William F. McDonnell

Pulmonary Function and Symptom Responses after 6.6-Hour Exposure to 0.12 ppm Ozone with Moderate Exercise

Episodes occasionally occur when ambient ozone (O3) levels remain at or near 0.12 ppm for more than 6 h. Small decrements In lung function have been reported following 2-h exposures to 0.12 ppm O3. For short exposures to higher O3 concentrations, lung function decrements are a function of exposure duration. Thus, we investigated the hypothesis that prolonged exposure to 0.12 ppm O3 would result in progressively larger changes in respiratory function and symptoms over time. Ten nonsmoking males (18-33 yr) were exposed once to clean air and once to 0.12 ppm O3 for 6.6 h. Exposures consisted of six 50-min exercise periods, each followed by 10-min rest and measurement; a 35-min lunch period followed the third exercise period. Exercise ventilation averaged approximately 40 L/min. Forced expiratory and inspiratory spirometry and respiratory symptoms were measured prior to exposure and after each exercise. Airway reactivity to methachollne was determined after each exposure. After correcting for the air exposure...

Relationships of mortality with the fine and coarse fractions of long-term ambient PM10 concentrations in nonsmokers.

In a cohort of 6338 California Seventh-day Adventists, we previously observed for males associations between long-term concentrations of particulate matter (PM) with an aerodynamic diameter less than 10 µm (PM10) and 15-year mortality due to all natural causes (ANC) and lung cancer (LC) listed as underlying causes of death and due to nonmalignant respiratory disease listed as either the underlying or a contributing (CRC) cause of death. The purpose of this analysis was to determine whether these outcomes were more strongly associated with the fine (PM2.5) or the coarse (PM2.5–10) fractions of PM10. For participants who lived near an airport (n=3769), daily PM2.5 concentrations were estimated from airport visibility, and on a monthly basis, PM2.5–10 concentrations were calculated as the differences between PM10 and PM2.5. Associations between ANC, CRC, and LC mortality (1977–1992) and mean PM10, PM2.5, and PM2.5–10 concentrations at study baseline (1973–1977) were assessed using Cox proportional hazards models. Magnitudes of the PM10 associations for the males of this subgroup were similar to those for the males in the entire cohort although not statistically significant due to the smaller numbers. In single-pollutant models, for an interquartile range (IQR) increase in PM10 (29.5 µg/m3), the rate ratios (RRs) and 95% confidence intervals (CI) were 1.15 (0.94, 1.41) for ANC, 1.48 (0.93, 2.34) for CRC, and 1.84 (0.59, 5.67) for LC. For an IQR increase in PM2.5 (24.3 µg/m3), corresponding RRs (95% CI) were 1.22 (0.95, 1.58), 1.64 (0.93, 2.90), and 2.23 (0.56, 8.94), and for an IQR increase in PM2.5–10 (9.7 µg/m3), corresponding RRs (95% CI) were 1.05 (0.92, 1.20), 1.19 (0.88, 1.62), and 1.25 (0.63, 2.49), respectively. When both PM2.5 and PM2.5–10 were entered into the same model, the PM2.5 estimates remained stable while those of PM2.5–10 decreased. We concluded that previously observed associations of long-term ambient PM10 concentration with mortality for males were best explained by a relationship of mortality with the fine fraction of PM10 rather than with the coarse fraction of PM10.

Time-dependent changes of markers associated with inflammation in the lungs of humans exposed to ambient levels of ozone.

The original purpose of the Aspen Cancer Conference series, as conceived a number of years ago, was to explore the relationship between toxicity and carcinogenesis with the idea that knowledge of the mechanisms involved would bring about, among other things, the development of an approach to the regulation of toxic substances in our environment, both mutagenic and nonmutagenic. As the Conference series evolved over the years, its original concept has, indeed, proven successful and has continued in this direction. Also, its format of holding small Workshops every other year, with participants giving both formal presentations followed by lengthy informal discussions and planning topics and presentations for the following year’s larger meeting, allows time to discuss and select areas which are of paramount and continued importance. This same type of format is then carried over to the following year to the larger (75-80 participants) Conference, thereby providing a unique opportunity for scientists from industry, academia, and government, working in widely diverse disciplines, to meet, present their most recent data

An Air Quality Data Analysis System for Interrelating Effects, Standards, and Needed Source Reductions: Part 11. A Lognormal Model Relating Human Lung Function Decrease to O3 Exposure

Forced expiratory volume in 1 second (FEV1) was measured in 21 men exercising while exposed to four O3 concentrations (0.0,0.08,0.10, and 0.12 ppm). A lognormal multiple linear regression model was fitted to their mean FEV1 measurements to predict FEV1 percent decrease as a function of O3 concentration and exposure duration. The exercise level used was probably comparable to heavy manual labor. The longest O3, exposure studied was 6 h. Extrapolating cautiously to an 8-h workday of heavy manual labor, the model predicts that O3 concentrations of 0.08, 0.10, and 0.12 ppm would decrease FEV1 by 9,15, and 20 percent, respectively.

The respiratory responses of subjects with allergic rhinitis to ozone exposure and their relationship to nonspecific airway reactivity.

Ozone exposure in man produces changes in respiratory function and symptoms. There is a large degree of unexplained intersubject variability in the magnitude of these responses. There is concern that individuals with chronic respiratory diseases may also be more responsive to ozone than normal individuals. The purpose of this study was to describe the responses of subjects with allergic rhinitis to ozone exposure and to compare these responses to those pre viously observed in normal individuals. A further purpose was to measure the association of baseline nonspecific airway reactivity with changes in lung function and respiratory symptoms following ozone exposure. A group of 26 nonasthmatic subjects with allergic rhinitis performed a bronchial inhalation challenge with histamine and subsequently underwent two hour exposures to both clean air and to 0.18 part per million ozone with alternating periods of rest and heavy exercise. The airway reactivity of this group of subjects was no greater than that of a comparable group of subjects without allergic rhinitis. The respiratory responses of these subjects to ozone exposure were similar to those previously reported for sub jects without allergic rhinitis with the exception that the allergic rhinitis subjects appeared to have a modestly increased broncho constrictor response compared to normals. Furthermore, we observed no significant relationships between nonspecific airway reactivity and response to ozone as measured by changes in lung function or the induction of symptoms.

Prediction of lung function response for populations exposed to a wide range of ozone conditions

Context: A human exposure–response (E–R) model previously demonstrated to accurately predict population mean FEV1 response to ozone exposure has been proposed as the foundation for future risk assessments for ambient ozone.Objective: Fit the original and related models to a larger data set with a wider range of exposure conditions and assess agreement between observed and population mean predicted values. Materials and methods: Existing individual E–R data for 23 human controlled ozone exposure studies with a wide range of concentrations, activity levels, and exposure patterns have been obtained. The data were fit to the original model and to a version of the model that contains a threshold below which no response occurs using a statistical program for fitting nonlinear mixed models. Results: Mean predicted FEV1 responses and the predicted proportions of individuals experiencing FEV1 responses greater than 10, 15, and 20% were found to be in agreement with observed responses across a wide range of exposure conditions for both models. The threshold model, however, provided a better fit to the data than the original, particularly at the lowest levels of exposure. Conclusion: The models identified in this manuscript predict population FEV1 response characteristics for 18–35-year-old individuals exposed to ozone over a wide range of conditions and represent a substantial improvement over earlier E–R models. Because of its better fit to the data, particularly at low levels of exposure, the threshold model is likely to provide more accurate estimates of risk in future risk assessments of ozone-induced FEV1 effects.

Biomarkers of Dose and effect of Inhaled Ozone in Resting versus exercising Human subjects: comparison with Resting Rats

To determine the influence of exercise on pulmonary dose of inhaled pollutants, we compared biomarkers of inhaled ozone (O3) dose and toxic effect between exercise levels in humans, and between humans and rats. Resting human subjects were exposed to labeled O3 (18O3, 0.4 ppm, for 2 hours) and alveolar O3 dose measured as the concentration of excess 18O in cells and extracellular material of nasal, bronchial, and bronchoalveolar lavage fluid (BALF). We related O3 dose to effects (changes in BALF protein, LDH, IL-6, and antioxidant substances) measurable in the BALF. A parallel study of resting subjects examined lung function (FEV1) changes following O3. Subjects exposed while resting had 18O concentrations in BALF cells that were 1/5th of those of exercising subjects and directly proportional to the amount of O3 breathed during exposure. Quantitative measures of alveolar O3 dose and toxicity that were observed previously in exercising subjects were greatly reduced or non-observable in O3 exposed resting subjects. Resting rats and resting humans were found to have a similar alveolar O3 dose.

Infant Death and Childhood Cancer Reductions after Nuclear Plant Closings in the United States

Abstract Subsequent to 1987, 8 U.S. nuclear plants located at least 113 km from other reactors ceased operations. Strontium-90 levels in local milk declined sharply after closings, as did deaths among infants who had lived downwind and within 64 km of each plant. These reductions occurred during the first 2 yr that followed closing of the plants, were sustained for at least 6 yr, and were especially pronounced for birth defects. Trends in infant deaths in proximate areas not downwind, and more than 64 km from the closed plants, were not different from the national patterns. In proximate areas for which data were available, cancer incidence in children younger than 5 yr of age fell significantly after the shutdowns. Changes in health following nuclear reactor closings may help elucidate the relationship between low-dose radiation exposure and disease.

The temporal dynamics of ozone-induced FEV1 changes in humans: an exposure-response model.

Although ozone is known to induce reversible decrements in forced expiratory volume in 1 s (FEV1), no exposure-response model has been identified that accurately describes the dynamics of response to the changing concentrations and activity patterns of normal ambient human exposure. The purpose of the current analysis was to identify and evaluate a dynamic model of FEV1 response using a large existing data set (541 volunteers, 864 exposures, 3485 FEV1 measures) with a wide range of exposure conditions (ozone = 0.0 to 0.4 ppm, activity level = rest to heavy exercise, duration = 1 to 7.6 h), including recovery in clean air. A previously described model containing a differential equation and a logistic function was modified to include a new between-subjects variance structure and was fitted to the data. The model described well the mean observed response data across the range of exposure conditions, including the periods of recovery in clean air. Predicted values of individual responses were distributed lognormally and appeared to accurately describe the distribution of observed responses. We observed that responsiveness to ozone decreased with age, that response was weakly related to body size, and that response was marginally more sensitive to changes in ozone concentration than to changes in minute ventilation. In summary, we have identified a dynamic ozone exposure-response model that accurately describes the temporal pattern of FEV1 response to a wide range of changing exposure conditions and that may have utility for predicting population responses to ambient exposures.

An unexpected rise in strontium-90 in US deciduous teeth in the 1990s.

For several decades, the United States has been without an ongoing program measuring levels of fission products in the body. Strontium-90 (Sr-90) concentrations in 2089 deciduous (baby) teeth, mostly from persons living near nuclear power reactors, reveal that average levels rose 48.5% for persons born in the late 1990s compared to those born in the late 1980s. This trend represents the first sustained increase since the early 1960s, before atmospheric weapons tests were banned. The trend was consistent for each of the five states for which at least 130 teeth are available. The highest averages were found in southeastern Pennsylvania, and the lowest in California (San Francisco and Sacramento), neither of which is near an operating nuclear reactor. In each state studied, the average Sr-90 concentration is highest in counties situated closest to nuclear reactors. It is likely that, 40 years after large-scale atmospheric atomic bomb tests ended, much of the current in-body radioactivity represents nuclear reactor emissions.