1999 Progress Report: Inflammatory Responses and Cardiovascular Risk Factors in Susceptible Populations

EPA Grant Number: R827354C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R827354
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Airborne PM - Rochester PM Center
Center Director: Oberd√∂rster, G√ľnter
Title: Inflammatory Responses and Cardiovascular Risk Factors in Susceptible Populations
Investigators: Wichmann, Heinz-Erich , Heyder, Joachim , Peters, Annette
Current Investigators: Wichmann, Heinz-Erich , Peters, Annette
Institution: GSF - Forschungszentrum fur Umwelt und Gesundheitand Ludwig Maximilian University, Neuherberg, Germany
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 1999 through May 31, 2000
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

Several epidemiological studies provide consistent information on the association between high particulate air pollution and an increase in mortality and morbidity. Ultrafine particles have been hypothesized to be in part responsible for observed health effects of particulate matter (Oberdörster, et al., 1992; Seaton, et al., 1995). Inflammatory processes in the airways and their translation into a systemic signal have been discussed as the main mechanisms responsible for the observed adverse health effects. Even though animal experiments show evidence that these processes can be induced by installation of particles or by inhalation of concentrated particles (Godleski, et al., 1996), it is unclear which of these mechanisms play a major role under ambient concentrations of particles. The only epidemiological evidence for a systemic response was shown in the MONICA Augsburg survey, which coincided with the Europe-wide air pollution episode in 1985. An increased risk of elevated levels of plasma viscosity was observed during the episode in a random sample of the population (Peters, et al., 1997b). Increases in hospital admissions for chronic obstructive pulmonary disease (COPD) and ischemic heart disease (Bascom, et al., 1996; Schwartz, 1998) indicate that patients with these conditions characterized by an underlying chronic inflammation are especially sensitive to air pollution. However, it is unclear, whether the same pathomechanisms are mediating the biological response in these two groups of patients.

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 of patients with stable coronary artery disease as well as of patients with COPD. Monitoring of the autonomic function of the heart will investigate how these changes in the inflammatory state relate to alterations in the autonomic control. The following hypotheses will be tested in patients with chronic diseases of the lung and the heart: (1) concentrations of ambient fine and ultrafine particles are associated with inflammation of the airways, as well as increases in plasma viscosity, fibrinogen, and other acute phase proteins in the blood; (2) increases in the coagulability of the blood are associated with changes in the autonomic control of the heart; and (3) exposure to ultrafine particles is more closely related to the health effects than the exposure to fine particulate mass.

Progress Summary:

Two prospective panel studies with 12 repeated medical examinations will be conducted in Erfurt, Germany. For the first panel study, taking place between September 2000, and March 2001, 60 subjects with stable angina pectoris will be recruited. The second panel study will take place between September 2001, and March 2002, and will be conducted with 60 subjects diagnosed with COPD. Only nonsmoking males with stable angina pectoris who do not take any anticoagulants (except ASA) are included in the study. Subjects with recent myocardial infarction (MI), balloon dilatation, or bypass surgery (less than 3 months ago) or subjects with diabetes, dementia, or a pacemaker will be excluded. The study protocol will comprise the following components for the angina pectoris patients:

  • 12 bimonthly clinical examinations with an interview, resting ECG, blood pressure measurement, urine sample, and blood sample.

  • 6 monthly 24-hour Holter recordings.

  • Daily blood pressure measurements for a period of 1 month.

  • Daily recording of symptoms and medication use for the entire study period.

For the COPD panel, additional lung function testing will be conducted during the clinical examinations.

The study protocol for the Angina Pectoris Panel will be tested and evaluated in a pilot study that will take place between May 2 and June 10. Twenty nonsmoking males between 50 and 80 with stable angina pectoris were recruited for the pilot study. Based on the data collected during the ULTRA II study (Exposure and risk assessment for fine and ultrafine particles in ambient air - ULTRA II), the study protocol was revised and some components were added to the protocol. The purpose of the pilot study is to test the following procedures and tools:

  • Ambulatory ECG recording: the protocol of the resting ECG was modified after evaluating the data collected in the ULTRA II study. The recording of additional parameters will require a slightly different preparation of the patient.

  • 24-hour ECG recording: the measurement has been newly introduced and the protocol needs to be tested.

  • Blood sampling: procedure, handling, storage, and shipment need to be checked.

  • Diary: the diary was slightly modified from the diary used in the ULTRA II panel study. We will test whether the reworded questions better characterize the variation in cardiac symptoms.

  • Daily blood pressure measurements at home without supervision: feasibility and acceptance by the study subjects need to be evaluated.

In addition to evaluating feasibility of the study protocol, reproducibility, and intra- and inter-individual variation will be assessed for all continuous variables (blood parameters, ECG-recordings, and blood pressure measurements).

Future Activities:

Between June and September, data from the pilot study will be evaluated, and the final protocol for the angina pectoris panel will be set up. The main panel study will be conducted between September 2000, and March 2001. Following the angina pectoris panel, the pilot study for the COPD panel will take place between May 2001, and June 2001, to test the protocol for the main COPD panel study in September 2001.

Journal Articles:

No journal articles submitted with this report: View all 11 publications for this subproject

Supplemental Keywords:

pollution prevention, atmosphere, particulates, metals, sensitive population., RFA, Health, Scientific Discipline, Air, Geographic Area, particulate matter, Virology, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Biochemistry, Atmospheric Sciences, Molecular Biology/Genetics, International, ambient air quality, cytokine production, particle size, particulates, sensitive populations, cardiopulmonary responses, fine particles, human health effects, morbidity, ambient air monitoring, cardiovascular vulnerability, pulmonary disease, susceptible populations, COPD, epidemelogy, environmental health effects, particle exposure, Germany, human exposure, particulate exposure, lung inflamation, coronary artery disease, inhalation toxicology, PM, mortality, urban environment, aerosols, human health risk, cardiovascular disease, ultrafine particles

Relevant Websites:

http://www2.envmed.rochester.edu/envmed/pmc/indexpmc.html Exit

Progress and Final Reports:

Original Abstract
  • 2000 Progress Report
  • 2001 Progress Report
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R827354    Airborne PM - Rochester PM Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827354C001 Characterization of the Chemical Composition of Atmospheric Ultrafine Particles
    R827354C002 Inflammatory Responses and Cardiovascular Risk Factors in Susceptible Populations
    R827354C003 Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
    R827354C004 Animal Models: Dosimetry, and Pulmonary and Cardiovascular Events
    R827354C005 Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression
    R827354C006 Development of an Electrodynamic Quadrupole Aerosol Concentrator
    R827354C007 Kinetics of Clearance and Relocation of Insoluble Ultrafine Iridium Particles From the Rat Lung Epithelium to Extrapulmonary Organs and Tissues (Pilot Project)
    R827354C008 Ultrafine Oil Aerosol Generation for Inhalation Studies