Effect measure modification of the association between short-term exposures to PM2.5 and hospitalizations by longs-term PM2.5 exposure among a cohort of people with Chronic Obstructive Pulmonary Disease (COPD) in North Carolina, 2002-2015.

BACKGROUND: Approximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM2.5 exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD. METHODS: In a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004-2016 (n = 520), and estimated ambient PM2.5 concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0-2 and 0-3 day lags of PM2.5 concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM2.5 concentration at the median value. RESULTS: We observed generally null or low-magnitude negative associations with short-term PM2.5 exposure and respiratory-related (OR per 5 µg/m3 increase in 3-day lag PM2.5: 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM2.5 exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 0.914 (0.804, 1.039)). CONCLUISONS: Differences in associations demonstrate that people in areas with higher annual PM2.5 exposure may be associated with higher risk of hospitalization during short-term increases in PM2.5 exposure.

Long-term exposure to ambient O3 and PM2.5 is associated with reduced cognitive performance in young adults: A retrospective longitudinal repeated measures study in adults aged 18-90 years.

A growing body of evidence indicates that exposure to air pollution affects cognitive performance; however, few studies have assessed this in the context of repeated measures within a large group of individuals or in a population with a large age range. In this study, we evaluated the associations between long-term exposure to fine particulate matter (PM2.5) and ozone (O3) in large cohort of adults aged 18-90 years. The study cohort included 29,091 Lumosity users in the contiguous US who completed 20 repetitions of the Lost in Migration game between 2017 and 2018. Game scores reflect the ability to filter information and avoid distracting information. Long-term air pollution data included ambient PM2.5 and O3 averaged for the 365-day period before each gameplay date. Generalized linear models were used to examine the associations between long-term PM2.5 and O3 and game score percentile. Co-pollutant models were adjusted for meteorology, time trend, age, gender, device, education, local socioeconomic factors, and urbanicity. Results represent the change in attention game score percentile per 1 µg/m3 increase in PM2.5 or 0.01 ppm increase in O3. In the entire cohort, a -0.10 (95% CI: -0.16, -0.04) change in score percentile was associated with PM2.5, while no significant association was observed with O3. Modification of these associations by age was observed for both PM2.5 and O3, with stronger associations observed in younger users. In users aged 18-29, a -0.25 (-0.45, -0.05) change in score percentile was associated with PM2.5, while no associations were observed in other age groups. With O3, there was a -2.92 (-4.63, -1.19) and -2.81 (-4.29, -1.25) change in score percentile for users aged 18-29 and 30-39, respectively. We observed that elevated long-term PM2.5 and O3 were associated with decreased focus scores in young adults, but follow-up research is necessary to further illuminate these associations.

Short-Term Exposure to Wildfire Smoke and PM2.5 and Cognitive Performance in a Brain-Training Game: A Longitudinal Study of U.S. Adults.

BACKGROUND: There is increasing evidence that long-term exposure to fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] may adversely impact cognitive performance. Wildfire smoke is one of the biggest sources of PM2.5 and concentrations are likely to increase under climate change. However, little is known about how short-term exposure impacts cognitive function. OBJECTIVES: We aimed to evaluate the associations between daily and subdaily (hourly) PM2.5 and wildfire smoke exposure and cognitive performance in adults. METHODS: Scores from 20 plays of an attention-oriented brain-training game were obtained for 10,228 adults in the United States (U.S.). We estimated daily and hourly PM2.5 exposure through a data fusion of observations from multiple monitoring networks. Daily smoke exposure in the western U.S. was obtained from satellite-derived estimates of smoke plume density. We used a longitudinal repeated measures design with linear mixed effects models to test for associations between short-term exposure and attention score. Results were also stratified by age, gender, user behavior, and region. RESULTS: Daily and subdaily PM2.5 were negatively associated with attention score. A 10 µg/m3 increase in PM2.5 in the 3 h prior to gameplay was associated with a 21.0 [95% confidence interval (CI): 3.3, 38.7]-point decrease in score. PM2.5 exposure over 20 plays accounted for an estimated average 3.7% (95% CI: 0.7%, 6.7%) reduction in final score. Associations were more pronounced in the wildfire-impacted western U.S. Medium and heavy smoke density were also negatively associated with score. Heavy smoke density the day prior to gameplay was associated with a 117.0 (95% CI: 1.7, 232.3)-point decrease in score relative to no smoke. Although differences between subgroups were not statistically significant, associations were most pronounced for younger (18-29 y), older (≥70y), habitual, and male users. DISCUSSION: Our results indicate that PM2.5 and wildfire smoke were associated with reduced attention in adults within hours and days of exposure, but further research is needed to elucidate these relationships. https://doi.org/10.1289/EHP10498.

Effects of short-term ambient PM2.5 exposure on cardiovascular disease incidence and mortality among U.S. hemodialysis patients: a retrospective cohort study.

BACKGROUND: Ambient PM2.5 is a ubiquitous air pollutant with demonstrated adverse health impacts in population. Hemodialysis patients are a highly vulnerable population and may be particularly susceptible to the effects of PM2.5 exposure. This study examines associations between short-term PM2.5 exposure and cardiovascular disease (CVD) and mortality among patients receiving maintenance in-center hemodialysis. METHODS: Using the United State Renal Data System (USRDS) registry, we enumerated a cohort of all US adult kidney failure patients who initiated in-center hemodialysis between 1/1/2011 and 12/31/2016. Daily ambient PM2.5 exposure estimates were assigned to cohort members based on the ZIP code of the dialysis clinic. CVD incidence and mortality were ascertained through 2016 based on USRDS records. Discrete time hazards regression was used to estimate the association between lagged PM2.5 exposure and CVD incidence, CVD-specific mortality, and all-cause mortality 1 t adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and comorbidities. RESULTS: Among 314,079 hemodialysis patients, a 10 µg/m3 increase in the average lag 0-1 daily PM2.5 exposure was associated with CVD incidence (HR: 1.03 (95% CI: 1.02, 1.04)), CVD mortality (1.05 (95% CI: 1.03, 1.08)), and all-cause mortality (1.04 (95% CI: 1.03, 1.06)). The association was larger for people who initiated dialysis at an older age, while minimal evidence of effect modification was observed across levels of sex, race, or baseline comorbidities. CONCLUSIONS: Short-term ambient PM2.5 exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM2.5-associated CVD events than younger hemodialysis patients.

Short-term PM2.5 exposure and early-readmission risk: a retrospective cohort study in North Carolina heart failure patients.

BACKGROUND: Short-term changes in ambient fine particulate matter (PM2.5) increase the risk for unplanned hospital readmissions. However, this association has not been fully evaluated for high-risk patients or examined to determine if the readmission risk differs based on time since discharge. Here we investigate the relation between ambient PM2.5 and 30-day readmission risk in heart failure (HF) patients using daily time windows and examine how this risk varies with respect to time following discharge. METHODS: We performed a retrospective cohort study of 17,674 patients with a recorded HF diagnosis between 2004 and 2016. The cohort was identified using the EPA CARES electronic health record resource. The association between ambient daily PM2.5 (µg/m3) concentration and 30-day readmissions was evaluated using time-dependent Cox proportional hazard models. PM2.5 associated readmission risk was examined throughout the 30-day readmission period and for early readmissions (1-3 days post-discharge). Models for 30-day readmissions included a parametric continuous function to estimate the daily PM2.5 associated readmission hazard. Fine-resolution ambient PM2.5 data were assigned to patient residential address and hazard ratios are expressed per 10 µg/m3 of PM2.5. Secondary analyses examined potential effect modification based on the time after a HF diagnosis, urbanicity, medication prescription, comorbidities, and type of HF. RESULTS: The hazard of a PM2.5-related readmission within 3 days of discharge was 1.33 (95% CI 1.18-1.51). This PM2.5 readmission hazard was slightly elevated in patients residing in non-urban areas (1.43, 95%CI 1.22-1.67) and for HF patients without a beta-blocker prescription prior to the readmission (1.35; 95% CI 1.19-1.53). CONCLUSION: Our findings add to the evidence indicating substantial air quality-related health risks in individuals with underlying cardiovascular disease. Hospital readmissions are key metrics for patients and providers alike. As a potentially modifiable risk factor, air pollution-related interventions may be enacted that might assist in reducing costly and burdensome unplanned readmissions.

Omega-3 fatty acids attenuate cardiovascular effects of short-term exposure to ambient air pollution.

BACKGROUND: Exposure to air pollution is associated with elevated cardiovascular risk. Evidence shows that omega-3 polyunsaturated fatty acids (omega-3 PUFA) may attenuate the adverse cardiovascular effects of exposure to fine particulate matter (PM2.5). However, it is unclear whether habitual dietary intake of omega-3 PUFA protects against the cardiovascular effects of short-term exposure to low-level ambient air pollution in healthy participants. In the present study, sixty-two adults with low or high dietary omega-3 PUFA intake were enrolled. Blood lipids, markers of vascular inflammation, coagulation and fibrinolysis, and heart rate variability (HRV) and repolarization were repeatedly assessed in 5 sessions separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily PM2.5 and maximum 8-h ozone (O3) concentrations were obtained from nearby air quality monitoring stations. Linear mixed-effects models were used to assess the associations between air pollutant concentrations and cardiovascular responses stratified by the omega-3 intake levels. RESULTS: The average concentrations of ambient PM2.5 and O3 were well below the U.S. National Ambient Air Quality Standards during the study period. Significant associations between exposure to PM2.5 and changes in total cholesterol, von Willebrand factor (vWF), tissue plasminogen activator, D-dimer, and very-low frequency HRV were observed in the low omega-3 group, but not in the high group. Similarly, O3-associated adverse changes in cardiovascular biomarkers (total cholesterol, high-density lipoprotein, serum amyloid A, soluable intracellular adhesion molecule 1, and vWF) were mainly observed in the low omega-3 group. Lag-time-dependent biphasic changes were observed for some biomarkers. CONCLUSIONS: This study demonstrates associations between short-term exposure to PM2.5 and O3, at concentrations below regulatory standard, and subclinical cardiovascular responses, and that dietary omega-3 PUFA consumption may provide protection against such cardiovascular effects in healthy adults.

Association of short-term exposure to ambient PM2.5 with hospital admissions and 30-day readmissions in end-stage renal disease patients: population-based retrospective cohort study.

OBJECTIVES: To examine the effect of short-term exposure to ambient fine particulate matter (PM2.5) on all-cause, cardiovascular and respiratory-related hospital admissions and readmissions among patients receiving outpatient haemodialysis. DESIGN: Retrospective cohort study. SETTING: Inpatient hospitalisation claims identified from the US Renal Data System in 530 US counties. PARTICIPANTS: All patients receiving in-centre haemodialysis between 2008 and 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk of all-cause, cardiovascular and respiratory-related hospital admissions and 30-day all-cause and cause-specific readmission following an all-cause, cardiovascular, and respiratory-related discharges. Readmission risk was evaluated for early (1-7 days postdischarge) and late (8-30 days postdischarge) readmission time periods. Relative risk is expressed per 10 µg/m3 of PM2.5. RESULTS: Same-day ambient PM2.5 was associated with increased hospital admission risk for cardiovascular causes (0.9%, 95% CI 0.2 to 1.7). Greater PM2.5-related associations were observed with 30-day readmission risk. Early-readmission risk was increased by 1.6%-1.8% following all-cause (1.6%, 95% CI 0.6% to 2.6%), cardiovascular (1.8%, 95% CI 0.4% to 3.2%) and respiratory (1.8%, 95% CI 0.4% to 3.2%) discharges; while late-readmission risk increased by 1.2%-1.3% following all-cause and cardiovascular discharges. PM2.5-related associations with readmission risk were greatest for certain cause-specific readmissions ranging 4.0%-6.5% for dysrhythmia and conduction disorder, heart failure, chronic obstructive pulmonary disease, other non-cardiac chest pain or respiratory syndrome and pneumonia. Following all-cause discharges, the cause-specific early-readmission risk was increased by 6.5% (95% CI 3.5% to 9.6%) for pneumonia, 4.8% (95% CI 2.3% to 7.4%) for dysrhythmia and conduction disorder, 3.7% (95% CI 1.4% to 6.0%) for heart failure and 2.7% (95% CI 1.2% to 4.2%) for other non-cardiac chest pain or respiratory syndrome-related causes. CONCLUSIONS: Daily ambient PM2.5 was associated with an increased risk of cardiovascular admissions and 30-day readmissions following cardiopulmonary-related discharges in a vulnerable end-stage renal disease population. In the first week following discharge, greater PM2.5-related risk of rehospitalisation was identified for some diagnoses.

Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults.

BACKGROUND: Fine particulate matter (PM2.5) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies. METHODS: To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM2.5, in the form of concentrated ambient particles (mean: 37.8 µg/m3, SD 6.5), and filtered air (mean: 2.1 µg/m3, SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure. RESULTS: Low-level PM2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM2.5 concentration (37.8 µg/m3) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV1) and FEV1/ forced vital capacity (FEV1/FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure. CONCLUSIONS: This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM2.5 particles at levels near the PM2.5 US NAAQS standard. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov ; Identifier: NCT03232086 . The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.

Annual PM2.5 and cardiovascular mortality rate data: Trends modified by county socioeconomic status in 2,132 US counties.

This article contains data on county-level socioeconomic status for 2132 US counties and each county's average annual cardiovascular mortality rate (CMR) and fine particulate matter (PM2.5) concentration for 21 years (1990-2010). County CMR, PM2.5, and socioeconomic data were obtained from the US National Center for Health Statistics, US Environmental Protection Agency's Community Multiscale Air Quality modeling system, and the US Census, respectively. Annual socioeconomic indices were created using seven county-level measures from the 1990, 2000, and 2010 US Census using factor analysis. Quintiles of this index were used to generate categories of county socioeconomic status. This national data set contains data for annual PM2.5 and CMR changes over a time-period when there was a significant reduction in US air pollutants (following the enactment of the 1970 Clean Air Act). These data are associated with the article "The contribution of improved air quality to reduced cardiovascular mortality: Declines in socioeconomic differences over time" [1]. Data are stored in a comma separated value format and can be downloaded from the USEPA ScienceHub data repository (https://doi.org/10.23719/1506014).

The contribution of improved air quality to reduced cardiovascular mortality: Declines in socioeconomic differences over time.

Major improvements in air quality since 1990, observed through reductions in fine particulate matter (PM2.5), have been associated with reduced cardiovascular mortality rates (CMR). However, it is not well understood whether the health benefit attributed to PM2.5 reductions has been similar across strata of socioeconomic deprivation (SED). Using mixed effect regression models, we estimated the PM2.5-related change in the CMR across 2,132 US counties in five SED strata between 1990 and 2010. The analysis included annual county CMR (deaths/100,000 person-year), annual county PM2.5 (µg/m3), and an index of county SED based on socioeconomic factors from the 1990 US Census. The contribution of PM2.5 reductions to decreased CMR varied by SED strata and over time. Yearly differences resulted from varying rates of PM2.5 reduction and because of the non-linear relationship between CMR and PM2.5 concentration. In early years, PM2.5-related CMR reductions were smallest in the most deprived counties compared to all other counties (range: 0.4-0.6 vs 0.7-1.6 fewer deaths/100,000 person-year), due to slower rates of PM2.5 reduction in these counties. However, in later years, PM2.5-related CMR reductions were highest counties with moderate to high deprivation, compared to counties with the least deprivation (range: 1.0-2.2 vs 0.5-0.9 fewer deaths/100,000 person-year) due to larger CMR reductions per decrease in PM2.5. We identified that CMR reductions related to air quality improvements have become more similar over time between socioeconomic strata.

Predictors of mitochondrial DNA copy number and damage in a mercury-exposed rural Peruvian population near artisanal and small-scale gold mining: An exploratory study.

Mitochondrial DNA (mtDNA) copy number (CN) and damage in circulating white blood cells have been proposed as effect biomarkers for pollutant exposures. Studies have shown that mercury accumulates in mitochondria and affects mitochondrial function and integrity; however, these data are derived largely from experiments in model systems, rather than human population studies that evaluate the potential utility of mitochondrial exposure biomarkers. We measured mtDNA CN and damage in white blood cells (WBCs) from 83 residents of nine communities in the Madre de Dios region of the Peruvian Amazon that vary in proximity to artisanal and small-scale gold mining. Prior research from this region reported high levels of mercury in fish and a significant association between food consumption and human total hair mercury level of residents. We observed that mtDNA CN and damage were both associated with consumption of fruit and vegetables, higher diversity of fruit consumed, residential location, and health characteristics, suggesting common environmental drivers. Surprisingly, we observed negative associations of mtDNA damage with both obesity and age. We did not observe any association between total hair mercury or, in contrast to previous results, age, with either mtDNA damage or CN. The results of this exploratory study highlight the importance of combining epidemiological and laboratory research in studying the effects of stressors on mitochondria, suggesting that future work should incorporate nutritional and social characteristics, and caution should be taken when applying conclusions from epidemiological studies conducted in the developed world to other regions, as results may not be easily translated. Environ. Mol. Mutagen. 60: 197-210, 2019. © 2018 Wiley Periodicals, Inc.

Effects of methyl and inorganic mercury exposure on genome homeostasis and mitochondrial function in Caenorhabditis elegans.

Mercury toxicity mechanisms have the potential to induce DNA damage and disrupt cellular processes, like mitochondrial function. Proper mitochondrial function is important for cellular bioenergetics and immune signaling and function. Reported impacts of mercury on the nuclear genome (nDNA) are conflicting and inconclusive, and mitochondrial DNA (mtDNA) impacts are relatively unknown. In this study, we assessed genotoxic (mtDNA and nDNA), metabolic, and innate immune impacts of inorganic and organic mercury exposure in Caenorhabditis elegans. Genotoxic outcomes measured included DNA damage, DNA damage repair (nucleotide excision repair, NER; base excision repair, BER), and genomic copy number following MeHg and HgCl2 exposure alone and in combination with known DNA damage-inducing agents ultraviolet C radiation (UVC) and hydrogen peroxide (H2O2), which cause bulky DNA lesions and oxidative DNA damage, respectively. Following exposure to both MeHg and HgCl2, low-level DNA damage (∼0.25 lesions/10kb mtDNA and nDNA) was observed. Unexpectedly, a higher MeHg concentration reduced damage in both genomes compared to controls. However, this observation was likely the result of developmental delay. In co-exposure treatments, both mercury compounds increased initial DNA damage (mtDNA and nDNA) in combination with H2O2 exposure, but had no impact in combination with UVC exposure. Mercury exposure both increased and decreased DNA damage removal via BER. DNA repair after H2O2 exposure in mercury-exposed nematodes resulted in damage levels lower than measured in controls. Impacts to NER were not detected. mtDNA copy number was significantly decreased in the MeHg-UVC and MeHg-H2O2 co-exposure treatments. Mercury exposure had metabolic impacts (steady-state ATP levels) that differed between the compounds; HgCl2 exposure decreased these levels, while MeHg slightly increased levels or had no impact. Both mercury species reduced mRNA levels for immune signaling-related genes, but had mild or no effects on survival on pathogenic bacteria. Overall, mercury exposure disrupted mitochondrial endpoints in a mercury-compound dependent fashion.

Antagonistic Growth Effects of Mercury and Selenium in Caenorhabditis elegans Are Chemical-Species-Dependent and Do Not Depend on Internal Hg/Se Ratios.

The relationship between mercury (Hg) and selenium (Se) toxicity is complex, with coexposure reported to reduce, increase, and have no effect on toxicity. Different interactions may be related to chemical compound, but this has not been systematically examined. Our goal was to assess the interactive effects between the two elements on growth in the nematode Caenorhabditis elegans, focusing on inorganic and organic Hg (HgCl2 and MeHgCl) and Se (selenomethionine, sodium selenite, and sodium selenate) compounds. We utilized aqueous Hg/Se dosing molar ratios that were either above, below, or equal to 1 and measured the internal nematode total Hg and Se concentrations for the highest concentrations of each Se compound. Observed interactions were complicated, differed between Se and Hg compounds, and included greater-than-additive, additive, and less-than-additive growth impacts. Biologically significant interactions were only observed when the dosing Se solution concentration was 100-25,000 times greater than the dosing Hg concentration. Mitigation of growth impacts was not predictable on the basis of internal Hg/Se molar ratio; improved growth was observed at some internal Hg/Se molar ratios both above and below 1. These findings suggest that future assessments of the Hg and Se relationship should incorporate chemical compound into the evaluation.