Chapter 21 Effects of Air Pollution on Human Health

In the 20th century, there were several major air pollution “disasters” (Meuse Valley, Belgium, 1930; Donora, Pennsylvania, 1948; London, 1952). To the extent that real changes in the control of air pollution occurred in the United States, these episodes apparently did not generate sufficient political or public health interest in the health effects of air pollutants. The Clean Air Act of 1963 and its subsequent amendment in 1970, along with formation of the Environmental Protection Agency led to implementation of National Ambient Air Quality standards for several major pollutants (photochemical oxidants [ozone], sulfur oxides, nitrogen oxides, carbon monoxide, hydrocarbons, and particulate matter; lead was added later, and hydrocarbons were incorporated in the ozone standard). The passage of the Clean Air Act sparked a renewed interest in the health effects of air pollutants that has continued to the present.

The investigation of the effects of air pollution on human health has followed a multidisciplinary approach using animal toxicology, epidemiology, controlled human exposure studies, and, more recently, molecular and cell biology. Air pollutants may, in addition to other responses, cause lung cell damage, inflammatory responses, impairment of pulmonary host defenses, and acute changes in lung function and respiratory symptoms as well as chronic changes in lung cells and airways. Substances subsequently absorbed into the blood, such as lead or carbon monoxide, can have a variety of effects on other tissues. Acute and chronic exposure to air pollutants is also associated with increased mortality and morbidity. The focus of this review is on the human health effects of air pollutants as determined through controlled human exposure studies and emphasizes the responses that have been shown with ozone, sulfur dioxide, and carbon monoxide. Not only vehicles, population increase,and urbanization are some of the major factors responsible for air pollution, several industries emit a great deal of pollutants into the air, including those related to cement, refineries, fine chemicals, petrol chemicals, thermal power plants, and mines.

Acidic Pollutants and Particulate Matter

Airborne Acid

Sulfuric acid (H2SO4) is thought to be one of the main ingredients in the London“killer fogs” of the 1950s. Today, in addition to H2SO4, nitric acid (HNO3) vapor is recognized as a significant component of airborne acidity. Despite the fact that investigations of the effects of sulfuric acid aerosols began in 1952, little is known about the possible mechanisms by which acid aerosols could contribute to increased mortality. Increased interest in sulfuric acid aerosols developed in 1975 with the advent of catalytic converters, early models of which produced substantial amounts of acid aerosol. More recent emphasis on acid rain and its important ecological effects has renewed interest in the human health effects of acid aerosols.

The most sensitive physiological end point for effects of sulfuric acid in healthy adults is a change in mucociliary clearance, apparently induced by increased airway acidity. Responses in humans have been reported at levels as low as 100 μg/m3. In healthy adults, there have been few lung function responses seen at acid levels below 500 μg/m3, a level approximately 10-fold greater than the highest ambient levels measured. At these levels, H2SO4also causes an increase in airway responsiveness. Recent work suggests that prolonged, repeated exposures to acid aerosols may induce increased airway responsiveness and changes in clearance. Adolescent allergic asthmatics are more sensitive to H2SO4, and responses have been observed at levels as low as 70-100 μg/m3. The broad range of response to acid aerosols may be in part attributable to the substantial and highly variable capability for neutralization of acid by airway ammonia, primarily from oral bacteria.

Studies of exposure to HNO3 vapor suggest possible pulmonary function responses in asthmatics and some alterations of macrophage function. Because HNO3 vapor is taken up almost entirely in the upper airways, it will be important to examine responses in the nose, an area that has at present been overlooked.

More work is necessary to understand the effects of acid inhalation on mucus-producing cells, mucus rheology and buffering capacity. Increased secretory cells are seen in rabbits after prolonged acid exposure, and increased frequency of bronchitis and respiratory illness has been associated with particulate sulfate exposure in children. It has also been postulated that there is a relationship between acid inhalation and the exacerbation of chronic bronchitis. Such a connection is speculative at this time but could possibly explain, in part, the relationship between particulate exposure and increased mortality.

Particulate Matter

Acute exposure to airborne particles is associated with increased mortality. The 1952 London fog was associated with about 4000 excess deaths, primarily among those with preexisting cardiovascular or respiratory disease. Schwartz and Dockery examined daily mortality and total suspended particulate (TSP) levels in Philadelphia using a Poisson regression model controlling for serial correlations and found a significant association of TSP level and mortality on the following day. The association was stronger for persons over the age of 65 and for respiratory deaths (COPD and pneumonia).

Exposure to particulate matter (PM) is also strongly associated with morbidity. Dockery et al. as part of the Harvard Six-Cities study, demonstrated a decrease in pulmonary function that was associated with episodes of PM and SO2 pollution. These decrements in lung function appear to persist for several weeks after the episode. Recent studies of children in a Utah community showed that respirable particulate (PM< 10 μm or PM10) levels of 150μg/m3were associated with a 3%-6% decline in peak expiratory flow, an effect that persisted for up to 3 days. Furthermore, Ware et al. showed that the prevalence of cough and bronchitis was positively associated with ambient particulate concentrations. Recent and very convincing evidence supports these observations. Pope demonstrated a doubling of respiratory hospital admissions for bronchitis and asthma associated with the operation of a steel mill, responsible for production of up to 70% of the regional PM10. Asthma and bronchitis admissions were also twice as high as in adjacent areas not impacted by the steel mill; these differences were much smaller when the steel mill was closed. These observations support an emerging view that particulate pollution is an important risk factor for acute changes in lung function and respiratory symptoms, increased acute and chronic respiratory illness, and death among high risk groups.

Lead

Lead can enter the body by either inhalation, dermal absorption, or ingestion; the effects generally cannot be differentiated between exposure routes. Although the effects of ingested lead were evident in ancient times, the public health significance of airborne lead dates back primarily to the extensive use of lead in gasoline, which may have accounted for as much as 90% of airborne lead before the mandated elimination of lead in motor vehicle fuels. Some of the most important health end points associated with low-level lead exposure are the complex of neurological deficits, particularly in children, modest elevations in blood pressure in adults, and developmental problems.

Controlled human exposures have played little if any important role in determining these problems, although more effort must be expended to understand the mechanisms of these responses in the future. High blood lead (Pb B) concentrations cause frank brain damage and slowing of nerve conduction. Intelligence (IQ) deficits in children have been associated with Pb B levels as low as 100-150 μg/L, and there appears to be no evidence of a threshold for the effect. In addition, hearing is adversely affected by increased Pb B levels also with no evidence for a threshold. Other electrophysiological responses have been reported in children with elevated Pb B levels and lead exposure in young monkeys has been shown to cause scotopic visual deficits.

Elevated Pb B levels are also associated with developmental abnormalities including fetal neurologic damage, reduced birth weight, reduced stature, and slower attainment of developmental milestones. The positive association of Pb B levels with blood pressure has been noted in several epidemiologic investigations. Modest elevations in pressure have been associated with Pb B levels in the range of 300 μg/L, although the mechanism of this response has not been established.

Ambient Air and Pollutant Mixtures

One of the problems of relating health effects of exposures to single pollutants in an environmental chamber to responses experienced in the ambient environment is that ambient air is a complex mixture of several gaseous and particulate pollutants that varies markedly from location to location and from day to day. Numerous chamber studies have been performed using gas-gas mixtures or gas-aerosol mixtures. In addition, field studies that take the controlled exposure methodology (minus the environmental controls) into the ambient environment have been important in validating chamber responses and vice versa.

One early study used the interesting approach of trying to generate a smog mixture directly from automotive engine exhaust piped through a transparent tube exposed to sunlight. Although this technique failed to catch on, the issue of aging or temporal changes in the makeup of pollutant mixtures has not been well studied. One of the early studies of gas-gas mixtures was the report of Hazucha and Bates, which purported to show a striking interactive effect of ozone and SO2in combination. Pulmonary function responses to ozone were increased substantially by the addition of SO2to the chamber atmosphere. Numerous attempts were made to replicate this study but none showed this striking “synergistic” response in healthy subjects. The principal investigators of all these studies would have perhaps saved valuable time and effort if they had examined the ambient air monitoring information and discovered, as Lefohn et al. did, that there are very few occasions when SO2and ozone coexist at near equivalent concentrations. Because of the complexities of the ambient air mixtures, it is, for all practical purposes, impossible to examine every possible mixture and temporal combination of gases and aerosols in a dose-response fashion. It is important to study mixtures, but primarily those that are likely to be present, and in a similar time frame, as they occur in the ambient environment.

Mixtures of ozone and NO2in controlled human exposures have typically yielded similar responses in pulmonary function as are seen with ozone alone. Mouse infectivity studies, on the other hand, have shown additive or synergistic effects of this mixture on pulmonary bacterial infections. Koenig et al. found no increase in response to SO2in allergic adolescents when a sodium chloride droplet aerosol, hypothesized to enhance SO2transport to the lower airways, was added to the SO2. Neither sequential nor simultaneous exposures to ozone and H2SO4change the pulmonary function response from that which would be expected alone. The absence of an additive effect for one end point does not imply that other responses, not easily measured noninvasively, will not show additive or synergistic responses. However, a presumably more interesting end point to examine for a synergistic response to ozone plus H2SO4would be mucociliary clearance, which is known to be altered by acid aerosol exposure.

Field studies have, in general, supported the findings of controlled exposure studies. The ozone dose-response study of Avol et al., involved controlled ozone exposures performed in a group of subjects also exposed to ambient air. The similarity of response between ambient air and purified air containing a similar ozone concentration suggested that the other pollutants in Los Angeles air did not add significantly to the pulmonary function response seen with ozone alone. Field studies of children attending summer camps in the northeastern United States have shown spirometric responses that are similar to those seen in controlled exposures to ozone. In general, mixtures of pollutants tend to produce effects that are additive. The acute responses to ambient air can typically be estimated by the sum of the responses to controlled levels of the pollutants. A more important question relates to the response to chronic ambient air pollution. With the continuing improvements in air quality in many areas of the globe, the answers to such questions may be forthcoming from studies of regions with more severe air pollution problems such as China, Eastern Europe, and Mexico.

Summary

Over the past four decades, important advances in the understanding of the health effects of air pollutants have been made. Dose-response functions for several pollutants are sufficiently refined in many cases to allow adequate risk characterization, although for many air pollutants and many markers of air pollutant-induced injury, the exposure response database needs to be expanded. The understanding of response mechanisms has improved greatly but remains incomplete, even for pollutants such as ozone and sulfur dioxide, which have been studied more comprehensively. The understanding of the human health effects of many“toxic” air pollutants will not be attained through controlled exposure studies and will be forced to rely on animal-to-human extrapolation using animal toxicology, in vitro human lung cell exposures, and occupational or epidemiological studies. The continued development of in vitro exposure techniques and appropriate comparisons to in vivo human exposures will be helpful in the understanding of mechanisms of response to air pollutants and in the improvement of dosimetry models necessary to the improvement of the extrapolation process. Atmospheric pollutants have serious effects on health and environment.