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Epidemiology:
Original Articles

Air Pollution and Incidence of Cardiac Arrhythmia

Peters, Annette1 2; Liu, Emerson3; Verrier, Richard L.3; Schwartz, Joel1; Gold, Diane R.1; Mittleman, Murray3; Baliff, Jeff1; Oh, J. Annie4; Allen, George4; Monahan, Kevin3; Dockery, Douglas W.1

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Author Information

From the 1Environmental Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA; 2Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany; 3Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; and 4Environmental Science and Engineering Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA.

This study was supported by pilot funds from National Institute of Environmental Health Sciences Grant ES-00002 and a grant from the Health Effects Institute. Emerson Liu was supported in part by a grant from the Harvard Medical School.

Submitted November 18, 1998; final version accepted July 27, 1999.

Address correspondence to: Douglas W. Dockery, Department of Environmental Health, Environmental Epidemiology Program, Harvard School of Public Health, 667 Huntington Avenue, Boston, MA 02115.

Editors’ note: See related editorial on page 2 of this issue.

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Abstract

Air pollution episodes have been associated with increased cardiovascular hospital admissions and mortality in time-series studies. We tested the hypothesis that patients with implanted cardioverter defibrillators experience potentially life-threatening arrhythmias after such air pollution episodes. We compared defibrillator discharge interventions among 100 patients with such devices in eastern Massachusetts, according to variations in concentrations of particulate matter, black carbon, and gaseous air pollutants that were measured daily for the years 1995 through 1997. A 26-ppb increase in nitrogen dioxide was associated with increased defibrillator interventions 2 days later (odds ratio = 1.8; 95% confidence interval = 1.1–2.9). Patients with ten or more interventions experienced increased arrhythmias in association with nitrogen dioxide, carbon monoxide, black carbon, and fine particle mass. These results suggest that elevated levels air pollutants are associated with potentially life-threatening arrhythmia leading to therapeutic interventions by an implanted cardioverter defibrillator.

Particulate air pollution episodes have been associated with increased hospital admissions for cardiovascular disease 1–4 and increased cardiovascular mortality 5–11 in epidemiologic studies. Persons with underlying heart disease appear to be at increased risk for the adverse health effects of particulate air pollution. 1–11

Controlled exposure of animals and natural exposures of humans to particulate pollution have shown possible effects of air pollution on the heart. Instillation of 250 micrograms of combustion particles into the lungs of rats with pharmacologically induced pulmonary hypertension produced arrhythmia and doubled their mortality rate. 12 Dogs inhaling concentrated ambient particles showed changes in heart rate variability and electrocardiographic morphology consistent with increased sympathetic nervous system activity. 13,14 Heart rates of elderly subjects in Utah Valley increased in association with elevated concentrations of inhalable particulates (particulate matter less than 10 micrometers in aerodynamic diameter; PM10). 15 In a subset of these subjects, heart rate variability decreased with increasing PM10 concentrations. 15 Increased heart rate and decreased heart rate variability are indicators of altered autonomic control, specifically increased sympathetic stress. Raised sympathetic activity increases the risk of ventricular fibrillation, a severe form of arrhythmia that, without intervention, leads to sudden death. 16

We tested the hypothesis that patients with a history of serious arrhythmia requiring implanted cardioverter defibrillators (ICDs) would experience potentially life-threatening arrhythmia associated with air pollution episodes. Traditionally, ventricular arrhythmia is treated with drug therapies. 17 Implantable cardioverter defibrillators monitor electrocardiographic abnormalities and initiate therapeutic interventions. On detection of ventricular fibrillation or ventricular tachycardia, the ICD device will initiate pacing and/or shock therapy to restore a normal cardiac rhythm. Several recent clinical trials have suggested that ICD devices are more effective at preventing death from heart rhythm abnormalities than medications alone. 18,19 The ICD devices provide objective and accurate records of the occurrence and timing of arrhythmic events. We report the results of a pilot study to assess the feasibility of linking cardiac arrhythmias detected by ICD devices with air pollution exposures.

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Subjects and Methods

Events of Cardiac Arrhythmia and Patient Follow-Up

We abstracted records of cardiac device clinic patients who had a device implanted before September 1997, survived until December 1997, had more than 30 days of follow-up, and lived in eastern Massachusetts (zip code areas 01800–02799). The 2 months after surgical implantation of the device were excluded to avoid effects of implantation and initial adjustment of programmable device settings. One hundred of the 120 patients seen at the clinic met the inclusion criteria.

Patients return to the clinic approximately every 3 to 6 months for follow-up. Records of detected arrhythmias and therapeutic interventions are downloaded from the implanted defibrillators, printed, and reviewed by the nurse managers. We copied the Episode Summary Report listing the date, time, type, and intervention for each detected arrhythmia. We restricted the analysis to defibrillator discharges precipitated by ventricular tachycardias or fibrillation and tabulated the subject- and day-specific arrhythmic interventions.

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Air Pollution Measurements

We measured particulate air pollution concentrations in South Boston starting in January 1995. We measured PM2.5 (mass of particles with an aerodynamic diameter below 2.5 μm) and PM10 (mass of particles with an aerodynamic diameter below 10 μm) concentrations with a tapered element oscillating microbalance (Rupprecht and Patashnick, model 1400A, Albany, NY). Elemental carbon was measured by the attenuation of light (effective center wavelength, 820 nm) of particles collected on a prefired quartz fiber filter (Aethalometer, Magee Scientific Inc, Berkeley, CA). Ozone (O3) concentration was measured using an ultraviolet photometer analyzer (model 49, Thermal Environmental Co, Franklin, MA). Carbon monoxide (CO) concentration was measured by a continuous nondispersive infrared analyzer (Bendix model 8501-5CA, Lewisburg, WV). Relative humidity and temperature were measured continuously using an in-line probe (Vaisala model MP113Y, Woburn, MA). Sulfur dioxide (SO2) and nitrogen dioxide (NO2) were measured hourly in Chelsea (approximately 7.5 kilometers north of South Boston) by the Massachusetts Department of Environmental Protection.

We calculated 24-hour means (midnight to midnight) for days with 16 or more valid hourly measurements. We calculated 5-day running means of the air pollutants when at least three 24-hour means were available.

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Statistical Analyses

Defibrillator discharge interventions were analyzed by logistic regression models using fixed effect models with individual intercepts for each patient. We used multivariate analysis to evaluate confounding by trend, season, meteorologic conditions and day of the week. The final model included a linear trend; sine and cosine terms with periods of one, one-half, one-third, and one-quarter year; quadratic functions of minimum temperature and humidity; and indicators for day of the week. We selected this model without considering air pollutants on the basis of a comparison of the log likelihood of nested models. We conducted sensitivity analyses for the subgroup of patients who had more than ten events using robust logistic regression in a generalized linear model. 4 We also assessed the potential nonlinear dependence of defibrillator discharges on season or weather using nonparametric smooth functions.

We considered mean air pollution concentrations on the same day and lags of 1, 2, and 3 days. We evaluated possible cumulative effects of the air pollutants on the basis of the 5-day mean concentration. The linearity of the air pollution defibrillator discharge associations were assessed through categorical analysis, in which residuals of a linear regression analyses of the pollutant concentrations were divided into quintiles after adjusting for season, trend, meteorology, and day of the week as in the logistic regression model.

We present odds ratios (ORs) and 95% confidence intervals (CIs) based on an increase in each air pollution concentration from the 5th to the 95th percentile. The magnitude of estimates for different pollutants is therefore based on comparable increments of exposure for the study period.

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Results

The study population was predominantly male (79%), with a mean age of 62.2 years. During 63,628 person-days of follow-up over 3 years in 100 patients, we observed 223 defibrillator discharges (Table 1). No discharges were recorded in 67 persons followed for a mean of 601 days (40,248 person-days). Ten or more events per follow-up occurred in 6 patients (18% of 33 patients with any discharge), accounting for a total of 136 events (61% of all interventions). Patients with 10 or more events were slightly younger on average and predominantly male (Table 1). Separate analyses were conducted for this group.

Table 1
Table 1
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Particle concentrations were modest, with mean concentrations of 19.3 μg/m 3 for PM10 and 12.7 μg/m 3 for PM2.5 at the South Boston site (Table 2). Black carbon contributed on average 11% of PM2.5. The concentrations of the gaseous pollutants—CO, O3, and NO2—were moderate, whereas sulfur dioxide concentrations were low. The concentrations of PM2.5 and PM10 were highly correlated (Table 3). Black carbon was strongly correlated with PM2.5, PM10, CO, and NO2. CO and NO2, however, were only moderately correlated with PM10 and PM2.5. In contrast, both SO2 and O3 were weakly correlated with the other pollutants, suggesting different seasonal patterns and sources. The highest PM2.5, PM10, O3, and SO2 concentrations were recorded during the summer, whereas black carbon, CO, and NO2 had elevated peak concentrations throughout the year (Figure 1).

Table 2
Table 2
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Table 3
Table 3
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Figure 1
Figure 1
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The rate of defibrillator discharge per person-day decreased over time in both the whole sample and a subgroup of persons with repeated events. Season was a strong predictor of the defibrillator discharges, with the highest frequency during the summer months and a second peak during the second half of the winter. In contrast, daily minimum temperature and daily relative humidity were only weak predictors of defibrillator discharges. No clear day-of-the-week pattern was observed. We found no consistent evidence of increased defibrillator discharges associated with the concentration of the air pollutants on the same day for the sample of patients with any discharges (Table 4). A positive association was observed between the defibrillator discharges and the NO2 concentrations on the previous day as well as with a 5-day mean. All other pollutants showed weaker and less consistent effects than NO2.

Table 4
Table 4
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Among the six patients who experienced ten or more discharges, defibrillator discharges were associated with exposures to PM10 as well as PM2.5 lagged by 2 days (Table 4). Consistent positive association was observed with black carbon and CO. The strongest associations were observed for NO2 (Table 4). Elevated concentrations of NO2 1 and 2 days before and the mean over the previous 5 days were associated with defibrillator discharges. No association was observed between the defibrillator discharges and SO2. The odds of defibrillator discharge increased monotonically with quintile of PM2.5 and NO2 lagged by 2 days (Figure 2).Including both pollutants into one model reduced the effect estimate of PM2.5 effectively to 0, whereas the effect estimate of NO2 was unchanged. Black carbon lagged by 2 days showed a linear increase in the odds ratio below 1.5 μg/m 3 with a potential plateau above 1.5 μg/m 3. There was weaker evidence for a linear association between the 5-day means of CO or black carbon and the defibrillator discharges. Discharge was as strongly associated with NO2 2 days before as it was with the 5-day mean. Two-pollutant models including 5-day means of NO2 and CO or black carbon found a consistent effect estimate for NO2 but not for CO or black carbon.

Figure 2
Figure 2
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Additional analyses, including nonparametric functions for season (9.9 degrees of freedom) and meteorologic variables (2.3 degrees of freedom for minimum temperature and 2.7 degrees of freedom for relative humidity) improved the model fit. The effect estimates of NO2 were reduced (OR = 2.03; 95% CI = 0.66–6.20) for 26 ppb NO2 (lagged 2 days) whereas the effect estimate for PM2.5 increased (OR = 1.87; 95% CI = 0.77–4.55) for 22 μg/m 3 PM2.5 (lagged 2 days).

Analyses of only those days with PM2.5 less than 30 μg/m 3 gave an effect estimate of 1.90 (95% CI = 0.99–3.68) for 22 μg/m 3 PM2.5 (lagged 2 days).

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Discussion

We observed increased risk of a cardiac arrhythmia in association with elevated concentrations of air pollutants in patients with ICDs. The odds of a therapeutic intervention to treat ventricular fibrillation or tachycardia in patients with at least 10 discharges nearly tripled in association with an increase of 26 ppb NO2 and increased 60% in association with an increase in PM2.5 concentrations of 22 μg/m 3. These associations were monotonic and close to linear. Defibrillator discharges did not follow exposures immediately but required an induction time of 1 or 2 days.

The subgroup of patients with repeated potentially life-threatening arrhythmias was most susceptible to exposure to ambient air pollution. Repeated discharges indicate that these patients belong to a subgroup of patients who experience acute arrhythmia in response to triggers. 20 This subgroup might be especially sensitive to air pollution. This group also provides most of the power for the analyses, because other potent triggers, such as transient ischemia, 20 add noise to the association of interest. Therefore, we would be more likely to detect an air pollution association in patients with repeated events than in patients who only experienced one or two events during the 3-year follow-up.

There was an induction period of 1–2 days between the exposure to air pollution and the observed defibrillator discharges. This is consistent with a hypothesized mechanism in which the deposition of particles in the lung elicit inflammatory responses resulting in a systemic signal. 21,22

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Possible Pathophysiologic Mechanisms

Most sudden cardiac deaths are caused by acute fatal arrhythmias—ventricular tachycardia/fibrillation. 17 Clinical trials that have evaluated the implantation of cardioverter defibrillator devices have shown that persons with known malignant arrhythmias benefit from the ICD devices compared with traditional drug therapy. 18,19

Time series analyses have shown an association between mortality and hospital admissions for coronary disease with episodes of elevated levels of air pollution. 1–4,23 Stratification by diagnosis showed specific associations between air pollution and ischemic heart diseases 2,3,5 and congestive heart diseases. 2,3,23 Both ischemic and congestive heart disease are chronic diseases that are risk factors for acute tachycardia and ventricular fibrillation. 20 Arrhythmias might have been the acute event leading to the hospitalization. Admissions for dysrhythmia were positively associated with particulate air pollution concentrations, but the CIs were broad. 2,3 In London, Fairley 5 found an association between hospital admissions for dysrhythmia and NO2 exposure. Hospital admission for arrhythmia increased 50% during a 1985 air pollution episode in Germany compared with a nonepisode period. 24

Increased plasma viscosity also was observed during this 1985 European air pollution episode, 25 which suggests a systemic response in association with exposure to air pollution. Increased plasma viscosity might lead to transient ischemic events in persons with severe coronary artery disease. Ischemic events are responsible for approximately 80% of sudden deaths. 20 Direct activation of the autonomic nervous system and the altered excitability of the heart cells caused by air pollution exposures may lead to fibrillation. Therefore, an altered sympathetic or diminished parasympathetic tone of the heart in response to particle exposures might result in life-threatening tachycardias, as observed in this study.

Whereas concentrations of individual air pollutants are correlated day to day, differences by season suggest different sources of particulate air pollution. The highest concentrations of PM2.5 were recorded in Boston during the summer months. Measurements throughout the east coast region indicate that these summer particulate air pollution episodes are caused by regional transport. 26 In contrast, NO2 was higher during the winter. Black carbon and CO were highly variable throughout the year. In the colder months local emissions are the dominant source of particulate air pollution. The primary hypothesis of the study was that PM2.5 would be associated with the incidence of defibrillator discharges. We found support for this hypothesis; however, a stronger association was found for NO2 and black carbon than for PM2.5. NO2 and black carbon might be markers for local traffic-related pollution, whereas PM2.5 is influenced both by local and by regional transported particulate matter. 27

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Strengths and Limitations

One major advantage of these data is the complete, passive monitoring of cardiac arrhythmias. On the other hand, discharges might be initiated in cases of normal rather than life-threatening events, because screening of cardiac arrhythmias is optimized to avoid underdetection of ventricular tachyarrhythmias. 28 For this pilot study, clinical review of detected arrhythmias was not included in the abstraction of the data. If misclassification of defibrillator discharges is independent of air pollution exposure, we would expect a loss of power (that is, wider CIs) but not any bias in the estimated association.

ICD discharges were rare events in this follow-up of 100 patients. The small number of subjects with multiple defibrillator discharges is a limitation. In particular, the power to adequately adjust for confounding might be limited in multivariate analyses. These patients clearly represent a highly selected cohort, and these results would not be generalizable to the entire population. On the other hand, this cohort is of special interest, because their previous history of cardiovascular disease might make them particularly sensitive to the effects of air pollution episodes. Indeed, effects were seen most strongly among the six subjects with repeated arrhythmias. Data on baseline clinical characteristics and prescribed antiarrhythmic medications were not available in this pilot study to determine the characteristics associated with increased (or decreased) responsiveness.

Misclassification of air pollution exposure is another potential source of bias in this study. Whereas patients were living in eastern Massachusetts, air pollution exposure was estimated based on a single monitor in Boston. The day-to-day correlations of fine-particle concentrations between sites is high across large regions in the eastern United States. Suh et al.27 reported correlations of more than 0.90 between fine-particle monitoring stations across the Washington, DC, metropolitan area and a correlation of 0.76 between monitors in Washington and Philadelphia. For the gaseous pollutants, there might be only weak correlation between monitoring sites within a region. 27 We would expect any exposure misclassification to be nondifferential with respect to ICD discharges and to bias the estimates toward the null.

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Acknowledgments

We thank Mark Josephson, Nanette Hallette, and Marianne Daoust of the Beth Israel Deaconess Medical Center Device Clinic.

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References

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Symons, JM; Wang, L; Guallar, E; Howell, E; Dominici, F; Schwab, M; Ange, BA; Samet, J; Ondov, J; Harrison, D; Geyh, A
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European Heart Journal
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Toxicology and Applied Pharmacology
Pulmonary and systemic effects of short-term inhalation exposure to ultrafine carbon black particles
Gilmour, PS; Ziesenis, A; Morrison, ER; Vickers, MA; Drost, EM; Ford, I; Karg, E; Mossa, C; Schroeppel, A; Ferron, GA; Heyder, J; Greaves, M; MacNee, W; Donaldson, K
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Inhalation Toxicology
Relative contributions of PM2.5 chemical constituents to acute arterial vasoconstriction in humans
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International Journal of Modern Physics B
Epr and magnetic susceptibility studies of copper ions in the 2B(2)O(3)center dot Ag2O glass matrix
Lucacel, RC; Ardelean, I
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Journal of Aerosol Medicine-Deposition Clearance and Effects in the Lung
Cardiovascular effects of fine and ultrafine particles
Schulz, H; Harder, V; Ibald-Mulli, A; Khandoga, A; Koenig, W; Krombach, F; Radykewicz, R; Stampfl, A; Thorand, B; Peters, A
Journal of Aerosol Medicine-Deposition Clearance and Effects in the Lung, 18(1): 1-22.

Inhalation Toxicology
Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: V. CAPs exacerbate aortic plaque development in hyperlipidemic mice
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Journal of Toxicology and Environmental Health-Part A-Current Issues
Testing the harvesting hypothesis by time-domain regression analysis. 1: Baseline analysis
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Aerosol Science and Technology
Development of a high volume cascade impactor for toxicological and chemical characterization studies
Demokritou, P; Kavouras, IG; Ferguson, ST; Koutrakis, P
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Circulation
Air pollution - An insidious and pervasive component of cardiac risk
Verrier, RL; Mittleman, MA; Stone, PH
Circulation, 106(8): 890-892.
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Inhalation Toxicology
Cardiovascular effects associated with air pollution: Potential mechanisms and methods of testing
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Clinics in Chest Medicine
Update on the health effects of outdoor air pollution
Vedal, S
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European Respiratory Journal
Determinants of prognosis of COPD in the elderly: mucus hypersecretion, infections, cardiovascular comorbidity
Pistelli, R; Lange, P; Miller, DL
European Respiratory Journal, 21(): 10S-14S.
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European Respiratory Journal
Particulate air pollution and hospital admissions for card iorespiratory diseases: are the elderly at greater risk?
Anderson, HR; Atkinson, RW; Bremner, SA; Marston, L
European Respiratory Journal, 21(): 39S-46S.
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Environmental Health Perspectives
Airborne particles are a risk factor for hospital admissions for heart and lung disease
Zanobetti, A; Schwartz, J; Dockery, DW
Environmental Health Perspectives, 108(): 1071-1077.

Atmospheric Environment
A comparison of two direct-reading aerosol monitors with the federal reference method for PM2.5 in indoor air
Yanosky, JD; Williams, PL; MacIntosh, DL
Atmospheric Environment, 36(1): 107-113.

American Journal of Respiratory and Critical Care Medicine
Rapid translocation of nanoparticles from the lung to the bloodstream?
Bennett, WD
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Pharmacology & Therapeutics
The pharmacology of particulate matter air pollution-induced cardiovascular dysfunction
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Journal of Toxicology and Environmental Health-Part A-Current Issues
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Environmental Health
A community study of the effect of particulate matter on blood measures of inflammation and thrombosis in an elderly population
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Environmental Health, 6(): -.
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Journal of Exposure Science and Environmental Epidemiology
Effect of particulate matter air pollution on hospital admissions and medical visits for lung and heart disease in two southeast Idaho cities
Ulirsch, GV; Ball, L; Kaye, W; Shy, C; Lee, CV; Crawford-Brown, D; Symons, M; Holloway, T
Journal of Exposure Science and Environmental Epidemiology, 17(5): 478-487.
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American Journal of Epidemiology
Vascular Function, Inflammation, and Variations in Cardiac Autonomic Responses to Particulate Matter Among Welders
Fang, SC; Cavallari, JM; Eisen, EA; Chen, JC; Mittleman, MA; Christiani, DC
American Journal of Epidemiology, 169(7): 848-856.
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Critical Reviews in Toxicology
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Environment and Planning A
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Journal of Toxicology and Environmental Health-Part A-Current Issues
Relationship between ambient air pollution and hospital admissions for cardiovascular diseases in Kaohsiung, Taiwan
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Modern Physics Letters B
Structural investigations of CuO-B2O3-Bi2O3 glasses by means of EPR and FT-IR spectroscopies
Ardelean, I; Cora, S; Ciceo-Lucacel, R
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Thorax
Association between short term exposure to fine particulate matter and heart rate variability in older subjects with and without heart disease
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American Journal of Respiratory and Critical Care Medicine
Glutathione-S-transferase M1, obesity, statins, and autonomic effects of particles - Gene-by-drug-by-environment interaction
Schwartz, J; Park, SK; O'Neill, MS; Vokonas, PS; Sparrow, D; Weiss, S; Kelsey, K
American Journal of Respiratory and Critical Care Medicine, 172(): 1529-1533.
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Inhalation Toxicology
Effects of ambient particles and carbon monoxide on supraventricular arrhythmias in a rat model of myocardial infarction
Wellenius, GA; Coull, BA; Batalha, JRF; Diaz, EA; Lawrence, J; Godleski, JJ
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Journal of Physiology and Pharmacology
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American Journal of Respiratory and Critical Care Medicine
Diffuse alveolar damage after exposure to an oil fly ash
Ghio, AJ; Gilbey, JG; Roggli, VL; Richards, JH; McGee, JK; Carson, JL; Devlin, RB; Cascio, WE
American Journal of Respiratory and Critical Care Medicine, 164(8): 1514-1518.

American Journal of Cardiology
Relation of Heart Failure Hospitalization to Exposure to Fine Particulate Air Pollution
Pope, CA; Renlund, DG; Kfoury, AG; May, HT; Horne, BD
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Brazilian Journal of Medical and Biological Research
Tracheal instillation of urban PM2.5 suspension promotes acute cardiac polarization changes in rats
Maatz, LF; Wood, GJA; Rivero, DHRF; Saldiva, PHN
Brazilian Journal of Medical and Biological Research, 42(2): 207-213.

Journal of Environmental Biology
Fine particles (PM2.5) in ambient air of Lucknow city due to fireworks on Diwali festival
Barman, SC; Singh, R; Negi, MPS; Bhargava, SK
Journal of Environmental Biology, 30(5): 625-632.

Journal of Toxicological Sciences
The effects of organic extract of diesel exhaust particles on ischemia/reperfusion-related arrhythmia and on pulmonary inflammation
Yokota, S; Ohara, N; Kobayashi, T
Journal of Toxicological Sciences, 33(1): 1-10.

Environmental Research
Effects of particulate air pollution on systolic blood pressure: A population-based approach
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Translational Research
Effect of ambient particulate matter exposure on hemostasis
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Critical Reviews in Toxicology
Issues in the design and interpretation of chronic toxicity and carcinogenicity studies in rodents: Approaches to dose selection
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Toxicology
Examination of mRNA expression in rat hearts and lungs for analysis of effects of exposure to concentrated ambient particles on cardiovascular function
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Journal of Toxicology and Environmental Health-Part A-Current Issues
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Yang, CY
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Progress in Biochemistry and Biophysics
Recent progress on the pro and cons of biological effects of nanomaterials
Zhou, GQ; Chen, CY; Li, YF; Li, W; Gao, YX; Zhao, YL
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Genetics
Genetic analysis of a synaptic calcium channel in drosophila: Intragenic modifiers of a temperature-sensitive paralytic mutant of cacophony
Brooks, IM; Felling, R; Kawasaki, F; Ordway, RW
Genetics, 164(1): 163-171.

European Heart Journal Supplements
What makes patients vulnerable to ventricular tachycardia or fibrillation?
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American Journal of Industrial Medicine
Ischemic heart disease mortality among heavy equipment operators
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Inhalation Toxicology
Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution
Gong, H; Linn, WS; Terrell, SL; Anderson, KR; Clark, KW; Sioutas, C; Cascio, WE; Alexis, N; Devlin, RB
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Environmental Health Perspectives
Global gene expression profiling in whole-blood samples from individuals exposed to metal fumes
Wang, ZX; Neuburg, D; Li, C; Su, L; Kim, JY; Chen, JC; Christiani, DC
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Environmental Research
PM2.5 induces acute electrocardiographic alterations in healthy rats
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Circulation
Increased particulate air pollution and the triggering of myocardial infarction
Peters, A; Dockery, DW; Muller, JE; Mittleman, MA
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Science of the Total Environment
PM2.5 measurements in ambient aerosol: comparison between Harvard impactor (HI) and the tapered element oscillating microbalance (TEOM) system
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Science of the Total Environment, 278(): 191-197.

Journal of the Air & Waste Management Association
Design of a cost-effective weighing facility for PM2.5 quality assurance
Carlton, AG; Teitz, A
Journal of the Air & Waste Management Association, 52(5): 506-510.

Inhalation Toxicology
Effects of subchronic exposures to concentrated ambient particles in mice: VI. Gene expression in heart and lung tissue
Gunnison, A; Chen, LC
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Environmental Health Perspectives
Association of air pollution with increased incidence of ventricular tachyarrhythmias recorded by implanted cardioverter defibrillators
Dockery, DW; Luttmann-Gibson, H; Rich, DQ; Link, MS; Mittleman, MA; Gold, DR; Koutrakis, P; Schwartz, JD; Verrier, RL
Environmental Health Perspectives, 113(6): 670-674.

Environmental Health Perspectives
Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans
Frampton, MW; Stewart, JC; Oberdorster, G; Morrow, PE; Chalupa, D; Pietropaoli, AP; Frasier, LM; Speers, DM; Cox, C; Huang, LS; Utell, MJ
Environmental Health Perspectives, 114(1): 51-58.
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Respiratory Research
Does respiratory health contribute to the effects of long-term air pollution exposure on cardiovascular mortality?
Schikowski, T; Sugiri, D; Ranft, U; Gehring, U; Heinrich, J; Wichmann, HE; Kramer, U
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American Journal of Epidemiology
Environmental Exposures and Invasive Meningococcal Disease: An Evaluation of Effects on Varying Time Scales
Kinlin, LM; Spain, CV; Ng, V; Johnson, CC; White, ANJ; Fisman, DN
American Journal of Epidemiology, 169(5): 588-595.
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Environmental Health Perspectives
Effects of particulate air pollution on blood pressure and heart rate in subjects with cardiovascular disease: A multicenter approach
Ibald-Mulli, A; Timonen, KL; Peters, A; Heinrich, J; Wolke, G; Lanki, T; Buzorius, G; Kreyling, WG; de Hartog, J; Hoek, G; ten Brink, HM; Pekkanen, J
Environmental Health Perspectives, 112(3): 369-377.
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Circulation
Ultrafine particles exert prothrombotic but not inflammatory effects on the hepatic microcirculation in healthy mice in vivo
Khandoga, A; Stampfl, A; Takenaka, S; Schulz, H; Radykewicz, R; Kreyling, W; Krombach, F
Circulation, 109(): 1320-1325.
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American Journal of Respiratory and Critical Care Medicine
Particulate matter exposure in cars is associated with cardiovascular effects in healthy young men
Riediker, M; Cascio, WE; Griggs, TR; Herbst, MC; Bromberg, PA; Neas, L; Williams, RW; Devlin, RB
American Journal of Respiratory and Critical Care Medicine, 169(8): 934-940.
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Inhalation Toxicology
Air pollution and cardiac arrhythmias in patients with implantable cardioverter defibrillators
Vedal, S; Rich, K; Brauer, M; White, R; Petkau, J
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Inhalation Toxicology
A case-crossover analysis of particulate air pollution and cardiac arrhythmia in patients with implantable cardioverter defibrillators
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Toxicological Sciences
Cardiac effects of carbon monoxide and ambient particles in a rat model of myocardial infarction
Wellenius, GA; Batalha, JRF; Diaz, EA; Lawrence, J; Coull, BA; Katz, T; Verrier, RL; Godleski, JJ
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Environmental Health
Air pollution and emergency department visits for cardiac and respiratory conditions: a multi-city time-series analysis
Stieb, DM; Szyszkowicz, M; Rowe, BH; Leech, JA
Environmental Health, 8(): -.
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Hybridoma and Hybridomics
Generation of a monoclonal antibody that blocks epithelial binding of unopsonized particles
Tao, F; Palecanda, A; Kumar, S; Kobzik, L
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Journal of Occupational Health
Effects of concentrated ambient particles on heart rate variability in spontaneously hypertensive rats
Chang, CC; Hwang, JS; Chan, CC; Wang, PY; Hu, TH; Cheng, TJ
Journal of Occupational Health, 47(6): 471-480.

Inhalation Toxicology
Air pollution and hospital admissions for congestive heart failure in a tropical city: Kaohsiung, Taiwan
Lee, IM; Tsai, SS; Ho, CK; Chiu, HF; Yang, C
Inhalation Toxicology, 19(): 899-904.
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Journal of Toxicology and Environmental Health-Part A-Current Issues
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Journal of the Air & Waste Management Association
Estimating the resuspension rate and residence time of indoor particles
Qian, J; Ferro, AR; Fowler, KR
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International Journal of Biometeorology
Weather-induced ischemia and arrhythmia in patients undergoing cardiac rehabilitation: another difference between men and women
Schneider, A; Schuh, A; Maetzel, FK; Ruckerl, R; Breitner, S; Peters, A
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Atmospheric Environment
Source analysis of high particulate matter days in Hong Kong
Huang, XF; Yu, JZ; Yuan, ZB; Lau, AKH; Louie, PKK
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Environmental Health Perspectives
A pilot investigation of the relative toxicity of indoor and outdoor fine particles: In vitro effects of endotoxin and other particulate properties
Long, CM; Suh, HH; Kobzik, L; Catalano, PJ; Ning, YY; Koutrakis, P
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Lancet
Air pollution and health
Brunekreef, B; Holgate, ST
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Inhalation Toxicology
On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats
Elder, A; Gelein, R; Finkelstein, J; Phipps, R; Frampton, M; Utell, M; Kittelson, DB; Watts, WF; Hopke, P; Jeong, CH; Kim, E; Liu, W; Zhao, WX; Zhuo, LM; Vincent, R; Kumarathasan, P; Oberdorster, G
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Qjm-An International Journal of Medicine
Cardiovascular implications of exposure to traffic air pollution during exercise
Sharman, JE; Cockcroft, JR; Coombes, JS
Qjm-An International Journal of Medicine, 97(): 637-643.
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Environmental Health Perspectives
Population health and the environment
Clark, NM
Environmental Health Perspectives, (): 138-147.
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European Heart Journal
Outdoor air pollution, mortality, and hospital admissions from coronary heart disease in Sheffield, UK: a small-area level ecological study
Maheswaran, R; Haining, RP; Brindley, P; Law, J; Pearson, T; Fryers, PR; Wise, S; Campbell, MJ
European Heart Journal, 26(): 2543-2549.
10.1093/eurheartj/ehi457
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Environnement Risques & Sante
Toxicity of dust released by the Annaba steel complex on some hematologic parameters of the Europeus rabbit
Tadjine, A; Djebar, H; Courtois, A
Environnement Risques & Sante, 7(3): 209-215.
10.1684/ers.2008.0150
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Journal of Cardiovascular Pharmacology and Therapeutics
Direct and acute cardiotoxic effects of ultrafine air pollutants in spontaneously hypertensive rats and Wistar-Kyoto rats
Hwang, H; Kloner, RA; Kleinman, MT; Simkhovich, BZ
Journal of Cardiovascular Pharmacology and Therapeutics, 13(3): 189-198.
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Inhalation Toxicology
Air pollution and emergency room visits for cardiac arrhythmia in a subtropical city: Taipei, Taiwan
Tsai, SS; Chiu, HF; Wu, TN; Yang, CY
Inhalation Toxicology, 21(): 1113-1118.
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International Journal of Environmental Research and Public Health
A Systematic Review of Occupational Exposure to Particulate Matter and Cardiovascular Disease
Fang, SC; Cassidy, A; Christiani, DC
International Journal of Environmental Research and Public Health, 7(4): 1773-1806.
10.3390/ijerph7041773
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Environmental Health Perspectives
Molecular and cellular mechanisms of cardiotoxicity
Kang, YJ
Environmental Health Perspectives, 109(): 27-34.

Thorax
Hypothesis: Ill health associated with low concentrations of nitrogen dioxide - an effect of ultrafine particles?
Seaton, A; Dennekamp, M
Thorax, 58(): 1012-1015.

Environmental Health Perspectives
Metal particulate matter components affect gene expression and beat frequency of neonatal rat ventricular myocytes
Graff, DW; Cascio, WE; Brackhan, JA; Devlin, RB
Environmental Health Perspectives, 112(7): 792-798.
10.1289/txg.6865
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Journal of Toxicology and Environmental Health-Part A-Current Issues
A new longitudinal design for identifying subgroups of the population who are susceptible to the short-term effects of ambient air pollution
Goldberg, MS; Burnett, RT
Journal of Toxicology and Environmental Health-Part A-Current Issues, 68(): 1111-1125.
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Inhalation Toxicology
Acute functional enhancement of circulatory neutrophils after intratracheal instillation with diesel exhaust particles in rats
Yokota, S; Seki, T; Furuya, M; Ohara, N
Inhalation Toxicology, 17(): 671-679.
10.1080/08958370500189628
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Inhalation Toxicology
Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats
Elder, A; Couderc, JP; Gelein, R; Eberly, S; Cox, C; Xia, XJ; Zareba, W; Hopke, P; Watts, W; Kittelson, D; Frampton, M; Utell, M; Oberdorster, G
Inhalation Toxicology, 19(1): 1-12.
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Environmental Health Perspectives
Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects
Shah, AP; Pietropaoli, AA; Frasier, LM; Speers, DM; Chalupa, DC; Delehanty, JM; Huang, LS; Utell, MJ; Frampton, MW
Environmental Health Perspectives, 116(3): 375-380.
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Journal of the Air & Waste Management Association
Hourly personal exposures to fine particles and gaseous pollutants - Results from Baltimore, Maryland
Chang, LT; Koutrakis, P; Catalano, PJ; Suh, HH
Journal of the Air & Waste Management Association, 50(7): 1223-1235.

Environmental Health Perspectives
Are there sensitive subgroups for the effects of airborne particles?
Zanobetti, A; Schwartz, J; Gold, D
Environmental Health Perspectives, 108(9): 841-845.

Clinical and Experimental Allergy
NO2: the gas, that won't go away
Brunekreef, B
Clinical and Experimental Allergy, 31(8): 1170-1172.

Inhalation Toxicology
Pulmonary effects of ultrafine and fine ammonium salts aerosols in healthy and monocrotaline-treated rats following short-term exposure
Cassee, FR; Arts, JHE; Fokkens, PHB; Spoor, SM; Boere, AJF; van Bree, L; Dormans, JAMA
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International Journal of Biometeorology
The lag-effect pattern in the relationship of particulate air pollution to daily mortality in Seoul, Korea
Kim, H; Kim, Y; Hong, YC
International Journal of Biometeorology, 48(1): 25-30.
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Journal of Toxicology and Environmental Health-Part A-Current Issues
Ambient Particulate Air Pollution and EctopyThe Environmental Epidemiology of Arrhythmogenesis in Women's Health Initiative Study, 1999-2004
Liao, DP; Whitsel, E; Duan, YK; Lin, HM; Quibrera, PM; Smith, R; Peuquet, D; Prineas, R; Zhang, ZM; Anderson, G
Journal of Toxicology and Environmental Health-Part A-Current Issues, 72(1): 30-38.
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Toxicological Sciences
Continuous Electrocardiogram Reveals Differences in the Short-Term Cardiotoxic Response of Wistar-Kyoto and Spontaneously Hypertensive Rats to Doxorubicin
Hazari, MS; Haykal-Coates, N; Winsett, DW; Costa, DL; Farraj, AK
Toxicological Sciences, 110(1): 224-234.
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Inhalation Toxicology
Effect of pre- and postnatal exposure to urban air pollution on myocardial lipid peroxidation levels in adult mice
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British Medical Bulletin
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American Journal of Medical Genetics Part A
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Current Hypertension Reports
You are what you breathe: Evidence linking air pollution and blood pressure
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Environmental Health Perspectives
Can we identify sources of fine particles responsible for exercise-induced ischemia on days with elevated air pollution? The ULTRA study
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Journal of the American Board of Family Medicine
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Environmental Health Perspectives
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American Journal of Respiratory and Critical Care Medicine
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Toxicological Sciences
Electrocardiographic changes during exposure to residual oil fly ash (ROFA) particles in a rat model of myocardial infarction
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Environmental Health Perspectives
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Heart
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Annals of Neurology
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Journal of Allergy and Clinical Immunology
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Fresenius Environmental Bulletin
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Seminars in Thrombosis and Hemostasis
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Aerosol Science and Technology
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Biochimica Et Biophysica Acta-General Subjects
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Environmental Health Perspectives
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Environment International
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Environmental Health Perspectives
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Ambio
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Lancet
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Current Hypertension Reports
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Inhalation Toxicology
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Toxicology and Applied Pharmacology
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Circulation
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Environmental Science & Technology
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Archives of Toxicology
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Occupational and Environmental Medicine
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Environmental Health
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Journal of Proteome Research
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Aerosol and Air Quality Research
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American Journal of Respiratory and Critical Care Medicine
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Inhalation Toxicology
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Environmental Research
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Journal of the Air & Waste Management Association
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Occupational and Environmental Medicine
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Presse Medicale
Air pollution and cardiovascular and cerebrovascular disease - Pathophysiologic basis and groups at risk
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Ultrastructural Pathology
Ambient atmospheric particles in the airways of human lungs
Churg, A; Brauer, M
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American Journal of Epidemiology
Assessment of deaths attributable to air pollution: Should we use risk estimates based on time series or on cohort studies?
Kunzli, N; Medina, S; Kaiser, R; Quenel, P; Horak, F; Studnicka, M
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Occupational and Environmental Medicine
Ultrafine particles and nitrogen oxides generated by gas and electric cooking
Dennekamp, M; Howarth, S; Dick, CAJ; Cherrie, JW; Donaldson, K; Seaton, A
Occupational and Environmental Medicine, 58(8): 511-516.

Proceedings of the Combustion Institute
Soot detection using excimer laser fragmentation fluorescence spectroscopy
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European Respiratory Journal
Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability
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Journal of the Air & Waste Management Association
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Environmental Science & Technology
Age-Related Differences in Pulmonary and Cardiovascular Responses to SiO2 Nanoparticle Inhalation: Nanotoxicity Has Susceptible Population
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American Journal of Physiology-Regulatory Integrative and Comparative Physiology
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Circulation
Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association
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Experimental Biology and Medicine
Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects: A brief communication
Takano, H; Yanagisawa, R; Inoue, K; Shimada, A; Ichinose, T; Sadakane, K; Yoshino, S; Yamaki, K; Morita, M; Yoshikawa, T
Experimental Biology and Medicine, 229(4): 361-364.

International Journal of Biometeorology
Weather changes associated with hospitalizations for cardiovascular diseases and stroke in California, 1983-1998
Ebi, KL; Exuzides, KA; Lau, E; Kelsh, M; Barnston, A
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Environmental Health Perspectives
The association between fatal coronary heart disease and ambient particulate air pollution: Are females at greater risk?
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Environmental Health Perspectives
Increased risk of paroxysmal atrial fibrillation episodes associated with acute increases in ambient air pollution
Rich, DQ; Mittleman, MA; Link, MS; Schwartz, J; Luttmann-Gibson, H; Catalano, PJ; Speizer, FE; Gold, DR; Dockery, DW
Environmental Health Perspectives, 114(1): 120-123.
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Cardiovascular Toxicology
In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias
Wold, LE; Simkhovich, BZ; Kleinman, MT; Nordlie, MA; Dow, JS; Sioutas, C; Kloner, RA
Cardiovascular Toxicology, 6(1): 69-78.

Occupational and Environmental Medicine
Ambient particulate air pollution and cardiac arrhythmia in a panel of older adults in Steubenville, Ohio
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Occupational and Environmental Medicine
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Fang, SC; Eisen, EA; Cavallari, JM; Mittleman, MA; Christiani, DC
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Circulation
Particulate air pollution and risk of ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart disease - The exposure and risk assessment for fine and ultrafine particles in ambient air (ULTRA) study
Pekkanen, J; Peters, A; Hoek, G; Tiittanen, P; Brunekreef, B; de Hartog, J; Heinrich, J; Ibald-Mulli, A; Kreyling, WG; Lanki, T; Timonen, KL; Vanninen, E
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Inhalation Toxicology
Atmospheric secondary inorganic particulate matter: The toxicological perspective as a basis for health effects risk assessment
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Inhalation Toxicology
The role of soluble components in ambient fine particles-induced changes in human lungs and blood
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Environmental Health Perspectives
The temporal pattern of respiratory and heart disease mortality in response to air pollution
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Circulation
Cardiovascular mortality and long-term exposure to particulate air pollution - Epidemiological evidence of general pathophysiological pathways of disease
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Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis
Ambient source-specific particles are associated with prolonged repolarization and increased levels of inflammation in male coronary artery disease patients
Yue, W; Schneider, A; Stozel, M; Ruckerl, R; Cyrys, J; Pan, XC; Zareba, W; Koenig, WG; Wichmann, HE; Peters, A
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Environmental Health Perspectives
The effect of dose and timing of dose on the association between airborne particles and survival
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Inhalation Toxicology
ECG Parameters and Exposure to Carbon Ultrafine Particles in Young Healthy Subjects
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Science of the Total Environment
The association between fine particulate air pollution and hospital emergency room visits for cardiovascular diseases in Beijing, China
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Environmental Health Perspectives
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Toxicology
Pulmonary exposure to diesel exhaust particles promotes cerebral microvessel thrombosis: Protective effect of a cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid
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Occupational Medicine-Oxford
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Journal of Infectious Diseases
It's not the heat, it's the humidity: Wet weather increases Legionellosis risk in the greater Philadelphia metropolitan area
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Croatian Medical Journal
Triggering of ventricular ectopic beats by emotional, physical, and meteorologic stress: Role of age, sex, medications, and chronic risk factors
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Toxicology in Vitro
Signal transduction pathways involved in particulate matter induced relaxation in rat aorta - Spontaneous hypertensive versus Wistar Kyoto rats
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Environmental Health Perspectives
Nanoparticles: Health effects - Pros and cons
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Environmental Health Perspectives
Mortality risk associated with short-term exposure to traffic particles and sulfates
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Archives of Environmental & Occupational Health
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Atmospheric Environment
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Planetary and Space Science
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Linnarsson, D; Carpenter, J; Fubini, B; Gerde, P; Karlsson, LL; Loftus, DJ; Prisk, GK; Staufer, U; Tranfield, EM; van Westrenen, W
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Journal of the Air & Waste Management Association
Receptor model source attributions for Utah's Salt Lake City airshed and the impacts of wintertime secondary ammonium nitrate and ammonium chloride aerosol
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Journal of Environmental Protection and Ecology
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Karaslavova, E; Dimitrova, T; Donchev, N; Teneva, B
Journal of Environmental Protection and Ecology, 14(1): 1-11.

Canadian Journal of Cardiology
Air Pollution and Arrhythmic Risk: The Smog Is Yet to Clear
Watkins, A; Danilewitz, M; Kusha, M; Masse, S; Urch, B; Quadros, K; Spears, D; Farid, T; Nanthakumar, K
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Current Opinion in Cardiology
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Epidemiology
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Long-Term Exposure to Urban Air Pollution and Myocardial Infarction
Rosenlund, M; Berglind, N; Pershagen, G; Hallqvist, J; Jonson, T; Bellander, T
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Dennekamp, M; Akram, M; Abramson, MJ; Tonkin, A; Sim, MR; Fridman, M; Erbas, B
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Epidemiology
Air Pollution and Myocardial Infarction in Rome: A Case-Crossover Analysis
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Keywords:

pollution; cardiovascular diseases; implantable cardioverter defibrillators; arrhythmias; nitrous dioxide; carbon monoxide; black carbon; particulate matter

© 2000 Lippincott Williams & Wilkins, Inc.

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