Exposure to ozone, a potent photochemical oxidant in the ambient air, is a major health concern in urban and rural communities throughout the United States. Nationally, average ozone levels have decreased by 14% from 1990 to 2008. In the Eastern United States, much of the improvement in ozone levels has occurred since 2002 due largely to reductions in emissions of oxides of nitrogen (an ozone precursor). Still, in 2009, 61.5 million people in the United States resided in counties where the ozone NAAQS was exceeded.
Based on the evidence integrated across human controlled exposure and epidemiological and toxicological studies, there is clear, consistent evidence of a causal relationship between short-term exposure (i.e., from days to weeks) to ozone and respiratory effects. Human clinical and toxicological studies show that short-term exposures to ozone cause lung function decrements, respiratory symptoms, lung inflammation, epithelial damage, and permeability, and increases in airway responsiveness (a condition in which the conducting airways have an enhanced bronchoconstriction following exposure to variety of stimuli, e.g., allergens, cold air, sulfur dioxide). Collectively, these findings provide biological plausibility for associations in epidemiological studies between short-term ambient exposure to ozone and asthma exacerbation, respiratory-related hospitalizations, and emergency department visits.
The magnitude of respiratory effects (e.g., decrements in pulmonary function and symptomatic responses) is generally a function of ozone concentration, minute ventilation rate (volume of air inhaled per minute), and exposure duration. Any physical activity will increase minute ventilation and therefore the dose of inhaled ozone. For healthy young adults exposed in a controlled clinical study at rest for 2 h, 500 ppb is the lowest ozone concentration reported to produce a statistically significant group mean decrements in lung function. With longer, 7-h exposures to as low as 60 ppb ozone, during a moderate level of exercise, statistically significant decrements in lung function, increases in respiratory symptoms, and pulmonary inflammation have been reported. Although there is a relatively rapid recovery in pulmonary function and respiratory symptoms over a few hours following exposure, the inflammatory response occurs shortly after exposure and persists for at least one day. An influx of neutrophils and an increase in a number of mediators including eicosanoids, neutrophil elastase, and cytokines have been measured in bronchoalveolar lavage fluid recovered from subjects exposed to near ambient concentrations of ozone.
In otherwise young healthy adults exposed for 2–8 h to ozone, controlled clinical studies have demonstrated a large degree of intersubject variability in lung function decrements, respiratory symptom responses, inflammation, airway responsiveness, and altered epithelial permeability. The magnitude of increases in inflammation, airway responsiveness, and epithelial permeability, in response to ozone exposure, do not appear to be correlated, nor are these responses correlated with changes in lung function. However, these responses of healthy individuals to ozone tend to be reproducible within a given person over a period of several months indicating differences in the intrinsic responsiveness of individuals. It should be noted that even when group mean responses are small and seem physiologically insignificant, some intrinsically more responsive individuals experience distinctly larger effects under the same exposure conditions. For example, small group mean changes (e.g., 2–3%) in forced expiratory volume in 1 s (FEV1) have been observed in healthy young adults exposed to 60 ppb ozone for 7 h. However, 10% of the group may experience FEV1 decrements in excess of 10% under these conditions, even with group mean decrements of less than 3%. Therefore, within the general population, a proportion of otherwise healthy individuals experience greater than average health effects and may be at increased risk of more adverse responses.
With repeated ozone exposures over several days, lung function and respiratory symptom responses become attenuated in both healthy individuals and asthmatics, but this tolerance is lost after about a week without exposure. Airway responsiveness also appears to be somewhat attenuated with repeated ozone exposures in healthy individuals, but becomes increased in individuals with preexisting allergic airway disease. Some indicators of pulmonary inflammation are attenuated with repeated ozone exposures, whereas other markers, such as epithelial integrity and damage, do not show attenuation, suggesting continued tissue damage during repeated ozone exposure. Both respiratory symptoms and decrements in pulmonary function have neural components and these responses decrease with increasing age beyond young adulthood. However, other cell and molecular responses to ozone exposure likely exist and may even increase as antioxidant defenses change with increasing age.
The adverse functional effects observed in controlled clinical studies are similar to those reported during exposure to ambient air. Decrements in lung function have been noted in a series of camp studies in which children were exposed to ambient ozone during normal outdoor play activity. Compared to controlled chamber studies, greater decrements in lung function were observed in the camp studies when the data were normalized for ozone concentration. A number of factors may explain the greater response in the camp study, but the most likely reason is the simultaneous exposure to ambient co-pollutants such as acid aerosols. Epidemiological studies have found strong correlations between respiratory symptoms such as cough, throat irritation, and chest discomfort and ambient ozone levels. Exacerbation of asthma increases in hospital admissions for respiratory infections, and excess mortality has also been reported to be associated with oxidant air pollution episodes. Older age, female sex, ethnicity, atrial fibrillation, socioeconomic status indicators (i.e., educational attainment, income level, employment status), and diabetes modify ozone mortality associations and may increase susceptibility to ozone-related mortality. Thus, a number of epidemiological, field, and clinical studies provide evidence that adverse respiratory effects occur after acute exposure to ozone at or below the current US NAAQS.
Population-based epidemiological and animal toxicology studies examining the effects of long-term ozone exposure (i.e., from months to years) show associations with long-term reductions in lung function, development of asthma, pathological changes, and premature mortality. Animal studies using concentrations well above the current NAAQS reveal that the centriacinar region of the airways and the nasal cavity are the most sensitive to pathological changes induced by chronic ozone. Studies of infant primates show changes in immune responses similar to asthma and the development of irreversible changes to the structure of the distal (deep) lung that decrease pulmonary function. Epidemiological studies have demonstrated that chronic exposure to ozone is associated with decrements in lung function and increases in the incidence and severity of asthma. Limited new epidemiological evidence also suggests that long-term exposure to ozone increases the risk of premature mortality. The ability of these epidemiological studies to establish cause and effect is hampered by confounding factors such as co-pollutants.
Overall, evidence shows that both short- and long-term exposure to ozone at ambient concentrations is associated with respiratory morbidity and premature mortality.