Canadian Smog Science Assessment Highlights and Key Messages: chapter 2
Effects on Human Health
The air health effects literature which examines linkages with mortality consists of two general study types: those that examine the relationship with long-term, or chronic, exposure (usually in terms of multi-year exposure); and those that examine short-term, or acute, exposure (in terms of same-day to a few days of exposure) and associated changes in mortality rates.
Long-term studies are usually based on cohorts of individuals who have been enrolled in a database for the purposes of studying their health relationships with a variety of risk factors (e.g., smoking, lifestyle). The focus on these studies is on the individual and factors that alter individual risk that can be examined to provide information on group risk. Short term studies generally utilize administrative records collected for various purposes such as billing and health care tracking to examine population-level reactions to risk factors. In both of these types of study, exposure to air pollution is estimated as the concentrations measured at air monitoring stations that have been established to monitor compliance with ambient air quality targets.
The cohort studies on which chronic effects are based have the advantage of containing extensive information on individual risk factors that can be examined in addition to the risk of air pollution over time. Additionally, because of their long-term (or “longitudinal”) structure, these studies make it possible to estimate the life shortening impact of an individual risk factor such as air pollution. However, longitudinal cohorts are relatively rare due to their significant financial and logistical demands. Additionally, because many of the outcomes associated with air pollution are also associated with other risk factors (e.g., cardiovascular disease, smoking and diet), extensive analyses are required to distinguish air pollution-related effects.
Acute studies are generally more common since the databases on which they depend are usually maintained by public health agencies and utilize standardized mortality classifications and collection methods over entire populations. In addition, because the time scale of these studies is comparatively short (in that they examine changes in mortality on a day-to-day basis), most other risk factors generally associated with mortality are not correlated with air pollution and do not need to be accounted for in these analyses. The most significant factors which must be dealt with in short-term studies, primarily weather variables, are available on a scale amenable to analysis, though this requires extensive statistical modelling. Unlike long-term studies, however, these analyses provide little additional information on risk factors and other factors (e.g., socio-economic status factors) which modify the air pollution relationship and cannot be assessed directly.
Both short- and long-term studies provide information on the magnitude of risk from air pollution exposure. Their results are likely additive (i.e., the mortalities observed in one type of study are not accounted for in the other) and can provide information on susceptibility by examining all-cause, respiratory, cardiovascular and other causes of death, as well as age-specific analyses. However, long-term cohort studies are regarded as more robust and informative because they can account for other risk factors, and the inherent follow-up time period which allows examination of important issues such as length of life lost.
Subsequent to the 1999 Canadian science assessments6 for particulate matter (PM) and ozone (O3), it was determined that the availability of Canadian studies examining short-term relationships with mortality, combined with questions concerning the analysis of the key U.S. chronic-exposure studies7 and their applicability to Canadians, favoured an emphasis on short-term associations. Thus the focus for both PM and O3 was on short-term exposure and resulted in the derivation of 8-hour (for O3) and 24-hour (for PM2.5) Canada-wide Standards. Work undertaken in the last decade indicates that, while short-term standards continue to reflect a robust body of evidence, there is now evidence which implicates long-term exposure in premature mortality and supplies a clear rationale for the derivation of a long-term (annual) air quality standard for Canada.
U.S. studies of chronic exposure mortality have been used worldwide by agencies (WHO, EU, etc.) to characterize PM-related mortality. Canadian cohorts, until recently, had not been available. However, two cohorts encompassing millions of Canadians have now been developed and are undergoing analysis for relationships with chronic exposure to several air pollutants including PM and O3. The advantage of these cohorts is that they will provide for examination of the relationships in the relatively low pollution levels of the Canadian environment, have a large amount of information on susceptibility not available in other cohorts, can be used in relation to a number of Canadian-specific risk factors, and will provide analysis related to the initiation of disease. First results are expected in 2011.
The major effort examining relationships between chronic air pollution exposure and mortality has been in the re-analysis of results from several cohorts, principally the American Cancer Society (ACS) Cohort, and the Harvard Six City Cohort. While these studies have been available since the mid-1990s, some issues related to analysis raised questions about interpretation of their results. Subsequent re-analyses have dealt with these issues and, in addition, have added a number of new insights to the overall understanding of effects. As well, several additional, though smaller, cohorts have also been analyzed. All of these analyses show positive, usually significant, relationships between long-term exposure to air pollution and premature mortality, including all-cause mortality as well as several cardiovascular and respiratory sub-categories.
One of the important results of these analyses is the predominant adverse health effect of fine PM, with coarse PM and other co-pollutants (such as nitrogen dioxide and carbon monoxide) showing little effect.
Sulphur dioxide (SO2) is, in some cases, also significantly related to adverse effects, although it has been argued that SO2 is as an indicator of PM from specific sources. Cardiac outcomes have also been better characterized; additionally, while respiratory mechanisms appear to play a role, it has become increasingly clear that cardiovascular effects underlie the majority of these air-pollution related mortalities.
While other cohorts have been analyzed, the ACS and Six City studies remain the most prominent and provide the most reliable risk estimates due principally to their design (e.g., large size, based on the general population). In these and other studies, the newer analyses have confirmed previous results but have also provided more precise evidence of the impact of PM on susceptible subgroups, such as those with ischemic heart disease. The ACS cohort, due to its larger size and extended follow-up, is generally used in estimating risk; however the Six City study is also used, and observed even higher risk estimates than in the ACS study. Both of these studies have been analyzed to estimate the length of life lost due to air pollutant exposure and, while there is some variation, the estimates are substantial, ranging from several months to two years. Additionally, the ACS cohort highlighted a significant link to lung cancer mortality, though the results do not definitively establish an association with the initiation of lung cancers. A few recent Canadian cohort studies, though with less statistical power due to smaller sample size and issues related to study design, also found significant mortality risk, with some results indicating that socio-economic factors may play a role in the exact nature of the effects (i.e., greater effects for lower socio-economic status).
While outside the review period of this assessment, a 2009 analysis of the ACS cohort is potentially of considerable importance and is, therefore, mentioned here. Among other issues, it used additional years of data to assess the relationship of O3 and PM with respiratory and cardiac causes of death. A primary finding was that, unlike previous ACS analyses, a significant relationship was found between long-term O3 exposure and premature mortality. Additionally, this relationship appeared to be confined to respiratory causes of mortality (PM was primarily associated with cardiac causes), was a function of summer time average (PM effects were a function of annual averages), and, the results appeared to suggest a threshold for the effect (unlike PM which exhibited no apparent threshold). This O3 finding may be due to improvement in analytical techniques, but is more likely due to the additional years of data, which improve the statistical power of the study (respiratory mortality is much less common than cardiac mortality, and thus it can be more difficult to observe these effects).
Overall, the database on chronic exposure mortality has been greatly enhanced since 1999, with new analyses and re-analysis of existing cohort data indicating a significant impact of fine PM on public health. Fine PM continues to be the dominant factor in explaining the long-term impacts of air pollution on premature mortality, and provides a strong scientific rationale for the establishment of a long-term ambient air quality target. Though little information was previously available to indicate that chronic exposure to O3 was related to mortality, very recent analysis of the ACS cohort study indicates the possible importance of O3 in explaining respiratory mortality, though these findings need confirmation, and additional insight is needed to interpret this result in the Canadian context.
While single-city studies are more common, multi-city studies are generally regarded as more robust. Multi-city studies often have greater variability in response (due to the wide variety of inter-city conditions incorporated), but they can be superior to single-city studies since they examine a greater variety of conditions, do not suffer from publication bias (the possibility that negative single-city studies would not get published) and having greater statistical power due to the larger sample size. This provides the ability to examine more specific age and disease categories than would otherwise be possible. Meta-analysis combines the results of multiple (usually single-city) studies.
In the 1999 Canadian science assessment documents, it was concluded that there was substantial evidence of an association between short-term exposures to increased O3 and fine PM and premature mortality. Since that time, a number of single-city and multi-city studies, as well as meta-analyses of studies, have become available.
The majority of these studies (both old and new) demonstrate positive and usually significant effects of PM on mortality. While these studies place an emphasis on the results of fine particulates, the coarse fraction of PM (PM2.5-10) may be implicated to some degree.
However, the risk estimates are almost always higher for fine particles, and especially in cases where studies have examined specific causes of death (i.e., respiratory and cardiovascular). In many studies, more specific mortality categories have been examined (e.g., stroke, myocardial infarction, ischaemic heart disease, chronic heart failure, pneumonia, and chronic obstructive pulmonary disease) and, in virtually all these cases, the risk is greater where there is pre-existing disease. Lags between increased exposure and resultant mortality are quite short, usually in the one day range, although longer multi-day lag periods indicate a prolonged effect with larger overall risk than for any single-day lag structure.
In the Canadian multi-city study, the effects of fine PM were similar to other analyses (both single and multi-city); however the study also noted a significant impact of nitrogen dioxide (NO2) and O3. In a large U.S. multi-city study (NMMAPS8) PM was the primary pollutant predicting mortality. Due to the large size of the NMMAPS study a number of important sub-issues could be examined. Among other findings, it was determined that weather variables could not explain the associations between air pollution and acute exposure mortality; effects were not confined to a single season, but appeared relatively uniform year-round. The statistical methodologies [i.e., the use of generalized additive models (GAM)] that had called into question earlier single-city results were not a significant issue. Model specifications (the exact manner in which the data are statistically treated), while modifying results somewhat, did not have significant impacts on the overall results. While PM was the major predictor of mortality in the NMMAPS study, O3 was also implicated as a significant risk factor, with the original study finding a positive and significant warm season effect and a positive, non-significant year-round effect. A follow-up analysis with more years of data reported similar effects for summer and a significant effect in the all-year analysis (possibly reflecting the increased statistical power of the larger dataset). As was the case for other studies, the NMMAPs analysis also indicated that: risk estimates for cardiopulmonary causes were greater than for all-cause mortality; O3 results were not affected by the inclusion of co-pollutants; and the highest relative risks were found for the shortest (0 and 1 day) lags, though there was evidence that elevated risks occurred for several days beyond this.
A major European multi-city study9 found results similar to those in North America, including greater overall impacts in the warm season, as well as greater risks attached to the categories of cardiovascular and respiratory mortality. This and other studies also examined the importance of specific O3 concentration averaging times (e.g., 1-hour versus 8-hour versus 24-hour) and, while shorter exposure times resulted in somewhat higher risk estimates, the differences were not statistically significant.
Single-city studies are generally consistent in finding significant relationships for premature mortality with both acute PM and O3 exposures. For O3, these types of studies reinforce a more pronounced effect in the warm season, while for PM, risks appear to be relatively consistent year-round.
Many of the short-term studies have examined the impact of adjusting for co-pollutant exposures on pollutant-mortality associations. For particulate matter, the risk estimates are fairly robust to adjustment for other pollutants. While they are sometimes reduced in models that include gaseous pollutants (particularly NO2, which is often highly correlated with PM), they remain positive and most often statistically significant.
Overall and with few exceptions, the O3 effect on premature mortality was not greatly influenced by particulate matter or other pollutants. Because O3 levels and temperature can be highly correlated, a number of studies have examined different ambient air temperature adjustments in their mortality models to determine if the O3 effects were sensitive to this variable. Results indicate that the methods used in epidemiological studies to account for temperature are adequate to account for its effects, and O3 and PM mortality relationships are not significantly affected by air temperature.
A number of population health studies have examined the phenomenon of thresholds for mortality effects of O3 and PM. Approaches have included the fitting of alternative models, and segregating high from low pollutant days (usually defined as above and below an air quality standard) to determine if risk estimates differ. The shape of the short-term PM-mortality dose-response curve has been examined in several studies. In each instance, the analysis revealed a quasi-linear association, with no apparent threshold. For O3, most of the available studies also fail to support the existence of a “no effect” level.
The relative lack of data at low exposure levels, the potential for exposure misclassification, and the inherent heterogeneity of human populations imposes some limits on the interpretation of the form of the exposure-mortality relationship, especially at low concentrations. However, an NMMAPS analysis specifically for O3 on this issue could find no evidence that risk was reduced at the lowest concentrations and concluded that a threshold, should it exist, could only occur at levels well below background. This is similar to analyses conducted for the 1999 Canadian science assessment documents that indicated that the associations with mortality and hospital admissions for both O3 and PM existed at the lowest ambient levels that could be examined. While it is very likely that effect thresholds exist for individuals, the presence of very large “subpopulations” with pre-existing cardio-respiratory disease, the large inter-individual variability in effects exhibited in controlled exposure studies, the existence of genetically-based susceptibility traits, and other factors indicate that thresholds for population level effects may not exist, or exist only at very low levels.
The issue of mortality displacement (the displacement of a date of death by only a few days) due to exposure to air pollutants has been examined in several acute exposure mortality studies. While difficult to study and interpret, those studies that examined the issue (usually by extending the analysis period over several days to a few weeks) could find little evidence that the date of death had been brought forward by only short time periods. This is important since a change by only a few days would have little public health significance. These results support the hypothesis that exposure to air pollution can significantly change date of death, and that these deaths were not occurring in frail individuals who were already dying and happened to die a few days earlier. Rather, short-term exposure to air pollution appears to advance deaths of susceptible people by weeks or months.
There have been a significant number of opportunities, especially over the last 10 years, to examine the public health benefits of situations where major decreases in air pollution result from intended or unintended emission reductions. For mortality, there were three cases of dramatic reductions in PM air pollution for long enough periods that permitted the study of associated health benefits. In each of these cases (a strike at a steel plant in the Utah Valley; a ban on coal use for home heating in Dublin; and significant improvement in fuel quality in Hong Kong), ambient PM pollution was reduced precipitously and persistently. Subsequent analysis indicated a concomitant reduction in mortality (and other adverse effects). Other studies have revealed that more incremental actions directed at a broader range of sources, such as those taken over the last 30 years or so in North America and in Europe, also reduced PM levels and resulted in attendant decreases in cardiovascular and respiratory mortality, and in children’s respiratory symptoms. While the results of such studies have some limitations due to analytic constraints, they can provide support for observations made in the standard epidemiological analyses discussed previously.
Overall, newer studies have confirmed earlier results and have also increased understanding of the impact of PM and O3 on premature mortality. Of particular importance is the confirmation of the impacts of long-term exposure to PM and the direction this gives to the adoption of an ambient target to reflect this relationship (i.e., an annual standard). While daily peaks in air pollution are important and indicate that short-term (i.e., 24-hours or less) standards are warranted, the long-term exposure findings indicate an effect significantly larger than the short-term. Since the risk management actions to address long-term exposure may be different than those for the short-term, standards that address both are warranted. The findings for cardiovascular outcomes, including specific endpoints such as ischaemic heart disease, indicate that the respiratory system, while being the first point of attack, is not the only system subject to the adverse effects of air pollution. In addition, many of the results indicate that in addition to exacerbating existing disease, PM is implicated in the development of cardiac disease.
Development of disease is regarded as more significant than exacerbation of existing disease since it implies the development of new cases and/or the progression of the disease to more advanced states. This indicates that current methods of valuing adverse effects of air pollution produce underestimates. More recent findings on the relationship of respiratory mortality with O3 indicates the potential for a future regulatory approach on O3 that incorporates a chronic exposure-related standard (possibly warm-season average), though more analysis appears warranted before this is formally considered. Newer information and the overall database also confirm the need to retain short-term average standards (24-hour for PM2.5, and 8-hour for O3). The scientific database also continues to indicate that mortality effects occur throughout the continuum of exposure experienced by Canadians, and that a population, non-threshold approach is the most appropriate interpretation of the data at this time.
The focus for chronic exposure morbidity continues to be cardiovascular and respiratory disease endpoints, though there are few new studies and to date the most important findings have been respiratory in nature. Previous studies had revealed significant impacts of O3 on lung health in children, but these results were largely based on high exposure levels not experienced in Canada. Results at more relevant O3 concentrations were equivocal, and overall there are relatively few studies examining chronic exposure and morbidity outcomes.
A significant research effort is ongoing, especially in relation to understanding the potential for air pollution to cause chronic disease, or contribute to the progression of chronic disease. Much of this work focuses on cardiovascular outcomes due to the general importance of this in modern society. This newer work provides indications of an involvement of air pollution (especially fine PM) in the progression of several important adverse cardiac effects.
The most important new study in this area of investigation is the California Children’s Health Study. This well-designed prospective cohort study examined a range of air pollutants and adverse outcomes over a wide range of concentrations. While fine PM (and elemental carbon) was associated with most outcomes examined (e.g., lung growth, symptoms, asthma), so too were other co-occurring pollutants such as acid vapour and nitrogen dioxide. For these pollutants, lung function, growth and development were all adversely impacted, though there was no clear relationship with one pollutant versus the others. Lung growth and development in these cases were affected through age 18, when lungs are mature and a point at which any damage is not likely to be repaired, thus compromising lung health later in life. It was also found that children who moved at earlier ages from areas of high PM levels to areas of low PM levels exhibited significant lung growth recovery, and vice versa. Most of the outcomes were not associated with ambient O3 levels. However, two particular adverse effects, school absenteeism for respiratory complaints and development of asthma, were associated with exposure to higher levels of O3, but not any other pollutant. In these analyses, asthma development was manifested only in groups of children in the highest-O3 (greater than levels experienced in Canada) communities and engaged in a high level of outdoor activity. School absenteeism was manifested across a broad range of concentrations, including ones relevant to Canadian air quality.
The California Children’s Health Study, which began in 1992, is a large, long-term study of the effects of chronic air pollution exposures on the health of children living in Southern California. Children may be more affected by air pollution than adults because their lungs and bodies are still developing. Children are also exposed to more air pollution than adults since they breathe faster and spend more time outdoors in strenuous activities.
About 5500 children in 12 communities were enrolled in the study; two-thirds of them fourth-graders. Data on the children’s health, their exposures to air pollution and many factors that affected their responses to air pollution were gathered annually until they graduated from high school. Research results first appeared in 2000, with new publications continuing to be made available as data is analyzed.
Several studies in Europe and North America (including the lower mainland of British Columbia) have found significant relationships between exposure to PM (and in some cases specific PM sources) and adverse effects on the auditory system of children. While often characterized as being of less importance than some other outcomes, middle ear infections (the major reason for the prescription of antibiotics in younger age groups) and related outcomes were demonstrated to be associated with existing levels of PM. These are significant for population health because they are, in some cases, the most common cause of hospitalization for younger age groups.
Previous studies of hospital admissions and emergency room visits (ERVs) indicated a relatively robust relationship to ambient O3 and PM levels (independent of each other), with most studies reaching statistical significance.
There are fewer examples of this type of study than for premature mortality, largely because centralized databases of hospital admissions are far less common and there are challenges in using the data. Overall, newer results from these types of studies are consistent with earlier ones. In general, the findings indicate significant relationships between unplanned hospital admissions and both particulate matter (generally PM10) and O3. Because the statistical power (i.e., sample size) in these studies tends to be less than for mortality, there is less opportunity to segregate specific causes; however, in studies large enough for specific analysis, the risk and level of statistical significance was greater for specific disease categories (especially cardio-respiratory), and for the elderly age-class (cardio-respiratory disease is far more prevalent after the age of 55). In addition, those suffering from asthma, especially children, appeared to be more susceptible to the effects of PM and O3 than the general population.
As was the case in mortality studies, there is some evidence of seasonal patterns in the relationship between hospital visits and O3 exposure. While there is, in general, a consistent relationship between O3 levels and adverse health effects, the relationship becomes especially strong during the warm season (possibly due to difficulties dealing with between-season variance or the greater likelihood of exposure during the warm season). This relationship holds true for ERV studies, especially for asthma. Associations between PM exposure and hospital visits do not show seasonality, with seasonally restricted analyses providing results similar to those for the full year.
Examination of the effect of co-pollutants provides evidence that the effects of O3 on ERVs and hospital admissions are not significantly affected by the inclusion of other pollutants potentially associated with acute exposure morbidity. The case was not as clear for PM, with some studies (including Canadian ones) finding that results for PM were sometimes sensitive to the inclusion of other pollutants (especially NO2). These studies often used varying indicators of PM (e.g., PM10 or PM2.5), which can make drawing exact conclusions difficult, but at the same time illustrating the fact that no one study provides the “best” fit for the outcomes.
Panel studies involve the examination of small groups of individuals as they undertake normal daily routines or specific activities. In these studies, personal data regarding activity and exposure is collected and examined for relationships to health outcomes. Panel studies can serve as a bridge between large-scale epidemiological analyses and studies conducted under controlled conditions in the laboratory, but are increasingly used to find important relationships on their own. Up to the date of this review, most panel studies had examined only respiratory endpoints. Newer work is focusing on cardiovascular disease and a range of findings in this area are expected in the near future.
Asthmatics have been a key target of air pollution research given their greater potential sensitivities and vulnerabilities to pollutants, with most studies examining relationships in children. Findings generally indicate increased respiratory symptoms and medication use accompanied by reduced lung function following exposure to air pollution. In the small number of studies that examined the severity of asthma response, it appears that those with the worst cases of asthma are vulnerable to greater adverse effects. For non-asthmatics, there is evidence of increased respiratory symptoms, but an effect on lung function is not as evident. Conversely, people with chronic obstructive pulmonary disease (COPD) show evidence of reduced lung function but little impact on medication use or symptoms, though the challenges of studying this often heavily medically-compromised group makes it difficult to draw firm conclusions.
Panel studies of acute morbidity found associations for both PM10 and PM2.5, with various respiratory symptoms and medication use. Though the studies are limited in number, there are some clear indications that PM10 is more likely to be associated with upper respiratory symptoms, while PM2.5 is more clearly associated with lower respiratory symptoms, corresponding to the regions of the lung where the particles preferentially deposit. In a small number of studies, ultra fine particles were also associated with both respiratory and cardiac outcomes, though results were not entirely consistent.
A newer area of research on biomarkers of effect (a physiological or biological measure that is not in itself adverse, but is indicative of a process that can or will lead to one) is less invasive than most laboratory and panel measurements of effect and therefore can be applied to a wider range of people, including those whose health is more compromised. The major areas of investigation for these studies are inflammatory and cardiovascular processes which are known to lead or suspected of leading to both acute and chronic effects. One of the primary findings in these studies is that the production of pulmonary inflammatory markers is greater in asthmatics versus non-asthmatics, possibly explaining some of the sensitivity of this sub-population to both O3 and PM.
Also examined in detail is a variety of markers of cardiac and circulatory inflammation which are possibly indicative of acute and chronic cardiovascular stress. Statistically significant findings have been found in elderly populations, but of note is the appearance of stress markers in healthy young subjects. These results provide evidence of pathways to both acute coronary events (for those with pre-existing disease) and long-term cardiac and circulatory tissue damage and dysfunction/disease. The most recent work has focused on indicators of coronary function (such as heart rate variability) and supports both direct and indirect impacts of inhaled PM on cardiac function. Overall, findings from studies using biomarkers are highly supportive of epidemiologic relationships with premature mortality and hospital admissions.
While there are relatively few recent O3 studies in this area, work characterizing O3 exposure at childrens’ summer camps and of hikers provides confirmation of findings from earlier studies, and some additional insights. These results indicate that lung function declines and respiratory symptoms increase with increasing exposure to O3, and that these effects may be more pronounced in asthmatics. These effects appear to be independent of PM and other co-pollutants and are observed at levels below those used in laboratory settings.
Long-term exposure studies on respiratory morbidity reported positive and statistically significant associations between fine particles and respiratory effects such as lung function decrements and chronic respiratory diseases, such as chronic bronchitis. For ozone, existing work indicated the potential for chronic respiratory effects, however, it was unclear if such effects were confined to the high exposures in such studies, and newer studies have not shed any light on this issue. However, the California Children’s Health Study does provide evidence of effects for both PM and ozone (as well as other pollutants) on a range of adverse respiratory outcomes, most notably the effect on lung growth.
Studies on cardiac morbidity have also provided some insights into the possible mechanisms (e.g., inflammation, cardiac arrhythmias and other cardiac output parameters) by which PM could cause long-term disease and create conditions leading to sudden cardiac events and resultant hospital admission or mortality.
The epidemiologic evidence includes associations between short-term exposure to PM2.5 and ozone and cardiorespiratory, hospitalization and emergency department visits. Studies examining specific causes (heart attacks, pneumonia) also indicate the involvement of both pollutants, however these studies are often limited by sample size and are less consistent than is the case for general classifications of disease.
Overall, the evidence base continues to indicate that both PM and ozone are associated with a range of respiratory effects; that PM2.5 is capable of eliciting a range of adverse cardiovascular effects, and that both pollutants are associated with increases in medical and hospital visits.
Most epidemiologic studies of the health effects of PM and O3 rely on measured air concentrations determined at central monitoring sites as a surrogate measure of exposure. This approach has often been questioned due to its potential to introduce a level of uncertainty to the studies, and reducing the validity of their findings. Recent work has addressed the question of whether central monitoring sites are good surrogates for individual exposures, and has largely found that these monitors are quite good at representing population exposure to ambient PM and O3. As such, studies using ambient measures from central sites monitors are appropriate for use in air pollution epidemiology studies. Other important findings include:
- PM2.5 appears to penetrate indoors with considerable efficiency, with the result that ambient PM2.5 levels are highly correlated with personal exposure to PM2.5 of ambient origin i.e., ambient monitors reflect exposure to particles of ambient origin, even in indoor environments;
- While there can be major sources of PM indoors, these sources do not confound outdoor sources indicating that outdoor monitors can be used to represent human exposure to outdoor PM, especially in the case of PM2.5 i.e., levels of indoor and outdoor particles are not correlated. Therefore, while there may be effects of indoor-sourced PM, such effects are not captured in the epidemiological studies of outdoor air;
- Ambient monitors are less representative of exposure to coarse PM and ultra fine PM, limiting the ability of studies using such monitors to identify effects;
- While there is great variability in individuals’ exposure to O3, studies indicate that this is strongly correlated to levels at ambient monitors;
- Ozone exposure is strongly influenced by building ventilation and time spent outdoors, and is much greater in the warm season. Hence, levels measured at ambient monitors are more representative of personal exposure in the warm season, and indeed O3 related health effects are often restricted to the warm season; and
- The relationship between ambient concentrations and personal exposure to PM and O3 will vary as a result of individual-, city-, or region-specific differences, resulting in measurement error and potential bias in risk estimates. The bias can be either upward or downward, but is expected to most often underestimate risks and to make it more difficult to detect a health effect.
Work with human volunteers in controlled laboratory settings (sometimes known as clinical studies) has provided several findings supporting observations made in epidemiological studies. While ethical and logistical considerations limit the extent of controlled human exposure investigations, they have provided evidence of the presence of sensitive groups within the general population, the time-course of damage to the cardio-pulmonary systems, and the mechanisms by which O3 and PM could elicit effects (though the evidence is much less for PM). Results include:
- Additional evidence of the presence in the population of individuals who respond to even very low levels of air pollution (specifically O3) who are otherwise healthy;
- The ability of O3 and possibly PM to enhance airway hyper responsiveness (AHR) in combination with common allergens. AHR is a hallmark of asthma, and these results provide a possible explanation for their greater risk sensitivity in hospital visit and other studies;
- Based on evidence from O3 exposure studies, lung inflammation, respiratory symptoms, lung function and cellular damage resolve (post-exposure) at very different rates, with cellular damage continuing after other measured responses return to normal;
- For all of the foregoing outcomes, there are very different levels of response in individuals indicating that there is a very wide range of variability and susceptibility in the general population; and
- Exercise, by increasing the effective dose, enhances the sensitivity of individuals to the adverse effects of O3.
Work in laboratory settings with experimental animals has been increasingly illuminating, even though there are some limitations imposed on interpretation due to issues related to cross-species extrapolation. Earlier work, albeit at high exposure concentrations, had provided a set of mechanisms by which O3 may exert significant health effects. This research has been enhanced to some degree, with extension to more complex mechanisms for the adverse effects of O3, and the delineation of an even more complex series of mechanisms by which PM can exert its adverse pulmonary and cardiac outcomes. These include:
- Pulmonary inflammation and modified immune responses with associated increased tendency of infection;
- AHR in animal models of asthma, mirroring such results in human volunteers and giving further weight to the findings for asthmatics in epidemiologic studies;
- The use of different genetic strains of laboratory animals indicates that there are genetically determined sensitivities to PM and O3, sometimes encompassing several orders of magnitude;
- Inter-individual variability in protective anti-oxidant regimes supports the findings in human studies of sensitive individuals and sub-populations;
- PM (and possibly O3) causes inflammation not only in the lung, but also and potentially more importantly, in the cardiovascular system. This inflammation, along with oxidative stress, has been shown to lead to a series of biological changes including increased clotting factors, altered vasoconstriction, and alterations in heart rate and heart rate variability, all of which are known risk factors for subsequent adverse cardiovascular events;
- A limited number of studies have found evidence that PM at near-ambient concentrations has the ability to cause the progression of atherosclerotic plaques, providing a specific mechanistic pathway for the observations obtained from both acute and chronic epidemiologic studies of PM-mortality relationships; and
- While different properties (both chemical and physical) of PM have been shown to elicit different effects in animal models, it cannot be yet stated that there are constituents or forms of PM that are without effect.
While much of the work on smog-related pollutants continues to focus on respiratory and cardiovascular outcomes, newer work has indicated that effects may be seen for other biological systems. Of particular note is work indicating effects on the reproductive system (e.g., low birth weights and other pregnancy related outcomes) and the possibility of neurologically-mediated effects. For both these and other outcomes, additional work is required before causal inferences can be made.
6. Federal-Provincial Working Group on Air Quality Objectives and Guidelines, op. cit.
7. American Cancer Society Study: Pope III, C.A. 1995. Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults.Am. J. Respir. Crit. Care Med. 151: 669-74.
Harvard Six City Study: Dockery, D.W. et al. 1993. An association between air pollution and mortality in six U.S. cities. New England Journal of Medicine 329: 1753-1759.
8. National Morbidity, Mortality and Air Pollution Study.
9. Air Pollution and Health: A European Approach.
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