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BACKGROUND: Increased exposure to ambient air pollution, especially fine particulate matter ≤2.5 μm (PM2.5) is associated with poorer brain health and increased risk for Alzheimer’s disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. OBJECTIVE: Our aim was to investigate if exposure to PM2.5 was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. METHODS: We examined the relationship between PM2.5 and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio (LCCNR) in 381 men [mean age = 67.3; standard deviation (SD)= 2.6] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to PM2.5 was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on LCCNR in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between PM2.5 exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. RESULTS: Multiple linear regressions revealed a significant association between PM2.5 and rostral-middle LCCNR (β= -0.16; 푝= 0.02), whereby higher exposure to PM2.5 was associated with lower LCCNR. A co-twin control analysis found that, within monozygotic pairs, individuals with higher PM2.5 exposure showed lower LCCNR (β= -0.11; 푝= 0.02), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between PM2.5 and caudal LCCNR or hippocampal volume, suggesting a degree of specificity to the rostralmiddle portion of the LC. DISCUSSION: Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear. OBJECTIVES: Our objective is to compare particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses. METHODS: We assigned annual PM2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women’s Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region. RESULTS: With a few exceptions, relative agreement of approach-specific PM2.5 exposure estimates was high for PM2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM2.5. There was no evidence of large differences in health effects associations with PM2.5 among estimation approaches in analyses adjusted for climate region. CONCLUSIONS: Different estimation approaches produced similar spatial patterns of PM2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM2.5-health effects associations were similar among estimation approaches. PM2.5 estimates and PM2.5-health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest [ABSTRACT FROM AUTHOR]

BACKGROUND: Poor olfaction is common in older adults and may have profound adverse implications on their health. However, little is known about the potential environmental contributors to poor olfaction. OBJECTIVE: We investigated ambient fine particulate matter [PM ≤ 2.5 μm in aerodynamic diameter (PM2.5)] and nitrogen dioxide (NO2) in relation to poor olfaction in middle-aged to older women. METHODS: The Sister Study is a nationwide cohort of 50,884 women in the United States with annual average air pollutant exposures estimated based on participants' residences from enrollment (2003-2009) through 2017. This analysis was limited to 3,345 women, 50-79 years of age as of January 2018, who completed the Brief Smell Identification Test (B-SIT) in 2018-2019. Poor olfaction was defined as a B-SIT score of ≤ 9 in the primary analysis. We conducted multivariable logistic regressions, accounting for covariates and study sampling design. RESULTS: Overall, we found little evidence for associations of air pollutants with poor olfaction. The odds ratio (OR) and 95% confidence interval (CI) of poor olfaction for each interquartile range (IQR) increment of air pollutants in 2006 were 1.03 (95% CI: 0.91, 1.17) for PM2.5 (per 3.3 μg/m³) and 1.08 (95% CI: 0.96, 1.22) for NO2 (per 5.7 ppb). Results were similar in the analyses using the most recent (2017) or the cumulative average (2006-2017) air pollutant exposure data. Secondary analyses suggested potential association in certain subgroups. The OR per IQR was 1.35 (95% CI: 1.11, 1.65) for PM2.5 among younger participants (< 54.2 years of age) and 1.87 (95% CI: 1.29, 2.71) for NO2 among current smokers. DISCUSSION: This study did not find convincing evidence that air pollutants have lasting detrimental effects on the sense of smell of women 50-79 years of age. The subgroup analyses are exploratory, and the findings need independent confirmation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters. OBJECTIVE: We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort. METHODS: This population-based retrospective cohort study included 294,937 mother–child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ≤2.5 μm (PM2.5)], nitrogen dioxide (NO2), and ozone (O3) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season. RESULTS: There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive PM2.5 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1-27 wk of gestation, cumulative hazard ratio (HR)= 1.14 [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) (7.4-μg/m³) increase]. O3 exposure during 34-37 wk of gestation was associated with increased risk [HR = 1.06 (95% CI: 1.01, 1.11) per IQR (17.4 ppb) increase] but with reduced risk during 20-28 wk of gestation [HR = 0.93 (95% CI: 0.89, 0.98)]. No associations were observed with NO2. Sex-stratified early gestational PM2.5 associations were stronger among boys [boys HR = 1.16 (95% CI: 1.08, 1.26); girls HR = 1.06 (95% CI: 0.89, 1.26)]. O3associations in later gestation were observed only in boys [boys HR = 1.10 (95% CI: 1.04, 1.16); girls HR = 0.94 (95% CI: 0.84, 1.05)]. CONCLUSIONS: Exposures to PM2.5in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of O3exposure on ASD risk merits further investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies suggest that certain dietary patterns and constituents may be beneficial to brain health. Airborne exposures to fine particulate matter [particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5)] are neurotoxic, but the combined effects of dietary patterns and PM2.5 have not been investigated. OBJECTIVES: We examined whether previously reported association between PM2.5 exposure and lower white matter volume (WMV) differed between women whose usual diet during the last 3 months before baseline was more or less consistent with a Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND)-like diet, a dietary pattern that may slow neurodegenerative changes. METHODS: This study included 1,302 U.S. women who were 65–79 y old and free of dementia in the period 1996–1998 (baseline). In the period 2005–2006, structural brain magnetic resonance imaging (MRI) scans were performed to estimate normal-appearing brain volumes (excluding areas with evidence of small vessel ischemic disease). Baseline MIND diet scores were derived from a food frequency questionnaire. Three-year average PM2.5 exposure prior to MRI was estimated using geocoded participant addresses and a spatiotemporal model. RESULTS: Average total and temporal lobe WMVs were 0.74 cm³ [95% confidence interval (CI): 0.001, 1.48) and 0.19 cm³ (95% CI: 0.002, 0.37) higher, respectively, with each 0.5-point increase in the MIND score and were 4.16 cm³ (95% CI: -6.99, -1.33) and 1.46 cm³ (95% CI: -2.16, -0.76) lower, respectively, with each interquartile range (IQR) (IQR = 3.22 μg/m³) increase in PM2.5. The inverse association between PM2.5 per IQR and WMV was stronger (p-interaction <0.001) among women with MIND scores below the median (for total WMV, -12.47 cm³; 95% CI: -17.17, -7.78), but absent in women with scores above the median (0.16 cm³; 95% CI: -3.41, 3.72), with similar patterns for WMV in the frontal, parietal, and temporal lobes. For total cerebral and hippocampus brain volumes or WMV in the corpus callosum, the associations with PM2.5 were not significantly different for women with high MIND scores and women with low MIND scores. DISCUSSION: In this cohort of U.S. women, PM2.5 exposure was associated with lower MRI-based WMV, an indication of brain aging, only among women whose usual diet was less consistent with the MIND-like dietary pattern at baseline. [ABSTRACT FROM AUTHOR]

BACKGROUND: Episodic memory decline varies by age and underlying neuropathology. Whether ambient air pollution contributes to the heterogeneity of episodic memory decline in older populations remains unclear. OBJECTIVES: We estimated associations between air pollution exposures and episodic memory decline according to pollutant, exposure time window, age, and latent class subgroups defined by episodic memory trajectories. METHODS: Participants were from the Women's Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes. Older women (푛 = 2,056; 74-92 years of age) completed annual (2008-2018) episodic memory assessments using the telephone-based California Verbal Learning Test (CVLT). We estimated 3-y average fine particulate matter [PM with an aerodynamic diameter of = 2.5µm (PM2.5)] and nitrogen dioxide (NO2) exposures at baseline and 10 y earlier (recent and remote exposures, respectively), using regionalized national universal kriging. Separate latent class mixed models were used to estimate associations between interquartile range increases in exposures and CVLT trajectories in women ≤80 and >80 years of age, adjusting for covariates. RESULTS: Two latent classes were identified for women ≤80 years of age (푛 = 828), "slow-decliners" {slope=-0.12/y [95% confidence interval (CI): -0.23, -0.01] and "fast-decliners" [slope=-1.79/y (95% CI: -2.08, -1.50)]}. In the slow-decliner class, but not the fast-decliner class, PM2.5 exposures were associated with a greater decline in CVLT scores over time, with a stronger association for recent vs. remote exposures [-0.16/y (95% CI: -2.08, -0.03) per 2.88 μg/m³ and -0.11/y (95% CI: -0.22, 0.01) per 3.27μg/m³, respectively]. Among women ≥ 80 years of age (푛 = 1,128), the largest latent class comprised "steady-decliners" [slope=-1.35/y (95% CI: -1.53, -1.17)], whereas the second class, "cognitively resilient", had no decline in CVLT on average. PM2.5 was not associated with episodic memory decline in either class. A 6.25-ppb increase in recent NO2 was associated with nonsignificant acceleration of episodic memory decline in the = 80-y-old fast-decliner class [-0.21/y (95% CI: -0.45, 0.04)], and in the >80-y-old cognitively resilient class [-0.10/y (95% CI: -0.24, 0.03)] and steady-decliner class [-0.11/y (95% CI: -0.27, 0.05)]. Associations with recent NO2 exposure in women >80 years of age were stronger and statistically significant when 267 women with incident probable dementia were excluded [e.g., -0.12/y (95% CI: -0.22, -0.02) for the cognitively resilient class]. In contrast with changes in CVLT over time, there were no associations between exposures and CVLT scores during follow-up in any subgroup. DISCUSSION: In a community-dwelling U.S. population of older women, associations between late-life exposure to ambient air pollution and episodic memory decline varied by age-related cognitive trajectories, exposure time windows, and pollutants. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood– brain barrier weakening, which may augment neurotoxic effects of PM. OBJECTIVES: This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter =200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS. METHODS: nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: a) FA, b) nPM, c) FA+BCAS, and d) nPM+BCAS. Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed. RESULTS: The joint nPM+BCAS group exhibited synergistic effects on white matter injury (2.3× the additive nPM and FA+BCAS scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and FA+BCAS effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of nPM+BCAS than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the nPM+BCAS cohort demonstrated impaired working memory when compared to the FA+BCAS group. DISCUSSION: Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. [ABSTRACT FROM AUTHOR]

BACKGROUND: In June 2020, the National Academies of Sciences, Engineering, and Medicine hosted a virtual workshop focused on integrating the science of aging and environmental health research. The concurrent COVID-19 pandemic and national attention on racism exposed shortcomings in the environmental research field's conceptualization and methodological use of race, which have subsequently hindered the ability of research to address racial health disparities. By the workshop's conclusion, the authors deduced that the utility of environmental aging biomarkers—aging biomarkers shown to be specifically influenced by environmental exposures—would be greatly diminished if these biomarkers are developed absent of considerations of broader societal factors—like structural racism—that impinge on racial health equity. OBJECTIVES: The authors reached a post-workshop consensus recommendation: To advance racial health equity, a "compound" exposome approach should be widely adopted in environmental aging biomarker research. We present this recommendation here. DISCUSSION: The authors believe that without explicit considerations of racial health equity, people in most need of the benefits afforded by a better understanding of the relationships between exposures and aging will be the least likely to receive them because biomarkers may not encompass cumulative impacts from their unique social and environmental stressors. Employing an exposome approach that allows for more comprehensive exposure–disease pathway characterization across broad domains, including the social exposome and neighborhood factors, is the first step. Exposomecentered study designs must then be supported with efforts aimed at increasing the recruitment and retention of racially diverse study populations and researchers and further "compounded" with strategies directed at improving the use and interpretation of race throughout the publication and dissemination process. This compound exposome approach maximizes the ability of our science to identify environmental aging biomarkers that explicate racial disparities in health and best positions the environmental research community to contribute to the elimination of racial health disparities. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human data linking inflammation with long-term particulate matter (PM) exposure are still lacking. Emerging evidence suggests that people with metabolic syndrome (MS) may be a more susceptible population. OBJECTIVES: Our goal was to examine potential inflammatory responses associated with long-term PM exposure and MS-dependent susceptibility. METHODS: We conducted secondary analyses of white blood cell (WBC) count and MS data from The Third National Health and Nutrition Examination Survey and PM10 (PM with aerodynamic diameter < 10 μm) data from the U.S. Environmental Protection Agency Aerometric Information Retrieval System. Estimated 1-year PM10 exposures were aggregated at the centroid of each residential census-block group, using distance-weighted averages from all monitors in the residing and adjoining counties. We restricted our analyses to adults (20-89 years of age) with normal WBC (4,000-11,000 × 106/L), no existing cardiovascular disease, complete PM10 and MS data, and living in current residences > 1 year (n = 2,978; age 48.5 ± 17.8 years). Mixed-effects models were constructed to account for autocorrelation and potential confounders. RESULTS: After adjustment for demographics, socioeconomic factors, lifestyles, residential characteristics, and MS, we observed a statistically significant association between WBC count and estimated local PM10 levels (p = 0.035). Participants from the least polluted areas (1-year PM10 < 1st quartile cutoff 27.8 μg/m³) had lower WBC counts than the others (difference = 145 × 106/L; 95% confidence interval, 10-281). We also noted a graded association between PM10 and WBC across subpopulations with increasing MS components, with 91 × 106/L difference in WBC for those with no MS versus 214, 338, and 461 × 106/L for those with 3, 4, and 5 metabolic abnormalities (trend-testp = 0.15). CONCLUSIONS: Our study revealed a positive association between long-term PM exposure and hematological markers of inflammation and supported the hypothesized MS-dependent susceptibility. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increasing evidence suggests that obesity may impart greater susceptibility to adverse effects of air pollution. Particulate matter, especially PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm), is associated with increased cardiac events and reduction of heart rate variability (HRV). OBJECTIVES: Our goal was to investigate whether particle-mediated autonomic modulation is aggravated in obese individuals. METHODS: We examined PM2.5-mediated acute effects on HRV and heart rate (HR) using 10 24-hr and 13 48-hr ambulatory electrocardiogram recordings collected from 18 boilermakers (39.5 ± 9.1 years of age) exposed to high levels of metal particulates. Average HR and 5-min HRV [SDNN: standard deviation of normal-to-normal intervals (NN); rMSSD: square-root of mean squared-differences of successive NN intervals; HF: high-frequency power 0.15-0.4 Hz] and personal PM2.5 exposures were continuously monitored. Subjects with body mass index ≥ 30 kg/m² were classified as obese. Mixed-effect models were used for statistical analyses. RESULTS: Half (50%) of the study subjects were obese. After adjustment for confounders, each 1-mg/m³ increase in 4-hr moving average PM2.5 was associated with HR increase of 5.9 bpm [95% confidence interval (CI), 4.2 to 7.7] and with 5-min HRV reduction by 6.5% (95% CI, 1.9 to 11.3%) for SDNN, 1.7% (95% CI, -4.9 to 8.4%) for rMSSD, and 8.8% (95% CI, -3.8 to 21.3%) for HF. Obese individuals had greater PM2.5-mediated HRV reductions (2- to 3-fold differences) than nonobese individuals, and had more PM2.5-mediated HR increases (9-bpm vs. 4-bpm increase in HR for each 1-mg/m³ increase in PM2.5; p < 0.001). CONCLUSIONS: Our study revealed greater autonomic cardiac responses to metal particulates in obese workers, supporting the hypothesis that obesity may impart greater susceptibility to acute cardiovascular effects of fine particles. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear. OBJECTIVE: Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM2.5 exposures. METHODS: We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNNi (SDNN for all 5-min segments) were summarized over 24-hr, day (0730-2130 hours), and night (0000-0700 hours) periods. PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors. RESULTS: Mean (± SD) PM2.5 exposure was 0.73 ± 0.50 mg/m³ and ranged from 0.04 to 2.70 mg/m³. We observed a consistent inverse exposure--response relationship, with a decrease in all HRV measures with increased PM2.5 exposure. However, the decrease was most pronounced at night, where a 1-mg/m³ increase in PM2.5 was associated with a change of -8.32 [95% confidence interval (CI), -16.29 to -0.35] msec nighttime rMSSD, -14.77 (95% CI, -31.52 to 1.97) msec nighttime SDNN, and -8.37 (95% CI, -17.93 to 1.20) msec nighttime SDNNi, after adjusting for nonworking nighttime HRV, age, and smoking. CONCLUSION: Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV. [ABSTRACT FROM AUTHOR]

Spatial estimations are increasingly used to estimate geocoded ambient particulate matter (PM) concentrations in epidemiologic studies because measures of daily PM concentrations are unavailable in most U.S. locations. This study was conducted to a) assess the feasibility of large-scale kriging estimations of daily residential-level ambient PM concentrations, b) perform and compare cross-validations of different kriging models, c) contrast three popular kriging approaches, and d) calculate SE of the kriging estimations. We used PM data for PM with aerodynamic diameter ≤ 10 μm (PM10) and aerodynamic diameter ≤ 2.5 μm (PM2.5) from the U.S. Environmental Protection Agency for the year 2000. Kriging estimations were performed at 94,135 geocoded addresses of Women's Health Initiative study participants using the ArcView geographic information system. We developed a semiautomated program to enable large-scale daily kriging estimation and assessed validity of semivariogram models using prediction error (PE), standardized prediction error (SPE), root mean square standardized (RMSS), and SE of the estimated PM. National- and regional-scale kriging performed satisfactorily, with the former slightly better. The average PE, SPE, and RMSS of daily PM10 semivariograms using regular ordinary kriging with a spherical model were 0.0629, -0.0011, and 1.255 μg/m3, respectively; the average SE of the estimated residential-level PM10 was 27.36 μg/m3. The values for PM2.5 were 0.049, 0.0085, 1.389, and 4.13 μg/m3, respectively. Lognormal ordinary kriging yielded a smaller average SE and effectively eliminated out-of-range predicted values compared to regular ordinary kriging. Semiautomated daily kriging estimations and semivariogram cross-validations are feasible on a national scale. Lognormal ordinary kriging with a spherical model is valid for estimating daily ambient PM at geocoded residential addresses. [ABSTRACT FROM AUTHOR]

Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze whole- blood total RNA in boilermakers before and after occupational exposure to metal fumes. A self- controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures. [ABSTRACT FROM AUTHOR]