2000 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, 2000 through May 31, 2001
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air


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:

The pilot study for the Angina Pectoris Panel took place between May 2 and June 20, 2000. A panel of 19 subjects was recruited to test the feasibility of the study protocol for the main phase. A total of 56 examinations, including blood sampling, ECG recording, and blood pressure measurements, were conducted. Further, 17 24-hour ECG's were recorded. In addition to the clinical examinations, every subject completed a symptom diary during the whole period and measured blood pressure twice a day for a period of 2 weeks. At the end of the pilot phase, subjects were given an evaluation sheet to evaluate tolerability of the protocol by study participants.

Overall, the study protocol proved to be feasible. Blood sampling and ECG recording were well tolerated. The protocol that accompanies the 24-hour ECG was modified in collaboration with Dr. Zareba of the cardiac core from a plain text protocol to a multiple-choice protocol. The clinical protocol was changed due to a different ECG device in the main study. As a result of the evaluation of the 24-hour Holter recordings, inclusion criteria of study subjects were changed in accordance with Dr. Zareba of the cardiac core. Patients with bundle branch blocks are no longer eligible for the study. Based on the pilot evaluation of the diary, some questions were changed slightly. Daily blood pressure measurements (self-measurement) over a period of 2 weeks were accepted by the patients without problems. Actual data (blood parameters, ECG-recordings, and blood pressure measurements) currently are being analyzed.

The main panel study of the Angina Pectoris Panel started on October 16, 2000, and will end in April 2001. A total of 61 patients were recruited from local practitioners. Two patients had to be excluded because of bundle branch blocks; 59 currently are being examined every second week at the study center. The final study protocol comprises 12 bimonthly clinical examinations with an interview, resting ECG, blood pressure measurement, urine sample, and blood sample. Further, 6 monthly 24-hour Holter recordings and daily blood pressure measurements for a period of 1 month will be taken. Throughout the whole study period, subjects are recording symptoms and medication use in a diary. So far, patient compliance for clinical visits is 95 percent and for 24-hour Holter recordings patient compliance is 70 percent.

Future Activities:

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. Only nonsmoking males, aged between 50 and 80 years with physician-diagnosed COPD will be included in the panel. For the pilot study, 15 subjects will be recruited from local practitioners. The main purpose of the pilot study will be to test acceptance, feasibility, and significance of additional measurements to assess the responses of the lung to ambient particles. Besides the main protocol used in the Angina Pectoris Panel, several lung function tests are discussed at the moment. Methods to be assessed will include impulse oscillometry, body plethysmography, and spirometry. Additional components such as a 6-minute-walking test, oxygen saturation, and sleeping apnea-hypopnea will be considered. Between June and September, data from the pilot study will be evaluated and the final protocol for the COPD panel will be set up. The main panel study will be conducted with 60 COPD patients between September 2001, and March 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
  • 1999 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