The Health Effects Institute

Synopsis
Research Report Number 81

Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes

This Statement, prepared by the Health Effects Institute and approved by its Board of Directors, is a summary of three research projects sponsored by HEI from 1993 to 1996. Dr. Ira Tager and colleagues of the University of California, Berkeley, CA, conducted the first study, Variability of Pulmonary Function Measures; and the second study, An Approach to Retrospective Estimation of Lifetime Ozone Exposure Using a Questionnaire and Ambient Monitoring Data (California Sites); and Dr. Patrick Kinney and colleagues of the University of Columbia, NY, conducted the third study, An Approach to Retrospective Estimation of Lifetime Ozone Exposure Using a Questionnaire and Ambient Monitoring Data (U.S. Sites).

BACKGROUND

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.

STUDY DESIGNS

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.

RESULTS AND IMPLICATIONS

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.

CODE:TAGER/TAGER/KINNEY81

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