Reducing Indoor Particulate Air Pollution Improves Student Test Scores: A Randomized Double-Blind Crossover Study.

Short-term exposure to air pollution is associated with a decline in cognitive function. Standardized test scores have been employed to evaluate the effects of air pollution exposure on cognitive performance. Few studies aimed to prove whether air pollution is responsible for reduced test scores; none have implemented a "gold-standard" method for assessing the association such as a randomized, double-blind intervention. This study used a "gold-standard" method─randomized, double-blind crossover─to assess whether reducing short-term indoor particle concentrations results in improved test scores in college students in Tianjin, China. Participants (n = 162) were randomly assigned to one of two similar classrooms and completed a standardized English test on two consecutive weekends. Air purifiers with active or sham (i.e., filter removed) particle filtration were placed in each classroom. The filtration mode was switched between the two test days. Linear mixed-effect models were used to evaluate the effect of the intervention mode on the test scores. The results show that air purification (i.e., reducing PM) was significantly associated with increases in the z score for combined (0.11 [95%CI: 0.02, 0.21]) and reading (0.11 [95%CI: 0.00, 0.22]) components. In conclusion, a short-term reduction in indoor particle concentration led to improved test scores in students, suggesting an improvement in cognitive function.

Blood Pressure Effect of Traffic-Related Air Pollution : A Crossover Trial of In-Vehicle Filtration.

BACKGROUND: Ambient air pollution, including traffic-related air pollution (TRAP), increases cardiovascular disease risk, possibly through vascular alterations. Limited information exists about in-vehicle TRAP exposure and vascular changes. OBJECTIVE: To determine via particle filtration the effect of on-roadway TRAP exposure on blood pressure and retinal vasculature. DESIGN: Randomized crossover trial. (ClinicalTrials.gov: NCT05454930). SETTING: In-vehicle scripted commutes driven through traffic in Seattle, Washington, during 2014 to 2016. PARTICIPANTS: Normotensive persons aged 22 to 45 years (n = 16). INTERVENTION: On 2 days, on-road air was entrained into the vehicle. On another day, the vehicle was equipped with high-efficiency particulate air (HEPA) filtration. Participants were blinded to the exposure and were randomly assigned to the sequence. MEASUREMENTS: Fourteen 3-minute periods of blood pressure were recorded before, during, and up to 24 hours after a drive. Image-based central retinal arteriolar equivalents (CRAEs) were measured before and after. Brachial artery diameter and gene expression were also measured and will be reported separately. RESULTS: Mean age was 29.7 years, predrive systolic blood pressure was 122.7 mm Hg, predrive diastolic blood pressure was 70.8 mm Hg, and drive duration was 122.3 minutes (IQR, 4 minutes). Filtration reduced particle count by 86%. Among persons with complete data (n = 13), at 1 hour, mean diastolic blood pressure, adjusted for predrive levels, order, and carryover, was 4.7 mm Hg higher (95% CI, 0.9 to 8.4 mm Hg) for unfiltered drives compared with filtered drives, and mean adjusted systolic blood pressure was 4.5 mm Hg higher (CI, -1.2 to 10.2 mm Hg). At 24 hours, adjusted mean diastolic blood pressure (unfiltered) was 3.8 mm Hg higher (CI, 0.02 to 7.5 mm Hg) and adjusted mean systolic blood pressure was 1.1 mm Hg higher (CI, -4.6 to 6.8 mm Hg). Adjusted mean CRAE (unfiltered) was 2.7 µm wider (CI, -1.5 to 6.8 µm). LIMITATIONS: Imprecise estimates due to small sample size; seasonal imbalance by exposure order. CONCLUSION: Filtration of TRAP may mitigate its adverse effects on blood pressure rapidly and at 24 hours. Validation is required in larger samples and different settings. PRIMARY FUNDING SOURCE: U.S. Environmental Protection Agency and National Institutes of Health.

Long-term exposure to ambient air pollution and cognitive function in older US adults: The Multi-Ethnic Study of Atherosclerosis.

Air pollution effects on cognitive function have been increasingly recognized. Little is known about the impact of different sources of fine particulate (PM2.5). We aim to evaluate the associations between long-term air pollution exposure, including source-specific components in PM2.5, and cognition in older adults. Methods: Cognitive assessment, including the Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS), was completed in 4392 older participants in the United States during 2010-2012. Residence-specific air pollution exposures (i.e., oxides of nitrogen [NO2/NOx], PM2.5 and its components: elemental carbon [EC], organic carbon [OC], sulfur [S], and silicon [Si]) were estimated by geo-statistical models. Linear and logistic regression models were used to estimate the associations between each air pollutants metric and cognitive function. Results: An interquartile range (IQR) increase in EC (0.8 µg/m3) and Si (23.1 ng/m3) was associated with -1.27 (95% confidence interval [CI]: -0.09, -2.45) and -0.88 (95% CI: -0.21, -1.54) lower CASI scores in global cognitive function. For each IQR increase in Si, the odds of low cognitive function (LCF) across domains was 1.29 times higher (95% CI: 1.04, 1.60). For other tests, NO X was associated with slower processing speed (DSC: -2.01, 95% CI: -3.50, -0.52) and worse working memory (total DS: -0.4, 95% CI: -0.78, -0.01). No associations were found for PM2.5 and two PM2.5 components (OC and S) with any cognitive function outcomes. Conclusion: Higher exposure to traffic-related air pollutants including both tailpipe (EC and NO x ) and non-tailpipe (Si) species were associated with lower cognitive function in older adults.

A Cross Sectional Study of Respiratory and Allergy Status in Dairy Workers.

INTRODUCTION: Workers on dairy farms face exposures to organic dusts and endotoxin. At the same time, a number of studies of farmers have reported a lower prevalence of asthma in farmworkers compared to persons without farm contact. The "hygiene hypothesis" suggests that early life exposures on farms could be protective against allergic disease and asthma. Such protective relationships are less well studied in adult farm workers. METHODS: A cross-sectional analysis of respiratory function and allergy status was performed in a sample of dairy farm workers (n = 42) and community controls (n = 40). Measures of respiratory status (spirometry, exhaled nitric oxide FeNO, self-reported symptoms) and levels of total and bovine-specific IgE were compared between the groups. RESULTS: Prevalence of self-reported asthma and most respiratory symptoms was similar in the two groups, with the exception of increased report of dyspnea among dairy workers. In the dairy workers, level of lung function was not reduced and FeNO was not increased. In unadjusted and adjusted models, dairy work was not associated with reduced lung function or increased airway inflammation. Mean IgE levels did not differ significantly between workers and controls, but elevated bovine-specific IgE was detected only among dairy workers, with an apparent association between elevated bovine IgE and increased FeNO. CONCLUSION: While dairy workers did not demonstrate increased asthma prevalence compared to controls, sensitization to bovine antigen in several workers appeared to be associated with airway inflammation. Occupational health programs for dairy workers should consider the risk of animal allergy as part of respiratory health protection efforts.

Acute cardiovascular effects of traffic-related air pollution (TRAP) exposure in healthy adults: A randomized, blinded, crossover intervention study.

Exposure to traffic-related air pollution (TRAP) may enhance the risk of cardiovascular disease. However, the short-term effects of TRAP components on the cardiovascular system are not well understood. We conducted a randomized, double-blinded, crossover intervention study in which 39 healthy university students spent 2 h next to a busy road. Participants wore a powered air-purifying respirator (PAPR) or an N95 mask. PAPRs were equipped with a filter for particulate matter (PM), a PM and volatile organic compounds (VOCs) filter or a sham filter. Participants were blinded to PAPR filter type and underwent randomized exposures four times, once for each intervention mode. Blood pressure (BP), heart rate (HR) and heart rate variability (HRV) were measured before, during and for 6 h after the roadside exposure. Linear mixed-effect models were used to evaluate the effects of the interventions relative to baseline controlling for other covariates. All HRV measures increased during and following exposure for all intervention modes. Some HRV measures (SDNN and rMSSD during exposure and SDNN after exposure) were marginally affected by PM filtration. Wearing the N95 mask affected VLF power and rMSSD responses to traffic exposure differently than the PAPR interventions. Both systolic and diastolic BP increased slightly during exposure, but then were generally lower than baseline after exposure for the sham and filter interventions. HR, which fell during exposure and mostly remained lower than baseline after exposure, was lower yet with all filter interventions compared to the sham mode following exposure. Therefore, short-term exposure to traffic acutely affects HRV, BP and HR, but N95 mask and PAPR interventions generally show little efficacy in reducing these effects. Removing the PM component of TRAP has some limited effects on HRV responses to exposure but exaggerates the traffic-related decrease in HR. HRV findings from N95 mask interventions need to be interpreted cautiously.

Short-term exposure to air pollution and biomarkers of cardiovascular effect: A repeated measures study.

To help understand the pathophysiologic mechanisms linking air pollutants and cardiovascular disease (CVD), we employed a repeated measures design to investigate the associations of four short-term air pollution exposures - particulate matter less than 2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and sulfur dioxide (SO2), with two blood markers involved in vascular effects of oxidative stress, soluble lectin-like oxidized LDL receptor-1 (sLOX-1) and nitrite, using data from the Multi-Ethnic Study of Atherosclerosis (MESA). Seven hundred and forty participants with plasma sLOX-1 and nitrite measurements at three exams between 2002 and 2007 were included. Daily PM2.5, NO2, O3 and SO2 zero to seven days prior to blood draw were estimated from central monitors in six MESA regions, pre-adjusted using site-specific splines of meteorology and temporal trends, and an indicator for day of the week. Unconstrained distributed lag generalized estimating equations were used to estimate net effects over eight days with adjustment for sociodemographic and behavioral factors. The results showed that higher short-term concentrations of PM2.5, but not other pollutants, were associated with increased sLOX-1 analyzed both as a continuous outcome (percent change per interquartile increase: 16.36%, 95%CI: 0.1-35.26%) and dichotomized at the median (odds ratio per interquartile increase: 1.21, 95%CI: 1.01-1.44). The findings were not meaningfully changed after adjustment for additional covariates or in several sensitivity analyses. Pollutant concentrations were not associated with nitrite levels. This study extends earlier experimental findings of increased sLOX-1 levels following PM inhalation to a much larger population and at ambient concentrations. In light of its known mechanistic role in promoting vascular disease, sLOX-1 may be a suitable translational biomarker linking air pollutant exposures and cardiovascular outcomes.

Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA).

BACKGROUND: Air pollution may affect the risk of respiratory infection, though research has focused on uncommon infections or infections in children. Whether ambient air pollutants increase the risk of common acute respiratory infections among adults is uncertain, yet this may help understand whether pollutants influence spread of pandemic respiratory infections like COVID-19. OBJECTIVE: To estimate the association between ambient air pollutant exposures and respiratory infections in adults. METHODS: During five study examinations over 12 years, 6536 participants in the multiethnic study of atherosclerosis (MESA) reported upper respiratory tract infections, bronchitis, pneumonia or febrile illness in the preceding 2 weeks. Using a validated spatiotemporal model, we estimated residential concentrations of ambient PM2.5, NOx and NO2 for the 2-6 weeks (short-term) and year (long-term) prior to each examination. RESULTS: In this population aged 44-84 years at baseline, 10%-32% of participants reported a recent respiratory infection, depending on month of examination and study region. PM2.5, NOx and NO2 concentrations over the prior 2-6 weeks were associated with increased reporting of recent respiratory infection, with risk ratios (95% CIs) of 1.04 (1.00 to 1.09), 1.15 (1.10 to 1.20) and 1.21 (1.10 to 1.33), respectively, per increase from 25th to 75th percentile in residential pollutant concentration. CONCLUSION: Higher short-term exposure to PM2.5 and traffic-related pollutants are associated with increased risk of symptomatic acute respiratory infections among adults. These findings may provide an insight into the epidemiology of COVID-19.

Improving Air Pollution Predictions of Long-Term Exposure Using Short-Term Mobile and Stationary Monitoring in Two US Metropolitan Regions.

Mobile monitoring is increasingly employed to measure fine spatial-scale variation in air pollutant concentrations. However, mobile measurement campaigns are typically conducted over periods much shorter than the decadal periods used for modeling chronic exposure for use in air pollution epidemiology. Using the regions of Los Angeles and Baltimore and the time period from 2005 to 2014 as our modeling domain, we investigate whether including mobile or stationary passive sampling device (PSD) monitoring data collected over a single 2-week period in one or two seasons using a unified spatio-temporal air pollution model can improve model performance in predicting NO2 and NOx concentrations throughout the 9-year study period beyond what is possible using only routine monitoring data. In this initial study, we use data from mobile measurement campaigns conducted contemporaneously with deployments of stationary PSDs and only use mobile data collected within 300 m of a stationary PSD location for inclusion in the model. We find that including either mobile or PSD data substantially improves model performance for pollutants and locations where model performance was initially the worst (with the most-improved R2 changing from 0.40 to 0.82) but does not meaningfully change performance in cases where performance was already very good. Results indicate that in many cases, additional spatial information from mobile monitoring and personal sampling is potentially cost-efficient inexpensive way of improving exposure predictions at both 2-week and decadal averaging periods, especially for the predictions that are located closer to features such as roadways targeted by the mobile short-term monitoring campaign.

A hybrid approach to estimating long-term and short-term exposure levels of ozone at the national scale in China using land use regression and Bayesian maximum entropy.

Because ambient ozone (O3) has fine spatial scale variability in addition to a large scale regional distribution, accurate exposure predictions for population health studies need to also capture fine spatial scale differences in exposure. To address these needs, we developed a 3-year average land use regression (LUR) and combined LUR and Bayesian maximum entropy (BME) by incorporating a national area variability LUR model for China from 2015 to 2017 along with data that take into account incompleteness of O3 monitoring data into a BME framework. Spatio-temporal kriging models that either included or did not include "soft" data were used for comparison. The final LUR model included five predictor variables: road length within a 1000 m buffer, temperature, wind speed, industrial land area within a 3000 m buffer and altitude. The 1-year predicted O3 concentrations based on the ratio method moderately agreed with the measured concentration, and the regression R2 values were 0.53, 0.57 and 0.59 in the year of 2015, 2016 and 2017, respectively. The LUR/BME model performed better (R2 = 0.80, root mean squared error [RMSE] = 23.5 µg/m3) than the ordinary spatio-temporal kriging model that either included "soft" data (R2 = 0.57, RMSE = 49.2 µg/m3) or did not include the "soft" data (R2 = 0.52, RMSE = 58.5 µg/m3). We have demonstrated that a hybrid LUR/BME model can provide accurate predictions of O3 concentrations with high spatio-temporal resolution at the national scale in mainland China.

Ambient air pollution, traffic proximity and coronary atherosclerotic phenotype in China.

BACKGROUND: Exposure to ambient air pollution is associated with cardiovascular risk, potentially via atherosclerosis promotion. The disease mechanisms underlying these associations remain uncertain. OBJECTIVES: We aim to investigate the relationship of air pollution and traffic proximity with subclinical atherosclerosis, using coronary plaque phenotypes to gain insight into potential mechanisms. METHODS: Coronary plaque total and component volumes, high-risk plaque (HRP) appearance, and luminal stenosis were characterized by coronary computed tomography angiography in 2279 patients with atherosclerosis at baseline between 2014 and 2017. Annual average exposure to air pollutants including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) was estimated by air pollution models for individual participants. Multiple linear regression models were used to assess the association of each exposure with plaque phenotypes and coronary stenosis, controlling for potential confounders. Multiple logistic regression models were used to estimate associations with plaque vulnerability. RESULTS: The studied population was 60.2±9.2 years old. PM2.5 and NO2 concentrations were significantly associated with a 5.0% (95%CI: 0.3, 9.9%, per 15 µg/m3 increase for PM2.5), 12.0% (95%CI: 2.5, 22.5% per 20 µg/m3 for NO2) larger volume of non-calcified plaque, respectively. Increase in O3 concentration was associated with a 12.2% (95%CI: 2.2, 23.2%, per 5 µg/m3 O3) larger volume of calcified plaque and a 12.8% (95%CI: 0.9, 26.2%) greater lumen narrowing. Increased PM2.5 and NO2, was also associated with increase in HRP, determined by the napkin ring sign (odds ratio: 1.41 [95%CI: 1.10, 1.80] for PM2.5 and 1.78 [95%CI: 1.20, 2.63] for NO2) and positive remodeling index (OR: 1.11 [95%CI: 1.01, 1.21] for PM2.5 and 1.20 [95%CI: 1.02, 1.42] for NO2), respectively, indicating increased plaque vulnerability. CONCLUSION: Long-term exposures to air pollution were associated with greater plaque volume and luminal stenosis, and increased plaque vulnerability with attendant risk of plaque rupture and erosion.

Ambient PM2.5 exposures and systemic biomarkers of lipid peroxidation and total antioxidant capacity in early pregnancy.

Evidence for effects of PM2.5 on systemic oxidative stress in pregnant women is limited, especially in early pregnancy. To estimate the associations between ambient PM2.5 exposures and biomarkers of lipid peroxidation and total antioxidant capacity (T-AOC) in women with normal early pregnancy (NEP) and women with clinically recognized early pregnancy loss (CREPL), 206 early pregnant women who had measurements of serum malondialdehyde (MDA) and T-AOC were recruited from a larger case-control study in Tianjin, China from December 2017 to July 2018. Ambient PM2.5 concentrations of eight single-day lags exposure time windows before blood collection at the women's residential addresses were estimated using temporally-adjusted land use regression models. Effects of PM2.5 exposures on percentage change in the biomarkers were estimated using multivariable linear regression models adjusted for month, temperature, relative humidity, gestational age and other covariates. Unconstrained distributed lag models were used to estimate net cumulative effects. Increased serum MDA and T-AOC were significantly associated with increases in PM2.5 at several lag exposure time windows in both groups. The net effects of each interquartile range increase in PM2.5 over the preceding 8 days on MDA were significantly higher (p < 0.001) in CREPL [52% (95% CI: 41%, 62%)] than NEP [22% (95% CI: 9%, 36%)] women. Net effects of each interquartile range increase in PM2.5 over the preceding 5 days on T-AOC were significantly lower (p = 0.010) in CREPL [14% (95% CI: 9%, 19%)] than NEP [24% (95% CI: 18%, 29%)] women. Exposure to ambient PM2.5 may induce systemic lipid peroxidation and antioxidant response in early pregnant women. More severe lipid peroxidation and insufficient antioxidant capacity associated with PM2.5 was found in CREPL women than NEP women. Future studies should focus on mechanisms of individual susceptibility and interventions to reduce PM2.5-related oxidative stress in the first trimester.

Estimated time-varying exposures to air emissions from animal feeding operations and childhood asthma.

BACKGROUND/AIM: Industrial-scale animal feeding operations (AFOs) have adverse impacts on regional air quality. Air emissions include endotoxins and other pro-inflammatory components, and exposure may cause airway inflammation and respiratory effects in susceptible individuals residing nearby. We aimed to develop and validate metrics for estimating time-varying exposure to AFO air pollution in surrounding communities and, secondly, to determine whether exposure is associated with health effects in children with asthma. METHODS: We conducted a longitudinal panel study of N = 58 children with asthma in an agricultural region of Washington State with a high density of dairy AFOs. Children were followed for up to 26 months with repeated measures of respiratory health (N = 2023 interviews; N = 3853 lung function measurements); urine was collected in a subcohort (N = 16) at six-day intervals over three months and analyzed for leukotriene E4 (LTE4), a biomarker of systemic inflammation (N = 138 measurements). We developed an approach to estimate daily exposure to AFO airborne emissions based on distance to AFOs, AFO size, and daily wind speed and direction, and validated the estimates against direct measurements of ammonia, a chemical marker of AFO emissions, measured biweekly at 18 sites across the region for 14 months. Short-term relationships between AFO pollutant exposure and outcomes were assessed using regression models accounting for within-participant correlation and several potential confounders. RESULTS: Estimates of daily AFO air pollution correlated moderately well with outdoor ammonia measurements (N = 842; r = 0.62). Forced expiratory volume in 1 s (FEV1) as percent of predicted was 2.0% (95% CI: 0.5, 3.5) lower with each interquartile increase in previous day exposure, but no associations with asthma symptoms were observed. There was suggestive evidence that LTE4 concentrations were higher following days of elevated exposure to AFO emissions (p = 0.06). CONCLUSIONS: A simple metric of time-varying exposure to AFO emissions was correlated with daily outdoor ammonia levels. Children with asthma may be adversely affected by exposure to AFO emissions.

Association Between Long-term Exposure to Ambient Air Pollution and Change in Quantitatively Assessed Emphysema and Lung Function.

Importance: While air pollutants at historical levels have been associated with cardiovascular and respiratory diseases, it is not known whether exposure to contemporary air pollutant concentrations is associated with progression of emphysema. Objective: To assess the longitudinal association of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon exposure with change in percent emphysema assessed via computed tomographic (CT) imaging and lung function. Design, Setting, and Participants: This cohort study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Air and Lung Studies conducted in 6 metropolitan regions of the United States, which included 6814 adults aged 45 to 84 years recruited between July 2000 and August 2002, and an additional 257 participants recruited from February 2005 to May 2007, with follow-up through November 2018. Exposures: Residence-specific air pollutant concentrations (O3, PM2.5, NOx, and black carbon) were estimated by validated spatiotemporal models incorporating cohort-specific monitoring, determined from 1999 through the end of follow-up. Main Outcomes and Measures: Percent emphysema, defined as the percent of lung pixels less than -950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scans (2010-2018). Spirometry was performed up to 3 times per participant (2004-2018). Results: Among 7071 study participants (mean [range] age at recruitment, 60 [45-84] years; 3330 [47.1%] were men), 5780 were assigned outdoor residential air pollution concentrations in the year of their baseline examination and during the follow-up period and had at least 1 follow-up CT scan, and 2772 had at least 1 follow-up spirometric assessment, over a median of 10 years. Median percent emphysema was 3% at baseline and increased a mean of 0.58 percentage points per 10 years. Mean ambient concentrations of PM2.5 and NOx, but not O3, decreased substantially during follow-up. Ambient concentrations of O3, PM2.5, NOx, and black carbon at study baseline were significantly associated with greater increases in percent emphysema per 10 years (O3: 0.13 per 3 parts per billion [95% CI, 0.03-0.24]; PM2.5: 0.11 per 2 µg/m3 [95% CI, 0.03-0.19]; NOx: 0.06 per 10 parts per billion [95% CI, 0.01-0.12]; black carbon: 0.10 per 0.2 µg/m3 [95% CI, 0.01-0.18]). Ambient O3 and NOx concentrations, but not PM2.5 concentrations, during follow-up were also significantly associated with greater increases in percent emphysema. Ambient O3 concentrations, but not other pollutants, at baseline and during follow-up were significantly associated with a greater decline in forced expiratory volume in 1 second per 10 years (baseline: 13.41 mL per 3 parts per billion [95% CI, 0.7-26.1]; follow-up: 18.15 mL per 3 parts per billion [95% CI, 1.59-34.71]). Conclusions and Relevance: In this cohort study conducted between 2000 and 2018 in 6 US metropolitan regions, long-term exposure to ambient air pollutants was significantly associated with increasing emphysema assessed quantitatively using CT imaging and lung function.

Association of Estimated Long-term Exposure to Air Pollution and Traffic Proximity With a Marker for Coronary Atherosclerosis in a Nationwide Study in China.

Importance: Epidemiologic evidence of the mechanisms of the association between long-term exposure to air pollution and coronary heart disease (CHD) is limited and relies heavily on studies performed in Europe and the United States, where air pollution levels are relatively low. In particular, the association between air pollution and CHD in patients with underlying risks for CHD is understudied. Objective: To determine whether air pollution and proximity to traffic are associated with the coronary artery calcium (CAC) score, a key atherosclerotic marker. Design, Setting, and Participants: In this prospective, population-based cross-sectional study in a large-scale setting in China, 8867 consecutive patients aged 25 to 92 years with suspected CHD were recruited between November 17, 2015, and September 13, 2017. Participants were excluded if they had previous myocardial infarction, stenting, or coronary artery bypass grafting or incomplete risk factors and exposure data. Each participant underwent assessment of CAC and CHD risk factors at baseline. Data were analyzed from December 2017 to November 2018. Exposures: Annual means of fine particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were estimated at the participants' residences using a validated geostatistical prediction model. Exposure to a nearby roadway was also estimated. Main Outcomes and Measures: Computed tomography measurement of CAC score. Results: The mean (SD) age of the 8867 participants was 56.9 (10.4) years; 4378 (53.6%) were men. Annual mean (SD) PM2.5, NO2, and O3 measurements were 70.1 (20.0), 41.4 (14.7), and 93.9 (10.5) µg/m3, respectively. The mean (SD) CAC score was 91.4 (322.2) Agatston units. Exposure to PM2.5 and NO2, adjusting for CHD risk factors and multiple pollutants, were independently associated with increases in CAC scores of 27.2% (95% CI, 10.8% to 46.1%) per 30 µg/m3 PM2.5 and 24.5% (95% CI, 3.6% to 49.7%) per 20 µg/m3 NO2. For PM2.5, odds of both detectable CAC (Agatston score >0; odds ratio, 1.28; 95% CI, 1.13 to 1.45) and severe CAC (Agatston score >400; odds ratio, 1.59; 95% CI, 1.20 to 2.12) were increased. Associations of CAC with PM2.5 and NO2 were greater among male participants (PM2.5: 42.2%; 95% CI, 24.3% to 62.7%; NO2: 45.7%; 95% CI, 25.3% to 69.5%) and elderly participants (PM2.5: 50.1%; 95% CI, 28.8% to 75.0%; NO2: 55.5%; 95% CI, 31.8% to 83.6%) and those with diabetes (PM2.5: 62.2%; 95% CI, 30.9% to 101.0%; NO2: 31.2%; 95% CI, 13.9% to 51.0%). Independent association with CAC score was 9.0% (95% CI, -1.4% to 20.4%) for O3 per 15 µg/m3 and 2.4% (95% CI, -0.6% to 5.4%) for distance near roadway per 50% decrease. Conclusions and Relevance: In this large Chinese study, long-term exposures to PM2.5 and NO2 were independently associated with severity of CAC. This finding may provide support for the pathophysiological role of coronary atherosclerosis through which air pollution exposure may be associated with CHD.

The Association between Long-Term Air Pollution and Urinary Catecholamines: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Autonomic nervous system effects have been hypothesized as a mechanism of air pollutant health effects, though scant prior epidemiologic research has examined the association between air pollutants and catecholamines. OBJECTIVES: To examine the association of long-term air pollutants with three urinary catecholamines: dopamine (DA), epinephrine (EPI), and norepinephrine (NE). As a secondary aim, we also examined the association between short-term (or acute) exposure to fine particulate matter [particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text])] and those catecholamines. METHODS: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) and two of its ancillary studies, the MESA Air Pollution Study and the MESA Stress Study, to provide exposure and outcome data. DA, EPI, and NE from urine samples were collected from 2004 to 2006 from 1,002 participants in the New York, New York, and Los Angeles, California, study sites. Spatiotemporal models incorporated cohort-specific monitoring and estimated annual average pollutant concentrations ([Formula: see text], [Formula: see text], [Formula: see text] and black carbon) at participants' homes the year prior to urine collection. Secondarily, short-term [Formula: see text] was evaluated (day of, day prior, and 2- to 5-d lags prior to urine collection). Several covariates were considered confounders (age, race, sex, site, socioeconomic status, cardiovascular disease risk factors, psychosocial stressors, and medication use) in linear regression models. RESULTS: A [Formula: see text] higher annual [Formula: see text] concentration was associated with 6.3% higher mean EPI level [95% confidence interval (CI): 0.3%, 12.6%]. A 2-[Formula: see text] higher annual ambient [Formula: see text] concentration was associated with 9.1% higher mean EPI (95% CI: 3.2%, 15.3%) and 4.4% higher DA level (95% CI: 1%, 7.9%). [Formula: see text], black carbon, and short-term [Formula: see text] exposures were not significantly associated with any of the catecholamines. CONCLUSIONS: We found an association between EPI and long-term concentrations of [Formula: see text] and [Formula: see text] and an association between DA and long-term ambient [Formula: see text]. These novel findings provide modest support for the hypothesis that air pollutant exposures are related to sympathetic nervous system activation. https://doi.org/10.1289/EHP3286.

Long-Term Exposure to Ambient Ozone and Progression of Subclinical Arterial Disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution.

BACKGROUND: Long-term ozone ([Formula: see text]) exposure is associated with cardiovascular mortality, but little is known about the associations between [Formula: see text] and subclinical arterial disease. OBJECTIVES: We studied the longitudinal association of exposure to [Formula: see text] and progression of key subclinical arterial markers in adults: intima-media thickness of common carotid artery ([Formula: see text]), carotid plaque (CP) burden, and coronary artery calcification (CAC). METHODS: CAC was measured one to four times at baseline and at follow-up exams (1999­2012) by computed tomography (CT) in 6,619 healthy adults, recruited at age 45-84 y without cardiovascular disease (CVD), over a mean of 6.5 y (standard deviation: 3.5 y). [Formula: see text] and CP burden were quantified in 3,392 participants using carotid artery ultrasound imaging acquired over a mean of 9 y (1.7 y). Over 91% and 89% participants had at least one follow-up [Formula: see text] and CAC measurement, respectively. Residence-specific [Formula: see text] concentrations were estimated by a validated spatiotemporal model spanning from 1999 to 2012. This model relied on comprehensive monitoring data and geographical variables to predict individualized long-term average concentrations since baseline. Linear mixed models and logistic regression model were used to evaluate relationships of long-term average exposure to [Formula: see text] with longitudinal change in [Formula: see text], CAC, and CP formation, respectively. RESULTS: Mean progression rates of [Formula: see text] and CAC were [Formula: see text] and [Formula: see text]. CP formation was identified in 55% of the subjects. A [Formula: see text] increase in long-term average [Formula: see text] exposure was associated with a [Formula: see text] [95% confidence interval (CI): 1.4, 9.7] greater increase in [Formula: see text] over 10 y. A [Formula: see text] increase in [Formula: see text] was also associated with new CP formation [odds ratio (OR): 1.2 (95% CI: 1.1, 1.4)] but not CAC progression [[Formula: see text] (95% CI: [Formula: see text], 2)]. Associations were robust in the analysis with extended covariate adjustment, including copollutants, i.e., nitrogen oxides ([Formula: see text]) and particulate matter with diameter [Formula: see text] ([Formula: see text]). CONCLUSION: Over almost a decade of follow-up, outdoor [Formula: see text] concentrations were associated with increased rate of carotid wall thickness progression and risk of new plaque formation, suggesting arterial injury in this cohort. https://doi.org/10.1289/EHP3325.

Ambient PM2.5 and clinically recognized early pregnancy loss: A case-control study with spatiotemporal exposure predictions.

BACKGROUND: Experimental research suggests that fine particulate matter (PM2.5) exposure might affect embryonic development. However, only few population-based studies have investigated the impact of maternal exposure to PM2.5 on the early pregnancy loss. OBJECTIVES: To estimate associations between clinically recognized early pregnancy loss (CREPL) and exposure to ambient PM2.5 at individual residences during peri-conception periods, with the aim to identify susceptible exposure time windows. METHODS: CREPL cases and normal early pregnancy controls (of similar age and gravidity presenting within one week, a total of 364 pairs) were recruited between July 2017 and July 2018 among women residing in Tianjin, China. Average ambient PM2.5 concentrations of ten exposure windows (4 weeks, 2 weeks and 1 week before conception; the first, second, third and fourth single week, the first and second 2-week periods, and the entire 4-week period after conception) at the women's residential addresses were estimated using temporally-adjusted land use regression models. Associations between PM2.5 exposures at specific peri-conception time windows and CREPL were examined using conditional logistic regression models, adjusted for covariates. RESULTS: Based on adjusted models, CREPL was significantly associated with a 10 µg/m3 increase in PM2.5 exposure during the second week after conception (OR = 1.15; 95% CI: 1.04, 1.27; p = 0.005), independent of effects at other time windows. There was also an association of CREPL with PM2.5 during the entire 4-week period after conception (OR = 1.22; 95% CI: 1.02, 1.46; p = 0.027). There was little evidence for associations with exposure during pre-conception exposure windows. CONCLUSIONS: Maternal exposures to ambient PM2.5 during a critical time window following conception are associated with CREPL, with the second week after conception possibly being the exposure window of most vulnerability. Future studies should focus on replicating these findings and on pathogenic mechanisms.

Author Correction: Integrating data from multiple time-location measurement methods for use in exposure assessment: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

In addition to the acknowledgments that were included, the authors wish to add the following: MESA was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute.

Estimating ambient-origin PM2.5 exposure for epidemiology: observations, prediction, and validation using personal sampling in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: We aim to characterize the qualities of estimation approaches for individual exposure to ambient-origin fine particulate matter (PM2.5), for use in epidemiological studies. METHODS: The analysis incorporates personal, home indoor, and home outdoor air monitoring data and spatio-temporal model predictions for 60 participants from the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). We compared measurement-based personal PM2.5 exposure with several measured or predicted estimates of outdoor, indoor, and personal exposures. RESULTS: The mean personal 2-week exposure was 7.6 (standard deviation 3.7) µg/m3. Outdoor model predictions performed far better than outdoor concentrations estimated using a nearest-monitor approach (R = 0.63 versus R = 0.43). Incorporating infiltration indoors of ambient-derived PM2.5 provided better estimates of the measurement-based personal exposures than outdoor concentration predictions (R = 0.81 versus R = 0.63) and better scaling of estimated exposure (mean difference 0.4 versus 5.4 µg/m3 higher than measurements), suggesting there is value to collecting data regarding home infiltration. Incorporating individual-level time-location information into exposure predictions did not increase correlations with measurement-based personal exposures (R = 0.80) in our sample consisting primarily of retired persons. CONCLUSIONS: This analysis demonstrates the importance of incorporating infiltration when estimating individual exposure to ambient air pollution. Spatio-temporal models provide substantial improvement in exposure estimation over a nearest monitor approach.

National PM2.5 and NO2 exposure models for China based on land use regression, satellite measurements, and universal kriging.

Outdoor air pollution is a major killer worldwide and the fourth largest contributor to the burden of disease in China. China is the most populous country in the world and also has the largest number of air pollution deaths per year, yet the spatial resolution of existing national air pollution estimates for China is generally relatively low. We address this knowledge gap by developing and evaluating national empirical models for China incorporating land-use regression (LUR), satellite measurements, and universal kriging (UK). Land use, traffic and meteorological variables were included for model building. We tested the resulting models in several ways, including (1) comparing models developed using forward variable selection vs. partial least squares (PLS) variable reduction, (2) comparing models developed with and without satellite measurements, and with and without UK, and (3) 10-fold cross-validation (CV), Leave-One-Province-Out CV (LOPO-CV), and Leave-One-City-Out CV (LOCO-CV). Satellite data and kriging are complementary in making predictions more accurate: kriging improved the models in well-sampled areas; satellite data substantially improved performance at locations far away from monitors. Variable-selection models performed similarly to PLS models in 10-fold CV, but better in LOPO-CV. Our best models employed forward variable selection and UK, with 10-fold CV R2 of 0.89 (for both 2014 and 2015) for PM2.5 and of 0.73 (year-2014) and 0.78 (year-2015) for NO2. Population-weighted concentrations during 2014-2015 decreased for PM2.5 (58.7 µg/m3 to 52.3 µg/m3) and NO2 (29.6 µg/m3 to 26.8 µg/m3). We produced the first high resolution national LUR models for annual-average concentrations in China. Models were applied on 1 km grid to support future research. In 2015, >80% of the Chinese population lived in areas that exceeded the Chinese national PM2.5 standard, 35 µg/m3. Results here will be publicly available and may be useful for epidemiology, risk assessment, and environmental justice research.