Ann. N.Y. Acad. Sci. ISSN 0077-8923
A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Cellular and Environmental Stressors in Biology and Medicine
Linking ambient particulate matter pollution effects with oxidative biology and immune responses Frank J. Kelly and Julia C. Fussell MRC-PHE Centre for Environment and Health, Facility of Life Sciences and Medicine, King’s College, London, United Kingdom Address for correspondence: Frank J. Kelly, MRC-PHE Centre for Environment and Health, Facility of Life Sciences and Medicine, King’s College London, 150 Stamford Street, London SE1 9NH, United Kingdom. [email protected]
Exposure to combustion-related particulate matter (PM), at concentrations experienced by populations throughout the world, contributes to pulmonary and cardiac disease through multiple mechanistic pathways that are complex and interdependent. Current evidence supports an interactive chain of events linking pollution-induced pulmonary and systemic oxidative stress, inflammatory events, and translocation of particle constituents with an associated risk of vascular dysfunction, atherosclerosis, altered cardiac autonomic function, and ischemic cardiovascular and obstructive pulmonary diseases. Because oxidative stress is believed to play such an instrumental role in these pathways, the capacity of particulate pollution to cause damaging oxidative reactions (the oxidative potential) has been used as an effective exposure metric, identifying toxic components and sources within diverse ambient PM mixes that vast populations are subjected to—from traffic emissions on busy roads in urban areas to biomass smoke that fills homes in rural areas of the developing world. Keywords: air pollution; particulate matter; oxidative stress; inflammation
Introduction The broad range of effects that air pollution inflicts on human health is commonly considered a feature of modern times, associated with global urbanization and concomitant intense energy consumption and increased emissions from transportation and industrial sources. However, people have been in close daily contact with environmental pollution, in the form of smoke, since fire was discovered and subsequently tamed. Indeed, paleopathological research on how ancient populations lived and died suggests that our oldest ancestors succumbed to cardiorespiratory diseases that are now linked to contemporary air pollution in urban areas. The Swiss Mummy Project, a systematic review of all computed tomography (CT) imaging studies performed on ancient Egyptian mummies over the past 30 years, not only identified evidence of pneumonia, emphysema, and pulmonary edema, but also related these diseases to the presence of carbon deposits in the lung.1 Moreover, smoke from oil lamps and from
cooking and heating fires in confined spaces has frequently been cited as a probable source of the latter.2 In another study into disease in ancient times, CT scanning of the bodies of mummies across a wide span of human history found atherosclerosis to be prevalent and, again, the authors speculated a link to the use of fire for warmth and cooking and the daily inhalation of smoke.3 A more common historical appreciation of air pollution and its effects on health dates back to the 12th century––when London’s notorious pollution problems began with the introduction of bituminous coal into the city. This affordable and abundant form of energy was initially used for manufacturing before becoming a common domestic fuel for heating and cooking. By the late 1700s, coal was fuelling the Industrial Revolution in addition to millions of domestic fires. As a consequence, London’s appalling mixture of fog, smoke, and sulphur dioxide emissions became a world-famous institution, and in 1905, during a public health lecture by Harold Des Voeux, a London physician doi: 10.1111/nyas.12720
84
C 2015 New York Academy of Sciences. Ann. N.Y. Acad. Sci. 1340 (2015) 84–94
Kelly & Fussell
Oxidative stress, inflammation, and particulate matter toxicity
and prominent advocate for smoke abatement, the lethal mix earned the term smog.4 The devastating health effects, especially for those with an underlying respiratory complaint, brought about by the vast smog became evident in December 1952, when a toxic combination of London’s cold, motionless, foggy air; coal-burning domestic chimneys and power stations; cars, trucks, and buses; and a host of factories and industrial plants brought about the worst pollution disaster in history. This great killer smog episode caused an estimated 4000–12,000 premature deaths and increased morbidity from cardiorespiratory causes.5 It was also the impetus for the 1956 Clean Air Act, which curtailed domestic coal burning in London and other major cities in the United Kingdom. The implementation of smokeless zones, controls imposed on industries, increased availability and use of natural gas, and changes in the industrial and economic structure of the United Kingdom led to a considerable reduction in concentrations of smoke and sulphur dioxide between the 1950s and the present day.
also demonstrated a consistent association between levels of PM in the ambient air and increases in respiratory and cardiovascular morbidity. Evidence is particularly strong for reduced lung function, heightened severity of symptoms in individuals with asthma and chronic obstructive pulmonary disease (COPD), and ischemic heart disease.10,11 In 2012, particulates in diesel fumes were classified as carcinogenic,12 and an increasing number of studies are now investigating the potential for particle exposures to exert a yet wider threat to human health by, for example, negatively influencing reproductive outcomes13 and children’s lung growth,14 as well as contributing to cognitive decline.15 Having firmly established associations between ambient PM and adverse health effects, two current critical goals are to better understand (1) the underlying biological basis of PM toxicity and (2) the differential toxicity from different sources. The subject of relative toxicity represents one of the most challenging areas of environmental health research in that PM is a complex, heterogeneous mixture that can exist as solids or liquids that vary not only in chemical composition, mass, size (few nm to tens of m), number, shape, and surface area, but also source, solubility, and reactivity. All of these properties have the potential to influence the health effects of ambient PM. For example, with respect to size––in addition to the relationship between particle diameter and penetration within the lung and to extrapulomonary sites––smaller particles have greater surface area relative to mass and a high capacity to adsorb toxic chemicals. In addition, the finer the particles, the greater the likelihood of penetration to indoor environments, as they may be suspended in the atmosphere for long periods and transported over large distances. It is not surprising, therefore, that current knowledge does not allow precise quantification or definitive ranking, and the capability of PM to induce disease may be the result of multiple components acting through different physiological mechanisms. Some results, however, suggest more consistent associations between traffic-related PM emissions, fine and ultrafine particles, specific metals, and elemental carbon (EC) and a range of serious health effects.16 Indeed, a growing number of studies have reported a host of adverse respiratory effects among individuals with high PM exposures at roadside locations.17–19
Particulate matter air pollution The most abundant air pollutants in today’s urban environments are ozone (O3 ), nitrogen dioxide (NO2 ), and particulate matter (PM), and they are also the ambient toxins of most concern to human health. Of these, PM has been held responsible for the majority of the adverse health effects of air pollution and has been the subject of an increasing number of studies that have investigated oxidative stress. For these reasons, the scope of this brief review article is limited to particulate pollution. In urban areas, the major source is fossil fuel combustion, primarily from road transport, as well as power stations and factories. In rural and semi-urban regions of developing countries, the burning of biomass fuels on open fires or traditional stoves creates indoor concentrations of PM that far exceed those considered safe in outdoor air. Epidemiological evidence that ambient particle exposures can reduce life expectancy initially emerged from American studies that reported associations between increased respiratory and cardiovascular mortality and acute and chronic exposures to particulate air pollution.6,7 These findings have subsequently been substantiated in epidemiological studies conducted outside of the United States, including rural areas in developing countries.8,9 Epidemiologic research has
C 2015 New York Academy of Sciences. Ann. N.Y. Acad. Sci. 1340 (2015) 84–94
85
Oxidative stress, inflammation, and particulate matter toxicity
Kelly & Fussell
Figure 1. Biological pathways linking PM exposure with oxidative and inflammatory pathways in the lung and cardiovasculature.
The main PM components originating from road traffic are engine emissions, largely comprising EC and organic carbon (OC), and nonexhaust sources that are often characterized by elevated concentrations of transition metals (brake wear (copper, antimony), tire abrasion (zinc), dust from road surfaces (iron)). The largest single source is derived from diesel exhaust (DE). Indeed, owing to the increased market penetration of diesel engines in many industrialized countries and the fact that they generate up to 100 times as many particles as comparable gasoline engines with three-way catalytic convertors,20 diesel exhaust particles (DEPs) contribute significantly to the airshed in many of the world’s largest cities. With increasing market penetration, directinjection gasoline engines with higher particle emissions may soon also contribute to this problem. DEPs have also been shown to have substantial toxicological capacity, eliciting oxidative stress via the generation of free radicals and the depletion of antioxidants. This activity is facilitated by the size (80% of DEPs have an aerodynamic diameter of
A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Cellular and Environmental Stressors in Biology and Medicine
Linking ambient particulate matter pollution effects with oxidative biology and immune responses Frank J. Kelly and Julia C. Fussell MRC-PHE Centre for Environment and Health, Facility of Life Sciences and Medicine, King’s College, London, United Kingdom Address for correspondence: Frank J. Kelly, MRC-PHE Centre for Environment and Health, Facility of Life Sciences and Medicine, King’s College London, 150 Stamford Street, London SE1 9NH, United Kingdom. [email protected]
Exposure to combustion-related particulate matter (PM), at concentrations experienced by populations throughout the world, contributes to pulmonary and cardiac disease through multiple mechanistic pathways that are complex and interdependent. Current evidence supports an interactive chain of events linking pollution-induced pulmonary and systemic oxidative stress, inflammatory events, and translocation of particle constituents with an associated risk of vascular dysfunction, atherosclerosis, altered cardiac autonomic function, and ischemic cardiovascular and obstructive pulmonary diseases. Because oxidative stress is believed to play such an instrumental role in these pathways, the capacity of particulate pollution to cause damaging oxidative reactions (the oxidative potential) has been used as an effective exposure metric, identifying toxic components and sources within diverse ambient PM mixes that vast populations are subjected to—from traffic emissions on busy roads in urban areas to biomass smoke that fills homes in rural areas of the developing world. Keywords: air pollution; particulate matter; oxidative stress; inflammation
Introduction The broad range of effects that air pollution inflicts on human health is commonly considered a feature of modern times, associated with global urbanization and concomitant intense energy consumption and increased emissions from transportation and industrial sources. However, people have been in close daily contact with environmental pollution, in the form of smoke, since fire was discovered and subsequently tamed. Indeed, paleopathological research on how ancient populations lived and died suggests that our oldest ancestors succumbed to cardiorespiratory diseases that are now linked to contemporary air pollution in urban areas. The Swiss Mummy Project, a systematic review of all computed tomography (CT) imaging studies performed on ancient Egyptian mummies over the past 30 years, not only identified evidence of pneumonia, emphysema, and pulmonary edema, but also related these diseases to the presence of carbon deposits in the lung.1 Moreover, smoke from oil lamps and from
cooking and heating fires in confined spaces has frequently been cited as a probable source of the latter.2 In another study into disease in ancient times, CT scanning of the bodies of mummies across a wide span of human history found atherosclerosis to be prevalent and, again, the authors speculated a link to the use of fire for warmth and cooking and the daily inhalation of smoke.3 A more common historical appreciation of air pollution and its effects on health dates back to the 12th century––when London’s notorious pollution problems began with the introduction of bituminous coal into the city. This affordable and abundant form of energy was initially used for manufacturing before becoming a common domestic fuel for heating and cooking. By the late 1700s, coal was fuelling the Industrial Revolution in addition to millions of domestic fires. As a consequence, London’s appalling mixture of fog, smoke, and sulphur dioxide emissions became a world-famous institution, and in 1905, during a public health lecture by Harold Des Voeux, a London physician doi: 10.1111/nyas.12720
84
C 2015 New York Academy of Sciences. Ann. N.Y. Acad. Sci. 1340 (2015) 84–94
Kelly & Fussell
Oxidative stress, inflammation, and particulate matter toxicity
and prominent advocate for smoke abatement, the lethal mix earned the term smog.4 The devastating health effects, especially for those with an underlying respiratory complaint, brought about by the vast smog became evident in December 1952, when a toxic combination of London’s cold, motionless, foggy air; coal-burning domestic chimneys and power stations; cars, trucks, and buses; and a host of factories and industrial plants brought about the worst pollution disaster in history. This great killer smog episode caused an estimated 4000–12,000 premature deaths and increased morbidity from cardiorespiratory causes.5 It was also the impetus for the 1956 Clean Air Act, which curtailed domestic coal burning in London and other major cities in the United Kingdom. The implementation of smokeless zones, controls imposed on industries, increased availability and use of natural gas, and changes in the industrial and economic structure of the United Kingdom led to a considerable reduction in concentrations of smoke and sulphur dioxide between the 1950s and the present day.
also demonstrated a consistent association between levels of PM in the ambient air and increases in respiratory and cardiovascular morbidity. Evidence is particularly strong for reduced lung function, heightened severity of symptoms in individuals with asthma and chronic obstructive pulmonary disease (COPD), and ischemic heart disease.10,11 In 2012, particulates in diesel fumes were classified as carcinogenic,12 and an increasing number of studies are now investigating the potential for particle exposures to exert a yet wider threat to human health by, for example, negatively influencing reproductive outcomes13 and children’s lung growth,14 as well as contributing to cognitive decline.15 Having firmly established associations between ambient PM and adverse health effects, two current critical goals are to better understand (1) the underlying biological basis of PM toxicity and (2) the differential toxicity from different sources. The subject of relative toxicity represents one of the most challenging areas of environmental health research in that PM is a complex, heterogeneous mixture that can exist as solids or liquids that vary not only in chemical composition, mass, size (few nm to tens of m), number, shape, and surface area, but also source, solubility, and reactivity. All of these properties have the potential to influence the health effects of ambient PM. For example, with respect to size––in addition to the relationship between particle diameter and penetration within the lung and to extrapulomonary sites––smaller particles have greater surface area relative to mass and a high capacity to adsorb toxic chemicals. In addition, the finer the particles, the greater the likelihood of penetration to indoor environments, as they may be suspended in the atmosphere for long periods and transported over large distances. It is not surprising, therefore, that current knowledge does not allow precise quantification or definitive ranking, and the capability of PM to induce disease may be the result of multiple components acting through different physiological mechanisms. Some results, however, suggest more consistent associations between traffic-related PM emissions, fine and ultrafine particles, specific metals, and elemental carbon (EC) and a range of serious health effects.16 Indeed, a growing number of studies have reported a host of adverse respiratory effects among individuals with high PM exposures at roadside locations.17–19
Particulate matter air pollution The most abundant air pollutants in today’s urban environments are ozone (O3 ), nitrogen dioxide (NO2 ), and particulate matter (PM), and they are also the ambient toxins of most concern to human health. Of these, PM has been held responsible for the majority of the adverse health effects of air pollution and has been the subject of an increasing number of studies that have investigated oxidative stress. For these reasons, the scope of this brief review article is limited to particulate pollution. In urban areas, the major source is fossil fuel combustion, primarily from road transport, as well as power stations and factories. In rural and semi-urban regions of developing countries, the burning of biomass fuels on open fires or traditional stoves creates indoor concentrations of PM that far exceed those considered safe in outdoor air. Epidemiological evidence that ambient particle exposures can reduce life expectancy initially emerged from American studies that reported associations between increased respiratory and cardiovascular mortality and acute and chronic exposures to particulate air pollution.6,7 These findings have subsequently been substantiated in epidemiological studies conducted outside of the United States, including rural areas in developing countries.8,9 Epidemiologic research has
C 2015 New York Academy of Sciences. Ann. N.Y. Acad. Sci. 1340 (2015) 84–94
85
Oxidative stress, inflammation, and particulate matter toxicity
Kelly & Fussell
Figure 1. Biological pathways linking PM exposure with oxidative and inflammatory pathways in the lung and cardiovasculature.
The main PM components originating from road traffic are engine emissions, largely comprising EC and organic carbon (OC), and nonexhaust sources that are often characterized by elevated concentrations of transition metals (brake wear (copper, antimony), tire abrasion (zinc), dust from road surfaces (iron)). The largest single source is derived from diesel exhaust (DE). Indeed, owing to the increased market penetration of diesel engines in many industrialized countries and the fact that they generate up to 100 times as many particles as comparable gasoline engines with three-way catalytic convertors,20 diesel exhaust particles (DEPs) contribute significantly to the airshed in many of the world’s largest cities. With increasing market penetration, directinjection gasoline engines with higher particle emissions may soon also contribute to this problem. DEPs have also been shown to have substantial toxicological capacity, eliciting oxidative stress via the generation of free radicals and the depletion of antioxidants. This activity is facilitated by the size (80% of DEPs have an aerodynamic diameter of
