Postural Changes in Blood Pressure Associated with Interactions between Candidate Genes for Chronic Respiratory Diseases and Exposure to Particulate Matter

Background

Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM_2.5)] has been associated with autonomic dysregulation.

Objective

We hypothesized that PM_2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease.

Methods

We measured blood pressure in participants every 3–5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM_2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP × PM_2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors.

Results

Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin–angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM_2.5.

Conclusions

PM_2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.     

Black Carbon Exposure,Oxidative Stress Genes,and Blood Pressure in a Repeated-Measures Study

Background

Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects.

Objectives

We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter ≤ 2.5 μm (PM_2.5)], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense.

Methods

We performed a repeated-measures analysis in elderly men to analyze associations between PM_2.5 and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1.

Results

A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1–2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2–1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM_2.5 and BP.

Conclusions

We observed positive associations between BP and BC, but not between BP and PM_2.5, and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.     

Chronic Fine and Coarse Particulate Exposure,Mortality, and Coronary Heart Disease in the Nurses’ Health Study

Background

The relationship of fine particulate matter < 2.5 μm in diameter (PM_2.5) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM_10–2.5), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to fine and coarse particles.

Objectives

We examined the relationship of chronic PM_2.5 and PM_10–2.5 exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates.

Methods

The current study included women from the Nurses’ Health Study living in metropolitan areas of the northeastern and midwestern United States. Follow-up was from 1992 to 2002. We used geographic information systems–based spatial smoothing models to estimate monthly exposures at each participant’s residence.

Results

We found increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02–1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07–3.78) associated with each 10-μg/m³ increase in annual PM_2.5 exposure. The association between fatal CHD and PM_10–2.5 was weaker.

Conclusions

Our findings contribute to growing evidence that chronic PM_2.5 exposure is associated with risk of all-cause and cardiovascular mortality.     

Triggering of Transmural Infarctions,but Not Nontransmural Infarctions,by Ambient Fine Particles

Background

Previous studies have reported increased risk of myocardial infarction (MI) after increases in ambient particulate matter (PM) air pollution concentrations in the hours and days before MI onset.

Objectives

We hypothesized that acute increases in fine PM with aerodynamic diameter ≤ 2.5 μm (PM_2.5) may be associated with increased risk of MI and that chronic obstructive pulmonary disease (COPD) and diabetes may increase susceptibility to PM_2.5. We also explored whether both transmural and nontransmural infarctions were acutely associated with ambient PM_2.5 concentrations.

Methods

We studied all hospital admissions from 2004 through 2006 for first acute MI of adult residents of New Jersey who lived within 10 km of a PM_2.5 monitoring site (n = 5,864), as well as ambient measurements of PM_2.5, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone.

Results

Using a time-stratified case-crossover design and conditional logistic regression showed that each interquartile-range increase in PM_2.5 concentration (10.8 μg/m³) in the 24 hr before arriving at the emergency department for MI was not associated with an increased risk of MI overall but was associated with an increased risk of a transmural infarction. We found no association between the same increase in PM_2.5 and risk of a nontransmural infarction. Further, subjects with COPD appeared to be particularly susceptible, but those with diabetes were not.

Conclusions

This PM–transmural infarction association is consistent with earlier studies of PM and MI. The lack of association with nontransmural infarction suggests that future studies that investigate the triggering of MI by ambient PM_2.5 concentrations should be stratified by infarction type.     

Short-Term Effects of Air Pollution on Wheeze in Asthmatic Children in Fresno,California

Background

Although studies have demonstrated that air pollution is associated with exacerbation of asthma symptoms in children with asthma, little is known about the susceptibility of subgroups, particularly those with atopy.

Objective

This study was designed to evaluate our a priori hypothesis that identifiable subgroups of asthmatic children are more likely to wheeze with exposure to ambient air pollution.

Methods

A cohort of 315 children with asthma, 6–11 years of age, was recruited for longitudinal follow-up in Fresno, California (USA). During the baseline visit, children were administered a respiratory symptom questionnaire and allergen skin-prick test. Three times a year, participants completed 14-day panels during which they answered symptom questions twice daily. Ambient air quality data from a central monitoring station were used to assign exposures to the following pollutants: particulate matter ≤ 2.5 μm in aerodynamic diameter, particulate matter between 2.5 and 10 μm in aerodynamic diameter (PM_10–2.5), elemental carbon, nitrogen dioxide (NO₂), nitrate, and O₃.

Results

For the group as a whole, wheeze was significantly associated with short-term exposures to NO₂ [odds ratio (OR) = 1.10 for 8.7-ppb increase; 95% confidence interval (CI), 1.02–1.20] and PM_10–2.5 (OR = 1.11 for 14.7-μg/m³ increase; 95% CI, 1.01–1.22). The association with wheeze was stronger for these two pollutants in children who were skin-test positive to cat or common fungi and in boys with mild intermittent asthma.

Conclusion

A pollutant associated with traffic emissions, NO₂, and a pollutant with bioactive constituents, PM_10–2.5, were associated with increased risk of wheeze in asthmatic children living in Fresno, California. Children with atopy to cat or common fungi and boys with mild intermittent asthma were the subgroups for which we observed the largest associations.     

Markers of Inflammation and Coagulation after Long-Term Exposure to Coarse Particulate Matter: A Cross-Sectional Analysis from the Multi-Ethnic Study of Atherosclerosis

Background

Toxicological research suggests that coarse particles (PM_10–2.5) are inflammatory, but responses are complex and may be best summarized by multiple inflammatory markers. Few human studies have investigated associations with PM_10–2.5 and, of those, none have explored long-term exposures. Here we examine long-term associations with inflammation and coagulation in the Multi-Ethnic Study of Atherosclerosis.

Methods

Participants included 3,295 adults (45–84 years of age) from three metropolitan areas. Site-specific spatial models were used to estimate 5-year concentrations of PM_10–2.5 mass and copper, zinc, phosphorus, silicon, and endotoxin found in PM_10–2.5. Outcomes included interleukin-6, C-reactive protein, fibrinogen, total homocysteine, D-dimer, factor VIII, plasmin–antiplasmin complex, and inflammation and coagulation scores. We used multivariable regression with multiply imputed data to estimate associations while controlling for potential confounders, including co-pollutants such as fine particulate matter.

Results

Some limited evidence was found of relationships between inflammation and coagulation and PM_10–2.5. Endotoxin was the PM_10–2.5 component most strongly associated with inflammation, with an interquartile range (IQR) increase (0.08 EU/m³) associated with 0.15 (95% CI: 0.01, 0.28; p = 0.03) and 0.08 (95% CI: –0.07, 0.23; p = 0.28) higher inflammation scores before and after control for city, respectively. Copper was the component with the strongest association with coagulation, with a 4-ng/m³ increase associated with 0.19 (95% CI: 0.08, 0.30; p = 0.0008) and 0.12 (95% CI: –0.05, 0.30; p = 0.16) unit higher coagulation scores before and after city adjustment, respectively.

Conclusions

Our cross-sectional analysis provided some evidence that long-term PM_10–2.5 exposure was associated with inflammation and coagulation, but associations were modest and depended on particle composition.

Citation

Adar SD, D’Souza J, Mendelsohn-Victor K, Jacobs DR Jr, Cushman M, Sheppard L, Thorne PS, Burke GL, Daviglus ML, Szpiro AA, Diez Roux AV, Kaufman JD, Larson TV. 2015. Markers of inflammation and coagulation after long-term exposure to coarse particulate matter: a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 123:541–548; http://dx.doi.org/10.1289/ehp.1308069     

Estimating Regional Spatial and Temporal Variability of PM2.5 Concentrations Using Satellite Data,Meteorology, and Land Use Information

Background

Studies of chronic health effects due to exposures to particulate matter with aerodynamic diameters ≤ 2.5 μm (PM_2.5) are often limited by sparse measurements. Satellite aerosol remote sensing data may be used to extend PM_2.5 ground networks to cover a much larger area.

Objectives

In this study we examined the benefits of using aerosol optical depth (AOD) retrieved by the Geostationary Operational Environmental Satellite (GOES) in conjunction with land use and meteorologic information to estimate ground-level PM_2.5 concentrations.

Methods

We developed a two-stage generalized additive model (GAM) for U.S. Environmental Protection Agency PM_2.5 concentrations in a domain centered in Massachusetts. The AOD model represents conditions when AOD retrieval is successful; the non-AOD model represents conditions when AOD is missing in the domain.

Results

The AOD model has a higher predicting power judged by adjusted R² (0.79) than does the non-AOD model (0.48). The predicted PM_2.5 concentrations by the AOD model are, on average, 0.8–0.9 μg/m³ higher than the non-AOD model predictions, with a more smooth spatial distribution, higher concentrations in rural areas, and the highest concentrations in areas other than major urban centers. Although AOD is a highly significant predictor of PM_2.5, meteorologic parameters are major contributors to the better performance of the AOD model.

Conclusions

GOES aerosol/smoke product (GASP) AOD is able to summarize a set of weather and land use conditions that stratify PM_2.5 concentrations into two different spatial patterns. Even if land use regression models do not include AOD as a predictor variable, two separate models should be fitted to account for different PM_2.5 spatial patterns related to AOD availability.     

Polymorphisms in GSTT1, GSTZ1, and CYP2E1, Disinfection By-products,and Risk of Bladder Cancer in Spain

Background

Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water.

Objectives

In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case–control study in Spain.

Methods

Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms.

Results

THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8–1.8), 1.8 (1.1–2.9), and 1.8 (0.9–3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/− versus GSTT1 null (p_interaction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (p_interaction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (p_interaction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7–3.5), 3.4 (1.4–8.2), and 5.9 (1.8–19.0), respectively.

Conclusions

Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.     

Predicting Chronic Fine and Coarse Particulate Exposures Using Spatiotemporal Models for the Northeastern and Midwestern United States

Background

Chronic epidemiologic studies of particulate matter (PM) are limited by the lack of monitoring data, relying instead on citywide ambient concentrations to estimate exposures. This method ignores within-city spatial gradients and restricts studies to areas with nearby monitoring data. This lack of data is particularly restrictive for fine particles (PM with aerodynamic diameter < 2.5 μm; PM_2.5) and coarse particles (PM with aerodynamic diameter 2.5–10 μm; PM_10–2.5), for which monitoring is limited before 1999. To address these limitations, we developed spatiotemporal models to predict monthly outdoor PM_2.5 and PM_10–2.5 concentrations for the northeastern and midwestern United States.

Methods

For PM_2.5, we developed models for two periods: 1988–1998 and 1999–2002. Both models included smooth spatial and regression terms of geographic information system-based and meteorologic predictors. To compensate for sparse monitoring data, the pre-1999 model also included predicted PM₁₀ (PM with aerodynamic diameter < 10 μm) and extinction coefficients (km⁻¹). PM_10–2.5 levels were estimated as the difference in monthly predicted PM₁₀ and PM_2.5, with predicted PM₁₀ from our previously developed PM₁₀ model.

Results

Predictive performance for PM_2.5 was strong (cross-validation R² = 0.77 and 0.69 for post-1999 and pre-1999 PM_2.5 models, respectively) with high precision (2.2 and 2.7 μg/m³, respectively). Models performed well irrespective of population density and season. Predictive performance for PM_10–2.5 was weaker (cross-validation R² = 0.39) with lower precision (5.5 μg/m³). PM_10–2.5 levels exhibited greater local spatial variability than PM₁₀ or PM_2.5, suggesting that PM_2.5 measurements at ambient monitoring sites are more representative for surrounding populations than for PM₁₀ and especially PM_10–2.5.

Conclusions

We provide semiempirical models to predict spatially and temporally resolved long-term average outdoor concentrations of PM_2.5 and PM_10–2.5 for estimating exposures of populations living in the northeastern and midwestern United States.     

California Wildfires of 2008: Coarse and Fine Particulate Matter Toxicity

Background

During the last week of June 2008, central and northern California experienced thousands of forest and brush fires, giving rise to a week of severe fire-related particulate air pollution throughout the region. California experienced PM_10–2.5 (particulate matter with mass median aerodynamic diameter > 2.5 μm to < 10 μm; coarse ) and PM_2.5 (particulate matter with mass median aerodynamic diameter < 2.5 μm; fine) concentrations greatly in excess of the air quality standards and among the highest values reported at these stations since data have been collected.

Objectives

These observations prompt a number of questions about the health impact of exposure to elevated levels of PM_10–2.5 and PM_2.5 and about the specific toxicity of PM arising from wildfires in this region.

Methods

Toxicity of PM_10–2.5 and PM_2.5 obtained during the time of peak concentrations of smoke in the air was determined with a mouse bioassay and compared with PM samples collected under normal conditions from the region during the month of June 2007.

Results

Concentrations of PM were not only higher during the wildfire episodes, but the PM was much more toxic to the lung on an equal weight basis than was PM collected from normal ambient air in the region. Toxicity was manifested as increased neutrophils and protein in lung lavage and by histologic indicators of increased cell influx and edema in the lung.

Conclusions

We conclude that the wildfire PM contains chemical components toxic to the lung, especially to alveolar macrophages, and they are more toxic to the lung than equal doses of PM collected from ambient air from the same region during a comparable season.     

Mortality in the Medicare Population and Chronic Exposure to Fine Particulate Air Pollution in Urban Centers (2000–2005)

Background

Prospective cohort studies constitute the major source of evidence about the mortality effects of chronic exposure to particulate air pollution. Additional studies are needed to provide evidence on the health effects of chronic exposure to particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) because few studies have been carried out and the cohorts have not been representative.

Objectives

This study was designed to estimate the relative risk of death associated with long-term exposure to PM_2.5 by region and age groups in a U.S. population of elderly, for the period 2000–2005.

Methods

By linking PM_2.5 monitoring data to the Medicare billing claims by ZIP code of residence of the enrollees, we have developed a new retrospective cohort study, the Medicare Cohort Air Pollution Study. The study population comprises 13.2 million participants living in 4,568 ZIP codes having centroids within 6 miles of a PM_2.5 monitor. We estimated relative risks adjusted by socioeconomic status and smoking by fitting log-linear regression models.

Results

In the eastern and central regions, a 10-μg/m³ increase in 6-year average of PM_2.5 is associated with 6.8% [95% confidence interval (CI), 4.9–8.7%] and 13.2% (95% CI, 9.5–16.9) increases in mortality, respectively. We found no evidence of an association in the western region or for persons ≥ 85 years of age.

Conclusions

We established a cohort of Medicare participants for investigating air pollution and mortality on longer-term time frames. Chronic exposure to PM_2.5 was associated with mortality in the eastern and central regions, but not in the western United States.     

Autism Spectrum Disorder and Particulate Matter Air Pollution before,during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort

Background

Autism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet has unclear etiology.

Objective

We explored the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child.

Methods

We conducted a nested case–control study of participants in the Nurses’ Health Study II (NHS II), a prospective cohort of 116,430 U.S. female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants’ children born 1990–2002 with ASD (n = 245), and children without ASD (n = 1,522) randomly selected using frequency matching for birth years. Diagnosis of ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤ 2.5 μm (PM_2.5) and 2.5–10 μm (PM_10–2.5) were predicted from a spatiotemporal model for the continental United States and linked to residential addresses.

Results

PM_2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range (IQR) higher PM_2.5 (4.42 μg/m³) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM_2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, whereas the association with the 9 months of pregnancy remained (OR = 1.63; 95% CI: 1.08, 2.47). The association between ASD and PM_2.5 was stronger for exposure during the third trimester (OR = 1.42 per IQR increase in PM_2.5; 95% CI: 1.09, 1.86) than during the first two trimesters (ORs = 1.06 and 1.00) when mutually adjusted. There was little association between PM_10–2.5 and ASD.

Conclusions

Higher maternal exposure to PM_2.5 during pregnancy, particularly the third trimester, was associated with greater odds of a child having ASD.

Citation

Raz R, Roberts AL, Lyall K, Hart JE, Just AC, Laden F, Weisskopf MG. 2015. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case–control analysis within the Nurses’ Health Study II cohort. Environ Health Perspect 123:264–270; http://dx.doi.org/10.1289/ehp.1408133     

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 (PM_0.25, PM_0.25–2.5, PM_2.5–10)], and hourly elemental and black carbon (EC–BC), estimated primary and secondary organic carbon (OC_pri, SOC), particle number (PN), carbon monoxide (CO), and nitrogen oxides–nitrogen dioxide (NO_x–NO₂). We analyzed the relation of biomarkers to exposures with mixed effects models adjusted for potential confounders.

Results

Primary combustion markers (EC–BC, OC_pri, CO, NO_x–NO₂), but not SOC, were positively associated with inflammatory biomarkers and inversely associated with erythrocyte anti-oxidant enzymes (n = 578). PN and PM_0.25 were more strongly associated with biomarkers than PM_0.25–2.5. Associations for all exposures were stronger during cooler periods when only OC_pri, PN, and NO_x 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.     

Particulate Air Pollution,Metabolic Syndrome,and Heart Rate Variability: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background

Cardiac autonomic dysfunction has been suggested as a possible biologic pathway for the association between fine particulate matter ≤ 2.5 μm in diameter (PM_2.5) and cardiovascular disease (CVD). We examined the associations of PM_2.5 with heart rate variability, a marker of autonomic function, and whether metabolic syndrome (MetS) modified these associations.

Methods

We used data from the Multi-Ethnic Study of Atherosclerosis to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences (rMSSD) of 5,465 participants 45–84 years old who were free of CVD at the baseline examination (2000–2002). Data from the U.S. regulatory monitor network were used to estimate ambient PM_2.5 concentrations at the participants’ residences. MetS was defined as having three or more of the following criteria: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose.

Results

After controlling for confounders, we found that an interquartile range (IQR) increase in 2-day average PM_2.5 (10.2 μg/m³) was associated with a 2.1% decrease in rMSSD [95% confidence interval (CI), −4.2 to 0.0] and nonsignificantly associated with a 1.8% decrease in SDNN (95% CI, −3.7 to 0.1). Associations were stronger among individuals with MetS than among those without MetS: an IQR elevation in 2-day PM_2.5 was associated with a 6.2% decrease in rMSSD (95% CI, −9.4 to −2.9) among participants with MetS, whereas almost no change was found among participants without MetS (p-interaction = 0.005). Similar effect modification was observed in SDNN (p-interaction = 0.011).

Conclusion

These findings suggest that autonomic dysfunction may be a mechanism through which PM exposure affects cardiovascular risk, especially among persons with MetS.     

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 (PM_0.25) 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 PM_0.25 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 PM_0.25 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 PM_0.25 with PAHs showed that nominal associations of IL-6 and sTNF-RII with PM_0.25 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.     

Acute Adverse Effects of Fine Particulate Air Pollution on Ventricular Repolarization

Background

The mechanisms for the relationship between particulate pollution and cardiac disease are not fully understood.

Objective

We examined the effects and time course of exposure to fine particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) on ventricular repolarization of 106 nonsmoking adults who were living in communities in central Pennsylvania.

Methods

The 24-hr beat-to-beat electrocardiogram (ECG) data were obtained using a high-resolution 12-lead Holter system. After visually identifying and removing artifacts and arrhythmic beats, we summarized normal beat-to-beat QTs from each 30-min segment as heart rate (HR)-corrected QT measures: QT prolongation index (QTI), Bazett’s HR-corrected QT (QTcB), and Fridericia’s HR-corrected QT (QTcF). A personal PM_2.5 monitor was used to measure individual-level real-time PM_2.5 exposures for 24 hr. We averaged these data and used 30-min time-specific average PM_2.5 exposures.

Results

The mean age of the participants was 56 ± 8 years, with 41% male and 74% white. The means ± SDs for QTI, QTcB, and QTcF were 111 ± 6.6, 438 ± 23 msec, and 422 ± 22 msec, respectively; and for PM_2.5, the mean ± SD was 14 ± 22 μg/m³. We used distributed lag models under a framework of linear mixed-effects models to assess the autocorrelation-corrected regression coefficients (β) between 30-min PM_2.5 and the HR-corrected QT measures. Most of the adverse ventricular repolarization effects from PM_2.5 exposure occurred within 3–4 hr. The multivariable adjusted β (SE, p-value) due to a 10-μg/m³ increase in lag 7 PM_2.5 on QTI, QTcB, and QTcF were 0.08 (0.04, p < 0.05), 0.22 (0.08, p < 0.01), and 0.09 (0.05, p < 0.05), respectively.

Conclusions

Our results suggest a significant adverse effect of PM_2.5 on ventricular repolarization. The time course of the effect is within 3–4 hr of elevated PM_2.5.     

Emergency Admissions for Cardiovascular and Respiratory Diseases and the Chemical Composition of Fine Particle Air Pollution

Background

Population-based studies have estimated health risks of short-term exposure to fine particles using mass of PM_2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) as the indicator. Evidence regarding the toxicity of the chemical components of the PM_2.5 mixture is limited.

Objective

In this study we investigated the association between hospital admission for cardiovascular disease (CVD) and respiratory disease and the chemical components of PM_2.5 in the United States.

Methods

We used a national database comprising daily data for 2000–2006 on emergency hospital admissions for cardiovascular and respiratory outcomes, ambient levels of major PM_2.5 chemical components [sulfate, nitrate, silicon, elemental carbon (EC), organic carbon matter (OCM), and sodium and ammonium ions], and weather. Using Bayesian hierarchical statistical models, we estimated the associations between daily levels of PM_2.5 components and risk of hospital admissions in 119 U.S. urban communities for 12 million Medicare enrollees (≥ 65 years of age).

Results

In multiple-pollutant models that adjust for the levels of other pollutants, an interquartile range (IQR) increase in EC was associated with a 0.80% [95% posterior interval (PI), 0.34–1.27%] increase in risk of same-day cardiovascular admissions, and an IQR increase in OCM was associated with a 1.01% (95% PI, 0.04–1.98%) increase in risk of respiratory admissions on the same day. Other components were not associated with cardiovascular or respiratory hospital admissions in multiple-pollutant models.

Conclusions

Ambient levels of EC and OCM, which are generated primarily from vehicle emissions, diesel, and wood burning, were associated with the largest risks of emergency hospitalization across the major chemical constituents of PM_2.5.     

Spatial Modeling of PM10 and NO2 in the Continental United States, 1985–2000

Background

Epidemiologic studies of air pollution have demonstrated a link between long-term air pollution exposures and mortality. However, many have been limited to city-specific average pollution measures or spatial or land-use regression exposure models in small geographic areas.

Objectives

Our objective was to develop nationwide models of annual exposure to particulate matter < 10 μm in diameter (PM₁₀) and nitrogen dioxide during 1985–2000.

Methods

We used generalized additive models (GAMs) to predict annual levels of the pollutants using smooth spatial surfaces of available monitoring data and geographic information system–derived covariates. Model performance was determined using a cross-validation (CV) procedure with 10% of the data. We also compared the results of these models with a commonly used spatial interpolation, inverse distance weighting.

Results

For PM₁₀, distance to road, elevation, proportion of low-intensity residential, high-intensity residential, and industrial, commercial, or transportation land use within 1 km were all statistically significant predictors of measured PM₁₀ (model R² = 0.49, CV R² = 0.55). Distance to road, population density, elevation, land use, and distance to and emissions of the nearest nitrogen oxides–emitting power plant were all statistically significant predictors of measured NO₂ (model R² = 0.88, CV R² = 0.90). The GAMs performed better overall than the inverse distance models, with higher CV R² and higher precision.

Conclusions

These models provide reasonably accurate and unbiased estimates of annual exposures for PM₁₀ and NO₂. This approach provides the spatial and temporal variability necessary to describe exposure in studies assessing the health effects of chronic air pollution.     

Determinants of the Proinflammatory Action of Ambient Particulate Matter in Immortalized Murine Macrophages

Background

Proximity to traffic-related pollution has been associated with poor respiratory health in adults and children.

Objectives

We wished to test the hypothesis that particulate matter (PM) from high-traffic sites would display an enhanced capacity to elicit inflammation.

Methods

We examined the inflammatory potential of coarse [2.5–10 μm in aerodynamic diameter (PM_2.5–10)] and fine [0.1–2.5 μm in aerodynamic diameter (PM_0.1–2.5)] PM collected from nine sites throughout Europe with contrasting traffic contributions. We incubated murine monocytic-macrophagic RAW264.7 cells with PM samples from these sites (20 or 60 μg/cm²) and quantified their capacity to stimulate the release of arachidonic acid (AA) or the production of interleukin-6 and tumor necrosis factor-α (TNFα) as measures of their inflammatory potential. Responses were then related to PM composition: metals, hydrocarbons, anions/cations, and endotoxin content.

Results

Inflammatory responses to ambient PM varied markedly on an equal mass basis, with PM_2.5–10 displaying the largest signals and contrasts among sites. Notably, we found no evidence of enhanced inflammatory potential at high-traffic sites and observed some of the largest responses at sites distant from traffic. Correlation analyses indicated that much of the sample-to-sample contrast in the proinflammatory response was related to the content of endotoxin and transition metals (especially iron and copper) in PM_2.5–10. Use of the metal chelator diethylene triamine pentaacetic acid inhibited AA release, whereas recombinant endotoxin-neutralizing protein partially inhibited TNFα production, demonstrating that different PM components triggered inflammatory responses through separate pathways.

Conclusions

We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells.     

The Effect of Fine and Coarse Particulate Air Pollution on Mortality: A National Analysis

Background

Although many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM_2.5; fine particles) and of coarse particles (particles with an aerodynamic diameter > 2.5 and < 10 μm; PM coarse). We conducted a national, multicity time-series study of the acute effect of PM_2.5 and PM coarse on the increased risk of death for all causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and respiratory mortality for the years 1999–2005.

Method

We applied a city- and season-specific Poisson regression in 112 U.S. cities to examine the association of mean (day of death and previous day) PM_2.5 and PM coarse with daily deaths. We combined the city-specific estimates using a random effects approach, in total, by season and by region.

Results

We found a 0.98% increase [95% confidence interval (CI), 0.75–1.22] in total mortality, a 0.85% increase (95% CI, 0.46–1.24) in CVD, a 1.18% increase (95% CI, 0.48–1.89) in MI, a 1.78% increase (95% CI, 0.96–2.62) in stroke, and a 1.68% increase (95% CI, 1.04–2.33) in respiratory deaths for a 10-μg/m³ increase in 2-day averaged PM_2.5. The effects were higher in spring. For PM coarse, we found significant but smaller increases for all causes analyzed.

Conclusions

We conclude that our analysis showed an increased risk of mortality for all and specific causes associated with PM_2.5, and the risks are higher than what was previously observed for PM₁₀. In addition, coarse particles are also associated with more deaths.