Coarse Particulate Matter and Markers of Inflammation and Coagulation in the Multi-Ethnic Study of Atherosclerosis (MESA) Population: A Repeat Measures Analysis.

BACKGROUND: In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter (PM10-2.5, particulate matter with aerodynamic diameter ≤10µm and>2.5µm). Toxicological research suggests that these pathways might be important processes by which PM10-2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM10-2.5 monitoring network. OBJECTIVES: We used new spatiotemporal exposure models to examine associations of both 1-y and 1-month average PM10-2.5 concentrations with markers of inflammation and coagulation. METHODS: We leveraged data from 7,071 Multi-Ethnic Study of Atherosclerosis and ancillary study participants 45-84 y of age who had repeated plasma measures of inflammatory and coagulation biomarkers. We estimated PM10-2.5 at participant addresses 1 y and 1 month before each of up to four exams (2000-2012) using spatiotemporal models that incorporated satellite, regulatory monitoring, and local geographic data and accounted for spatial correlation. We used random effects models to estimate associations with interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and D-dimer, controlling for potential confounders. RESULTS: Increases in PM10-2.5 were not associated with greater levels of inflammation or coagulation. A 10-µg/m3 increase in annual average PM10-2.5 was associated with a 2.5% decrease in CRP [95% confidence interval (CI): -5.5, 0.6]. We saw no association between annual average PM10-2.5 and the other markers (IL-6: -0.7%, 95% CI: -2.6, 1.2; fibrinogen: -0.3%, 95% CI: -0.9, 0.3; D-dimer: -0.2%, 95% CI: -2.6, 2.4). Associations consistently showed that a 10-µg/m3 increase in 1-month average PM10-2.5 was associated with reduced inflammation and coagulation, though none were distinguishable from no association (IL-6: -1.2%, 95% CI: -3.0 , 0.5; CRP: -2.5%, 95% CI: -5.3, 0.4; fibrinogen: -0.4%, 95% CI: -1.0, 0.1; D-dimer: -2.0%, 95% CI: -4.3, 0.3). DISCUSSION: We found no evidence that PM10-2.5 is associated with higher inflammation or coagulation levels. More research is needed to determine whether the inflammation and coagulation pathways are as important in explaining observed PM10-2.5 health impacts in humans as they have been shown to be in toxicology studies or whether PM10-2.5 might impact human health through alternative biological mechanisms. https://doi.org/10.1289/EHP12972.

Impact of Mobile Monitoring Network Design on Air Pollution Exposure Assessment Models.

Short-term mobile monitoring campaigns are increasingly used to assess long-term air pollution exposure in epidemiology. Little is known about how monitoring network design features, including the number of stops and sampling temporality, impacts exposure assessment models. We address this gap by leveraging an extensive mobile monitoring campaign conducted in the greater Seattle area over the course of a year during all days of the week and most hours. The campaign measured total particle number concentration (PNC; sheds light on ultrafine particulate (UFP) number concentration), black carbon (BC), nitrogen dioxide (NO2), fine particulate matter (PM2.5), and carbon dioxide (CO2). In Monte Carlo sampling of 7327 total stops (278 sites × 26 visits each), we restricted the number of sites and visits used to estimate annual averages. Predictions from the all-data campaign performed well, with cross-validated R2s of 0.51-0.77. We found similar model performances (85% of the all-data campaign R2) with ∼1000 to 3000 randomly selected stops for NO2, PNC, and BC, and ∼4000 to 5000 stops for PM2.5 and CO2. Campaigns with additional temporal restrictions (e.g., business hours, rush hours, weekdays, or fewer seasons) had reduced model performances and different spatial surfaces. Mobile monitoring campaigns wanting to assess long-term exposure should carefully consider their monitoring designs.

Characterization of Annual Average Traffic-Related Air Pollution Concentrations in the Greater Seattle Area from a Year-Long Mobile Monitoring Campaign.

Growing evidence links traffic-related air pollution (TRAP) to adverse health effects. We designed an innovative and extensive mobile monitoring campaign to characterize TRAP exposure levels for the Adult Changes in Thought (ACT) study, a Seattle-based cohort. The campaign measured particle number concentration (PNC) to capture ultrafine particles (UFP), black carbon (BC), nitrogen dioxide (NO2), fine particulate matter (PM2.5), and carbon dioxide (CO2) at 309 roadside sites within a large, 1200 land km2 (463 mi2) area representative of the cohort. We collected about 29 two-minute measurements at each site during all seasons, days of the week, and most times of the day over a 1-year period. Validation showed good agreement between our BC, NO2, and PM2.5 measurements and monitoring agency sites (R2 = 0.68-0.73). Universal kriging-partial least squares models of annual average pollutant concentrations had cross-validated mean square error-based R2 (and root mean square error) values of 0.77 (1177 pt/cm3) for PNC, 0.60 (102 ng/m3) for BC, 0.77 (1.3 ppb) for NO2, 0.70 (0.3 µg/m3) for PM2.5, and 0.51 (4.2 ppm) for CO2. Overall, we found that the design of this extensive campaign captured the spatial pollutant variations well and these were explained by sensible land use features, including those related to traffic.

Environmental manganese exposure and cognitive control in a South African population.

OBJECTIVE: To characterize the association between environmental (residential air) manganese (Mn) exposure and cognitive performance, focusing on cognitive control, in a Black African population. METHODS: We administered the Go-No-Go, Digit Span, and Matrix Reasoning tests to population-based samples age ≥40 from a high Mn (smelter) exposed community, Meyerton (N = 629), and a demographically comparable low (background levels) non-exposed community, Ethembalethu, (N = 96) in Gauteng province, South Africa. We investigated the associations between community and performance on the cognitive tests, using linear regression. We adjusted a priori for age and sex, and examined the effect of adjustment for education, nonverbal IQ, smoking, and alcohol consumption. We measured airborne PM2.5-Mn to confirm community exposure differences. RESULTS: Compared to Ethembalethu residents, Meyerton residents' test scores were lower (poorer) for all tests: 0.55 (95 % confidence interval [CI] 0.08, 1.03) lower scores for Matrix Reasoning, 0.34 (95 % CI -0.07, 0.75) lower for Digit Span, and 0.15 (95 % CI 0.09, 0.21) lower for Go-No-Go (high frequency discriminability index [probability]). The latter represented the most marked difference in terms of z-scores (0.50, 95 % CI 0.30, 0.71 standard deviations lower). The mean of the z-score of each of the three tests was also lower (0.34, 95 % CI 0.18, 0.50 standard deviations lower). These associations were similar in men and women, but attenuated with adjustment for education. Differences for Matrix Reasoning and Digit Span between the two communities were observed only among those who had lived in Meyerton ≥10 years, whereas for Go-No-Go, differences were also apparent among those who had lived in Meyerton <10 years. Mean PM2.5-Mn at a long-term fixed site in Meyerton was 203 ng/m3 and 10 ng/m3 in Ethembalethu. CONCLUSION: Residence in a community near a high Mn emission source is associated with cognitive dysfunction, including aspects of cognitive control as assessed by the Go-No-Go test.

Associations of Household Income with Health-Related Quality of Life Following a Colorectal Cancer Diagnosis Varies With Neighborhood Socioeconomic Status.

BACKGROUND: Existing evidence indicates household income as a predictor of health-related quality of life (HRQoL) following a colorectal cancer diagnosis. This association likely varies with neighborhood socioeconomic status (nSES), but evidence is limited. METHODS: We included data from 1,355 colorectal cancer survivors participating in the population-based Puget Sound Colorectal Cancer Cohort (PSCCC). Survivors reported current annual household income; we measured HRQoL via the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) tool. Using neighborhood data summarized within a 1-km radial buffer of Census block group centroids, we constructed a multidimensional nSES index measure. We employed survivors' geocoded residential addresses to append nSES score for Census block group of residence. With linear generalized estimating equations clustered on survivor location, we evaluated associations of household income with differences in FACT-C mean score, overall and stratified by nSES. We used separate models to explore relationships for wellbeing subscales. RESULTS: We found lower household income to be associated with clinically meaningful differences in overall FACT-C scores [<$30K: -13.6; 95% confidence interval (CI): -16.8 to -10.4] and subscale wellbeing after a recent colorectal cancer diagnosis. Relationships were slightly greater in magnitude for survivors living in lower SES neighborhoods. CONCLUSIONS: Our findings suggest that recently diagnosed lower income colorectal cancer survivors are likely to report lower HRQoL, and modestly more so in lower SES neighborhoods. IMPACT: The findings from this work will aid future investigators' ability to further consider the contexts in which the income of survivors can be leveraged as a means of improving HRQoL.

Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence.

Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.

The evidence of human exposure to glyphosate: a review.

BACKGROUND: Despite the growing and widespread use of glyphosate, a broad-spectrum herbicide and desiccant, very few studies have evaluated the extent and amount of human exposure. OBJECTIVE: We review documented levels of human exposure among workers in occupational settings and the general population. METHODS: We conducted a review of scientific publications on glyphosate levels in humans; 19 studies were identified, of which five investigated occupational exposure to glyphosate, 11 documented the exposure in general populations, and three reported on both. RESULTS: Eight studies reported urinary levels in 423 occupationally and para-occupationally exposed subjects; 14 studies reported glyphosate levels in various biofluids on 3298 subjects from the general population. Average urinary levels in occupationally exposed subjects varied from 0.26 to 73.5 µg/L; environmental exposure urinary levels ranged from 0.16 to 7.6 µg/L. Only two studies measured temporal trends in exposure, both of which show increasing proportions of individuals with detectable levels of glyphosate in their urine over time. CONCLUSIONS: The current review highlights the paucity of data on glyphosate levels among individuals exposed occupationally, para-occupationally, or environmentally to the herbicide. As such, it is challenging to fully understand the extent of exposure overall and in vulnerable populations such as children. We recommend further work to evaluate exposure across populations and geographic regions, apportion the exposure sources (e.g., occupational, household use, food residues), and understand temporal trends.

Exposure to ambient air pollution and calcification of the mitral annulus and aortic valve: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Long-term exposure to high ambient air pollution has been associated with coronary artery calcium (CAC), a marker of cardiovascular disease (CVD). Calcifications of left-sided heart valves are also markers of CVD risk. We investigated whether air pollution was associated with valvular calcification and its progression. METHODS: We studied 6253 MESA participants aged 45-84 years who underwent two cardiac CT scans 2.5 years apart to quantify aortic valve calcium (AVC) and mitral annular calcium (MAC). CAC was included for the same timeframe for comparison with AVC/MAC. Ambient particulate matter <2.5 µm (PM2.5) and oxides of nitrogen (NOx) concentrations were predicted from residence-specific spatio-temporal models. RESULTS: The mean age (SD) of the study sample was 62 (10) years, 39% were white, 27% black, 22% Hispanic, and 12% Chinese. The prevalence of AVC and MAC at baseline were 13% and 9% respectively, compared to 50% prevalence of CAC. The adjusted prevalence ratios of AVC and MAC for each 5 µg/m3 higher PM2.5 was 1.19 (95% CI 0.87, 1.62) and 1.20 (0.81, 1.77) respectively, and for CAC was 1.14 (1.01, 1.27). Over 2.5 years, the mean change in Agatston units/year for each 5 µg/m3 higher PM2.5 concentration was 0.29 (-5.05, 5.63) for AVC and 4.38 (-9.13, 17.88) for MAC, compared to 8.66 (0.61, 16.71) for CAC. We found no significant associations of NOx with AVC and MAC. CONCLUSION: Our findings suggest a trend towards increased 2.5-year progression of MAC with exposure to outdoor PM2.5, although this association could not be confirmed. Additional well-powered studies with longer periods of follow-up are needed to further study associations of air pollution with valvular calcium. TRIAL REGISTRATION: Although MESA is not a clinical trial, this cohort is registered at ClinicalTrials.gov Identifier: NCT00005487; Date of registration May 25, 2000.

Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study.

We studied whether ambient air pollution is associated with interstitial lung abnormalities (ILAs) and high attenuation areas (HAAs), which are qualitative and quantitative measurements of subclinical interstitial lung disease (ILD) on computed tomography (CT).We performed analyses of community-based dwellers enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. We used cohort-specific spatio-temporal models to estimate ambient pollution (fine particulate matter (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2) and ozone (O3)) at each home. A total of 5495 participants underwent serial assessment of HAAs by cardiac CT; 2671 participants were assessed for ILAs using full lung CT at the 10-year follow-up. We used multivariable logistic regression and linear mixed models adjusted for age, sex, ethnicity, education, tobacco use, scanner technology and study site.The odds of ILAs increased 1.77-fold per 40 ppb increment in NOx (95% CI 1.06 to 2.95, p = 0.03). There was an overall trend towards an association between higher exposure to NOx and greater progression of HAAs (0.45% annual increase in HAAs per 40 ppb increment in NOx; 95% CI -0.02 to 0.92, p = 0.06). Associations of ambient fine particulate matter (PM2.5), NOx and NO2 concentrations with progression of HAAs varied by race/ethnicity (p = 0.002, 0.007, 0.04, respectively, for interaction) and were strongest among non-Hispanic white people.We conclude that ambient air pollution exposures were associated with subclinical ILD.

Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study.

BACKGROUND: Long-term exposure to fine particulate matter less than 2.5 µm in diameter (PM2.5) and traffic-related air pollutant concentrations are associated with cardiovascular risk. The disease process underlying these associations remains uncertain. We aim to assess association between long-term exposure to ambient air pollution and progression of coronary artery calcium and common carotid artery intima-media thickness. METHODS: In this prospective 10-year cohort study, we repeatedly measured coronary artery calcium by CT in 6795 participants aged 45-84 years enrolled in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) in six metropolitan areas in the USA. Repeated scans were done for nearly all participants between 2002 and 2005, for a subset of participants between 2005 and 2007, and for half of all participants between 2010 and 2012. Common carotid artery intima-media thickness was measured by ultrasound in all participants at baseline and in 2010-12 for 3459 participants. Residence-specific spatio-temporal pollution concentration models, incorporating community-specific measurements, agency monitoring data, and geographical predictors, estimated concentrations of PM2.5 and nitrogen oxides (NOX) between 1999 and 2012. The primary aim was to examine the association between both progression of coronary artery calcium and mean carotid artery intima-media thickness and long-term exposure to ambient air pollutant concentrations (PM2.5, NOX, and black carbon) between examinations and within the six metropolitan areas, adjusting for baseline age, sex, ethnicity, socioeconomic characteristics, cardiovascular risk factors, site, and CT scanner technology. FINDINGS: In this population, coronary calcium increased on average by 24 Agatston units per year (SD 58), and intima-media thickness by 12 µm per year (10), before adjusting for risk factors or air pollutant exposures. Participant-specific pollutant concentrations averaged over the years 2000-10 ranged from 9.2-22.6 µg PM2.5/m(3) and 7.2-139.2 parts per billion (ppb) NOX. For each 5 µg PM2.5/m(3) increase, coronary calcium progressed by 4.1 Agatston units per year (95% CI 1.4-6.8) and for each 40 ppb NOX coronary calcium progressed by 4.8 Agatston units per year (0.9-8.7). Pollutant exposures were not associated with intima-media thickness change. The estimate for the effect of a 5 µg/m(3) higher long-term exposure to PM2.5 in intima-media thickness was -0.9 µm per year (95% CI -3.0 to 1.3). For 40 ppb higher NOX, the estimate was 0.2 µm per year (-1.9 to 2.4). INTERPRETATION: Increased concentrations of PM2.5 and traffic-related air pollution within metropolitan areas, in ranges commonly encountered worldwide, are associated with progression in coronary calcification, consistent with acceleration of atherosclerosis. This study supports the case for global efforts of pollution reduction in prevention of cardiovascular diseases. FUNDING: US Environmental Protection Agency and US National Institutes of Health.

Contribution of health behaviors to the association between area-level socioeconomic status and cancer mortality.

Cancer mortality is higher among residents of low-socioeconomic status (SES) areas than those of high-SES areas; however, the contribution of modifiable risk factors to this disparity is not known. We used data from 54,737 participants in the VITamins And Lifestyle (VITAL) Study, aged 50-76 with no history of cancer at baseline (2000-2002). Of these, 1488 died of cancer over an average of 7.7 years of follow-up. Data on modifiable risk factors including body mass index (BMI), physical activity, diet, alcohol, smoking and screening were taken from baseline questionnaires. We constructed a block group-level SES index using data from the 2000 United States Census and fit Cox proportional hazards models estimating the association between area-level SES and total cancer mortality with and without control for modifiable risk factors. All statistical tests are 2-sided. Cancer mortality was 77% (95% CI: 50%, 111%) higher in the lowest-SES areas compared with the highest. Modifiable risk factors accounted for 45% (95% CI: 34%, 62%) of this association. Smoking explained the greatest proportion (29%; 95% CI: 22%, 40%) of the observed association, followed by diet (11%; 95% CI: 7%, 17%), physical activity (10%; 95% CI: 7%, 16%), screening (9%; 6%, 13%), and BMI (5%; 95% CI: 1%, 10%). Results were similar in models controlling for individual education and income. The association between area-level SES and cancer mortality is partially explained by modifiable risk factors, which could suggest the appropriate targets to reduce socioeconomic disparities.

Chemical characterization and in vitro toxicity of diesel exhaust particulate matter generated under varying conditions.

Epidemiologic studies have linked diesel exhaust (DE) to cardiovascular and respiratory morbidity and mortality, as well as lung cancer. DE composition is known to vary with many factors, although it is unclear how this influences toxicity. We generated eight DE atmospheres by applying a 2×2×2 factorial design and altering three parameters in a controlled exposure facility: (1) engine load (27 vs 82 %), (2) particle aging (residence time ~5 s vs ~5 min prior to particle collection), and (3) oxidation (with or without ozonation during dilution). Selected exposure concentrations of both diesel exhaust particles (DEPs) and DE gases, DEP oxidative reactivity via DTT activity, and in vitro DEP toxicity in murine endothelial cells were measured for each DE atmosphere. Cell toxicity was assessed via measurement of cell proliferation (colony formation assay), cell viability (MTT assay), and wound healing (scratch assay). Differences in DE composition were observed as a function of engine load. The mean 1-nitropyrene concentration was 15 times higher and oxidative reactivity was two times higher for low engine load versus high load. There were no substantial differences in measured toxicity among the three DE exposure parameters. These results indicate that alteration of applied engine load shifts the composition and can modify the biological reactivity of DE. While engine conditions did not affect the selected in vitro toxicity measures, the change in oxidative reactivity suggests that toxicological studies with DE need to take into account engine conditions in characterizing biological effects.

Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.

Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci.

The short-term association of selected components of fine particulate matter and mortality in the Denver Aerosol Sources and Health (DASH) study.

BACKGROUND: Associations of short-term exposure to fine particulate matter (PM2.5) with daily mortality may be due to specific PM2.5 chemical components. Daily concentrations of PM2.5 components were measured over five years in Denver to investigate whether specific PM2.5 components are associated with daily mortality. METHODS: Daily counts of total and cause-specific deaths were obtained for the 5-county Denver metropolitan region from 2003 through 2007. Daily 24-hour concentrations of PM2.5, elemental carbon (EC), organic carbon (OC), sulfate and nitrate were measured at a central residential monitoring site. Using generalized additive models, we estimated relative risks (RRs) of daily death counts for daily PM2.5 and four PM2.5 component concentrations at single and distributed lags between the current and three previous days, while controlling for longer-term time trend and meteorology. RESULTS: RR of total non-accidental mortality for an inter-quartile increase of 4.55 µg/m(3) in PM2.5 distributed over 4 days was 1.012 (95 % confidence interval: 0.999, 1.025); RRs for EC and OC were larger (1.024 [1.005, 1.043] and 1.020 [1.000, 1.040] for 0.33 and 1.67 µg/m(3) increases, respectively) than those for sulfate and nitrate. We generally did not observe associations with cardiovascular and respiratory mortality except for associations with ischemic heart disease mortality at lags 3 and 0-3 depending on the component. In addition, there were associations with cancer mortality, particularly for EC and OC, possibly reflecting advanced deaths of a frail population. CONCLUSIONS: PM2.5 components possibly from combustion-related sources are more strongly associated with daily mortality than are secondary inorganic aerosols.

Disparities in cancer incidence and mortality by area-level socioeconomic status: a multilevel analysis.

BACKGROUND: Disparities in cancer incidence and mortality have been observed by measures of area-level socioeconomic status (SES); however, the extent to which these disparities are explained by individual SES is unclear. METHODS: Participants included 60 756 men and women in the VITamins And Lifestyle (VITAL) study cohort, aged 50-76 years at baseline (2000-2002) and followed through 2010. We constructed a block group SES index using the 2000 US Census and fit Cox proportional hazards models to estimate the association between area-level SES (by quintile) and total and site-specific cancer incidence and total cancer mortality, with and without household income and individual education in the models. RESULTS: Lower area-level SES was weakly associated with higher total cancer incidence and lower prostate cancer risk, but was not associated with risk of breast cancer. Compared with the highest-SES areas, living in the lowest-SES areas was associated with higher lung (HR: 2.21, 95% CI 1.69 to 2.90) and colorectal cancer incidence (HR: 1.52, 95% CI 1.11 to 2.09) and total cancer mortality (HR: 1.68, 95% CI 1.47 to 1.93). Controlling for individual education and household income weakened the observed associations, but did not eliminate them (lung cancer HR: 1.43, 95% CI 1.07 to 1.91; colorectal cancer HR: 1.35, 95% CI 0.97 to 1.88; cancer mortality HR: 1.28, 95% CI 1.11 to 1.48). CONCLUSIONS: Area-level socioeconomic disparities exist for several cancer outcomes. These differences are not fully explained by individual SES, suggesting area-level factors may play a role.

Predictors of carotid thickness and plaque progression during a decade: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND PURPOSE: Carotid artery intima-media thickness (IMT) and plaque are noninvasive markers of subclinical arterial injury that predict incident cardiovascular disease. We evaluated predictors of longitudinal changes in IMT and new plaque during a decade in a longitudinal multiethnic cohort. METHODS: Carotid IMT and plaque were evaluated in Multi-Ethnic Study of Atherosclerosis (MESA) participants at exams 1 and 5, a mean (standard deviation) of 9.4 (0.5) years later. Far wall carotid IMT was measured in both common and internal carotid arteries. A plaque score was calculated from all carotid segments. Mixed-effects longitudinal and multivariate regression models evaluated associations of baseline risk factors and time-updated medication use with IMT progression and plaque formation. RESULTS: The 3441 MESA participants were aged 60.3 (9.4) years (53% women; 26% blacks, 22% Hispanic, 13% Chinese); 1620 (47%) had carotid plaque. Mean common carotid artery IMT progression was 11.8 (12.8) µm/year, and 1923 (56%) subjects developed new plaque. IMT progressed more slowly in Chinese (ß=-2.89; P=0.001) and Hispanic participants (ß=-1.81; P=0.02), and with higher baseline high-density lipoprotein cholesterol (per 5 mg/dL; ß=-0.22; P=0.03), antihypertensive use (ß=-2.06; P=0.0004), and time on antihypertensive medications (years; ß=-0.29; P<0.0001). Traditional risk factors were associated with new plaque formation, with strong associations for cigarette use (odds ratio, 2.31; P<0.0001) and protection by black ethnicity (odds ratio, 0.68; P<0.0001). CONCLUSIONS: In a large, multiethnic cohort with a decade of follow-up, ethnicity was a strong, independent predictor of carotid IMT and plaque progression. Antihypertensive medication use was associated with less subclinical disease progression.

Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women.

BACKGROUND: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. OBJECTIVES: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. METHODS: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. RESULTS: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. CONCLUSIONS: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function.

Adherence to the WCRF/AICR cancer prevention recommendations and cancer-specific mortality: results from the Vitamins and Lifestyle (VITAL) Study.

PURPOSE: In 2007, the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) released eight recommendations related to body fatness, physical activity, and diet aimed at preventing the most common cancers worldwide. The purpose of this paper is to estimate the association between meeting these recommendations and cancer-specific mortality. METHODS: We operationalized six recommendations (related to body fatness; physical activity; and consumption of foods that promote weight gain, plant foods, red and processed meat, and alcohol) and examined their association with cancer-specific mortality over 7.7 years of follow-up in the Vitamins and Lifestyle (VITAL) Study cohort. Participants included 57,841 men and women ages 50-76 in 2000-2002 who had not been diagnosed with cancer prior to baseline. Cancer-specific deaths (n = 1,595) were tracked through the Washington State death file. RESULTS: Meeting the recommendations related to plant foods and foods that promote weight gain were most strongly associated with lower cancer-specific mortality [hazard ratio (HR) 0.82, 95 % confidence interval (CI) 0.67, 1.00 and HR 0.82, 95 % CI 0.70, 0.96, respectively]. Cancer-specific mortality was 61 % lower in respondents who met at least five recommendations compared to those who met none (HR 0.39, 95 % CI 0.24, 0.62). Cancer-specific mortality was 10 % lower on an average with each additional recommendation met (per-recommendation HR 0.90, 95 % CI 0.85, 0.94; p trend < 0.001). This association did not differ by sex or age but was stronger in non-smokers (HR 0.84, 95 % CI 0.76, 0.92) than in smokers (HR 0.93, 95 % CI 0.87, 0.98; p interaction = 0.086). CONCLUSION: Adherence to the WCRF/AICR cancer prevention recommendations developed to reduce incidence of common cancers could substantially reduce cancer-specific mortality in older adults.

Fine particulate air pollution and the progression of carotid intima-medial thickness: a prospective cohort study from the multi-ethnic study of atherosclerosis and air pollution.

BACKGROUND: Fine particulate matter (PM2.5) has been linked to cardiovascular disease, possibly via accelerated atherosclerosis. We examined associations between the progression of the intima-medial thickness (IMT) of the common carotid artery, as an indicator of atherosclerosis, and long-term PM2.5 concentrations in participants from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: MESA, a prospective cohort study, enrolled 6,814 participants at the baseline exam (2000-2002), with 5,660 (83%) of those participants completing two ultrasound examinations between 2000 and 2005 (mean follow-up: 2.5 years). PM2.5 was estimated over the year preceding baseline and between ultrasounds using a spatio-temporal model. Cross-sectional and longitudinal associations were examined using mixed models adjusted for confounders including age, sex, race/ethnicity, smoking, and socio-economic indicators. Among 5,362 participants (5% of participants had missing data) with a mean annual progression of 14 µm/y, 2.5 µg/m(3) higher levels of residential PM2.5 during the follow-up period were associated with 5.0 µm/y (95% CI 2.6 to 7.4 µm/y) greater IMT progressions among persons in the same metropolitan area. Although significant associations were not found with IMT progression without adjustment for metropolitan area (0.4 µm/y [95% CI -0.4 to 1.2 µm/y] per 2.5 µg/m(3)), all of the six areas showed positive associations. Greater reductions in PM2.5 over follow-up for a fixed baseline PM2.5 were also associated with slowed IMT progression (-2.8 µm/y [95% CI -1.6 to -3.9 µm/y] per 1 µg/m(3) reduction). Study limitations include the use of a surrogate measure of atherosclerosis, some loss to follow-up, and the lack of estimates for air pollution concentrations prior to 1999. CONCLUSIONS: This early analysis from MESA suggests that higher long-term PM2.5 concentrations are associated with increased IMT progression and that greater reductions in PM2.5 are related to slower IMT progression. These findings, even over a relatively short follow-up period, add to the limited literature on air pollution and the progression of atherosclerotic processes in humans. If confirmed by future analyses of the full 10 years of follow-up in this cohort, these findings will help to explain associations between long-term PM2.5 concentrations and clinical cardiovascular events.