Thomas Tjoa

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.

The relationship of respiratory and cardiovascular hospital admissions to the southern California wildfires of 2003

Objective: There is limited information on the public health impact of wildfires. The relationship of cardiorespiratory hospital admissions (n = 40 856) to wildfire-related particulate matter (PM2.5) during catastrophic wildfires in southern California in October 2003 was evaluated. Methods: Zip code level PM2.5 concentrations were estimated using spatial interpolations from measured PM2.5, light extinction, meteorological conditions, and smoke information from MODIS satellite images at 250 m resolution. Generalised estimating equations for Poisson data were used to assess the relationship between daily admissions and PM2.5, adjusted for weather, fungal spores (associated with asthma), weekend, zip code-level population and sociodemographics. Results: Associations of 2-day average PM2.5 with respiratory admissions were stronger during than before or after the fires. Average increases of 70 μg/m3 PM2.5 during heavy smoke conditions compared with PM2.5 in the pre-wildfire period were associated with 34% increases in asthma admissions. The strongest wildfire-related PM2.5 associations were for people ages 65–99 years (10.1% increase per 10 μg/m3 PM2.5, 95% CI 3.0% to 17.8%) and ages 0–4 years (8.3%, 95% CI 2.2% to 14.9%) followed by ages 20–64 years (4.1%, 95% CI −0.5% to 9.0%). There were no PM2.5–asthma associations in children ages 5–18 years, although their admission rates significantly increased after the fires. Per 10 μg/m3 wildfire-related PM2.5, acute bronchitis admissions across all ages increased by 9.6% (95% CI 1.8% to 17.9%), chronic obstructive pulmonary disease admissions for ages 20–64 years by 6.9% (95% CI 0.9% to 13.1%), and pneumonia admissions for ages 5–18 years by 6.4% (95% CI −1.0% to 14.2%). Acute bronchitis and pneumonia admissions also increased after the fires. There was limited evidence of a small impact of wildfire-related PM2.5 on cardiovascular admissions. Conclusions: Wildfire-related PM2.5 led to increased respiratory hospital admissions, especially asthma, suggesting that better preventive measures are required to reduce morbidity among vulnerable populations.

Personal and Ambient Air Pollution is Associated with Increased Exhaled Nitric Oxide in Children with Asthma

Background Research has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined. Methods We followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 μm in aerodynamic diameter (PM2.5), 24-hr PM2.5 elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM2.5, PM2.5 EC and OC, and NO2. Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period. Results The strongest positive associations were between FeNO and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 μg/m3 personal PM2.5, 1.1 ppb FeNO [95% confidence interval (CI), 0.1–1.9]; for 0.6 μg/m3 personal EC, 0.7 ppb FeNO (95% CI, 0.3–1.1); for 17 ppb personal NO2, 1.6 ppb FeNO (95% CI, 0.4–2.8). Larger associations were found for ambient EC and smaller associations for ambient NO2. Ambient PM2.5 and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM2.5 in the preceding 5 hr was associated with FeNO. In two-pollutant models, the most robust associations were for personal and ambient EC and NO2, and for personal but not ambient PM2.5. Conclusion PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.

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.

Personal and Ambient Air Pollution Exposures and Lung Function Decrements in Children with Asthma

Background Epidemiologic studies have shown associations between asthma outcomes and outdoor air pollutants such as nitrogen dioxide and particulate matter mass < 2.5 μm in diameter (PM2.5). Independent effects of specific pollutants have been difficult to detect because most studies have relied on highly correlated central-site measurements. Objectives This study was designed to evaluate the relationship of daily changes in percent-predicted forced expiratory volume in 1 sec (FEV1) with personal and ambient air pollutant exposures. Methods For 10 days each, we followed 53 subjects with asthma who were 9–18 years of age and living in the Los Angeles, California, air basin. Subjects self-administered home spirometry in themorning, afternoon, and evening. We measured personal hourly PM2.5 mass, 24-hr PM2.5 elemental and organic carbon (EC–OC), and 24-hr NO2, and the same 24-hr average outdoor central-site(ambient) exposures. We analyzed data with transitional mixed models controlling for personal temperature and humidity, and as-needed β2-agonist inhaler use. Results FEV1 decrements were significantly associated with increasing hourly peak and daily average personal PM2.5, but not ambient PM2.5. Personal NO2 was also inversely associated with FEV1. Ambient NO2 was more weakly associated. We found stronger associations among 37 subjects not taking controller bronchodilators as follows: Personal EC–OC was inversely associated with morning FEV1; for an interquartile increase of 71 μg/m3 1-hr maximum personal PM2.5, overall percent-predicted FEV1 decreased by 1.32% [95% confidence interval (CI), −2.00 to −0.65%]; and for an interquartile increase of 16.8 ppb 2-day average personal NO2, overall percent-predicted FEV1 decreased by 2.45% (95% CI, −3.57 to −1.33%). Associations of both personal PM2.5 and NO2 with FEV1 remained when co-regressed, and both confounded ambient NO2. Conclusions Independent pollutant associations with lung function might be missed using ambient data alone. Different sets of causal components are suggested by independence of FEV1 associations with personal PM2.5 mass from associations with personal NO2.

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.

Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel

Airborne particulate matter (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS). Reported associations between worsening asthma and PM2.5 mass could be related to PM oxidative potential to induce airway oxidative stress and inflammation (hallmarks of asthma pathology). We followed 45 schoolchildren with persistent asthma in their southern California homes daily over 10 days with offline fractional exhaled nitric oxide (FENO), a biomarker of airway inflammation. Ambient exposures included daily average PM2.5, PM2.5 elemental and organic carbon (EC, OC), NO2, O3, and endotoxin. We assessed PM2.5 oxidative potential using both an abiotic and an in vitro bioassay on aqueous extracts of daily particle filters: (1) dithiothreitol (DTT) assay (abiotic), representing chemically produced ROS; and (2) ROS generated intracellularly in a rat alveolar macrophage model using the fluorescent probe 2′7′-dicholorohidroflourescin diacetate. We analyzed relations of FENO to air pollutants in mixed linear regression models. FENO was significantly positively associated with lag 1-day and 2-day averages of traffic-related markers (EC, OC, and NO2), DTT and macrophage ROS, but not PM2.5 mass. DTT associations were nearly twice as strong as other exposures per interquartile range: median FENO increased 8.7–9.9% per 0.43 nmole/min/m3 DTT. Findings suggest that future research in oxidative stress-related illnesses such as asthma and PM exposure would benefit from assessments of PM oxidative potential and composition.

Repeated hospital encounters for asthma in children and exposure to traffic-related air pollution near the home

BACKGROUND Aggregate hospital encounters for asthma (admissions or emergency department visits) have been associated with daily regional air pollution. There are fewer data on relationships between repeated hospital encounters and traffic-related air pollution near the home. OBJECTIVE To estimate the association of local traffic-generated air pollution with repeated hospital encounters for asthma in children. METHODS Hospital records for 2,768 children aged 0 to 18 years (697 of whom had > or = 2 encounters) were obtained for a catchment area of 2 hospitals in northern Orange County, California. Residential addresses were geocoded. A line source dispersion model was used to estimate individual seasonal exposures to local traffic-generated pollutants (nitrogen oxides and carbon monoxide) longitudinally beginning with the first hospital encounter. Recurrent proportional hazards analysis was used to estimate risk of exposure to air pollution adjusting for sex, age, health insurance, census-derived poverty, race/ethnicity, residence distance to hospital, and season. The adjustment variables and census-derived median household income were tested for effect modification. RESULTS Adjusted hazard ratios for interquartile range increases in nitrogen oxides (4.00 ppb) and carbon monoxide (0.056 ppm) were 1.10 (95% confidence interval, 1.03-1.16) and 1.07 (1.01-1.14), respectively. Associations were strongest for girls and infants but were not significantly different from other groups. Stronger associations in children from higher-income block groups (P < .09 for trend) may have been due to more accurate data. CONCLUSIONS Associations for repeated hospital encounters suggest that locally generated air pollution near the home affects asthma severity in children. Risk may begin during infancy and continue in later childhood, when asthma diagnoses are clearer.