Publications

Dr. Lester Kobzik and colleagues at the Harvard School of Public Health used a mouse model of asthma to evaluate how inhaling pollutants affects the airways. The mice were sensitized to the allergen ovalbumin, which induces a lung condition in the mice similar to that found in people with asthma. The investigators hypothesized that exposure to concentrated ambient particles (CAPs) plus ozone would cause a synergistic (or greater-than-additive) response in the mice.

Dr Günter Oberdörster and colleagues at the University of Rochester School of Medicine and Dentistry hypothesized that inhaled ultrafine particles induce an inflammatory response in the airways of mice and rats and that animals with preexisting airway inflammatory conditions may be particularly vulnerable. The investigators focused on inhaled carbon and platinum particles because these elements are constituents of particles found in urban atmospheres.

Dr. Eastmond and colleagures at the University of California, Riverside investigated whether chromosomal changes could be used as biomarkers of benzene exposure in mice and humans. The first part of the study involved detecting chromosomal alterations in cells using a modification of a molecular cytogenetic technique known as fluorescence in situ hybridization (FISH). Eastmond and colleagues evaluated the frequency of such chromosomal aberrations in the erythrocytes (red blood cells) from the bone marrow of mice exposed to various doses of benzene and for different exposure durations.

The three research projects contained in this report were initiated to increase our knowledge of the metabolism of ether oxygenates in humans and other species. Adding oxygenates, such as MTBE (methyl tert-butyl ether), to gasoline promotes more efficient combustion and reduces emission of carbon monoxide, ozone-forming hydrocarbons, and some air toxics, by increasing the oxygen content of the fuel. On the other hand, some oxygenates may increase emission of toxic compounds such as formaldehyde or acetaldehyde, and increased use of MTBE in fuel in the early 1990s led to complaints of unpleasant odor, headaches, and burning of eyes and throat. The studies were conducted by Dr Jun-Yan Hong (the University of Medicine and Dentistry of New Jersey – Robert Wood Johnson Medical School), Dr Wolfgang Dekant (University of Würzburg), and Dr Janet Benson (Lovelace Respiratory Research Institute).

Dr. Moss of CIIT evaluated the effects of rats exposed to ambient air in a highly polluted area in southwestern Mexico City. Pathologists have found evidence of cell damage and inflammation in nasal tissue from some human residents of this highly polluted area that was not present in people living in areas of the country with cleaner air and this study sought to determine if those effects could be replicated in rats.

Report of a workshop held November 29-30, 2000, sponsored by The H. John Heinz III Center for Science, Economics and the Environment, and the Health Effects Institute. 

Dr. Mark Goldberg and his colleagues at McGill University conducted a time-series study in Montreal using available data from the Quebec Health Insurance Plan and mortality and air pollution data to better the understanding of the mortality-particulate association. Because of the comprehensive nature of this health insurance database, the investigators were able to link individual deaths in Montreal to medical information up to 5 years before death.

A Special Report of the Institute's Particle Epidemiology Reanalysis Project. The overall objective of this project was to conduct a rigorous and independent assessment of the findings of the Harvard Six Cities and American Cancer Society Studies of air pollution and mortality. This objective was met in two parts. In Part I: Replication and Validation, the Reanalysis Team led by Dr. Daniel Krewski sought to replicate the original studies via a quality assurance audit of a sample of the original data and to validate the original numeric results.

In an effort to address the uncertainties regarding the association between PM and daily mortality, and to determine the effects of other pollutants on this association, HEI funded the National Morbidity, Mortality, and Air Pollution Study (NMMAPS). Dr Jonathan Samet and his colleagues at Johns Hopkins University, in collaboration with investigators at Harvard University, conducted this time-series study in large cities across the US where levels of PM and gaseous pollutants were varied.

As part of the Health Effects Institute's air toxics research program, five independent studies were designed to advance our understanding of the roles of different metabolites in 1,3-butadiene (BD)-induced carcinogenesis and of the differences in sensitivity among species, and to develop methods for identifying and measuring biomarkers. The investigators focused on two BD metabolites (1,2-epoxy-3-butene [BDO] and 1,2,3,4-diepoxybutane [BDO₂]) that researchers had suspected may play a role in BD carcinogenesis. The studies were conducted by Dr. Rogene Henderson (Lovelace Respiratory Research Institute), Dr. Leslie Recio (CIIT), Dr. Vernon Walker (New York State Department of Health), Dr. Ian Blair (University of Pennsylvania), and Dr. James Swenberg (University of North Carolina at Chapel Hill).

Dr. Pryor and colleagues at Louisiana State University developed methods for measuring ozone reaction products in in vitro models of lung lining fluids exposed to ozone and in lung fluids from rats exposed to ozone. During the study, Dr. Mark Frampton of the University of Rochester provided Pryor with lung fluids from humans exposed to air or ozone under controlled conditions. Frampton and colleagues exposed exercising smokers and nonsmokers to filtered air or to 0.22 parts per million (ppm) ozone for four hours.

In a follow-up study to previous research, Dr. Mercer and colleagues at Duke University exposed three groups of rats continuously for six weeks to 2 or 6 ppm nitric oxide (NO) or to filtered air to learn more about the toxicity of NO so as to compare it with two other important oxidants, ozone and nitrogen dioxide (NO₂). At the end of the exposure period he used an electron microscope to measure the number of holes in the alveolar septa and to observe other structural changes, such as in the surface area and the number and type of other abnormalities in the alveolar septa.

A Special Report of the Institute's Diesel Epidemiology Expert Panel. Although epidemiologic data have been used generally to identify the hazards associated with exposure to diesel exhaust, questions remain as to whether the human data can be used to develop reliable estimates of the magnitude of any risk for lung cancer (that is, through quantitative risk assessment [QRA]), and whether new research efforts could provide any additional data needed. In response to such issues, the Health Effects Institute initiated the Diesel Epidemiology Project in 1998.

Dr. Kleeberger and colleagues at Johns Hopkins University compared ozone-induced inflammation, epithelial cell injury, and epithelial cell proliferation (a marker of cell injury) in three types of mice: mice with a normal content of mast cells, mutant mice without mast cells, and mutant mice whose mast cells were repleted by a bone marrow transplant from normal mice. Each group of mice was exposed to clean air or to ozone for varying lengths of time.

Drs. Douglas Dockery at the Harvard School of Public Health and C. Arden Pope III at Brigham Young University speculated that exposure to PM might lead to a transient drop in blood oxygenation, which might have serious consequences in humans with heart or lung problems. The investigators designed a study to increase the possibility of observing PM effects by testing a potentially at-risk group (the elderly) at a time of year that historically had experienced relatively high levels of PM (the winter).

Daniel L. Albritton and Daniel S. Greenbaum, cochairs. Report of the PM Measurements Research Workshop, Chapel Hill NC, July 22 and 23, 1998. Aeronomy Laboratory of the National Oceanic and Atmospheric Administration, Boulder, CO, and Health Effects Institute, Cambridge, MA.

Dr. John Peters and colleagues of the University of Southern California School of Medicine compared the lung function, respiratory symptoms, activity levels, and bronchodilator use of 10- to 12-year-old healthy, asthmatic, and wheezy children. They conducted the study in Southern California during mid-spring (when ozone levels were expected to be low) and late summer (when ozone levels were expected to be high).

Dr. Thom and Dr. Ischiropoulos at the University of Pennsylvania Medical Center examined the effects of low concentrations of carbon monoxide on platelets and cells isolated from blood vessels. The investigators exposed blood platelets (taken from rats) and endothelial cells (isolated from bovine blood vessels) to varying concentrations of carbon monoxide and measured how much nitric oxide was released. To determine if exposure to carbon monoxide causes endothelial cells to produce peroxynitrite, the investigators looked for markers of its presence in the culture medium and in the cells.

Communication 5 contains proceedings of a workshop held in Cambridge, MA, December 3–4 1996. Presentations included: Current Understanding of the Health Effects of Particles and the Characteristics That Determine Dose or Effect; Particle Formation in Combustion; The EPA Particle Emissions Testing Procedure; Characterizing Particulate Matter in Motor Vehicle Exhaust; Atmospheric Aerosol Transformation; Generating Particles for Laboratory Studies; and Issues and Research Needs for Particle Characterization.

Dr. John Balmes and colleagues of the University of California, San Francisco, and Dr. Mark Frampton and associates of the University of Rochester characterized ozone-induced responses in two different study populations: normal and asthmatic men and women in the Balmes study (Part I), and male and female nonsmokers and smokers in the Frampton study (Part II). The investigators addressed three issues: (1) Is an individual's reactivity to inhaled methacholine related to changes in lung function after exposure to ozone? (2) What is the relation between ozone-induced airway inflammation and changes in lung function? and (3) Do the changes in lung function and markers of inflammation in response to ozone exposure differ between normal people and people with asthma?

The Phase I.B Report of the Particle Epidemiology Evaluation Project. The Health Effects Institute began the Particle Epidemiology Evaluation Project in 1994 to evaluate the emerging epidemiologic evidence of a relation between particulate air pollution and daily mortality. In Phase I.B, Drs. Jonathan M. Samet and Scott L. Zeger and their colleagues at the Johns Hopkins University School of Hygiene and Public Health (1) compared approaches for controlling the effects of weather variables when analyzing the connection between air pollution and daily mortality, primarily focusing on Synoptic Weather Categories, an approach newly proposed by Dr. Laurence S. Kalkstein of the University of Delaware; and (2) evaluated the association between particulate air pollution and daily mortality in the Philadelphia metropolitan area using statistical models that included data for five pollutants regulated under the Clean Air Act Amendments of 1990 (referred to as criteria pollutants).

Dr. Loomis and colleagues at the University of North Carolina and Dr. Víctor Borja-Aburto of the Instituto Nacional de Salud Pública in Cuernavaca, Mexico, collected mortality, air quality, and weather data from records and monitoring stations in Mexico City from 1990 through 1992. Using statistical techniques, the investigators evaluated the association between mortality and ambient levels of ozone, sulfur dioxide, and total suspended particles, both individually and in a model that included all three pollutants.

Drs. Pollack and Brouwer at the University of North Carolina determined the relationship between methanol exposure and its uptake into and elimination from the blood of nonpregnant and pregnant rodents. The investigators exposed rats and mice at several different stages of gestation to methanol intravenously or orally (doses ranged from 100 mg/kg of body weight to 2,500 mg/kg) or by inhalation (1,000 to 20,000 ppm for 8 hours). They measured blood, urine, and amniotic fluid concentrations of methanol and used the data to develop a model of methanol distribution in rodents.

A Special Report of the Institute's Oxygenates Evaluation Committee. Oxygenated fuel (usually referred to as oxyfuel) was formulated to reduce carbon monoxide emissions and contains at least 2.7% oxygen by adding methyl tert-butyl ether (MTBE) or ethanol. Reformulated gasoline was formulated to help reduce ground-level ozone concentrations and contains at least 2% oxygen, has a reduced content of benzene and other aromatic compounds, and produces limited emissions of total air toxics. The introduction of fuels containing oxygenates elicited concerns from workers and the general public in some areas, including reports of unpleasant odors, headaches, or other symptoms attributed to the fuels, and questions about their effects on the cost of gasoline, the performance of engines, and fuel economy. This Special Report summarizes an intensive review of (1) the existing science of the health effects of oxygenates, (2) the risk evaluations done by the EPA in 1993 and 1994, and (3) in a qualitative way, the health effects of exposure to the new additives as they relate to the health effects of other pollutants whose levels in emissions change when fuels containing oxygenates are used.

In Part III of this study, Dr. Belinsky and his associates at the Lovelace Biomedical and Environmental Research Institute examined lung tumors from rats that had inhaled high concentrations of diesel engine exhaust or carbon black particles (see Part I by Dr. Joe Mauderly). The investigators applied molecular biology techniques to measure mutations in selected genes in the DNA from the tumors.

Dr. Beland and his associates at the University of Arkansas School of Medical Sciences developed an assay to measure mutations induced by dinitropyrenes, a class of diesel engine exhaust, in rats. The investigators analyzed the mutations in a selected gene in spleen T lymphocytes from rats treated with 1,6-dinitropyrene under conditions that induced lung tumors at the highest dose tested. They also examined DNA adduct levels in lung and liver tissues and in spleen lymphocytes and white blood cells.

The Phase I.A Report of the Particle Epidemiology Evaluation Project. The Health Effects Institute began the Particle Epidemiology Evaluation Project in 1994 to evaluate the emerging epidemiologic evidence of a relation between particulate air pollution and daily mortality. In Phase I.A, Drs. Jonathan M. Samet and Scott L. Zeger and their colleagues at the Johns Hopkins University School of Hygiene and Public Health (1) reconstructed from original sources the data set for Philadelphia used in earlier studies and confirmed previous numerical results from analyzing these data; (2) developed an analytic approach (including new statistical methods) based on the Philadelphia data set; and (3) applied this approach to data sets for six locations: Philadelphia; Utah Valley; St. Louis, MO; Eastern Tennessee; Birmingham, AL; and Santa Clara County, CA.

A Special Report of the Institute's Diesel Working Group. Diesel engine emissions have the potential to cause adverse health effects, including cancer and other pulmonary and cardiovascular diseases. However, it is difficult to distinguish the potential health risks attributable to exposure to diesel exhaust from those attributable to other air pollutants. For over a decade, HEI has supported a broad-based research program to evaluate the health risks of diesel emissions, including investigations of carcinogenesis, modeling studies, and emissions characterization. The purpose of this Special Report is to examine what is known, not known, and still uncertain about the health risks of exposure to diesel emissions.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. In this report, two of studies and in the NTP/HEI Collaborative Ozone Project, were conducted to determine whether prolonged inhalation of ozone produces lasting effects on lung structure, potentially contributing to or aggravating chronic lung disease. Drs. Chang and Pinkerton and their respective colleagues investigated the effects of this prolonged ozone exposure on respiratory tract structure in healthy male and female F344/N rats. 

In two separate studies, Drs. Koenig and Utell examined the effects of exposing healthy subjects and subjects with asthma to combined oxidant and acid pollutants. Each team of investigators conducted studies in which human volunteers received either combined or sequential exposures to oxidant gases and acid aerosols and standard pulmonary function tests were performed and symptoms were recorded. Dr. Koenig and colleagues exposed 28 adolescents with asthma to varying concentrations of ozone, nitrogen dioxide, and sulfuric acid. Dr. Utell and colleagues examined the effects of sequential exposures to sulfuric acid and ozone on pulmonary function in 30 subjects with asthma and 30 healthy subjects between the ages of 18 and 45. 

Ozone is the major pollutant in smog. It is formed by complex photochemical reactions between nitrogen oxides and volatile organic compounds in the presence of sunlight. Motor vehicle and industrial emissions are prominent sources of these compounds. Peak atmospheric ozone concentrations generally occur during the summer months because the photochemical reactions that produce ozone are enhanced by sunlight and high temperature.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. Prolonged ozone exposure may injure respiratory tissue, leading to the development or exacerbation of chronic lung diseases such as fibrosis or emphysema. An excess of connective tissue can lead to fibrosis and changes in connective tissue are believed to be an underlying cause of emphysema. Dr.

Dr. James Ultman and colleagues at Pennsylvania State University used a fast-responding ozone measurement system, which they had developed with previous HEI support, to noninvasively measure the absorption of inhaled ozone in different regions of the respiratory tract of healthy adult men. While the subject was breathing through the measurement apparatus, a narrow 10-mL bolus of ozone was introduced into the inhaled air at a predetermined point.

This report describes the quality assurance and quality control program developed for the previously reported epidemiologic study of nitrogen dioxide (NO₂) and respiratory illness in children (Health Effects Institute Research Report 58, Parts I and II). The specific aims of the program were to make certain that data were sufficiently accurate, complete, verifiable, and retrievable.

High doses of inhaled diesel engine exhaust produce lung tumors in laboratory animals and may cause cancer in humans. Nitropyrenes are products of diesel engine exhaust and can be activated by the body\'s metabolism to form highly reactive products that interact with DNA to form DNA adducts. The adducts can interfere with the normal processes of DNA replication and can lead to genetic mutations that may result in carcinogenesis. Dr.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. The study of the effects of long-term ozone exposure on lung collagen, described in this report, was one of eight studies in a Collaborative Project supported by the NTP and the HEI. The others included studies of lung biochemistry, structure, and function, and one study of nasal structure and function. Dr.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. Assessing the risk of adverse health effects from such exposures is difficult because only limited data are available on the actual ozone concentrations that people experience. Under the HEI ozone sampler program, three studies were designed to advance the development and testing of personal ozone samplers. The studies were conducted by Dr. Hackney and colleagues at Rancho Los Amigos Medical Center (Part I), Dr. Koutrakis and colleagues at the Harvard School of Public Health (Part II), and Dr. Yanagisawa from the Harvard School of Public Health (Part III). 

Both environmental and genetic factors are believed to contribute to the multistage process that results in carcinogenesis. Therefore, determining the health risks associated with exposure to known and suspected carcinogenic chemicals is essential for informed decision-making by regulatory agencies. Dr. Roger W. Giese and colleagues at Northeastern University developed sensitive and specific techniques for measuring polycyclic aromatic hydrocarbon (PAH)-DNA adducts, a class of DNA adducts associated with exposure to constituents of diesel emissions and other combustion products.

Devices have been developed to reduce particle emissions from vehicles with diesel engines, such as a trap that filters the particles from the exhaust. Periodically, the trap is cleaned (regenerated) by electric heating, thereby burning the particles before they can clog the trap. There is concern that potentially harmful chemicals associated with the particles may be emitted from the trap during normal use and regeneration. Dr.

HEI's Research Plan to Narrow the Uncertainties. This report of the HEI Electric and Magnetic Fields (EMF) Research Planning Committee presents a 5-7 year research program intended to clarify whether or not there are adverse health effects from exposure of the public to EMF from electric power transmission, machinery, or household appliances.

Carbon monoxide is a ubiquitous air pollutant. It is found in cigarette smoke and emissions from motor vehicles, industrial processes, and poorly ventilated combustion sources. Dr. Penn and his colleagues at New York University Medical Center sought to determine whether chronic exposure to ambient levels of carbon monoxide is also a risk factor for developing atherosclerosis because this disease is the leading contributor to deaths by heart attack and stroke in the United States.

Nitropyrenes, which form during diesel fuel combustion, cause mutations and are carcinogenic in some animals. Dr. Veronica Maher and colleagues at Michigan State University studied the effect of nitropyrene-DNA adducts on gene mutation. The investigators exposed a specific gene, in culture, to each of two nitropyrene derivatives. They then (1) compared the number of adducts formed by each derivative, (2) analyzed the chemical structure of the adducts, and (3) determined in which region of the DNA the adducts formed.

Dr. George Jakab and associates the Johns Hopkins University School of Public Health examined the effects of inhaled formaldehyde, an airway irritant that is part of motor vehicle emissions, on alveolar macrophages. The investigators exposed mice to varying levels of formaldehyde alone or to formaldehyde mixed with carbon black particles. Carbon black particles were chosen because of their similarity to combustion derived particles. Different alveolar macrophage functions were evaluated using two assays.

Dr. Klein-Szanto and colleagues at the Fox Chase Cancer Center employed a novel exposure system to explore the capacity of formaldehyde to cause cancerous changes in human epithelial cells. Formaldehyde is classified as a toxic air pollutant and is emitted in exhaust of motor vehicles, but whether or not formaldehyde is injurious to human health is controversial. The investigators obtained autopsy samples from human infant airways and from adult nasal tissue.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns; however the health significance of these effects is unknown. Dr. David Thomassen and coworkers examined the ability of ozone to alter the structure and growth characteristics of epithelial cells from rat tracheas in ways consistent with precancerous changes.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns; however the health significance of these effects is unknown. Dr. Philip Bromberg and coworkers at the University of North Carolina, Chapel Hill examined whether exposure to ozone alters properties of the airway epithelium.

Nitropyrenes are a class of chemicals found in diesel engine exhaust that can form DNA adducts and are suspected animal carcinogens. Dr. Beland at the University of Arkansas for Medical Sciences examined the relationship between DNA adducts and cancer in laboratory animals treated with 1-nitropyrene, the major nitropyrene present in diesel engine exhaust. The investigator used state-of-the-art techniques to study DNA adducts formed from 1-nitropyrene under different conditions of exposure, with an emphasis on identifying unique adducts that had not been recognized before.

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns; however the health significance of these effects is unknown. Drs. Kenneth Donaldson and coworkers at the Institute of Occupational Medicine examined whether exposure to ozone activates white blood cells to release substances that can damage lung tissue.