Previous Project

EPA STAR 1: "Inflammatory Response and cardiovascular risk factors in elderly subjects with angina pectoris or COPD in association with fine and ultrafine particles" (completed)

Study objectives:
The objective of the study is to characterize the association between ambient particle exposures and changes in biomarkers of inflammation in the airways and the blood as well as changes in ECG parameters of patients with stable coronary artery disease (CAD) and patients with chronic obstructive pulmonary disease (COPD).

Specific aims:
To assess:

  • Whether the concentration of fine and ultrafine particles is associated with an inflammatory response in the airways and/or a rise of plasmaviscosity and the concentration of fibrinogen and other acute phase proteins in the blood.
  • Whether an increased blood coagulation is connected to a change in the autonomic control of the heart in association with fine and ultrafine particles.
  • Whether the impact of ultrafine particles on health is stronger compared to the impact of fine particles.
  • Whether there is an association between the autonomic control of the heart and ultrafine particles.


Study design:
Prospective panel study with repeated clinical examinations.

Study population:

  • Panel 1: (Coronary Artery Disease):
    61 male non-smokers, aged between 50 and 80 years, recruited from local practitioners. Further participants had physician diagnosed coronary artery disease or stable angina pectoris or take angina pectoris (AP) medication. People with fresh (less than three months) cardiac events (e.g. MI, stroke, by-pass, surgery, PTCA), pace makers, instable AP, right/left bundle branch block, insulin dependent diabetes mellitus and patients on anticoagulant therapy were excluded from the panel. Patients with right/left bundle branch block were excluded from the ECG analyses.
  • Panel 2 (Chronic Obstructive Pulmonary Disease):
    39 males, recruited from local practitioners and through newspaper adverts with physician diagnosed chronic obstructive pulmonary disease (COPD), chronic asthma or chronic bronchitis. People with recent (less than three months) cardiac events (e.g. MI, stroke, by-pass, surgery, PTCA), pace makers, instable AP, insulin dependent diabetes mellitus and patients that are taking anticoagulants or need permanent oxygen supply were excluded from the study. Also patients who were on antibiotics more than 4 times in the preceding summer or winter were not allowed to enrol. Patients with right/left bundle branch block were excluded from the ECG analyses.

Study area:
Erfurt, Germany

Study methods:
Health assessment:
Each subject was followed over a period of 6 months. Clinical examinations included.

  • a total of 12 examinations (every 2 weeks) with lung function testing (only COPD-patients), ECG-recording (to determine e.g. heart rate, heart rate variability, heart rate turbulence, ST-segments and T-wave complexity) including a sub-maximal exercise challenge on a bicycle ergometer and pulse oximetry for the COPD-panel, urine sampling, blood sampling (to determine fibrinogen, prothrombin, D-Dimer, C-reactive protein (CRP), Interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (ICAM-1), E-selectin, and soluble CD40 ligand), blood pressure measurements, and breathing frequency
  • monthly 24 hour ECG-recordings
  • information on respiratory and cardiovascular symptoms collected through a questionnaire at each clinical visit
  • diary information on respiratory and cardiovascular symptoms as well as medication use
  • daily blood pressure measurements for a period of 1 month.

Assessment of ambient air pollution:
Air pollution was measured at a fixed monitoring site in Erfurt, Germany. The measurements consist of

  • outdoor number concentrations of particles sized between 0.01 µm - 2.5 µm measured with an aerosol size spectrometer
  • outdoor 24 hour PM2.5 and PM10 measured by Harvard Impactors
  • outdoor concentrations of O3 and NO2
  • assessment of chemical composition (through PIXE)
  • SO2 and CO concentrations collected through the local air quality network.

Study period:

  • Pilot study CAD panel 05/00 - 06/00
  • Field phase CAD panel 10/00 - 04/01
  • Pilot study COPD panel 05/01 - 06/01
  • Field phase COPD panel 10/01 - 04/02


Study status:
Completed

Investigators:
Helmholtz Zentrum München - Institute of Epidemiology: Annette Peters (PI), H.-Erich Wichmann (PI), Josef Cyrys (exposure assessment), Annette Berger (statistical analyses), Susanne Breitner (statistical analyses), Alexandra Schneider (statistical analyses), Angela Ibald-Mulli (study coordination, statistical analyses until 2004), Sabine Kött (field work), Mike Pitz (exposure assessment), Regina Rückerl (quality assurance, statistical analyses), Gabriele Wölke (coordination of field work), Katrin Zetzsche (data management).

Collaboration:
University of Rochester – Department of Environmental Medicine, Rochester, USA [Link]: Günter Oberdörster, Mark Utell, Wojciech Zareba, Betty Jane Mykins
UCLA School of Medicine – Vascular Medicine Program, Los Angeles, USA: Victor J. Marder, Joel Kanouse, Elizabeth Vandeventer
University of Ulm – Abteilung für Innere Medizin II, Ulm, Germany: Wolfgang Koenig
Praxis für Hygiene und Umweltmedizin, Erfurt, Germany: Olaf Manuwald, Gisela Bock, Brigitte Manuwald, Cornelia Schlegelmilch

Funding:
Environmental Protection Agency (EPA) USA. Grant Number: R-827354 (1999-2006)
Helmholtz Zentrum München - Institute of Epidemiology, Germany

Related Publications:

  • Schneider A, Hampel R, Ibald-Mulli A, Zareba W, Schmidt G, Schneider R, Rückerl R, Couderc JP, Mykins B, Oberdörster G, Wölke G, Pitz M, Wichmann HE, Peters A: Changes in Deceleration Capacity of Heart Rate and Heart Rate Variability Induced by Ambient Air Pollution in Individuals with Coronary Artery Disease Part Fibre Toxicol 7:29
    Abstract

  • Hampel R, Breitner S, Rückerl R, Frampton MW, Koenig W, Phipps RP, Wichmann HE, Peters A, Schneider A. Air temperature and inflammatory and coagulation responses in men with coronary or pulmonary disease during the winter season. Occup Environ Med. 67(6): 408-16. (2010)
    Abstract

  • Brüske I, Hampel R, Socher MM, Rückerl R, Schneider A, Heinrich J, Oberdörster G, Wichmann HE, Peters A: Impact of ambient air pollution on the differential white blood cell count in patients with chronic pulmonary disease. Inhal Toxicol. 2010 Feb;22(3):245-52.
    Abstract

  • Hildebrandt K, Rückerl R, Koenig W, Schneider A, Pitz M, Heinrich J, Marder V, Frampton M, Oberdörster G, Wichmann HE, Peters A: Short-term effects of air pollution: a panel study of blood markers in patients with chronic pulmonary disease. Part Fibre Toxicol. 2009 Sep 26;6:25.
    Abstract

  • Yue W, Stölzel M, Cyrys J, Pitz M, Heinrich J, Kreyling WG, Wichmann HE, Peters A, Wang S, Hopke PK (2008)
    Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany.
    Sci Total Environ 398(1-3), 133-144
    Abstract

  • Ruckerl R, Phipps RP, Schneider A, Frampton M, Cyrys J, Oberdorster G, Wichmann HE, Peters A (2007) Ultrafine particles and platelet activation in patients with coronary heart disease - results from a prospective panel study. Part Fibre Toxicol 4 (1):1
    Abstract

  • Yue W, Schneider A, Ruckerl R, Koenig W, Marder V, Wang S, Wichmann HE, Peters A, Zareba W (2007)
    Relationship between electrocardiographic and biochemical variables in coronary artery disease.
    Int J Cardiol. 119 (2):185-191
    Abstract

  • Yue W, Schneider A, Stolzel M, Ruckerl R, Cyrys J, Pan X, Zareba W, Koenig W, Wichmann HE, Peters A (2007) Ambient source-specific particles are associated with prolonged repolarization and increased levels of inflammation in male coronary artery disease patients. Mutat Res 621 (1-2):50-60
    Abstract

  • Berger A, Zareba W, Schneider A, Ruckerl R, Ibald-Mulli A, Cyrys J, Wichmann HE, Peters A (2006) Runs of ventricular and supraventricular tachycardia triggered by air pollution in patients with coronary heart disease. J Occup Environ Med. 48 (11):1149-1158
    Abstract

  • Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A (2006)
    Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Respir Crit Care Med 173:432-441
    Abstract

  • Henneberger A, Zareba W, Ibald-Mulli A, Rückerl R, Cyrys J, Couderc J-P, Mykins B, Woelke G, Wichmann HE, Peters A (2005) Repolarization Changes Induced by Air Pollution in Ischemic HeartDisease Patients. Env Health Persp 113:440-446
    Abstract

  • Lippmann M, Frampton M, Schwartz J, Dockery D, Schlesinger R, Koutrakis P, Froines J, Nel A, Finkelstein J, Godleski J, Kaufman J, Koenig J, Larson T, Luchtel D, Liu LJ, Oberdorster G, Peters A, Sarnat J, Sioutas C, Suh H, Sullivan J, Utell M, Wichmann E, Zelikoff J (2003) The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans. [Review] [80 refs]. Environ Health Perspect. 111:1074-1092.
    Abstract



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