2010 Progress Report: Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources

EPA Grant Number: R832415C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R832415
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Rochester PM Center
Center Director: Oberdörster, Günter
Title: Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
Investigators: Peters, Annette , Breitner, Susanne , Henneberger, Alexandra , Phipps, Richard , Rückerl, Regina , Stoelzel, M , Utell, Mark J. , Wichmann, Heinz-Erich , Zareba, Wojciech
Institution: GSF-National Research Center for Environment and Health , University of Rochester
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
Project Period Covered by this Report: June 30, 2009 through July 1,2010
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The objective of the epidemiological study is to examine the effect of fine and ultrafine particles on systemic responses, endothelial and cardiac function. The study was conducted in Augsburg, Germany, between March 19th 2007 and December 17th 2008.

The specific aims of the study are to:

Aim #1: Determine the effect of ambient fine and ultrafine particles on an acute phase reaction in the blood of subjects with type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT) and potential genetic susceptibility (gen. susc.).

Aim #2: Determine the effect of ambient fine and ultrafine particles on pro-thrombotic states of the blood in the above subject panels.

Aim #3: Determine the effect of ambient fine and ultrafine particles on endothelial dysfunction as a key element of coronary vulnerability in a subset of the above subject panels.

Aim #4: Determine the effect of ultrafine particles on cardiac function as characterized by ECG measures of autonomic function and repolarization in a subset of the above subject panels.

The objectives have not been altered during this reporting period.

Progress Summary:

The period covered by the report included:

  1. The completion of nearly all parts of data management. Only datasets including the information about participants’ medication and the description of activities during the personal measurement period are still being prepared.
  2. The performing of statistical analyses with emphasis on effects on ECG parameters.
  3. The preparing of manuscripts with emphasis on effects on ECG parameters.

In the following we give an overview over selected descriptive and regression results.

Descriptive Results

275 individuals participated in 1797 visits with a mean of 6.5 visits per person. At each visit (base program) a blood withdrawal was conducted. Air pollution was measured at a central measurement site in Augsburg throughout the complete study period. In addition (add-on program), for a subgroup of 112 participants personal measurements of ultrafine particles using a portable condensation particle counter (CPC) as well as temperature, humidity and noise were conducted in up to four visits. Furthermore, endothelial function as a key element of coronary vulnerability as well as cardiac function characterized by electrocardiogram (ECG) measures were assessed in this subset.

Substantially higher variation in PNC was observed during personal monitoring compared to the background level. Overall, the median personal PNC exposure was 11,134 per cm3 with an interquartile range of 15,633 per cm3. Elevated personal PNC exposure was observed when subjects spent time in traffic (median/mean = 25292/24804, N = 5817), were cooking (median/mean = 19186/4358, N = 582) or were exposed to environmental tobacco smoke (ETS) (median/mean = 22082/52635, N = 403). In contrast, personal PNC exposure was lower during times spent at home without cooking or ETS exposure (median/mean = 8752/19063, N = 12596).

Regression Results

Effects of personally measured PNC and ambient air pollution on heart rate (HR) and heart rate variability (HRV) parameters in diseased individuals (with T2DM and IGT)

We investigated the association between 5-minute averages of personal PNC exposure and 5-minute intervals of HR as well as HRV parameters such as standard deviation of normal-tonormal intervals (SDNN) and root mean square of successive differences (RMSSD) in 32 participants with T2DM and 32 participants with IGT. In total, we analyzed more than 14,000 5-minute intervals for which ECG parameters were available. Additionally, effects of 1-hour averages of ambient air pollutants (PM10, PM2.5, and UFP) on 1-hour intervals of HR, SDNN, and RMSSD were analyzed. Additive mixed models with random participant effects and a firstorder autoregressive covariance structure accounting for autocorrelation between the repeated measurements were applied. Models were adjusted for ambient meteorology and time trends. Penalized splines were used to allow for non-linear confounder adjustment. Results are presented as %-change from the mean outcome level, either per an increase of 16,000 personal PNC particles/cm3 or the respective interquartile ranges of the ambient particle concentrations, together with 95% confidence intervals. Data were analyzed with SAS statistical package (version 9.2; SAS Institute Inc., Cary, NC, USA).

Table 8: Associations between personal measurements of 5-minute average particle number concentrations and 5-minute ECG-measures. Analyses considered concurrent and up to 15 minutes delayed exposures and adjusted for trend, meteorology and time of day.

 
Concurrent
0 – 4 min
5 – 9 min
10 – 15 min
 
%-change
95% CI
%-change
95% CI
%-change
95% CI
%-change
95% CI
HR
-0.06
-0.18; 0.07
0.23**
0.11; 0.36
0.16*
0.04; 0.28
-0.01
-0.13; 0.11
SDNN
-0.56*
-1.02; -0.09
0.36
-0.11; 0.83
0.02
-0.45; 0.48
-0.15
-0.62; 0.32
RMSSD
-0.13
-0.74; 0.48
0.08
-0.54; 0.70
0.14
-0.48; 0.77
-0.16
-0.77; 0.46

* p-value <0.05, **p-value < 0.01.

CI, confidence interval; HR, heart rate; RMSSD, root mean square of successive differences; SDNN, standard deviation of normal-to-normal intervals.

Table 8 shows the associations between 5-minute exposures to PNC and HR and HRV assessing concurrent and exposures lagged up to 15 minutes. It shows a slightly delayed response of HR and an immediate increase in SDNN as well as RMSSD. Figure 1 shows, that while results from individuals with type 2 diabetes and IGT are not statistically different, responses appear to be more pronounced in individuals with T2DM.

Figure 1: Effects of personally measured particle number concentrations (5-minute intervals) on 5-minute averages of SDNN in patients with type 2 diabetes or impaired glucose tolerance (IGT).

Table 9 shows the association between 1h average concentrations of personal PNC and ambient UFP, PM10 and PM2.5 and concurrent measures of HR and HRV. No consistent associations between personal or ambient particles and HR were observed. In contrast, concurrent association of PM10 and PM2.5 were associated both with SDNN and RMSSD. Effect estimates suggested slightly stronger associations between PM2.5 and HRV. The association between PM2.5 and HRV was stronger in individuals with IGT than those with T2DM (Figure 2), but the differences did not achieve statistical significance.

Figure 2: Immediate effects of 1-hour average concentrations of ambient air pollutants and personal PNC on 1-hour averages of SDNN and RMSSD in patients with type 2 diabetes or impaired glucose tolerance (IGT).

Table 9: Associations between ambient 1-hour average air pollution concentrations at the central monitoring site and 1-hour average ECG-measures. Analyses considered concurrent exposures and adjusted for trend, meteorology and time of day.

 
HR
SDNN
RMSSD
 
%-change
95% CI
%-change
95% CI
%-change
95% CI
Personal PNC
0.13
0.19; -0.45
-0.93
2.01; -0.16
0.53;
-0.70; 1.77
UFP
0.40
.016; -0.95
0.99
0.66; -2.64
-0.12;
-2.40; 2.21
PM10
0.67
0.20; -1.54
-2.79*
4.99; -0.59
-5.00;*
-8.88; -0.95
PM2.5
0.63
0.44; -1.71
-3.27*
5.84; -0.69
-6.86;**
11.73; 1.72

†p-value <0.1, *p-value <0.05, **p-value <0.01.

CI, confidence interval; HR, heart rate; RMSSD, root mean square of successive differences; SDNN, standard deviation of normal-to-normal intervals; PM10, particulate matter with an aerodynamic diameter <10μm; PM2.5, particulate matter with an aerodynamic diameter <2.5μm; UFP, ultrafine particles.

The study provides a clear indication that personal activities modify the personal exposures to particle number concentrations. In contrast, PM2.5 measured at a central monitoring station quantifies the overall particulate matter level at this day’s particular hour and is predominantly determined by meteorological conditions.

The data presented here suggests that both freshly emitted ultrafine particles as well as aged aerosol in urban areas are associated with changes in cardiac function. These exposures occurred repeatedly in urban settings of medium size which lack major truck routes or large industrial complexes. The study was conducted in subjects with type 2 diabetes and impaired glucose tolerance suggesting that these subgroups of the population might be at risk for cardiovascular disease exacerbation when transiently exposed to fresh and aged urban particulate matter.

By looking at traffic-related PM and aged aerosols characterized at an urban background site our epidemiological study contributes to the center’s goal of identifying sources with higher toxicity and pathophysiological mechanisms by which ambient ultrafine and fine PM trigger cardiovascular adverse health effects.

The study was conducted in adults with diagnosed type 2 diabetes or impaired glucose tolerance which have been hypothesized to be a susceptible subpopulation with respect to PM responses.

This research may provide evidence to adequately protect potentially susceptible subpopulations in the future. Moreover, the results of this study will help to evaluate the recently established low emission zone in Augsburg, Germany.

Finally, our results will add to the body of evidence that will be the basis for the planned setting up of new air quality standards in the United States as well as in Europe.

Future Activities:

For the period of the No-cost Extension for the PM Center the following activities are planned:

1. Further statistical analyses using the innovative particle characterisation at the central measurement site including particle number, surface and mass concentrations of all particles and the non-volatile fraction as well as source indicators. In addition to ECG measures, blood biomarker of inflammation, coagulation and endothelial dysfunction will be analysed to further characterize the pathomechanisms. While the current report focuses on subjects with metabolic disorders, the final year of the study will in particular assess the effects of particles in the panel of genetic susceptible individuals and will test the potential for genetic susceptibility in all participants.

2. Further preparation of publication manuscripts.


Journal Articles on this Report : 11 Displayed | Download in RIS Format

Other subproject views: All 19 publications 18 publications in selected types All 18 journal articles
Other center views: All 190 publications 156 publications in selected types All 143 journal articles
Type Citation Sub Project Document Sources
Journal Article Breitner S, Stolzel M, Cyrys J, Pitz M, Wolke G, Kreyling W, Kuchenhoff H, Heinrich J, Wichmann H-E, Peters A. Short-term mortality rates during a decade of improved air quality in Erfurt, Germany. Environmental Health Perspectives 2009;117(3):448-454. R832415 (2010)
R832415 (Final)
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  • Journal Article Bruske I, Hampel R, Socher MM, Ruckerl R, Schneider A, Heinrich J, Oberdorster G, Wichmann H-E, Peters A. Impact of ambient air pollution on the differential white blood cell count in patients with chronic pulmonary disease. Inhalation Toxicology 2010;22(3):245-252. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C002 (2010)
    R832415C002 (2011)
    R832415C004 (2010)
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  • Journal Article Hildebrandt K, Ruckerl R, Koenig W, Schneider A, Pitz M, Heinrich J, Marder V, Frampton M, Oberdorster G, Wichmann HE, Peters A. Short-term effects of air pollution: a panel study of blood markers in patients with chronic pulmonary disease. Particle and Fibre Toxicology 2009;6:25. R832415 (2009)
    R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C002 (2009)
    R832415C002 (2010)
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  • Journal Article Ljungman P, Bellander T, Nyberg F, Lampa E, Jacquemin B, Kolz M, Lanki T, Mitropoulos J, Muller M, Picciotto S, Pistelli R, Ruckerl R, Koenig W, Peters A, AIRGENE Study Group. DNA variants, plasma levels and variability of Interleukin-6 in myocardial infarction survivors: results from the AIRGENE study. Thrombosis Research 2009;124(1):57-64. R832415 (2010)
    R832415 (Final)
    R832415C002 (2010)
    R832415C002 (2011)
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  • Journal Article Peters A, Greven S, Heid IM, Baldari F, Breitner S, Bellander T, Chrysohoou C, Illig T, Jacquemin B, Koenig W, Lanki T, Nyberg F, Pekkanen J, Pistelli R, Ruckerl R, Stefanadis C, Schneider A, Sunyer J, Wichmann HE, AIRGENE Study Group. Fibrinogen genes modify the fibrinogen response to ambient particulate matter. American Journal of Respiratory and Critical Care Medicine 2009;179(6):484-491. R832415 (2009)
    R832415 (2010)
    R832415 (Final)
    R832415C002 (2009)
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  • Journal Article Peters A. Air quality and cardiovascular health:smoke and pollution matter. Circulation 2009;120(11):924-927. R832415 (2010)
    R832415 (Final)
    R832415C002 (2010)
    R832415C002 (2011)
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  • Full-text: Circulation-Full Text HTML
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  • Journal Article Pitz M, Birmili W, Schmid O, Peters A, Wichmann HE, Cyrys J. Quality control and quality assurance for particle size distribution measurements at an urban monitoring station in Augsburg, Germany. Journal of Environmental Monitoring 2008;10(9):1017-1024. R832415 (2007)
    R832415 (2008)
    R832415 (2010)
    R832415 (Final)
    R832415C002 (2006)
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  • Journal Article Schneider A, Neas L, Herbst MC, Case M, Williams RW, Cascio W, Hinderliter A, Holguin F, Buse JB, Dungan K, Styner M, Peters A, Devlin RB. Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. Environmental Health Perspectives 2008;116(12):1666-1674. R832415 (2008)
    R832415 (2010)
    R832415 (Final)
    R832415C002 (2010)
    R832415C002 (2011)
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  • Journal Article Schneider A, Neas LM, Graff DW, Herbst MC, Cascio WE, Schmitt MT, Buse JB, Peters A, Devlin RB. Association of cardiac and vascular changes with ambient PM2.5 in diabetic individuals. Particle and Fibre Toxicology 2010;7:14. R832415 (2010)
    R832415 (Final)
    R832415C002 (2010)
    R832415C002 (2011)
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  • Other: Partcle and Fibre Toxicology-Full Text PDF
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  • Journal Article Yue W, Stolzel M, Cyrys J, Pitz M, Heinrich J, Kreyling WG, Wichmann H-E, Peters A, Wang S, Hopke PK. Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany. Science of the Total Environment 2008;398(1-3):133-144. R832415 (2007)
    R832415 (2008)
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    R832415C001 (2008)
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    R827354 (Final)
    R834797 (2016)
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  • Journal Article Zareba W, Couderc JP, Oberdorster G, Chalupa D, Cox C, Huang L-S, Peters A, Utell MJ, Frampton MW. ECG parameters and exposure to carbon ultrafine particles in young healthy subjects. Inhalation Toxicology 2009;21(3):223-233. R832415 (2008)
    R832415 (2009)
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    R832415 (Final)
    R832415C002 (2010)
    R832415C002 (2011)
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    R832415C003 (2011)
    R832415C004 (2009)
    R832415C004 (2010)
    R832415C004 (2011)
    R827354 (Final)
  • Full-text from PubMed
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  • Abstract: Taylor and Francis-Abstract
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, particulate matter, Health Risk Assessment, Epidemiology, Risk Assessments, Physical Processes, atmospheric particulate matter, atmospheric particles, long term exposure, acute cardiovascular effects, airway disease, exposure, human exposure, ambient particle health effects, atmospheric aerosol particles, PM, aersol particles, cardiovascular disease

    Relevant Websites:

    None.

    Progress and Final Reports:

    Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009 Progress Report
  • 2011 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R832415    Rochester PM Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832415C001 Characterization and Source Apportionment
    R832415C002 Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
    R832415C003 Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
    R832415C004 Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
    R832415C005 Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition