Grantee Research Project Results
Final Report: Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes
EPA Grant Number: R828112C081Subproject: this is subproject number 081 , established and managed by the Center Director under grant R828112
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes
Investigators: Tager, Ira , Kinney, Patrick L.
Institution: University of California - Berkeley , Columbia University in the City of New York
EPA Project Officer: Chung, Serena
Project Period: April 1, 2000 through March 31, 2005
RFA: Health Effects Institute (1996) RFA Text | Recipients Lists
Research Category: Air , Human Health
Objective:
Short-term exposure to ozone, a ubiquitous air pollutant, is known to have adverse effects on the respiratory system. These effects, which include cough, shortness of breath, an inflammatory response in the airways, and transient changes in results on some tests of lung function, depend on the duration and intensity of exposure, as well as individual susceptibility. Although these effects appear to be reversible, there is concern that the inflammation associated with prolonged or repeated exposure may lead to permanent changes that affect the small airways. However, the effects of long-term exposure to ozone in humans are difficult to study. One major problem is estimating the concentrations of ozone that individuals have been exposed to over their lifetimes; a second issue is the variability in tests capable of measuring physiologic changes in the small airways. Thus, developing accurate methods for estimating past exposure to ozone and developing precise (that is, reliable or reproducible) tests of small airway function are critical for future studies of long-term human ozone exposure. This report describes the results of two feasibility studies that were designed to address these needs.Summary/Accomplishments (Outputs/Outcomes):
The studies described in this report were conducted by two independent investigator groups: Dr. Ira Tager and colleagues at the University of California at Berkeley (UCB), and Dr. Patrick Kinney and colleagues at the School of Public Health, Columbia University. The objective of both groups was to develop new methods for estimating an individual's past exposure to ozone. To estimate personal exposure to ozone, both groups of investigators combined historical data from a network of ozone monitoring sites (nationwide in Kinney's study, and California-based in Tager's) with data from questionnaires that obtained information about residence history, time spent outdoors, and level of activity while outdoors. To determine the precision of the residence and activity information, both investigators administered the questionnaire a second time to their study subjects.Tager and coworkers studied UCB students who were lifetime residents of areas of California with either high or low levels of air pollution (the Los Angeles Basin or San Francisco Bay Area, respectively). In addition to estimating personal exposure to ozone, they also determined which tests of lung function, particularly small airway function, would be the most precise to use in a future, larger epidemiologic study. As part of his study, Tager then measured lung function in subjects whose long-term exposure to ozone he had previously estimated. Kinney studied Yale University students who had lived in different regions of the United States. He focused on evaluating the accuracy of different statistical methods for estimating previous ozone exposure, and in particular, on determining how many ozone monitoring sites were needed to provide data to make accurate estimates.
The studies of Tager and Kinney are important efforts to develop retrospective methods for estimating an individual's lifetime exposure to ozone. Of the methods Kinney tested on the nationwide data set, a statistical regression technique that incorporated data from the three nearest ozone monitoring sites, was the most accurate and straightforward. The largest differences between predicted ozone estimates and actual readings were found predominantly in California, mostly around Los Angeles, and in the New York/New Jersey/Connecticut metropolitan area. This finding suggests that it may be difficult to make exposure estimates in locations where ozone levels are high and variable. Using this method, Kinney found that distance from the nearest monitoring site (up to 30 miles) did not affect the accuracy of the estimate. This is a reassuring finding, implying that accurate estimates of ozone can be made even in rural areas where ozone monitors are far apart. However, when Kinney applied a different statistical method (known as "kriging" and based on distance) to a subset of his data, he found that the exposure estimates improved. This implies that more work is needed to determine the impact of distance from a monitoring site on ozone exposure estimates.
Tager combined questionnaire information about residential history and activity patterns with long-term data from California ozone monitoring sites. The precision of responses from subjects on retest after a five- to seven-day interval was high. However, subjects' responses to Kinney's questionnaire about residence and activity patterns were in only moderate agreement after a one-month interval. Neither investigator attempted to confirm this information with an independent source, such as the subjects' parents. Not unexpectedly, Tager found that subjects who had resided for a long time in the Los Angeles Basin had higher estimated lifetime ozone exposures than subjects who had lived in the San Francisco Bay Area.
Tager also found in a laboratory setting that two measures of airflow through small airways (FEF75% and FEF25%?75%) were reproducible both from person to person and from test to test, whereas one other measure Of small airway function, [DELTA]N2, was not. This finding confirms results from previous studies, and suggests that FEF75% and FEF25%?75% may be useful measures of small airway function in future large-scale epidemiologic studies of air pollution health effects.
In a preliminary study, Tager found that the subjects who had the highest estimates of cumulative ozone exposure (those who had lived in the Los Angeles Basin) had lower FEF75% and FEF25%?75% values than those who had the lowest estimates of cumulative exposure (residents of the San Francisco Bay Area). This is a provocative and potentially important finding because it suggests that subjects who have spent a long time in an environment containing high levels of ozone (and other air pollutants) may have decreased small airway function (compared with those living in a low-pollutant environment). However, because other study factors may influence these observations (such as differences between regions or among the ethnic backgrounds of subjects in different regions, and lack of overlapping ozone levels between the regions), these results should be interpreted cautiously. Studying appropriately matched subjects who have been exposed to a range of ozone levels is needed to substantiate the findings.
Tager and Kinney have taken important steps in developing approaches for retrospective estimation of past exposure to ozone. Both investigators used fixed-site ambient monitoring data accumulated over many years and devised statistical models to estimate ozone concentrations at locations distant from the monitoring sites. Their approaches are based on a number of reasonable assumptions about what influences an individual's received dose. The investigators are now ready to test and, to the extent possible, validate their methods. If such studies are successful, the investigators' methods should advance air pollution epidemiology.
Supplemental Keywords:
Air, ambient air quality, air toxics, epidemiology, health effects, particulate matter, human health risk assessment, mobile sources, ozone, inhalation studies, human exposure, biochemistry, cumulative effects., RFA, Health, Scientific Discipline, Air, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, mobile sources, Biochemistry, indoor air, ambient air quality, particulates, lung injury, motor vehicles, exposure and effects, human health effects, inhalability, air pollutants, lung, engines, epithelial cells, ozone, animal model, epidemelogy, ambient air, air pollution, environmental health effects, ozone samplers, automobiles, emissions, human exposure, inhalation, carcinogens, ambient particle health effects, particulate exposure, lung inflammation, inhalation toxicology, ozone monitoring, inhaled, indoor air quality, human health, human health risk, air quality, long-term exposureProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R828112 Center for Integrative Research on Childhood Leukemia and the Environment - 2015 Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R828112C042 Does Inhalation of Methanol Vapor Affect Human Neurobehavior?
R828112C043 Human Responses to Nitrogen Dioxide
R828112C044 The Role of Inflammation in Ozone-Induced Lung Injury
R828112C045 How Does Exercise Affect the Dose of Inhaled Air Pollutants?
R828112C046 How Do Chemicals in Diesel Engine Exhaust Damage DNA?
R828112C047 Effect of Nitrogen Dioxide on Bacterial Respiratory infectionin Mice
R828112C048 Effects of Ozone Exposure on Airway Epithelium
R828112C049 Inhalation of Aldehydes and Effects on Breathing
R828112C050 Does Ozone Cause Precancerous Changes in Cells?
R828112C051 Effects of Formaldehyde on Human Airway Epithelial Cells Exposed in a Novel Culture System
R828112C052 Carbon Monoxide and Cardiac Arrhythmias
R828112C053 Effects of Formaldehyde and Particle-Bound Formaldehyde on Lung Macrophage Functions
R828112C054 Mechanisms for Protecting Lung Epithelial Cells Against Oxidant Injury
R828112C055 Relationship of Nitropyrene-Derived DNA Adducts to Carcinogenesis
R828112C056 Particle Trap Effects on Heavy-Duty Diesel Engine Emissions
R828112C057 Carbon Monoxide and Atherosclerosis
R828112C058 Nitrogen Dioxide and Respiratory Illness in Children
R828112C059 Noninvasive Methods for Measuring Ventilation in Mobile Subjects
R828112C060 Oxidant Air Pollutants and Lung Cancer: An Animal Model
R828112C061 Detection of Carcinogen-DNA Adducts: Development of New Methods
R828112C062 Effects of Carbon Monoxide on Heart Muscle Cells
R828112C063 Development of Personal Ozone Samplers: Three Approaches
R828112C064 Development of Biomarkers to Monitor Carcinogen Exposure
R828112C065 Effects of Prolonged Ozone Inhalation on Collagen Structure and Content in Rat Lungs
R828112C065II Prolonged Ozone Exposure and the Contractile Properties of Isolated Rat Airways
R828112C065III Changes in Complex Carbohydrate Content and Structure in Rat Lungs Caused by Prolonged Ozone Inhalation
R828112C065IV Genetic Control of Connective Tissue Protein Synthesis After Prolonged Ozone Inhalation
R828112C065V Pulmonary Function Alterations in Rats After Chronic Ozone Inhalation
R828112C065VII Prolonged Ozone Exposure Leads to Functional and Structural Changes in the Rat Nose
R828112C065VIII - IX Studies of Changes in Lung Structure and Enzyme Activitiesin Rats After Prolonged Exposure to Ozone
R828112C065X An Innovative Approach to Analyzing Multiple Experimental Outcomes: A Case Study of Rats Exposed to Ozone
R828112C065XI The Consequences of Prolonged Inhalation of Ozone on Rats:
An Integrative Summary of the Results of Eight Collaborative Studies
R828112C066 Interactive Effects of Nitropyrenes in Diesel Exhaust
R828112C067 Detection of FormaldehydeDNA Adducts: Development of New Methods
R828112C068I Comparison of the Carcinogenicity of Diesel Exhaust and Carbon Black in Rat Lungs
R828112C068II An Investigation of DNA Damage in the Lungs of Rats Exposed to Diesel Exhaust
R828112C068III No Evidence For Genetic Mutations Found In Lung Tumors From Rats Exposed To Diesel Exhaust or Carbon Black
R828112C069 Noninvasive Determination of Respiratory Ozone Absorption: The Bolus-Response Method
R828112C070 The Effects of Inhaled Oxidants and Acid Aerosols on Pulmonary Function
R828112C071 Biochemical Consequences of Ozone Reacting with Membrane Fatty Acids
R828112C072 DNA Mutations in Rats Treated with a Carcinogen Present in Diesel Exhaust
R828112C073 Developmental Neurotoxicity of Inhaled Methanol in Rats
R828112C074 Methanol Distribution in Non Pregnant and Pregnant Rodents
R828112C075 Is Increased Mortality Associated with Ozone Exposure in Mexico City?
R828112C076 Effects of Fuel Modification and Emission Control Devices on Heavy-Duty Diesel Engine Emissions
R828112C077 Metabolic Studies in Monkeys Exposed to Methanol Vapors
R828112C078 Effects of Ozone on Pulmonary Function and Airway Inflammation in Normal and Potentially Sensitive Human Subjects
R828112C079 Improvement of a Respiratory Ozone Analyzer
R828112C080 Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide
R828112C081 Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes
R828112C082 Effects of Ambient Ozone on Healthy, Wheezy, and Asthmatic Children
R828112C083 Daily Changes in Oxygen Saturation and Pulse Rate Associated with Particulate Air Pollution and Barometric Pressure
R828112C084 Evaluation of The Potential Health Effects of the Atmospheric Reaction Products of Polycyclic Aromatic Hydrocarbons
R828112C085 Mechanisms of Response to Ozone Exposure: The Role of Mast Cells in Mice
R828112C086 Statistical Methods for Epidemiologic Studies of the Health Effects of Air Pollution
R828112C087 Development of New Methods to Measure Benzene Biomarkers
R828112C088 Alveolar Changes in Rat Lungs After Long-Term Exposure to Nitric Oxide
R828112C089 Effects of Prenatal Exposure to Inhaled Methanol on Nonhuman Primates and Their Infant Offspring
R828112C090 A Pilot Study of Potential Biomarkers of Ozone Exposure
R828112C091 Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs
R828112C092 Cancer, Mutations, and Adducts in Rats and Mice Exposed to Butadiene and Its Metabolites
R828112C093 Effects of Concentrated Ambient Particles in Rats and Hamsters: An Exploratory Study
R828112C094I The National Morbidity, Mortality, and Air Pollution Study: Methods and Methodologic Issues
R828112C094II The National Morbidity, Mortality, and Air Pollution Study: Morbidity and Mortality from Air Pollution in the United States
R828112C095 Association of Particulate Matter Components with Daily Mortality and Morbidity in Urban Populations
R828112C096 Acute Pulmonary Effects of Ultrafine Particles in Rats and Mice
R828112C097 Identifying Subgroups of the General Population That May Be Susceptible to Short-Term Increases in Particulate Air Pollution
R828112C098 Daily Mortality and Fine and Ultrafine Particles in Erfurt, Germany
R828112C099 A Case-Crossover Analysis of Fine Particulate Matter Air Pollution and Out-of-Hospital Sudden Cardiac Arrest
R828112C100 Effects of Mexico City Air on Rat Nose
R828112C101 Penetration of Lung Lining and Clearance of Particles Containing Benzo[a]pyrene
R828112C102 Metabolism of Ether Oxygenates Added to Gasoline
R828112C103 Characterization and Mechanisms of Chromosomal Alterations Induced by Benzene in Mice and Humans
R828112C104 Acute Cardiovascular Effects in Rats from Exposure to Urban Ambient Particles
R828112C105 Genetic Differences in Induction of Acute Lung Injury and Inflammation in Mice
R828112C106 Effects on Mice of Exposure to Ozone and Ambient Particle Pollution
R828112C107 Emissions from Diesel and Gasoline Engines Measured in Highway Tunnels
R828112C108 Case-Cohort Study of Styrene Exposure and Ischemic Heart Disease Investigators
R828112C110 Effects of Metals Bound to Particulate Matter on Human Lung Epithelial Cells
R828112C111 Effect of Concentrated Ambient Particulate Matter on Blood Coagulation Parameters in Rats
R828112C112 Health Effects of Acute Exposure to Air Pollution
R828112C113 Benzene Metabolism in Rodents at Doses Relevant to Human Exposure from Urban Air
R828112C114 A Personal Particle Speciation Sampler
R828112C115 Validation and Evaluation of Biomarkers in Workers Exposed to Benzene in China
R828112C116 Biomarkers in Czech Workers Exposed to 1,3-Butadiene: A Transitional Epidemiologic Study
R828112C117 Peroxides and Macrophages in the Toxicity of Fine Particulate Matter in Rats
R828112C118 Controlled Exposures of Healthy and Asthmatic Volunteers to Concentrated Ambient Particles in Metropolitan Los Angeles
R828112C119 Manganese Toxicokinetics at the Blood-Brain Barrier
R828112C120 Effects of Exposure to Concentrated Ambient Particles from Detroit Air on Healthy Rats and Rats with Features of Asthma or Mild Bronchitis
R828112C121 Field Evaluation of Nanofilm Detectors for Measuring Acidic Particles in Indoor and Outdoor Air
R828112C123 Time-Series Analysis of Air Pollution and Mortality: A Statistical Review
R828112C126 Effects of Exposure to Ultrafine Carbon Particles in Healthy Subjects and Subjects with Asthma
R828112C128 Neurogenic Responses of Rat Lung to Diesel Exhaust
R828112C130-I Relationships of Indoor, Outdoor, and Personal Air (RIOPA). Part I. Collection Methods and Descriptive Analyses
R828112C132 An Updated Study of Mortality Among North American Synthetic Rubber Industry Workers
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.