Abstract
The health effects of air pollution are difficult to characterize because of the large number of air pollutants present in the atmosphere and the relatively small contribution of their health effects compared to all other causes. In addition, air pollution does not affect all people in the same way. Some persons are more sensitive than others: for example, those suffering from asthma, chronic obstructive pulmonary disease (COPD) or cardiovascular problems, the elderly, and children. Also, some individuals are more vulnerable than others: those include, for example, workers and residents who tend to be in locations where air pollution exposure is greater than average. This chapter describes first how adverse health effects of air pollution can be identified and quantified using toxicological and epidemiological studies. Next, methods commonly used to conduct health risk assessments related to air pollution are presented. The use of such information to set up air quality regulations is presented in Chapter 15.
The health effects of air pollution are difficult to characterize because of the large number of air pollutants present in the atmosphere and the relatively small contribution of their health effects compared to all other causes. In addition, air pollution does not affect all people in the same way. Some persons are more sensitive than others: for example, those suffering from asthma, chronic obstructive pulmonary disease (COPD) or cardiovascular problems, the elderly, and children. Also, some individuals are more vulnerable than others: those include, for example, workers and residents who tend to be in locations where air pollution exposure is greater than average. This chapter describes first how adverse health effects of air pollution can be identified and quantified using toxicological and epidemiological studies. Next, methods commonly used to conduct health risk assessments related to air pollution are presented. The use of such information to set up air quality regulations is presented in Chapter 15.
12.1 Identification and Characterization of Health Effects
12.1.1 Toxicology and Epidemiology
Two large categories of health studies are used to understand and quantify the health effects of air pollution. Those are toxicological studies and epidemiological studies. The former are conducted in laboratories under controlled conditions and are useful to study specific pollutants. The latter are field studies that estimate the adverse health effects of air pollution in the ambient environment and aim to isolate the components of the individual air pollutants using statistical methods. These two types of studies present advantages and shortcomings and it is preferable to obtain results from both types of studies in order to properly characterize the health effects of an air pollutant. Brief descriptions of toxicological and epidemiological studies are presented in Sections 12.1.2 and 12.1.3, respectively. Next, the approaches used to combine the results obtained from such distinct types of health effect studies are summarized in Section 12.1.4.
12.1.2 Toxicological Studies
The term “toxicological studies” is used here to represent an ensemble of studies characterized by controlled experimental conditions. However, these studies may be extremely different: for example, in vitro versus in vivo studies. Furthermore, in vivo studies may be conducted with human volunteers or animals, such as rats, mice, monkeys or dogs (e.g., Wichers Stanek et al., 2011).
In vitro studies allow one to formulate hypotheses concerning the toxicity of a chemical substance and also to investigate the mechanisms leading to adverse health effects at the cellular or even molecular level (e.g., Devlin et al., 2005). For example, the Ames test allows one to characterize the mutagenicity of chemical substances and, therefore, to identify the substances that could be carcinogenic, since most carcinogenic substances are mutagenic (Ames et al., 1975). These in vitro studies are conducted with cell cultures in the laboratory. In the case of atmospheric particles, for example, cell cultures of the epithelium of the lung are used to understand how particle size may affect the transfer of those particles in such tissues. The oxidative stress of cells and tissues, which could lead, for example, to the production of inflammatory mediators, has also been studied in vitro with cell cultures.
In vivo studies conducted with human volunteers typically involve exposing several individuals to various concentration levels of an air pollutant in order to determine at which concentration level some adverse health effect is observed. These studies are performed in a clinical laboratory and the exposure conditions are, therefore, well controlled. However, such studies are limited to short exposure durations (referred to as acute exposure). In addition, sensitive individuals are generally not exposed, because of the significant health risks that could be associated with their exposure to moderate and high air pollutant concentrations.
Toxicological studies conducted on animals offer several advantages: more hypotheses may be tested, the reproducibility of the results can be tested, longer exposure durations can be used (referred to as chronic exposure), and sensitive animals can be exposed. Furthermore, exposure can be continued until death of the animal so that autopsies may then be performed to better understand the biological phenomena involved. Therefore, more information may be obtained with animal studies than with human studies, but the study protocols must be defined so that animal suffering is minimized. However, the results obtained from animal studies must be extrapolated to humans. Models are used to perform these extrapolations, but there are many associated uncertainties, particularly when the physiological functions of the animal differ significantly from those of humans. For example, the dosimetry of fine particles in the respiratory system may be different in some animals (e.g., rodents, monkeys, dogs) and humans. Therefore, the extrapolation of such animal studies to humans would be adversely affected by this different dosimetry if it were not explicitly taken into account. Indeed, particles deposit within the respiratory system and only a fraction penetrates deeply to reach the lungs and deposit there. These particle deposition processes depend on particle size, on the characteristics of the airflow within the respiratory system, and on the surfaces available for deposition (see Chapter 11). Figure 12.1 illustrates the efficiency of particle deposition in the human respiratory system as a function of particle size. Ultrafine particles (diameter <0.1 μm) are those that deposit the most in the lungs. Coarse particles (diameter >2.5 μm) deposit in the upper part of the respiratory system (nose, mouth) and, therefore, do not penetrate deeply into the respiratory system. Fine particles (diameter between 0.1 and 2.5 μm) deposit little in the upper part of the respiratory system and, therefore, may reach the lungs; however, they do not deposit significantly within the lungs compared to ultrafine particles.
Figure 12.1. Fraction of particles deposited in different regions of the human respiratory system as a function of particle size for different breathing intensity levels (light, normal, and heavy).
The advantage of toxicological studies is that a specific pollutant may be studied under controlled and reproducible conditions. In the case of human studies, the concentration levels above which an adverse health effect is observed can be quantified for short-term exposure of healthy individuals. In the case of animal studies, chronic exposure studies may be conducted and higher concentration levels may be used. After autopsy, detailed information on the causes of death may be obtained, which could not be obtained otherwise.
Shortcomings of toxicological studies include the fact that the concentrations used are generally greater than those observed in the ambient atmosphere and that the effect of an individual air pollutant may differ from its effect in the presence of other air pollutants. In addition, although some studies may be conducted with sensitive animals, that is typically not the case with sensitive human individuals.
12.1.3 Epidemiological Studies
In an epidemiological study, the objective is to quantify the statistical relationship between the concentration of a pollutant and an adverse health effect (Rothman, 2012). The large number of pollutants present in the ambient air makes the characterization of the effects of a single pollutant difficult because of interference by other pollutants that may have similar effects. These are called confounding factors. Other confounding factors are present due to personal behavior (e.g., smoking) or environmental conditions (e.g., heat wave, cold weather). In addition, the adverse health effects due to air pollution are generally small in terms of excess relative risk (a few %), which makes their quantification in the presence of confounding factors even more difficult. Therefore, the statistical analysis plays a major role in epidemiological studies, because it must be sufficiently powerful and robust to isolate and quantify the relationship between the pollutant concentration and the corresponding adverse health effect.
Epidemiological studies provide quantitative results that are statistical associations between a pollutant concentration and an adverse health effect. However, they do not provide any information on a cause-effect relationship. Therefore, cause-effect relationships must be obtained from toxicological studies. In addition, there is a large number of uncertainties associated with the pollutant concentration measurements, the exposure of the population or individuals, confounding factors, etc., which must be taken into account when presenting the results of an epidemiological study. For example, individuals may be exposed to pollutants outdoor and indoor (at home, at work, etc.). Pollutant concentrations may vary considerably among those various microenvironments, for example, because of indoor pollution sources, various indoor penetration rates for outdoor pollutants, loss processes for indoor pollutants by deposition on walls, furniture, etc. (e.g., Abt et al., 2000). Outdoor ambient pollutant concentrations are generally used in epidemiological studies, because they are the most readily available via air quality monitoring networks. Therefore, the characterization of the actual exposure of the subjects is approximate if exposure to indoor air is significantly different from exposure to outdoor ambient air. All these uncertainties must be quantified and the results of an epidemiological study are presented with error bounds (for example, the 95 % confidence interval; i.e., the interval that has a 95 % probability of including the true value).
There are several types of epidemiological studies. Two categories of epidemiological studies that are the most widely used in air pollution are briefly described next. They are (1) longitudinal studies, where the adverse health effects are analyzed as a function of air pollution levels that vary with time and (2) cross-sectional studies, where health risks are quantified in terms of their spatial variation.
Longitudinal Studies
In a longitudinal study, the occurrence of adverse health effects is observed as a function of time and correlation with exposure to air pollution is analyzed. Generally, ambient air pollutant concentrations are used as a surrogate for exposure.
Longitudinal studies may be ecological studies. Then, the adverse health effects are studied for a whole population (hospital admissions, deaths …) as a function of air pollutant concentrations. A latency period for the health effect (one day or a few days) may be used to account for the fact that the health effect may not be maximum shortly after exposure to the air pollution, but instead after some time. In an ecological study, there is no information on the specific exposure of individuals to the air pollution (some may have been exposed to greater air pollutant concentrations than others, depending on their activity, location of residence, etc.). Therefore, the statistical power of the ecological study must be sufficiently large to smooth out the exposure variability.
Longitudinal studies may follow a cohort of individuals during a specific period. In such cases, the exposure of the individuals can be characterized with some level of accuracy. A cohort study is more expensive than an ecological study since it requires collecting additional information on the cohort members, but it provides more accurate data in terms of the individual exposure and specific health effects.
An approach used to minimize the cost associated with a longitudinal study, while taking into account the exposure and health effects of specific individuals, is to conduct a case-control study. A case-control study is particularly useful in cases where the health risks related to air pollution are low compared to those of other causes. Identifying and quantifying comparatively low health risks in a cohort requires following a large number of individuals in order to have sufficient statistical power; therefore, large resources are needed and the associated costs may be significant. In a case-control study, the individuals that show adverse health effects are identified first: they are the “case” group. Next, individuals with similar behavior, but who do not show those adverse health effects are identified. These individuals must be at least as many as those of the case group; they are generally selected to be in greater number to obtain a larger statistical sample. These individuals are the “control” group. The exposures of the case and control groups to air pollution are then estimated retrospectively.
There are two major differences between a cohort study and a case-control study. In the cohort study, the exposure of the individuals constituting the cohort are estimated first and the adverse health effects are identified next and correlated with the estimated exposure. In the case-control study, the individuals with adverse health effects are identified first and the exposures of individuals with and without the health effects are estimated next. The other difference is that a case-control study uses a smaller number of individuals than a cohort study. Thus, a case-control study is less costly than a cohort study. However, its statistical power is less and the results are less robust. In addition, exposure is estimated, but is generally not documented with precision. Therefore, the incidence rates (see definition in the section on Definitions of Various Terms) of the health effect cannot be determined, because there is no information on the population corresponding to the selected individuals with the adverse health effects. Therefore, absolute risks cannot be calculated and only relative risks are estimated. The result of such a calculation in a case-control study is called an odds ratio (OR): the ratio of the odds of an adverse health effect for exposed individuals and the odds of the same adverse health effect for non-exposed individuals (see the calculation of the odds ratio in the section on Definitions of Various Terms).
Cross-sectional Studies
In a cross-sectional study, the difference in adverse health effects is analyzed between two populations that have different exposures to air pollution. A cross-sectional study may be conducted, for example, as an ecological study at the level of urban areas. Then, the exposure of the population in each urban area may be estimated from air pollutant concentrations measured by the air quality monitoring network and the adverse health effects may be estimated from hospital admissions (morbidity studies) and death certificates (mortality studies). Cross-sectional studies may also be conducted with smaller areas and populations, such as populations living at different distances of a major roadway or industrial site. Cross-sectional studies pertain to chronic exposure to air pollution.
Definitions of Various Terms Used in Epidemiology: Incidence, Risk, and Odds-ratio
The main terms used in epidemiology to quantify adverse health effects are defined further in this section. In the examples provided, one refers to exposed and non-exposed groups for the sake of clarity. Actually, air pollutants are always present in some amount in the atmosphere, but at different concentration levels. Therefore, epidemiological studies that pertain to air pollution compare groups exposed to air pollution levels that are significantly different, rather than groups exposed to zero and non-zero air pollutant levels. The results of air pollution epidemiological studies are presented either in terms of relative risk or odds-ratio per increment of air pollutant concentration; for example, for an increment of 10 μg m−3 or 10 ppb. An example of results from epidemiological studies conducted to characterize the adverse health effects due to fine particles, PM2.5, in terms of concentration differences of 10 μg m−3 is shown in Figure 12.2.
Figure 12.2. Relative risk for the statistical association between premature death (all causes) and an increase in PM2.5 concentration of 10 μg m−3 from the meta-analysis of Hoek et al. (2013). The relative risk is noted ES for effect estimate. The 95 % confidence intervals are indicated in parentheses and by the solid black lines; the weight given to each study is listed in % in the far-right column and illustrated by the gray squares. The result of the meta-analysis is indicated by the diamond. See Hoek et al. (2013) for details on the different studies and the method used for the meta-analysis.
Incidence: The incidence rate, IH (or simply incidence), is defined as the number of individuals who develop an adverse health effect (NH) divided by the duration of the exposure to the pollutant for all individuals in the cohort (TN):
(12.1) If all individuals (total number: NT) have been exposed over the same duration DE:
(12.2) Risk: The health risk, RH, is defined as the incidence rate multiplied by the exposure duration:
The health risk is therefore a unitless fraction. If the exposure duration is identical for all exposed individuals:
(12.4) The excess relative risk, ER, of an air pollutant is defined as the excess risk due to the pollutant (i.e., the difference in the risk for two distinct levels of exposure to the pollutant, RH1 and RH0) divided by the risk for the lowest level of exposure to the pollutant (RH0):
(12.5) The relative risk, RR, may be written in terms of a risk ratio or an incidence ratio (assuming identical exposure durations):
(12.6) Therefore:
As mentioned previously, the excess relative risk is typically calculated for an increment in pollutant concentration, rather than with respect to a zero concentration of the pollutant.
The etiologic fraction of risk (EFR) is defined as the difference between the risks for two distinct levels of exposure to the pollutant (the current level of exposure of the population to the pollutant and a lower level of exposure, typically considered safe) divided by the risk of the population exposed to the current level of the pollutant (i.e., it is the health risk fraction that is due to the pollutant):
(12.8) If RR ≈ 1, then: EFR ≈ ER.
Odds ratio: In the case of case-control studies, the case group (individuals showing an adverse health effect) includes a subgroup exposed to the pollutant, which is represented here by a number of individuals aN, and a subgroup not exposed to the pollutant (or exposed to a significantly lower concentration level of that pollutant), represented by a number of individuals bN. The incidence rates are respectively:
(12.9) There is no information available to define TN1 and TN0. Therefore, they must be estimated. If one selects in the control group an exposed subgroup with a number of individuals cN and a non-exposed subgroup (or a subgroup exposed to a lower concentration level) with a number of individuals dN, such that:
(12.10)