4 to February 18, 2006 (P2). Overall, the magnitude of indoor and outdoor measurements was similar, probably because of the major influence of outdoor sources on indoor particle and gas levels. However, G2 showed a substantial increase in indoor OC, PN, and PM2.5 between 6:00 and 9:00 a.m., probably from cooking. The contributions of primary and secondary OC (SOA) to measured outdoor OC were estimated from collected OC and EC concentrations using EC as a tracer of primary combustion-generated OC (i.e., “EC tracer method”). The study average outdoor SOA accounted for 40% of outdoor particulate OC (40–45% in the summer and 32–40% in the winter). Air exchange rates (hr-1) and infiltration factors (F inf; dimensionless) at each site were also determined. Estimated F inf and measured particle concentrations were then used in a single compartment mass balance model to assess the contributions of indoor and/or outdoor sources to measured indoor OC, EC, PM2.5, and PN. The average percentage contributions of indoor SOA of outdoor origin to measured indoor OC were ∼35% (during G1P1 and G1P2) and ∼45% (for G2P1 and G2P2). On average, 36% (G2P1) to 44% (G1P1) of measured indoor OC was composed of outdoor-generated primary OC.

Application of a Diffusion Charger for the Measurement of Particle Surface Concentration in Different Environments

Particle surface area has recently been considered as a possible metric in an attempt to correlate particle characteristics with health effects. In order to provide input to such studies, two Nanoparticle Surface Area Monitors (NSAMs, TSI, Inc.) were deployed in different urban sites within Los Angeles to measure the concentration levels and the diurnal profiles of the surface area of ambient particles. The NSAMs principle of operation is based on the unipolar diffusion charging of particles. Results show that the particle surface concentration decreases from ∼150 μ m2 cm−3 next to a freeway to ∼ 100 μ m2 cm−3 at 100 m downwind of the freeway, and levels decline to 50–70 μ m2 cm−3 at urban background sites. Up to 51% and 30% of the total surface area corresponded to particles < 40 nm next to the freeway and at an urban background site, respectively. The NSAM signal was well correlated with a reconstructed surface concentration based on the particle number size distribution measured with collocated Scanning Mobility Particle Sizers (SMPSs, TSI, Inc.). In addition, the mean surface diameter calculated by combination of the NSAM and the total particle number concentration measured by a Condensation Particle Counter (CPC, TSI, Inc.) was in reasonable agreement with the arithmetic mean SMPS diameter, especially at the urban site. This study corroborates earlier findings on the application of diffusion chargers for ambient particle monitoring by demonstrating that they can be effectively used to monitor the particle surface concentration, or combined with a CPC to derive the mean surface diameter with high temporal resolution.