The recent medical literature concerning air pollution is more convincing than ever, indicating that ozone and particulate air pollutants cause serious health effects to the general public. Air pollution causes increased chest symptoms, days lost from school and work due to chest illness, asthma attacks, increases in emergency room and hospital admissions, and increased mortality rates. The association between ozone and many adverse health effects is certainly causal, and the association with excess mortality is certainly robust and may well be causal. The causal nature of the association between particulate air pollution and adverse health effects and higher mortality rates appears to be firmly established according to the National Institutes of Health. The effect of particulate on mortality does not seem to have a safe threshold. The value of the health benefits nationally of lower particulate air pollution levels is estimated at $32 billion, and the benefit to public health of reduced power plant emissions seems well worth the cost.
This report reviews the recent medical literature concerning emissions of criteria pollutants (NOx, SO2, PM, and O3) derived from power plants which burn oil and coal. The structure of this report reflects a de facto evolution in scientific thinking which coincided with the legislatively mandated periodic review of the National Ambient Air Quality Standards (NAAQS) for ozone and particulate which occurred in 1996-7. At that time the medical literature reflected a remarkably robust set of data implicating ozone and particulate in clinically significant and serious health effects. This new report summarizes the medical literature accumulated between 1996 and early 2000, categorized according to study type.
Nitrogen oxides (NO2 and NO constitute "NOx" ) and sulfur dioxide (SO2) are primary pollutants, derived from combustion of sulfur and nitrogen containing fossil fuels, and are directly emitted by power plants. In a complex series of atmospheric reactions, nitrogen oxides are converted to nitric (HNO3) and nitrous (HNO2) acids and acid aerosols (a form of particulate matter (PM), or soot), and SO2 is converted to sulfuric acid, which is another constituent of acid aerosols. Acid aerosols are sometimes referred to as a component of "acid fog". Nitrogen oxides are also converted in another series of complex reactions in the presence of sunlight to ozone (O3).
The results of the recent health effects research are overwhelming. The new data describe a coherent picture of serious adverse health effects due to air pollution.
Ozone causes symptoms of chest tightness, shortness of breath, cough, wheeze, pulmonary inflammation, declines in lung function, increases in bronchial hyperreactivity, exacerbations of allergen induced asthma, and is associated in epidemiologic studies with de novo development of asthma as well as increased emergency room visits, increased hospitalizations, and increased mortality rates.
Particulate matter of the size which results from fossil fuel combustion penetrates efficiently into the gas exchange portions of the lung and is associated in epidemiologic studies with chest symptoms, small declines in lung function, increased asthma attacks, increased asthma medication use, increased days lost from school and work due to chest illness, increased emergency room use, increased hospitalizations, and increased mortality.
Data increasingly suggest that these pollutants are also associated with lung cancer.
The recent research is divided into 16 sections according to study type.
The new data on ozone effects on lung function are consistent with previous data. The recent advance in this area is the combining of many previous studies to develop a model which describes the impairment of lung function. The important determinants of lung function decline include: ozone concentration, duration of exposure, ventilatory rate (exercise level) during exposure, age, and smoking status. The presence of chronic obstructive lung disease (COPD) was identified as a factor which, when combined with exercise, produced greater than expected declines in lung function. Hence, COPD patients may be added to the list of groups unusually susceptible to adverse health effects from ozone: children who play outdoors, adults who work or exercise outdoor, and asthmatics.
Data continue to be generated indicating that ozone causes inflammation in the distal airways, with increases in white blood cells, proteins, cytokines, interleukins, and other inflammatory mediators leaving the blood stream and accumulating in the lung. These studies use the bronchoalveolar lavage technique (BAL), which measures abnormal exudative contents of the distal airways and alveoli. Some reports continue to find that allergic asthmatics may be more vulnerable to these effects. In addition, new data indicate that declines in spirometric lung function measurements do not correlate strongly with bronchial hyperreactivity or markers of inflammation. Hence, understanding exactly how lung function declines, increases in inflammation, and increases in bronchial hyperreactivity function independently continues to be an area of active research.
One of the most innovative new studies looked at BAL results of recreational joggers in New York City, and found that ozone air pollution correlated well with BAL markers of inflammation in these subjects.
The data on ozone exacerbations of allergen induced spirometric declines continues to evolve. While some previous observations found relatively low levels of ozone to aggravate allergen induced bronchial obstruction, more recent studies find that in most people, ozone induced exacerbation of allergen induced spirometric impairment occurs only at higher levels. The caveat remains that these studies are performed only on persons with mild allergic asthma, and not on persons with severe, persistent asthma. Hence, extrapolation to the broader population of persons with varying asthma severity is precluded.
Time series studies examining the relationship between community air pollution levels with asthmatic peak expiratory flow rates (PEFR) and medication use continue to find that air pollution is associated with declines in PEFRs and increases in asthma medication use. Two new studies performed combined analysis of previous time series PEFR studies in children. One examined the relationship with particulate air pollution and the other with ozone. Both found impairment in lung function as measured by PEFR in children to be associated with air pollution.
Several new studies examined cross sectionally the relationship between spirometric lung function and air pollution levels. All found air pollution to be associated with lower lung function levels, most robustly with particulates and acid aerosols. One innovative new study looked at lung function growth in children and found that lung growth was lower in children living in high ozone air pollution areas. This study is not conclusive and needs to be replicated before any conclusions can be drawn, but is consistent with pathophysiologic observations and a previously performed autopsy study which implicates pulmonary inflammation and scarring.
An interesting new study looked at de novo development of asthma over 15 years in a non-smoking prospective cohort and found that ozone air pollution was associated with new onset asthma in men, but not women. Because analysis was not adjusted for amount of time working outdoors, and replicating the study will be quite expensive and time consuming, firm conclusions cannot be drawn.
One of the areas of most active research looks to understand the cardiac effects of particulate air pollution. This research is compelled by observations in many other studies which find that particulate air pollution is not only associated with death from pulmonary causes, but also with cardiac etiologies. The new research looks at cardiac function as measured by 24 hour EKG (Holter), and finds, among other things, decreased heart rate variability when subjects are exposed to higher particulate levels. Decreased heart rate variability has been identified as a risk factor for cardiac disease.
Time series studies looking the relationship between air pollution levels and emergency room visits for asthma and other respiratory disease continue to overwhelmingly find significant and robust associations with particulate and ozone.
A couple new prospective cohort studies of asthmatics find that higher air pollution levels are associated with increased emergency room visits. One model which combined weather variables with air pollution variables accounted for 69% of the variability in asthmatic emergency room use.
The flow of studies of hospitalization rates as a function of air pollution levels continues unabated, with overwhelming evidence of elevated hospitalization rates due to air pollution.
Nineteen new studies examined the association between particulates and hospitalization rates. Only one of these studies failed to find an association between combustion derived air pollution and increased hospitalization rates. Two of the studies found the association with SO2 instead, and one found the association with particulate only when NOx was also in the model. Hence, in 18 of 19 studies, the association with particulate air pollution or its chemical antecedents was observed.
Fifteen new studies examined the association between ozone air pollution and hospitalization rates. Twelve studies found a significant association, one study found the association with NO2 instead. Two studies failed to find the association. In all, 13 of 15 studies found the association with ozone or its chemical antecedents.
The cascade of studies finding associations between air pollution and excess mortality rates continues unabated.
Eighteen new studies examined the association between particulate air pollution and excess mortality. Seventeen of these studies found the association.
Twelve new studies examined the association between ozone air pollution and excess mortality. Ten found the association and one found the association with NO2 instead. One study found ozone to be only marginally significant. No study completely failed to find an association between ozone or its chemical antecedent, NO2, and excess mortality rates.
One new meta-analysis of particulate time series mortality studies appeared in the literature. The results are entirely consistent with previous meta-analyses. The additional feature of this study was to reinforce the notion that when the contribution of fine fraction (smaller) particulate is higher (which occurs when the particulate is from fossil fuel combustion sources), the association between particulate and excess mortality rates is even stronger.
One new prospective cohort was recently reported. Not surprisingly, it found that particulate air pollution was associated with premature mortality, with the mortality rates among the more exposed groups being about 18% higher. In addition, as with all the previously reported prospective cohorts, air pollution was associated with increased lung cancer rates.
In sum, the data describing the health effects of ozone and particulate is robust and convincing. Air pollution causes increased chest symptoms, chest illness, asthma attacks, increases in emergency room and hospital admissions, and increased mortality rates. The association between ozone and many adverse health effects is certainly causal, and the association with excess mortality is certainly robust and may well be causal. The causal nature of the association between particulate air pollution and adverse health effects and higher mortality rates appears to be firmly established.
The National Institutes of Health has published in its scientific publication, Environmental Health Perspectives, an article which observes that the data associating particulate air pollution with adverse health outcomes is conclusive. While many researchers had previously taken that position, dissenting views were also published. With the panoply of data now before us, however, avoiding public responsibility to reduce air pollution levels is not tenable. With a major contribution to particulate and ozone air pollution coming from very outdated power plants, and with newer, much less polluting power plants increasingly satisfying power generating needs, the justification for maintaining outdated technology has faded. The time has come to clean up outdated, highly polluting power plants.
In 1996, many of the academic researchers published reviews of the health effects of air pollution in the peer reviewed medical literature. This was mostly in anticipation of the legislature and court mandated EPA review of the ozone and particulate National Ambient Air Quality Standards (NAAQS). Most of these reviews recognized the substantial association in laboratory and epidemiologic studies between air pollutants and adverse health outcomes. The EPA agreed, and promulgated new NAAQS for ozone and particulate. A few researchers felt the case for particulate to have already been shown to be causal.1 While the evidence was substantial, coherent, consistent, robust, and almost overwhelming, a minority of researchers dissented.2 Many researchers found the associations compelling but felt the need to ask additional questions.3 Similarly, regarding ozone, few doubted the evidence that it could cause adverse effects, the question was whether the magnitude of the effects were sufficient to be considered of public health import. Substantial recent data is finding associations between ozone levels and acute and chronic declines in lung function, onset of chronic lung disease, and daily mortality rates.
This review is limited to the criteria air pollutants which would be expected to result from power plant emissions. This report does not address data on pollutants which are unique to motor vehicles (diesel exhaust), nor does it address mercury, which is emitted by power plants and is increasingly being recognized as causing potentially serious environmental contamination.
Hence, this review addresses NOx, SO2, ozone, and particulate (PM) air pollution. Not every study done in the last 4 years is addressed; however, a substantial effort is made to include every study which has implications for considering the health effects of these pollutants in the general population. I begin with a review of the major pollutants, their sources, a sense of the levels to which the general population has been exposed, and a summary of the health literature developed up until 1996.
Then, the recent health effects literature is summarized with emphasis on the data developed since 1996. The recent literature is divided into 15 sections according to the general type of study design. This analysis finds that within each study type, substantial data has emerged which supports the notion that air pollution of the types derived from power plant emissions is associated with clinically significant impairment public health. Taken as a whole, the coherence of the data inexorably leads to the suggestion that these air pollutants are causing substantial adverse health outcomes.
In February 2000, Environmental Health Perspectives, a scientific journal published by the National Institutes of Health environmental division, published an editorial stating that the evidence on particulate air pollution was now sufficient to be considered causal. With considerations of unnecessarily high air pollutant output from outdated power plants, and substantial new research on health effects of those pollutants, the time seemed appropriate to review the recent data and facilitate its public dissemination.
"Air pollution" encompasses a diverse array of anthropogenic chemical emissions including gaseous combustion products, volatile chemicals, aerosols (particulate), and their atmospheric reaction products. Atmospheric chemistry of air pollution has recently been reviewed.4
Information on local and regional air pollution levels and major sources is usually available on the US EPA website (www.epa.gov).
While visibility has improved in the west but perhaps worsened in the east, improvement has been seen with many measures of air pollution over the last couple decades (60% lower sulfur dioxide and carbon monoxide levels); however, in 1996 roughly 46 million people in the USA still lived in areas not meeting the US EPA National Ambient Air Quality Standards (NAAQS), remaining at risk for adverse health consequences.
Sulfur Dioxide (SO2) gas is formed during the combustion of sulfur-containing fossil fuel (coal and oil), during metal smelting, paper manufacturing, food preparation, and other industrial processes. It is an important contributor to acid aerosols and "acid rain", and is typically a component of complex pollutant mixtures. Peak one hour SO2 values recently reported by the EPA occur in the 0.4 to 0.8 ppm range, with rare higher excursions. Relatively cheap high-sulfur coal is most extensively used by power plants in the U.S. midwest and east, leading to downwind acidification of lakes in New England and eastern Canada.
Fossil fuel combustion generates nitrogen dioxide (NO2) and nitric oxide (NO) which is rapidly oxidized to NO2. NO2 reacts in the presence of sunlight and VOCs to form ozone, and contributes through atmospheric reactions to the formation of nitrous and nitric acid aerosols. Hence, in epidemiologic studies differentiation of individual pollutant effects is very difficult and often impossible. Major sources are motor vehicles, power plants, and other fossil fuel burning industries. Local levels tend to vary with traffic density. Indoor exposures to NO2 can be substantial from unvented combustion sources, such as gas stoves, and space heaters. In the absence of indoor sources, indoor levels are about half of those outdoors. Individual NO2 exposure is correlated rather poorly with the fixed site ambient air NO2 levels at least partially because of the high proportion of time spent indoors. The highest ambient one hour exposures reported by EPA are over 0.200 ppm, and the highest annual mean exposures are over 0.040 ppm.
Ozone has different health implications in the stratosphere and the troposphere. In the stratosphere (the "ozone layer"), 10-50 km (6-30 miles) above the earth, ozone provides a critical barrier to solar ultraviolet radiation, and protection from skin cancers, cataracts, and serious ecological disruption. International treaties phasing out ozone-depleting chemicals like chlorofluorocarbons have eased, but not eliminated the threat to this layer's integrity. Stratospheric ozone is good, tropospheric ozone is bad.
We focus on tropospheric (ground level) ozone pollution. Excessive ozone exposure is widespread: over 70 million people lived in areas not meeting the EPA ozone standard in 1995; that number will increase markedly with implementation of the updated 1997 standard. The highest recent domestic ozone levels have occurred in southern California and Texas, with peak levels in the mid to high 200 ppb range.
Ambient ozone concentrations rise as a result of a solar UV irradiation driving a complex series of reactions involving volatile organic compounds (VOCs) and nitrogen oxides (NOx). Community sources of VOCs include gasoline vapors, chemical solvents, combustion products of fuels, terpenes, and consumer products, while NOx is largely generated by fossil fuel combustion (power plants, diesel, and industrial boilers). Ozone levels may paradoxically be as high or higher downwind from cities than in the cities themselves, reflecting the time needed for the atmospheric photochemical reactions to occur. Similarly, when air masses are stagnant for a few days, precursor concentrations rise and react in the sunlight resulting in exceptionally high levels. This is most likely where large urban areas are surrounded by mountains, such as Los Angeles and Mexico City, but significantly elevated ozone levels occur sporadically in many areas of the U.S.
About 24 million persons in the U.S. lived in areas not meeting the U.S. EPA's National Ambient Air Quality Standard (NAAQS) for airborne particles less than 10 micrometers in aerodynamic diameter (PM10) in 1995.
Particulate air pollution (PM: particulate matter) is a heterogeneous classification of liquid and solid aerosols which includes anthropogenic emissions from power plants and other fuel combustion (coal, oil, biomass), transportation, and high temperature industrial processes. Smaller particles (often less than PM3) include viruses and some bacteria, but mostly come from anthropogenic sources, including sulfate and nitrate aerosols and other combustion derived atmospheric reaction products; whereas larger particles (PM3 to 30) include pollen, spores, crustal dusts, and other mechanically generated dusts. Size is a critical determinant of deposition site, with larger particles (greater than PM3) tending to deposit in the nasal and tracheobronchial regions), and smaller particles (less than PM10) penetrating deeper into the lungs. Regional air pollution exacerbations may be due to intermediate and long range tropospheric transport in addition to local influences such strong emission sources, proximity to heavily used roadways, stagnant air masses, and local weather temperature inversions. Recent EPA data shows typical peak community levels in the low 200s to mid 300s, with rare exposures as high as 700 mcg/m3. Contributing species include sulfur and nitrogen oxides (forming sulfuric, nitric, and nitrous acids), metals, ammonium salts, mechanically generated dusts (silica, etc), some with adherent polycyclic aromatic hydrocarbons, dioxins, dibenzofurans, etc, and is usually present as a complex mixture with atmospheric reaction byproducts. Acid aerosols refers to particulate which consists of acidic chemicals (including hydrated sulfur and nitrogen oxides).
The major health concerns associated with exposure to high concentrations of SO2 include effects on breathing, respiratory illness, alterations in pulmonary defenses, and aggravation of existing cardiovascular disease. Children, the elderly, and people with asthma, cardiovascular disease or chronic lung disease (such as bronchitis or emphysema), are most susceptible to adverse health effects associated with exposure to SO2. The odor threshold is about 0.5 ppm and 6-10 ppm causes irritation of the eyes, nose, and throat. SO2 may cause chronic obstructive lung disease after high dose exposure. SO2 causes asthma exacerbations in some exercising asthmatics at levels as low as 0.25 ppm, an adverse health effect which the US EPA has heretofore failed to regulate.
Sulfur dioxide reacts in the atmosphere to create H2SO4, which forms an acid aerosol. This may be the actual species responsible for many of the health effects observed in epidemiologic studies (see section on particulates). It is epidemiologically difficult to separate SO2 from particulate effects, hence SO2 is commonly associated with increases in hospitalization and mortality rates from cardiorespiratory disease. However, some studies find evidence of health effects of aerosols in virtual absence of sulfur, implying that SO2 may be an important but not necessary component of these acid aerosols.5
Nitrogen dioxide (NO2) is absorbed in both large and small airways. Very high concentrations (>200 ppm) are very dangerous, causing lung injury, fatal pulmonary edema, and bronchopneumonia. Lower concentrations cause impaired mucociliary clearance, particle transport, macrophage function, and local immunity. A recent report of railroad car accident resulted in a substantial but unmeasured community exposure. Headache and respiratory symptoms were reported, especially in those with underlying pulmonary disease. Animal studies find increased mortality with concomitant microbial pathogen exposure. In humans, high exposures (2 to 5 ppm) for 3 hours cause airway inflammation and higher levels of antigen-specific serum IgE, local IgA, IgG, and IgE antibody. Moderate exposure to NO2 to 260 ppb (0.260 ppm or 0.490 mg/m3) for 30 minutes causes increased nonspecific hyperreactivity, and in a 6.6% lower PEFR in the late phase of asthmatic reaction to antigen. Levels around 80 ppb have been associated with a significant increase in acute respiratory infections, sore throat, colds and absences from school.
Epidemiologically, commonly encountered exposures (>30 ppb) have been associated with airways hyper reactivity, and even lower exposures (15 ppb) with stuffy nose and cough. While ambient NO2 levels have been associated in epidemiologic meta-analyses with declines in spirometry and cardiorespiratory events, NO2 is less clearly implicated than particulate, sulfur dioxide, and ozone.
Ambient tropospheric ozone pollution at sufficient levels can cause upper and lower respiratory irritative symptoms, restrictive and obstructive spirometric changes, and increased responsiveness to methacholine and allergen bronchoprovocation. In epidemiologic studies, ozone has been associated with increased de novo development of chronic respiratory illness and increased incidence of emergency department visits and hospitalizations for asthma and respiratory disease. Animal studies suggest increased susceptibility to bacterial infection. Some evidence supports an association between ambient ozone exposure and increased daily mortality rates. Ozone induced illness is probably very infrequently recognized as such, but may be suspected especially during formation and especially persistence of relatively stagnant hot ambient air masses. Since bright sunlight is present driving the chemical reactions, health effects from heat exposure may be concomitant.
Ozone gas is a very strong oxidant, reacting with biomolecules (alkanes, alkenes, amines, sterols, sulfhydryls, lipids and others) to form ozonides, then free radicals. This triggers inflammation which includes prostaglandins (PGE2, PGF2, TXB2), neutrophils, fibronectin, interleukin-6, lactate dehydrogenase, cytokines, fibronectin, elastase, plasminogen activator, coagulation factors, and other proteins in association with increases in airway permeability. Macrophage function is impaired (possibly related to the increase in PGE2), and this has been associated with increased susceptibility to bacterial pulmonary infection in animal experiments. Pre-treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduces this effect. Some evidence indicates chronic lung scarring, especially at the bronchoalveolar junction.
Ozone induced illness observed in the laboratory includes conjunctival irritation, upper respiratory irritation, cough, shortness of breath, wheezing, decreased tidal volume, nausea, malaise, and headache. Also associated with ozone pollution is a peculiar chest pain which is substernal, commonly tearing or burning in character, which gradually increases in intensity with inspiration and declines during expiration. Asthmatic children playing outdoors on high ozone air pollution days are roughly 20 to 40% more likely to suffer an asthmatic exacerbation.
Pulmonary function is variably impaired. DLCO (diffusion capacity - a measure of gas exchange) may drop. Declines in FEV1 and FVC show great interindividual variability. Laboratory exposures provide the following data but probably underestimate the effects of community exposures (due to interactive effects of other pollutants, allergens, and to other exposure dynamics). While spirometric changes tend to decrease after several sequential days exposure, tolerance does not seem to develop to bronchial hyper responsiveness. Although ozone has been shown to decrease athletic performance, it has not been shown to exacerbate exercise induced asthma.
| 1 - 2 hours @ 120 ppb | 10 - 20 % of population | 12% decline FEV1 |
| 6.6 hours @ 80 ppb | few individuals | 38% decline FEV1 |
| 8 hours @ 120 ppb | population average | 20% decline FEV1 |
| 6.6 hours @ 120 ppb | general population | bronchial hyperreactivity |
Great interindividual variability exists in ozone responsiveness, with a few individuals suffering clinically important reactions, most persons experiencing mild responses, with the remainder little affected. Persons at risk include persons with asthma or chronic lung disease, and those who are active outdoors for prolonged periods. Examples of this latter group are athletes, children at play, and outdoor workers such as laborers, policemen and firemen, farmers, linemen, loading dock workers, construction workers, and foresters. Ozone related spirometric compromise is more marked in individuals with chronic obstructive lung disease, than in otherwise healthy smokers. Increasing evidence suggests that asthmatics, after exposure to ozone, have increased bronchial reactivity to subsequent allergens. Some non-asthmatics show a similar pattern.
The precise clinical syndrome resulting from particulate has not been well defined clinically, and the clinician will often be uncertain about the contribution of these pollutants in a given patient's exacerbation of lung or heart disease. Adverse health effects from PM are suggested by extensive epidemiologic observation, and by animal and human studies following laboratory exposures. Epidemiologic studies have difficulty describing the effects of individual pollutants in what are typically mixed exposures. Nonetheless the case that particulate pollution represents a substantial public health concern is bolstered by the remarkable consistency across different study techniques, geographies, weather conditions, particle sources, and investigators, as well as the coherence seen across a wide range of health effects and outcome measures.
Particulate airway distribution, and apparently health effects, are dependent on size of the particles, and on the structural and functional characteristics of the airways. Near universal pulmonary access is achieved by smaller particles (<PM3); nearly all particles larger than PM10 are trapped in the upper airways where they tend to be cleared by mucociliary mechanisms. A recent study has confirmed at autopsy the deposition distribution observed in the exposure chamber - the apical parenchyma of the lung retains particles smaller than 2.5 micron aerodynamic diameter.7 Persons with obstructive pulmonary disease (smokers, asthmatics, and patients with small airway disease or chronic obstructive pulmonary disease [COPD]) have greater distal airway deposition of particles, and this effect is inversely and well correlated with predicted FEV1.
A robust epidemiologic data set associates PM10 with adverse health effects.1, 8-12
However, more recent epidemiologic studies have contributed to understanding the size specificity of health effects, and have increasingly implicated the gasses and smaller particles as the more relevant components of hazardous particulate exposure.13-16
National Research Council has urged EPA to increase research into the toxicology of particulate chemical components and the relationship between monitored community exposures and personal exposure.17
Acute symptoms and signs include restricted activity (including days lost from school and work due to respiratory illness), respiratory illnesses, and exacerbations of asthma and COPD. Clinical observations include declines in lung function, increased asthma medication use, increased emergency department visits, increased hospitalization, increased cardiac and respiratory mortality. Although asthmatics seem to increase bronchodilator use during acid aerosol air pollution episodes, they see relatively little improvement in their peak flow meter recordings. Groups at particular risk of acute illness include the elderly (>65 years), and persons with chronic heart and lung diseases.
Clinical associations with chronic particulate pollution observed in epidemiologic studies include bronchitis, chronic cough, respiratory illness, COPD and asthma exacerbations, decreased longevity, and lung cancer.
The most important data on life expectancy and lung cancer come from two prospective cohort studies in the United States. Both the Harvard six cities study13 and the American Cancer Society cohorts16 found higher community exposures to fine particulate air pollution to be associated with premature mortality and increased lung cancer incidence after adjusting for cigarette smoking and other risk factors. The premature mortality findings are consistent with studies using cross sectional, time series, and case control methodologies, and with the several meta-analyses of the time series studies.1, 11, 18 The lung cancer findings are not unexpected in light of the recent data which have elucidated a mechanism by which polycyclic aromatic hydrocarbons (commonly adsorbed on particulate air pollution) cause lung cancer.
Total mortality 1%
Cardiovascular mortality 1.4%
Respiratory mortality 3.4%
Respiratory hospitalizations 0.8%
Asthma hospitalizations 1.9%
Asthma ED visits 3.4%
Asthma exacerbations and increase in bronchodilator use 3%
Health effects may be observed for several days after peak exposures, and detectable for up to several weeks after substantial air pollution episodes. At relevant concentrations the mortality dose response relationship is essentially linear, with increases seen even with very low exposures. The annual attributable mortality in the USA is estimated to be in the tens of thousands, (http://www.nrdc.org/nrdcpro/bt/tableGu.html) and the World Health Organization estimates that about 460,000 excess deaths globally are due to suspended particulate matter.
Perhaps the most interesting observations of a "natural experiment" of human mortality due to particulate air pollution were performed by Dr. Arden Pope12 at Brigham Young University in Utah. His summary of his observations follows:
"Utah Valley has provided an interesting and unique opportunity to evaluate the health effects of respirable particulate air pollution (PM10). Residents of this valley are predominantly nonsmoking members of the Church of Jesus Christ of Latter-day Saints (Mormons). The area has moderately high average PM10 levels with periods of highly elevated PM10 concentrations due to local emissions being trapped in a stagnant air mass near the valley floor during low-level temperature inversion episodes. Due to a labor dispute, there was intermittent operation of the single largest pollution source, an old integrated steel mill. Levels of other common pollutants including sulfur dioxide, ozone, and acidic aerosol are relatively low. Studies specific to Utah Valley have observed that elevated PM10 concentrations are associated with: (1) decreased lung function; (2) increased incidence of respiratory symptoms; (3) increased school absenteeism; (4) increased respiratory hospital admissions; and (5) increased mortality, especially respiratory and cardiovascular mortality."
The summary of pre-1996 data above essentially reflects the thinking in the medical literature prior to 1996, which is about when most of the major academic reviews were published in anticipation of the EPA revision of the NAAQS for ozone and particulate. The pre-1996 data is perhaps best summarized by the review published by the Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society in January 1996.3 This provides a convenient and expert point of departure for a review of the more recent research. I have excerpted the relevant conclusions from this 50 page review tome.
"Ambient air O3 is generated in the troposphere from precursors (hydrocarbons and NOx) in complex reactions catalyzed by light energy. ... During acute O3 exposure, many children and young adults progressively develop substernal pain on deep inspiration, irritative cough, and a reduced vital capacity and FEV1. These changes recede initially fairly rapidly and then somewhat more slowly over a period of several hours after exposure cessation, though some FEV1 decrement and symptoms may persist for as long as 24 hours.
"There is evidence from animal and human studies that certain alveolar macrophage antimicrobial defense functions are impaired after exposure to O3. In mice, O3-impaired macrophage function contributes to increased mortality after challenge with aerosolized inhaled bacteria, although in humans O3 exposure has not been shown to be directly associated with increased morbidity from respiratory infections.
"Acute exposure to O3 also provokes an upper and lower airway inflammatory response that includes mucosal hyperemia, increased permeability to serum proteins and to water soluble probe molecules placed on the airway surface, and infiltration of the mucosa with neutrophils. O3 exopsure also results in a large increase in inflammatory mediators and factors present in bronchial and alveolar lining fluids. Many of these mediators are likely released by epithelial cells in the lung. In view of the potent irritant like effects of O3 on the airways and of O3 induced bronchial hyperreactivity and airway inflammation, one might expect individuals with chronic airways disease to exhibit enhanced acute susceptibility to this pollutant. Indeed, studies of panels of asthmatics in the Los Angeles and Houston areas relating symptoms and medication use to air pollution levels, and associations between fluctuations in summertime O3 levels and hospital admissions from asthma, lend some support to this hypothesis. However, the reality is that O3 and other pollutants such as sulfates and acid aerosols commonly rise together, and, for this reason, it is difficult to attribute increased acute respiratory admissions to a single pollutant.
"Long term exposures of animals to O3 do not result in diffuse parenchymal lesions such as emphysema or diffuse fibrosis nor are pressure-volume curves usually displaced. However, there appears to be an emerging consensus that the principal effect of chronic O3 exposure in animals is a centri-acinar lesion in the terminal or respiratory bronchioles in which metaplastic airways epithelium extends into the proximal acinar regions accompanied by peribronchiolar mononuclear infiltrates, localized deposition of collagen, and remodeled peribronchiolar airspace. More severe degrees of injury are accompanied by restrictive impairments in airflow. These findings indicate the importance of and support the need for additional longitudinal and cross sectional population studies to look for evidence of excessive obstructive airways impairment among residents of perennially O3 polluted areas in the Los Angeles basin or elsewhere."
"Particles, SOx, and acid aerosols are a complex group of distinct pollutants that have common sources and usually covary in concentration. During the past two decades, the chemical characteristics and the geographic distribution of sulfur oxide and particulate pollution have been altered by control strategies, specifically taller stacks for power plants, put in place in response to air pollution regulations adopted in the early 1970s. While the increasing stack heights have lowered local ambient levels, the residence time of SOx and particles in the air have been increased, thereby promoting transformation to various particulate sulfate compounds, including acidic sulfates. These sulfate particles constitute a large fraction of the total mass of smaller particles (< 3 microns in aerodynamic diameter). Epidemiologic studies have consistently provided evidence of adverse health effects of these air pollutants. Particulate and SO2 pollution were strongly implicated in the acute morbidity and mortality associated with the severe pollution episodes in Donora (Pennsylvania), London, and New York in the 1940s, 1950s, and 1960s. There is new evidence that even current ambient levels of PM10 (30 to 150 micrograms/m3) are associated with increases in daily cardiorespiratory mortality and in total mortality, excluding accidental and suicide deaths. These associations have been shown in many different communities, as widely different in particle composition and climate as Philadelphia, St. Louis, Utah Valley, and Santa Clara County, California. It has recently been shown in a long-term prospective study of adults in the United States that chronic levels of higher PM10 pollution are associated with increased mortality after adjusting for several individual risk factors. Daily fluctuations in PM10 levels have also been shown to be related to acute respiratory hospital admissions in children, to school and kindergarten absences, to decrements in peak flow rates in normal children, and to increased medication use in children and adults with asthma. Although some epidemiologic studies suggest that acid aerosols are an important toxic component of PM10, other studies do not support this hypothesis. Dockery and Pope (408) recently reviewed the epidemiologic literature for adverse effects, assuming that reported associations can be attributed to acute particle mass exposures. Combined effects were estimated as percent increase in comparable measures of mortality and morbidity, associated with each 10 micrograms/m3 increase in daily mean PM10 exposure (Table 7). While total mortality increased by 1% for each 10 micrograms/m3 increase in PM10, respiratory mortality increased by 3.4% and cardiovascular mortality increased by 1.4%. Hospital admissions and emergency department visits increased approximately 1% for all respiratory complaints, and 2% to 3% for asthma. Exacerbation of asthma increased by about 3%, as did lower respiratory symptoms. Small decreases in lung function, approximately 0.1%, have also been observed. This review suggests that the epidemiologic studies of adverse morbidity measures are coherent with the mortality studies showing quantitatively similar adverse effects of acute exposures to particulate pollution."
A new model has been published which seems to better predict the mean decrease in FEV1 as a function of ozone concentration, minute ventilation, duration of exposure, and age. We currently know that the magnitude of the FEV1 decline increases with ozone concentration, minute ventilation, and duration of exposure, and decreases with age. McDonnell, et al19 combined the results of a series of chamber - spirometry studies performed at the US EPA Clinical Research Facility over a 13 year period on 485 non-smoking healthy subjects. Ozone concentrations ranged from 0 to 400 ppb; ventilation rates varied from about 5 L/min/m2BSA (body surface area) at rest to about 40 L/min/m2BSA. The latter represents a moderately heavy workload. Spirometry was performed at zero, 1 and 2 hours after exposure began.
This model is quite useful within its constraints. Exposures are limited to 2 hours. Exposure to persons working or exercising outdoors in the community are commonly 6 or 8 hours. The subjects were healthy young men. Sensitive subgroups, especially those with asthma, may be more vulnerable. Nonetheless, this model is probably the most useful data set for predicting FEV1 decline as a result of relatively short duration of ozone exposures.
A recent study confirmed previous observations that ozone induced declines in FEV1 do not correlate with development of bronchial hyperreactivity. In chamber exposures to 400 ppb for 3 hours per day on 5 consecutive days at moderate exercise (about 32 L/min), asthmatic subjects demonstrated attenuated FEV1 decline after several days of exposure. However, the ozone caused bronchial hyper responsiveness which did not attenuate.20
Another study of elderly subjects with COPD were much more susceptible to ozone induced declines in FEV1 and increased airway resistance than subjects without COPD. The COPD subgroup decline in FEV1 after 4 hours exposure to 240 ppb ozone with intermittent light exercise was 19% compared with 2% in the healthy controls. About half of this effect was due to ozone and half to the effect of exercise in COPD.21
One study of ozone effects on cardiac parameters found that 300 ppb ozone for 3 hours with intermittent exercise resulted in an increase in cardiac rate and heart rate * blood pressure product, but otherwise no major effects on right heart catheterization cardiac parameters.22
One study exposed 41 subjects aged 9-12 years, both with and without asthma, to a combination of 100 ppb ozone, 0.10 ppm SO2, and 100 mcg/m3 H2SO4 for 4 hours with intermittent exercise. The subjects responded with changes in spirometry, symptoms, and overall discomfort level, but the results were not statistically significant.23
Overall, the chamber spirometry studies continue to find decrements in pulmonary function as a result of ozone exposure. The magnitude of the decrements are relatively small or are observed after prolonged exposure. The clinical implications for pulmonary function declines, hence, continue to be limited to sensitive subpopulations - those with underlying lung disease and those with prolonged outdoor exposures with elevated ventilation rates (children playing outdoors and adults working or exercising outdoors).
A handful of studies address the effects of air pollution on bronchoalveolar lavage measures of inflammation and its consequences. Some of the more interesting ones are summarized here.
In an attempt to better understand interindividual variability, a chamber study of healthy subjects exposed to 220 ppb of ozone for 4 hours with exercise was performed. The expected declines in FEV1 occurred with interindividual variability - some persons experienced a greater than 15% decline in FEV1 (designated responders) and some experienced a less than 5% decline (non-responders). Increases in BAL polymorphonuclear leukocytes, and interleukins 6 and 8 appeared early, and lymphocytes, mast cells, and eosinophils increased later in all groups, regardless of smoker or FEV1 responder status.24
A similar result occurred in a study which exposed asthmatic and healthy individuals to 125 and 250 ppb ozone over 3 hours of intermittent exercise. The magnitude of the inflammatory response measured on BAL was consistent within individuals, and the decrement in FEV1 was highly reproducible, but the BAL inflammation was not highly correlated with the decrement in FEV1.25
These studies help clarify the poor correlation between lung inflammation and declines in lung function.
Previous work has shown that the decline in FEV1 attenuates after several days of exposure to ozone, although the bronchial hyperreactivity tends to persist. A newer study finds that when subjects are repeatedly exposed to ozone (200 ppb over 4 hours over 4 days), significant decreases in the number of PMNs, fibronectin, and IL-6 were found after 4-d exposure versus single-day exposure.26
One study of dust mite allergic asthmatics found ozone exposure (160 ppb) to be associated with significant increases of eosinophils in the BAL fluid.27 Another study compared BAL of asthmatic subjects with that of normal subjects after exposure to ozone (200 ppb over 4 hours). The asthmatic subjects showed significantly greater O3-induced increases in several inflammatory endpoints (percent neutrophils and total protein concentration) in BAL as compared with normal subjects.28
Substance P (a neurotransmitter with many functions, incuding nocioception) has been shown to be observed in greater amounts in BAL fluid in larger amounts after ozone exposure.29
In sum, although the exposures above are generally higher than commonly encountered in the community, data continue to accrue that ozone induces bronchioalveolar inflammation, that asthmatics may have a heightened response, and that ozone induced inflammation observed on BAL does not correlate well with declines in FEV1.
One of the more interesting BAL studies examined the effects of community air pollution on recreational joggers in New York City.30 15 subjects were examined during summer (high ozone period) and retested during winter (low ozone period). Release of reactive oxygen species was lower in the summer than the winter. In contrast, LDH, IL-8, and PGE2 levels were all roughly two fold higher in summer. These results suggest a possible ongoing inflammatory response in the lungs of recreational joggers exposed to ozone and associated co-pollutants during the summer months, and that the inflammatory response observed during controlled chamber exposures seems to be occurring during community exposures.
One of the most interesting areas of current research concerns the potential for ozone to exacerbate asthmatic allergen induced bronchoconstriction. Previous work had discovered that ozone at higher doses increased asthmatic allergen sensitivity, but it was controversial whether lower ozone doses had the same effect. The current data suggest that 1 hour exposure of mild asthmatics at rest to 120 ppb, or with intermittent moderate exercise to 100 ppb ozone, does not enhance allergen sensitivity, but 3 hours exposure to 200 ppb with intermittent moderate exercise does. Unanswered at this time is whether asthmatics with more severe disease, or exposed to lower levels for longer periods or with higher activity levels (minute ventilation rates), would demonstrate ozone induced allergen hypersensitivity.31-33
Unusually high exposures to NO2 (with our without SO2) appear to increase asthmatic sensitivity to allergen as well.32, 34-36
Although this data suggests that air pollutants at levels uncommonly encountered in most areas of the USA will enhance asthmatic allergen sensitivity, at lower levels which are commonly encountered, the pollutants do not consistently enhance asthmatic allergen sensitivity.
I identified 24 studies which examined the relationship between air pollutants and asthma exacerbations and declines in peak flow rates. All studies except one demonstrated significant associations between air pollution levels and one of the health effects. Generally, studies which failed to find associations with drops in peak flow rates found increases in asthma medication use.37-60
I found 2 studies which performed combined analysis of time series peak flow studies in children. One61 looked at 5 previously performed studies of peak flow decrements as a function of PM10 particulate air pollution levels. They found a particulate to be associated with lower average peak flow rates and a higher prevalence of significant drops in peak flow rates.
The other study62 re-analyzed six studies which examined the effect of ozone air pollution on children playing outside at summer camps in New Jersey, New York, Ontario, and southern California. All of the studies found ozone to be associated with drops in FEV1. Combining the data, the authors estimate a decline of 0.5 ml of FEV1 per ppb O3. This is a surprisingly large, clinically important result, and suggests that chamber exposure studies are underestimating the effect of exposure in the community.
I identified 7 studies which examined the association between air pollution and cross sectional measures of lung function. All found significant associations between air pollution levels and lower lung function. This type of study is generally much less likely to differentiate between the effects of different types of pollutants unless very large numbers of cities are examined.
Abbey et al63 examined a group of 1,391 non-smokers and found that PM10, ozone, and SO2 all had significant associations with lower lung function. Interestingly, persons with a family history of lung disease (asthma, bronchitis, emphysema, or hay fever) may be much more vulnerable to the air pollution effects.
Peters et al64 studied 3,293 school children from 12 southern California communities with different air pollution levels. Significant associations were found between measures of lung function (FEV1 and FVC) and PM10, PM2.5, NO2, and O3 in girls, and O3 in boys. Both effects were stronger when stratified according to the amount of time the child spent outdoors. This study is forming the basis of a prospective cohort, and follow up data will be available in a few years.
In the largest study of its kind, Raizenne et al65 examined 10,251 children from 24 US and Canadian cities and found that acid aerosols were associated with about a 3% lower lung function (FEV1 and FVC).
Two studies examined the association between bronchial hyperreactivity and air pollution. Both found bronchial hyperreactivity to be associated with air pollution.66, 67
Other studies found significant associations between air pollution and cross sectional lung fucntion decrements.68, 69
I found one study70 which examined the relationship between chronic air pollution and lung growth in children. This study followed 1,150 children prospectively for 3 years, performing spirometry at the beginning and end of each summer. Air pollution in the various communities was evaluated for PM10, SO2, NO2, and O3. Adjusting for a child's sex, atopy, passive smoking, baseline lung function, and increase in height, the researchers found that summertime ozone was associated with a lesser summertime children’s lung growth as reflected by a lower than expected increase in FEV(1) and FVC. PM10, SO2, and NO2 did not show this association. One study should never be considered to have proven anything, and this is no exception. Alternative explanations are not excluded; however, this study suggests that ozone air pollution may impair normal lung growth in children.
Data continue to be generated by one of the most important ongoing prospective cohort projects - the Seventh Day Adventists study. This study is following a large cohort of a non-smoking population and associating local air pollution levels with health outcomes. In this analysis, 3,091 non-smoking subjects were followed for 15 years and about 3.5% of them reported a new diagnosis of asthma.71 The authors report that, regardless of adjusting for other air pollutants, the asthma rates were roughly doubled in the men exposed to the higher mean ozone levels. This effect was not observed in women. The analysis was not adjusted for the percentage of time working outdoors. While this analysis cannot be considered to have proven that ozone causes asthma, because the results are consistent with expectations generated from pathophysiologic studies, it raises important questions about whether ozone causes asthma. Unfortunately, this study is going to be difficult to replicate because of the unique population, large group size, and long duration required.
Many of the epidemiologic studies examining the cause of death in persons dying on high particulate air pollution days
I found 2 studies72, 73 which examined cardiac rate (24 hour holter monitor) in association with particulate air pollution levels. Both studies found elevated cardiac rates on days with elevated particulate levels. One of these studies additionally examined heart rate variability and found particulate to be associated with decreased overall heart rate variability.
I identified 14 studies in the recent medical literature which examined the association between air pollution and acute physician consultations or emergency room visits. Eight of these specifically examined asthma or acute wheezy episodes; 3 additional studies examined respiratory complaints generally; 1 each reviewed doctors house calls in Paris, France and childrens’ ER visits in Santiago, Chile. One study looked at ER visits during a series of bush fires in Sidney, Australia. I could not obtain the results of one study.74
Only the study of Australian bush fires75, and another in Switzerland76 (which admitted to potentially poor exposure assessment) failed to find significant associations.
One important study examined ER visits in one summer for respiratory disease in Montreal. Ozone, PM10, PM2.5 and sulfate were all associated with emergency room use for persons over the age of 65. A 36% increase in ozone levels was associated with a 21% increase in ER visits for respiratory complaints. In examining the effects of particulate and acid aerosols, the relative mass effects were PM2.5 > PM10 > SO4.77
The association between asthma ER visits and particulate was observed even when air pollution levels were below the new NAAQS for PM2.5. In this study, a moderate increase in air pollution (11 microg/m3 in fine PM) was associated with a 15% increase in the rate of ER visits.78
All the other studies also found consistent associations between air pollution levels and emergency room visits and respiratory disease.79-87
In all, 11 of the 13 studies for which results were available found significant associations between air pollution and emergency room use or acute physician consultations.
Two recent prospective cohort studies of asthmatics examined the relationship between air pollution levels and emergency room visits (a relatively new epidemiologic technique). One88 found a significant association between acid aerosol fog (a complex mixture of pollutants) and ER visits for asthma; the other89 found significant air pollution associations, with air pollution (NOx, SO2, and ozone) plus weather accounting for 69% of the variance.
I identified 19 studies which examined the association between air pollution and daily hospital admissions. Ozone and particulate air pollution were robustly associated with hospital admissions. One additional study examined the relationship between characteristic of air masses and asthma hospital admissions. It found that during the spring and summer, air masses with high air pollution levels were more likely to be associated with increased asthma admissions.
Nineteen90-108 new studies examined the association between particulates and hospitalization rates. Only one98 of these studies failed to find an association between combustion derived air pollution and increased hospitalization rates. Two97, 104 of the studies found the association with SO2 instead, and one found the association with particulate only when NOx was also in the model. Hence, in 18 of 19 studies, the association with particulate air pollution or its chemical antecedents was observed.
Fifteen new studies examined the association between ozone air pollution and hospitalization rates. Twelve90-94, 96, 97, 99, 102, 103, 107, 108 studies found a significant association, and one104 study found the association with NO2 instead. Two95, 98 studies failed to find the association. In all, 13 of 15 studies found the association with ozone or its chemical antecedents.
Outcomes which were commonly associated with air pollution included asthma, COPD (chronic obstructive pulmonary disease = chronic bronchitis and emphysema), and heart disease.
In summary, ozone and particulate air pollution were robustly associated with hospital admission rates. Common outcomes were asthma, COPD, and heart disease.
In late 1995 and early 1996 most of the major review articles emerged examining the relationship between air pollution and adverse health effects. These reviews found consistent and coherent associations between particulate air pollution and daily mortality levels. In addition, data was beginning to emerge suggesting that ozone air pollution was associated with daily mortality. While some authors considered the association between particulate air pollution and daily mortality to be causal, others were more circumspect. Hence, I examined the subsequent data in search of validation or refutation of these concerns.
I was able to identify 21 time series studies published since 1996 examining the association between daily air pollutant levels and daily mortality. These studies generally are quite well designed, adjusting for weather variables and other considerations.
Eighteen14, 105, 106, 109-123 new studies examined the association between particulate air pollution and excess mortality. One120 of these, a study of asthma mortality, failed to find the association.
Twelve new studies examined the association between ozone air pollution and excess mortality. Ten92, 110, 111, 113, 115, 118, 120-122, 124 found the association and one114 found the association with NO2 instead. One study109 found ozone to be marginally associated. No study completely failed to find an association with ozone or its chemical antecedent, NO2.
One120 study specifically examined the relationship between asthma mortality and air pollution. Only NO2 and ozone air pollution were found to be associated with asthma mortality.
I identified 1 study which attempted to differentiate the fine fraction (PM2.5) of particulate air pollution from the coarse fraction (PM2.5 - PM10).14 This study found the fine fraction to be implicated in elevated mortality rates. One106 studies examined acid sulfate aerosol, a common constituent of particulate fine fraction. Those studies found sulfate aerosol to be strongly associated with mortality. (Note is made that previous studies have shown that sulfate aerosol is sufficient, but not necessary, to be associated with mortality).12
Time series studies have continued to flood the medical journal market in the last few years, and continue to overwhelmingly find that particulate air pollution is associated with mortality. Data increasingly suggest that the fine fraction, which generally arises from combustion sources, is consistently implicated. In addition, a remarkably robust data set is emerging associating high ozone exposure with daily mortality. Although some studies find associations between SO2 and NO2 and daily mortality, these association are less consistent.
Several meta-analyses of the association between particulate air pollution and daily mortality have appeared previously in the literature. All have found significant associations between particulate air pollution and daily mortality. I have found one meta-analysis published in the recent literature.
This meta-analysis125 examined the effect of between study variability on the effect estimate of the association between particulate and daily mortality. More precisely, they examined the possible effects of air pollution patterns and characteristics of the exposed population. There was some evidence that PM effects were influenced by climate, housing characteristics, demographics, and the presence of sulfur dioxide and ozone. However, the effect of particulate on mortality was robust, not changing with inclusion of potential confounders and effect modifiers. The increase in daily mortality rate of 0.7% per 10 mcg/m3 increase in PM10 is similar to previous meta-analysis estimates (1% per 10 mcg/m3 increase in PM10), and was found to be higher in locations which had a higher proportion of PM10 attributed to the fine fraction (PM10). In other words, the effect estimate of this meta-analysis was quite consistent with previous meta-analyses, was able to adjust for the presence of many potential confounders and effect modifiers, and supported evidence from other studies which implicates the fine fraction of particulate in excess mortality.
Three large prospective cohort studies examining the relationship between particulate air pollution and premature mortality were conducted in the last decade.13, 16, 126 Prospective cohort studies are considered the most reliable study possible in air pollution epidemiology because individual subjects are identified and individual risk factors for mortality (such as smoking) are considered and adjusted for. All three prospective cohort studies found significant associations between particulate air pollution levels and premature mortality. Interestingly, all three studies also found associations between air pollution and lung cancer.
The most recent prospective cohort was published in 1999.126 This is a cohort of 6,338 nonsmoking Seventh-day Adventists. PM10 was strongly associated with non-malignant respiratory mortality adjusting for a wide range of potentially confounding factors, including occupational and indoor sources of air pollutants. The mortality rate was 18% higher for persons exposed to 43 days per year with PM10 levels higher than 100 mcg/m3. Both ozone and PM10 were associated with lung cancer in males, and sulfur dioxide showed strong associations with lung cancer in both sexes. Other pollutants showed weak or no associations with mortality.
The new data on health effects or air pollution has been reviewed above. One substantial new review of particulate air pollution has recently been published by the National Institutes of Health127 in their academic journal, Environmental Health Perspectives. This new review concludes that the case for adverse health effects from particulate air pollution has been made, and that the effect should be considered causal.
"The question of when it would be appropriate to conclude that the associations between particulate pollution and various outcomes (including mortality) should be judged as causal in nature has been difficult and controversial. Although such a judgment must be subject to revision, the volume of new information and new experimental findings has been so great that such a reevaluation is required at frequent intervals. The useful summary by Gamble [PM2.5 and Mortality in Long-Term Prospective Cohort Studies: Cause-Effect or Statistical Associations? Environ Health Perspect 106:535-554 (1998)] of the reasons why a causal inference was, in his opinion, not justified provides a basis for reevaluation in the light of new data. Such a reexamination indicates that the associative evidence is now stronger and that the biologic basis for a number of adverse effects has now been demonstrated. All of the useful guideline criteria customarily applied to such questions seem to have been met, although there is still much to be learned about interactive effects and the possibility of statistical thresholds."
A recent review has examined the health based financial benefit of reducing particulate air pollution in the USA.128
"Most Americans are exposed daily to airborne particulate matter (PM), a pollutant regulated by the U.S. Environmental Protection Agency. Current national standards are set for PM10 (particles less than 10 microns in diameter) and new standards have been promulgated for PM2.5 (particles less than 2.5 microns in diameter). Both particle sizes have been associated with mortality and morbidity in studies in the United States and elsewhere and an unambiguously safe level of ambient PM has been difficult to identify. PM10 concentrations have been reduced significantly in U.S. cities over the past two decades and relatively few locations continue to exceed national PM10 standards. However, the new PM2.5 standards will require further reductions in PM concentrations and additional expenditures for emission controls. Information about the health and economic benefits of achieving lower PM concentrations is important because: (1) expected costs of further PM reductions rise after the least-cost options are exhausted, and (2) there is uncertainty about the existence of a threshold safe level for PM. This paper develops and applies a methodology for quantifying the health benefits of potential reductions in ambient PM. Although uncertainties exist about several components of the methodology, the results indicate that the annual nationwide health benefits of achieving the new standards for PM2.5 relative to 1994-1996 ambient concentrations are likely to be between $14 billion and $55 billion annually, with a mean estimate of $32 billion."
Finally, lest one doubt that the public health community is behind curtailing air pollution as a needed public health measure, a journal of the American Public Health Association has published a recent review.129
"The connection between energy policy and increased levels of respiratory and cardiopulmonary disease has become clearer in the past few years. People living in cities with high levels of pollution have a higher risk of mortality than those living in less polluted cities. The pollutants most directly linked to increased morbidity and mortality include ozone, particulates, carbon monoxide, sulfur dioxide, volatile organic compounds, and oxides of nitrogen. Energy-related emissions generate the vast majority of these polluting chemicals. Technologies to prevent pollution in the transportation, manufacturing, building, and utility sectors can significantly reduce these emissions while reducing the energy bills of consumers and businesses. In short, clean energy technologies represent a very cost-effective investment in public health."
I have reviewed the medical literature and find that the air pollutants emitted by power plants causes many and serious adverse health effects. Outdated power plants emit high levels of nitrogen and sulfur oxides, which are converted in atmospheric reactions to ozone and particulate air pollution. In cross sectional, time series, and prospective cohort studies; in community and laboratory exposure studies; these pollutants have been associated with pulmonary inflammation, declines in lung function, chest illnesses, asthma attacks, increased rates of emergency room visits, increased rates of hospitalizations, and increased rates of mortality. The data are convincing. The association between ozone and many adverse health effects is certainly causal, and the association with excess mortality is certainly robust and may well be causal. The National Institutes of Health has published the conclusion that the association between particulate air pollution and adverse health effects should be considered causal. The health benefit to the public nationally of mitigating particulate air pollution is estimated to be $32 billion. A review of energy policy in Public Health Reports, a publication of the American Public Health Association finds that "Technologies to prevent (air) pollution in the ... utility sector(s) can significantly reduce these emissions while reducing the energy bills of consumers and businesses. In short, clean energy technologies represent a very cost-effective investment in public health." Sacrificing human life and health for utility industry interests in outdated technology is incomprehensible in a modern and civilized society.
1. Schwartz J. Air pollution and daily mortality: a review and meta analysis. Environmental Research 1994; 64:36-52.
2. Lipfert FW. Air pollution and human health: perspectives for the '90s and beyond. Risk Analysis 1997; 17:137-46.
3. ATS. Health effects of outdoor air pollution. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. American Journal of Respiratory & Critical Care Medicine 1996; 153:3-50.
4. Finlayson-Pitts B, Pitts J, Jr. Tropospheric air pollution: ozone, airborne toxics, polycyclic aromatic hydrocarbons, and particles. Science 1997; 276.
5. Schwartz J. Short term fluctuations in air pollution and hospital admissions of the elderly for respiratory disease. Thorax 1995; 50:531-8.
6. Lippmann M. Ozone. In: W R, ed. Environmental and Occupational Medicine. Philadelphia: Lippincott-Raven, 1998:601-615.
7. Churg A, Brauer M. Human lung parenchyma retains PM2.5. American Journal of Respiratory & Critical Care Medicine 1997; 155:2109-11.
8. Schwartz J, Dockery DW. Increased mortality in Philadelphia associated with daily air pollution concentrations. American Review of Respiratory Disease 1992; 145:600-4.
9. Schwartz J. What are people dying of on high air pollution days? Environmental Research 1994; 64:26-35.
10. Brunekreef B, Dockery DW, Krzyzanowski M. Epidemiologic studies on short-term effects of low levels of major ambient air pollution components. Environmental Health Perspectives 1995; 103:3-13.
11. Ostro B. The association of air pollution and mortality: examining the case for inference. Archives of Environmental Health 1993; 48:336-42.
12. Pope CA, 3rd. Adverse health effects of air pollutants in a nonsmoking population. Toxicology 1996; 111:149-55.
13. Dockery DW, Pope ACd, Xu X, et al. An association between air pollution and mortality in six U.S. cities [see comments]. New England Journal of Medicine 1993; 329:1753-9.
14. Schwartz J, Dockery DW, Neas LM. Is daily mortality associated specifically with fine particles? Journal of the Air & Waste Management Association 1996; 46:927-39.
15. Thurston GD. A critical review of PM10-mortality time-series studies. Journal of Exposure Analysis & Environmental Epidemiology 1996; 6:3-21.
16. Pope CA, 3rd, Thun MJ, Namboodiri MM, et al. Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. American Journal of Respiratory & Critical Care Medicine 1995; 151:669-74.
17. Kaiser J. Panel scores EPA on clean air science. Science 1988; 280:193-4.
18. Dockery DW, Pope CA, 3rd. Acute respiratory effects of particulate air pollution. Annual Review of Public Health 1994; 15:107-32.
19. McDonnell WF, Stewart PW, Andreoni S, et al. Prediction of ozone-induced FEV1 changes. Effects of concentration, duration, and ventilation. American Journal of Respiratory & Critical Care Medicine 1997; 156:715-22.
20. Gong H, Jr., McManus MS, Linn WS. Attenuated response to repeated daily ozone exposures in asthmatic subjects. Archives of Environmental Health 1997; 52:34-41.
21. Gong H, Jr., Shamoo DA, Anderson KR, Linn WS. Responses of older men with and without chronic obstructive pulmonary disease to prolonged ozone exposure. Archives of Environmental Health 1997; 52:18-25.
22. Gong H, Jr., Wong R, Sarma RJ, et al. Cardiovascular effects of ozone exposure in human volunteers. American Journal of Respiratory & Critical Care Medicine 1998; 158:538-46.
23. Linn WS, Gong H, Jr., Shamoo DA, Anderson KR, Avol EL. Chamber exposures of children to mixed ozone, sulfur dioxide, and sulfuric acid. Archives of Environmental Health 1997; 52:179-87.
24. Torres A, Utell MJ, Morow PE, et al. Airway inflammation in smokers and nonsmokers with varying responsiveness to ozone. American Journal of Respiratory & Critical Care Medicine 1997; 156:728-36.
25. Holz O, Jorres RA, Timm P, et al. Ozone-induced airway inflammatory changes differ between individuals and are reproducible. American Journal of Respiratory & Critical Care Medicine 1999; 159:776-84.
26. Christian DL, Chen LL, Scannell CH, Ferrando RE, Welch BS, Balmes JR. Ozone-induced inflammation is attenuated with multiday exposure. American Journal of Respiratory & Critical Care Medicine 1998; 158:532-7.
27. Peden DB, Boehlecke B, Horstman D, Devlin R. Prolonged acute exposure to 0.16 ppm ozone induces eosinophilic airway inflammation in asthmatic subjects with allergies. Journal of Allergy & Clinical Immunology 1997; 100:802-8.
28. Scannell C, Chen L, Aris RM, et al. Greater ozone-induced inflammatory responses in subjects with asthma. American Journal of Respiratory & Critical Care Medicine 1996; 154:24-9.
29. Krishna MT, Springall D, Meng QH, et al. Effects of ozone on epithelium and sensory nerves in the bronchial mucosa of healthy humans. American Journal of Respiratory & Critical Care Medicine 1997; 156:943-50.
30. Kinney PL, Nilsen DM, Lippmann M, et al. Biomarkers of lung inflammation in recreational joggers exposed to ozone. American Journal of Respiratory & Critical Care Medicine 1996; 154:1430-5.
31. Hanania NA, Tarlo SM, Silverman F, et al. Effect of exposure to low levels of ozone on the response to inhaled allergen in allergic asthmatic patients. Chest 1998; 114:752-6.
32. Jenkins HS, Devalia JL, Mister RL, Bevan AM, Rusznak C, Davies RJ. The effect of exposure to ozone and nitrogen dioxide on the airway response of atopic asthmatics to inhaled allergen: dose- and time-dependent effects. American Journal of Respiratory & Critical Care Medicine 1999; 160:33-9.
33. Jorres R, Nowak D, Magnussen H. The effect of ozone exposure on allergen responsiveness in subjects with asthma or rhinitis. American Journal of Respiratory & Critical Care Medicine 1996; 153:56-64.
34. Rusznak C, Devalia JL, Davies RJ. Airway response of asthmatic subjects to inhaled allergen after exposure to pollutants. Thorax 1996; 51:1105-8.
35. Strand V, Rak S, Svartengren M, Bylin G. Nitrogen dioxide exposure enhances asthmatic reaction to inhaled allergen in subjects with asthma. American Journal of Respiratory & Critical Care Medicine 1997; 155:881-7.
36. Strand V, Svartengren M, Rak S, Barck C, Bylin G. Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose. European Respiratory Journal 1998; 12:6-12.
37. Boezen HM, van der Zee SC, Postma DS, et al. Effects of ambient air pollution on upper and lower respiratory symptoms and peak expiratory flow in children [see comments]. Lancet 1999; 353:874-8.
38. Boezen M, Schouten J, Rijcken B, et al. Peak expiratory flow variability, bronchial responsiveness, and susceptibility to ambient air pollution in adults. American Journal of Respiratory & Critical Care Medicine 1998; 158:1848-54.
39. Delfino RJ, Coate BD, Zeiger RS, Seltzer JM, Street DH, Koutrakis P. Daily asthma severity in relation to personal ozone exposure and outdoor fungal spores. American Journal of Respiratory & Critical Care Medicine 1996; 154:633-41.
40. Delfino RJ, Zeiger RS, Seltzer JM, et al. The effect of outdoor fungal spore concentrations on daily asthma severity. Environmental Health Perspectives 1997; 105:622-35.
41. Forsberg B, Stjernberg N, Linne R, Segerstedt B, Wall S. Daily air pollution levels and acute asthma in southern Sweden. European Respiratory Journal 1998; 12:900-5.
42. Gold DR, Damokosh AI, Pope CA, 3rd, et al. Particulate and ozone pollutant effects on the respiratory function of children in southwest Mexico City [see comments] [published erratum appears in Epidemiology 1999 Jul;10(4):470]. Epidemiology 1999; 10:8-16.
43. Hiltermann TJ, Stolk J, van der Zee SC, et al. Asthma severity and susceptibility to air pollution. European Respiratory Journal 1998; 11:686-93.
44. Lippmann M, Spektor DM. Peak flow rate changes in O3 exposed children: spirometry vs miniWright flow meters. Journal of Exposure Analysis & Environmental Epidemiology 1998; 8:101-7.
45. Naeher LP, Holford TR, Beckett WS, et al. Healthy women's PEF variations with ambient summer concentrations of PM10, PM2.5, SO42-, H+, and O3. American Journal of Respiratory & Critical Care Medicine 1999; 160:117-25.
46. Neas LM, Dockery DW, Burge H, Koutrakis P, Speizer FE. Fungus spores, air pollutants, and other determinants of peak expiratory flow rate in children. American Journal of Epidemiology 1996; 143:797-807.
47. Neas LM, Dockery DW, Koutrakis P, Speizer FE. Fine particles and peak flow in children: acidity versus mass. Epidemiology 1999; 10:550-3.
48. Neukirch F, Segala C, Le Moullec Y, Korobaeff M, Aubier M. Short-term effects of low-level winter pollution on respiratory health of asthmatic adults. Archives of Environmental Health 1998; 53:320-8.
49. Pekkanen J, Timonen KL, Ruuskanen J, Reponen A, Mirme A. Effects of ultrafine and fine particles in urban air on peak expiratory flow among children with asthmatic symptoms. Environmental Research 1997; 74:24-33.
50. Peters A, Dockery DW, Heinrich J, Wichmann HE. Medication use modifies the health effects of particulate sulfate air pollution in children with asthma. Environmental Health Perspectives 1997; 105:430-5.
51. Peters A, Dockery DW, Heinrich J, Wichmann HE. Short-term effects of particulate air pollution on respiratory morbidity in asthmatic children. European Respiratory Journal 1997; 10:872-9.
52. Peters A, Goldstein IF, Beyer U, et al. Acute health effects of exposure to high levels of air pollution in eastern Europe. American Journal of Epidemiology 1996; 144:570-81.
53. Peters A, Wichmann HE, Tuch T, Heinrich J, Heyder J. Respiratory effects are associated with the number of ultrafine particles. American Journal of Respiratory & Critical Care Medicine 1997; 155:1376-83.
54. Roemer W, Clench-Aas J, Englert N, et al. Inhomogeneity in response to air pollution in European children (PEACE project). Occupational & Environmental Medicine 1999; 56:86-92.
55. Roemer W, Hoek G, Brunekreef B, Haluszka J, Kalandidi A, Pekkanen J. Daily variations in air pollution and respiratory health in a multicentre study: the PEACE project. Pollution Effects on Asthmatic Children in Europe. European Respiratory Journal 1998; 12:1354-61.
56. Romieu I, Meneses F, Ruiz S, et al. Effects of intermittent ozone exposure on peak expiratory flow and respiratory symptoms among asthmatic children in Mexico City. Archives of Environmental Health 1997; 52:368-76.
57. Romieu I, Meneses F, Ruiz S, et al. Effects of air pollution on the respiratory health of asthmatic children living in Mexico City. American Journal of Respiratory & Critical Care Medicine 1996; 154:300-7.
58. Segala C, Fauroux B, Just J, Pascual L, Grimfeld A, Neukirch F. Short-term effect of winter air pollution on respiratory health of asthmatic children in Paris. European Respiratory Journal 1998; 11:677-85.
59. Thurston GD, Lippmann M, Scott MB, Fine JM. Summertime haze air pollution and children with asthma [see comments]. American Journal of Respiratory & Critical Care Medicine 1997; 155:654-60.
60. Timonen KL, Pekkanen J. Air pollution and respiratory health among children with asthmatic or cough symptoms. American Journal of Respiratory & Critical Care Medicine 1997; 156:546-52.
61. Hoek G, Dockery DW, Pope A, Neas L, Roemer W, Brunekreef B. Association between PM10 and decrements in peak expiratory flow rates in children: reanalysis of data from five panel studies. European Respiratory Journal 1998; 11:1307-11.
62. Kinney PL, Thurston GD, Raizenne M. The effects of ambient ozone on lung function in children: a reanalysis of six summer camp studies. Environmental Health Perspectives 1996; 104:170-4.
63. Abbey DE, Burchette RJ, Knutsen SF, McDonnell WF, Lebowitz MD, Enright PL. Long-term particulate and other air pollutants and lung function in nonsmokers. American Journal of Respiratory & Critical Care Medicine 1998; 158:289-98.
64. Peters JM, Avol E, Gauderman WJ, et al. A study of twelve Southern California communities with differing levels and types of air pollution. II. Effects on pulmonary function. American Journal of Respiratory & Critical Care Medicine 1999; 159:768-75.
65. Raizenne M, Neas LM, Damokosh AI, et al. Health effects of acid aerosols on North American children: pulmonary function. Environmental Health Perspectives 1996; 104:506-14.
66. Jammes Y, Delpierre S, Delvolgo MJ, Humbert-Tena C, Burnet H. Long-term exposure of adults to outdoor air pollution is associated with increased airway obstruction and higher prevalence of bronchial hyperresponsiveness. Archives of Environmental Health 1998; 53:372-7.
67. Wong CM, Lam TH, Peters J, et al. Comparison between two districts of the effects of an air pollution intervention on bronchial responsiveness in primary school children in Hong Kong. Journal of Epidemiology & Community Health 1998; 52:571-8.
68. Horstman D, Kotesovec F, Vitnerova N, et al. Pulmonary functions of school children in highly polluted northern Bohemia. Archives of Environmental Health 1997; 52:56-62.
69. Nakai S, Nitta H, Maeda K. Respiratory health associated with exposure to automobile exhaust. III. Results of a cross-sectional study in 1987, and repeated pulmonary function tests from 1987 to 1990. Archives of Environmental Health 1999; 54:26-33.
70. Frischer T, Studnicka M, Gartner C, et al. Lung function growth and ambient ozone: a three-year population study in school children [see comments]. American Journal of Respiratory & Critical Care Medicine 1999; 160:390-6.
71. McDonnell WF, Abbey DE, Nishino N, Lebowitz MD. Long-term ambient ozone concentration and the incidence of asthma in nonsmoking adults: the AHSMOG Study. Environmental Research 1999; 80:110-21.
72. Pope CA, 3rd, Verrier RL, Lovett EG, et al. Heart rate variability associated with particulate air pollution [see comments]. American Heart Journal 1999; 138:890-9.
73. Pope CAr, Dockery DW, Kanner RE, Villegas GM, Schwartz J. Oxygen saturation, pulse rate, and particulate air pollution: A daily time-series panel study [see comments]. American Journal of Respiratory & Critical Care Medicine 1999; 159:365-72.
74. Atkinson RW, Anderson HR, Strachan DP, Bland JM, Bremner SA, Ponce de Leon A. Short-term associations between outdoor air pollution and visits to accident and emergency departments in London for respiratory complaints. European Respiratory Journal 1999; 13:257-65.
75. Smith MA, Jalaludin B, Byles JE, Lim L, Leeder SR. Asthma presentations to emergency departments in western Sydney during the January 1994 Bushfires. International Journal of Epidemiology 1996; 25:1227-36.
76. Guntzel O, Bollag U, Helfenstein U. Asthma and exacerbation of chronic bronchitis: sentinel and environmental data in a time series analysis. Zentralblatt fur Hygiene und Umweltmedizin 1996; 198:383-93.
77. Delfino RJ, Murphy-Moulton AM, Burnett RT, Brook JR, Becklake MR. Effects of air pollution on emergency room visits for respiratory illnesses in Montreal, Quebec. American Journal of Respiratory & Critical Care Medicine 1997; 155:568-76.
78. Norris G, YoungPong SN, Koenig JQ, Larson TV, Sheppard L, Stout JW. An association between fine particles and asthma emergency department visits for children in Seattle. Environmental Health Perspectives 1999; 107:489-93.
79. Buchdahl R, Parker A, Stebbings T, Babiker A. Association between air pollution and acute childhood wheezy episodes: prospective observational study [see comments]. Bmj 1996; 312:661-5.
80. Chew FT, Goh DY, Ooi BC, Saharom R, Hui JK, Lee BW. Association of ambient air-pollution levels with acute asthma exacerbation among children in Singapore. Allergy 1999; 54:320-9.
81. de Diego Damia A, Leon Fabregas M, Perpina Tordera M, Compte Torrero L. Effects of air pollution and weather conditions on asthma exacerbation. Respiration 1999; 66:52-8.
82. Hajat S, Haines A, Goubet SA, Atkinson RW, Anderson HR. Association of air pollution with daily GP consultations for asthma and other lower respiratory conditions in London. Thorax 1999; 54:597-605.
83. Lipsett M, Hurley S, Ostro B. Air pollution and emergency room visits for asthma in Santa Clara County, California. Environmental Health Perspectives 1997; 105:216-22.
84. Medina S, Le Tertre A, Quenel P, et al. Air pollution and doctors' house calls: results from the ERPURS system for monitoring the effects of air pollution on public health in Greater Paris, France, 1991-1995. Evaluation des Risques de la Pollution Urbaine pour la Sante. Environmental Research 1997; 75:73-84.
85. Ostro BD, Eskeland GS, Sanchez JM, Feyzioglu T. Air pollution and health effects: A study of medical visits among children in Santiago, Chile. Environmental Health Perspectives 1999; 107:69-73.
86. Stedman JR, Anderson HR, Atkinson RW, Maynard RL. Emergency hospital admissions for respiratory disorders attributable to summer time ozone episodes in Great Britain [see comments]. Thorax 1997; 52:958-63.
87. Tenias JM, Ballester F, Rivera ML. Association between hospital emergency visits for asthma and air pollution in Valencia, Spain. Occupational & Environmental Medicine 1998; 55:541-7.
88. Tanaka H, Honma S, Nishi M, et al. Acid fog and hospital visits for asthma: an epidemiological study. European Respiratory Journal 1998; 11:1301-6.
89. Garty BZ, Kosman E, Ganor E, et al. Emergency room visits of asthmatic children, relation to air pollution, weather, and airborne allergens. Annals of Allergy, Asthma, & Immunology 1998; 81:563-70.
90. Anderson HR, Spix C, Medina S, et al. Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project [see comments]. European Respiratory Journal 1997; 10:1064-71.
91. Anderson HR, Ponce de Leon A, Bland JM, Bower JS, Emberlin J, Strachan DP. Air pollution, pollens, and daily admissions for asthma in London 1987-92. Thorax 1998; 53:842-8.
92. Burnett RT, Smith-Doiron M, Stieb D, Cakmak S, Brook JR. Effects of particulate and gaseous air pollution on cardiorespiratory hospitalizations. Archives of Environmental Health 1999; 54:130-9.
93. Goldsmith JR, Friger MD, Abramson M. Associations between health and air pollution in time-series analyses. Archives of Environmental Health 1996; 51:359-67.
94. Morgan G, Corbett S, Wlodarczyk J. Air pollution and hospital admissions in Sydney, Australia, 1990 to 1994 [see comments]. American Journal of Public Health 1998; 88:1761-6.
95. Nauenberg E, Basu K. Effect of insurance coverage on the relationship between asthma hospitalizations and exposure to air pollution. Public Health Reports 1999; 114:135-48.
96. Ponka A, Virtanen M. Asthma and ambient air pollution in Helsinki. Journal of Epidemiology & Community Health 1996; 50:s59-62.
97. Ponka A, Virtanen M. Low-level air pollution and hospital admissions for cardiac and cerebrovascular diseases in Helsinki. American Journal of Public Health 1996; 86:1273-80.
98. Rosas I, McCartney HA, Payne RW, et al. Analysis of the relationships between environmental factors (aeroallergens, air pollution, and weather) and asthma emergency admissions to a hospital in Mexico City. Allergy 1998; 53:394-401.
99. Schwartz J. Air pollution and hospital admissions for respiratory disease. Epidemiology 1996; 7:20-8.
100. Schwartz J. Air pollution and hospital admissions for cardiovascular disease in Tucson [see comments]. Epidemiology 1997; 8:371-7.
101. Schwartz J. Air pollution and hospital admissions for heart disease in eight U.S. counties [see comments]. Epidemiology 1999; 10.
102. Sheppard L, Levy D, Norris G, Larson TV, Koenig JQ. Effects of ambient air pollution on nonelderly asthma hospital admissions in Seattle, Washington, 1987-1994 [see comments]. Epidemiology 1999; 10:23-30.
103. Spix C, Anderson HR, Schwartz J, et al. Short-term effects of air pollution on hospital admissions of respiratory diseases in Europe: a quantitative summary of APHEA study results. Air Pollution and Health: a European Approach. Archives of Environmental Health 1998; 53:54-64.
104. Sunyer J, Spix C, Quenel P, et al. Urban air pollution and emergency admissions for asthma in four European cities: the APHEA Project. Thorax 1997; 52:760-5.
105. Vigotti MA, Rossi G, Bisanti L, Zanobetti A, Schwartz J. Short term effects of urban air pollution on respiratory health in Milan, Italy, 1980-89. Journal of Epidemiology & Community Health 1996; 50:s71-5.
106. Gwynn RC, Burnett RT, Thurston GD. A Time-Series Analysis of Acidic Particulate Matter and Daily Mortality and Morbidity in the Buffalo, New York, Region. Environmental Health Perspectives 2000; 108.
107. Burnett RT, Cakmak S, Brook JR, Krewski D. The role of particulate size and chemistry in the association between summertime ambient air pollution and hospitalization for cardiorespiratory diseases. Environmental Health Perspectives 1997; 105:614-20.
108. Burnett RT, Brook JR, Yung WT, Dales RE, Krewski D. Association between ozone and hospitalization for respiratory diseases in 16 Canadian cities. Environmental Research 1997; 72:24-31.
109. Zmirou D, Schwartz J, Saez M, et al. Time-series analysis of air pollution and cause-specific mortality. Epidemiology 1998; 9:495-503.
110. Hoek G, Schwartz JD, Groot B, Eilers P. Effects of ambient particulate matter and ozone on daily mortality in Rotterdam, The Netherlands. Archives of Environmental Health 1997; 52:455-63.
111. Ito K, Thurston GD. Daily PM10/mortality associations: an investigations of at-risk subpopulations. Journal of Exposure Analysis & Environmental Epidemiology 1996; 6:79-95.
112. Katsouyanni K, Touloumi G, Spix C, et al. Short-term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: results from time series data from the APHEA project. Air Pollution and Health: a European Approach [see comments]. Bmj 1997; 314:1658-63.
113. Lee JT, Schwartz J. Reanalysis of the effects of air pollution on daily mortality in Seoul, Korea: A case-crossover design. Environmental Health Perspectives 1999; 107:633-6.
114. Michelozzi P, Forastiere F, Fusco D, et al. Air pollution and daily mortality in Rome, Italy. Occupational & Environmental Medicine 1998; 55:605-10.
115. Morgan G, Corbett S, Wlodarczyk J, Lewis P. Air pollution and daily mortality in Sydney, Australia, 1989 through 1993 [see comments]. American Journal of Public Health 1998; 88:759-64.
116. Neas LM, Schwartz J, Dockery D. A case-crossover analysis of air pollution and mortality in Philadelphia. Environmental Health Perspectives 1999; 107:629-31.
117. Ostro B, Sanchez JM, Aranda C, Eskeland GS. Air pollution and mortality: results from a study of Santiago, Chile. Journal of Exposure Analysis & Environmental Epidemiology 1996; 6:97-114.
118. Ponka A, Savela M, Virtanen M. Mortality and air pollution in Helsinki. Archives of Environmental Health 1998; 53:281-6.
119. Rossi G, Vigotti MA, Zanobetti A, Repetto F, Gianelle V, Schwartz J. Air pollution and cause-specific mortality in Milan, Italy, 1980-1989. Archives of Environmental Health 1999; 54:158-64.
120. Saez M, Tobias A, Munoz P, Campbell MJ. A GEE moving average analysis of the relationship between air pollution and mortality for asthma in Barcelona, Spain. Statistics in Medicine 1999; 18:2077-86.
121. Simpson RW, Williams G, Petroeschevsky A, Morgan G, Rutherford S. Associations between outdoor air pollution and daily mortality in Brisbane, Australia. Archives of Environmental Health 1997; 52:442-54.
122. Verhoeff AP, Hoek G, Schwartz J, van Wijnen JH. Air pollution and daily mortality in Amsterdam. Epidemiology 1996; 7:225-30.
123. Burnett RT, Cakmak S, Raizenne ME, et al. The association between ambient carbon monoxide levels and daily mortality in Toronto, Canada. Journal of the Air & Waste Management Association 1998; 48:689-700.
124. Touloumi G, Katsouyanni K, Zmirou D, et al. Short-term effects of ambient oxidant exposure on mortality: a combined analysis within the APHEA project. Air Pollution and Health: a European Approach. American Journal of Epidemiology 1997; 146:177-85.
125. Levy JI, Hammitt JK, Spengler JD. Estimating the Mortality Impacts of Particulate Matter: What Can Be Learned from Between-Study Variability? Environmental Health Perspectives 2000; 108.
126. Abbey DE, Nishino N, McDonnell WF, et al. Long-term inhalable particles and other air pollutants related to mortality in nonsmokers [see comments]. American Journal of Respiratory & Critical Care Medicine 1999; 159:373-82.
127. Bates D. Lines That Connect: Assessing the Causality Inference in the Case of Particulate Pollution. Environmental Health Perspectives 2000; 108.
128. Ostro B, Chestnut L. Assessing the health benefits of reducing particulate matter air pollution in the United States. Environmental Research 1998; 76:94-106.
129. Romm JJ, Ervin CA. How energy policies affect public health. Public Health Reports 1996; 111:390-9.
