Mechanisms of Morbidity and Mortality from Exposure to Ambient Air Particles RESEARCH REPORT

RESEARCH REPORT Mechanisms of Morbidity and Mortality from Exposure 955 Massachusetts Avenue Number 91 to Ambient Air Particles Cambridge MA 02139 USA February 2000 John J Godleski, Richard L Verrier, Petros Koutrakis, +1-617-876-6700 and Paul Catalano www.healtheffects.org RESEARCH REPORT Number 91 February 2000 Includes the Commentary of the Institute’s Health Review Committee BOARD OF DIRECTORS Archibald Cox Chair Alice Huang Carl M Loeb University Professor (Emeritus), Harvard Law School Senior Councilor for External Relations, California Institute of Technology Donald Kennedy Vice Chair Susan B King The Health Effects Institute, established HEALTH Editor-in-Chief, Science; President (Emeritus) and Bing Professor of Fellow, Sanford Institute of Public Policy, Duke University EFFECTS in 1980, is an independent and unbiased Biological Sciences, Stanford University Richard B Stewart INSTITUTE source of information on the health Douglas Costle Professor, New York University School of Law effects of motor vehicle emissions. HEI Chairman of the Board and Distinguished Senior Fellow, Robert M White Institute for Sustainable Communities President (Emeritus), National Academy of Engineering, and Senior studies all major pollutants, including Fellow, University Corporation for Atmospheric Research regulated pollutants (such as carbon HEALTH RESEARCH COMMITTEE monoxide, ozone, nitrogen dioxide, and Bernard D Goldstein Chair Jonathan M Samet particulate matter) and unregulated Director, Environmental and Occupational Health Sciences Institute Professor and Chairman, Department of Epidemiology, School of pollutants (such as diesel engine exhaust, Glen R Cass Hygiene and Public Health, Johns Hopkins University Professor and Chairman, School of Earth and Atmospheric Sciences, methanol, and aldehydes). To date, HEI Robert F Sawyer Georgia Institute of Technology Class of 1935 Professor of Energy (Emeritus), Professor of the Graduate has supported more than 200 projects at Seymour J Garte School, University of California, Berkeley institutions in North America and Europe Professor of Environmental and Community Medicine, Environmental Frank E Speizer and Occupational Health Sciences Institute and has published over 200 research Edward H Kass Professor of Medicine, Channing Laboratory, Harvard Rogene Henderson Medical School, Department of Medicine, reports. Senior Scientist, Lovelace Respiratory Research Institute Brigham and Women’s Hospital Typically, HEI receives half its funds Stephen I Rennard Gerald van Belle from the US Environmental Protection Larson Professor, Pulmonary and Critical Care Medicine Section, Professor, Departments of Environmental Health and Statistics, Department of Internal Medicine, University of Nebraska Agency and half from 28 manufacturers University of Washington Medical Center and marketers of motor vehicles and HEALTH REVIEW COMMITTEE engines in the US. Occasionally, funds Daniel C Tosteson Chair Edo D Pellizzari from other public and private Professor of Cell Biology, Dean Emeritus, Harvard Medical School Vice President for Analytical and Chemical Sciences, Research Triangle organizations either support special John C Bailar III Institute Professor, Department of Health Studies, Biological Sciences Division, Donald J Reed projects or provide resources for a portion The University of Chicago Distinguished Professor of Biochemistry, Department of Biochemistry of an HEI study. Regardless of funding Ralph D’Agostino and Biophysics, and Environmental Health Sciences Center, Oregon Professor of Mathematics/Statistics and Public Health, Boston State University sources, HEI exercises complete University David J Riley autonomy in setting its research priorities Thomas W Kensler Professor of Medicine, University of Medicine and Dentistry of New Professor, Division of Toxicological Sciences, Department of Jersey-Robert Wood Johnson Medical School and in reaching its conclusions. An Environmental Sciences, Johns Hopkins University Sverre Vedal independent Board of Directors governs Brian Leaderer Professor of Medicine, University of British Columbia Professor, Department of Epidemiology and Public Health, Yale HEI. The Institute’s Health Research and University School of Medicine Health Review Committees serve complementary scientific purposes and OFFICERS & STAFF draw distinguished scientists as Daniel S Greenbaum President Gail V Allosso Office and Contracts Manager Richard M Cooper Corporate Secretary Thomas Atwood Manager of Publications and Information members. The results of HEI-funded Howard E Garsh Director of Finance and Administration Julia F Campeti Scientific Copy Editor studies are made available as Research Robert M O’Keefe Vice President John R DeRosa Desktop Publishing Specialist Jane Warren Director of Science Reports, which contain both the Sally Edwards Managing Editor Aaron J Cohen Senior Scientist Terésa Fasulo Senior Administrative Assistant Maria G Costantini Senior Scientist Investigators’ Report and the Review L Virgi Hepner Senior Scientific Editor Alison Geyh Staff Scientist Committee’s evaluation of the work’s Darlene Jones Senior Administrative Assistant Bernard Jacobson Staff Scientist Judith Lopez Receptionist scientific quality and regulatory Debra A Kaden Senior Scientist Francine Marmenout Senior Executive Assistant relevance. Diane J Mundt Staff Scientist Martha E Richmond Staff Scientist Teresina McGuire Accounting Assistant Geoffrey H Sunshine Staff Scientist Beverly Morse Administrative Assistant JoAnn Ten Brinke Staff Scientist Jacqueline C Rutledge Controller Annemoon van Erp Staff Scientist STATEMENT Synopsis of Research Report 91 Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs INTRODUCTION animals showed a shortened time to ST segment elevation Epidemiology studies have indicated that short-term expo- and an increased magnitude of the ST segment compared to sure to low-level increases in particulate matter is associated controls. These findings suggest what may be a plausible with an increase in morbidity and daily mortality, particularly mechanism to explain PM’s effects on individuals with car- in individuals with cardiopulmonary conditions. A plausible diopulmonary conditions: exposure to particulate pollution biologic mechanism linking low-level particle exposure and may make patients with ischemic heart disease more suscep- pathophysiologic effects has not been established, however. tible to developing serious cardiac effects. If substantiated in Assessing the effects of particulate matter in appropriate larger groups of animals, the evidence may help to explain the animal models is important to learning how particulate previously described association between increased particu- matter may exert adverse health effects. The Health Effects late pollution and cardiopulmonary morbidity and mortality. Institute funded the study described in this report as part of a Animals with an induced coronary occlusion also showed research program to reduce this information gap. other changes in cardiac and respiratory parameters after exposure to CAPs. APPROACH The investigators also reported that normal dogs showed Dr John Godleski and colleagues at Harvard School of Public CAPs-induced changes in heart rate variability and average Health conducted an exploratory study to test the effects of heart rate (which fluctuated widely from day to day during the particulate matter exposure in dogs, which share many fea- course of the study), decreases in T wave alternans, and tures of the human cardiovascular system. The investigators changes in respiratory parameters such as breathing rates and hypothesized that particulate matter might affect the animals’ air flow rates. They did not identify whether the variability in cardiac function, leading to arrhythmia, and might induce responses was due to day-to-day fluctuation of a specific inflammatory responses and changes in pulmonary mechan- ical measurements. To maximize possible effects, they used a component of the particulate mixture. In addition, the inves- device to concentrate particles up to 30 times their level in tigators reported that CAPs had little or no effect on inflam- ambient Boston air and exposed dogs to these concentrated matory mediators, suggesting that changes in cardiac and ambient particles (CAPs) via inhalation. The investigators pulmonary responses occurred in the absence of significant physically and chemically identified components of the CAPs airway inflammation. and tested their effects in 12 dogs, in 6 of which they also The investigators interpreted their findings to indicate that induced a coronary occlusion to simulate human coronary CAPs influenced the nervous system’s control of the normal artery disease. They evaluated the effects of CAPs on electro- dog’s heart but did not necessarily induce arrhythmia. This cardiographic (ECG) wave patterns and performed a sophisti- interpretation may be reasonable, but the statistical approach cated analysis of each dog’s ECG to measure possible effects the investigators used to identify changes in heart rate vari- of particulate matter on other electrical properties of the ability is not clearly applicable to the small number of dogs heart: heart rate variability, which is influenced by the invol- tested. In addition, it is not apparent whether it is appropriate untary nervous system, and T wave alternans, a change in the to extrapolate these results to humans because the human heart beat pattern. These two are among the measures

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