The Respiratory Risks of Ambient/Outdoor Air Pollution

Introduction

Humans are exposed to a wide range of air pollutants known to be associated with adverse health effects. These pollutants can be associated with a wide range of activities and sources, including: the burning of fossil fuels, traffic-related emissions, industrial activities, agricultural activities, and wildfires, as well as a diverse group of pollutants that originate indoors (Figure 1). For an individual, their totality of exposure is determined by concentrations of pollutants in the various microenvironments where they spend time (home, school, work, etc.), and their time activity patterns (how much time is spent in each of these spaces). Indoor exposures are strongly influenced by the characteristics of the building, its location, and ambient sources, due to the exchange of air between indoor and outdoor spaces. Because of these relationships, and due to the fact that most individuals spend the majority of their time indoors, the majority of human exposure to pollutants of outdoor origin actually occurs indoors. This review will focus on ambient pollutants, those which are emitted or formed in the atmosphere and primarily measured by outdoor monitoring stations or models that depend on outdoor metrics.

Figure 1.

Key sources of ambient air pollutants. Schematic of source apportionment for major ambient/outdoor air pollutants. SO₂, sulfur dioxide; NO_x, oxides of nitrogen; PM_2.5, particulate matter less than 2.5 microns in diameter; O₃, ozone; VOCs, volatile organic compounds.

Any process that includes fossil fuel combustion is likely releasing pollutants that have been shown to cause health effects. Traffic-related emissions (including diesel), combustion related to electricity production (coal, natural gas, etc.), and other fuel burning can release particulate matter, oxides of nitrogen and other pollutants into the atmosphere. Once released, these pollutants can be transported, removed and/or chemically transformed.

Air pollution exposure has been implicated in myriad disease processes in almost every organ system¹ and is currently the 5^th highest risk factor for mortality worldwide². A recent estimate shows that outdoor air pollution, mostly by driven by exposure to fine particulate matter (PM_2.5, described below), leads to 3.3 (95% confidence interval 1.61–4.81) million premature deaths per year worldwide, with most of these deaths occurring in Asia³. These risks are in addition to the significant global burden of disease from household air pollution from the burning of solid fuels for cooking and heating⁴. In general, ambient air pollution levels have increased in low- and middle-income countries², while notable progress has been made in the U.S.⁵ In addition to these global differences in exposure and health effects, many studies have highlighted the disproportionate burden of air pollution within low-income populations and communities of color in the U.S.⁶

We focus this article on key air pollutants (see Table 1) that have an extensive evidence base linking exposure to respiratory health effects with the exception of wildfire smoke which is addressed elsewhere in this issue. We aim to describe the most important ambient pollutants implicated in human health and disease and discuss the sources of ambient pollution. Recognizing that many of these individual pollutants are encountered as pollutant mixtures, we will outline the major respiratory risks of ambient pollution, as a whole and fractioned by pollutant or source where data is available. Focus will be on the inception, exacerbation and mortality related to chronic respiratory diseases and vulnerable populations. As the burden of air pollution on respiratory morbidity and mortality is high, clinicians must be aware of the potentially harmful exposures in order to properly advise vulnerable patients on avoidance strategies and/or affect change through public policy efforts.

Table 1.

Overview of ambient air pollutant sources and health effects. Data from Refs^{7, 19, 20, 27, 37, 39, 45, 55–57, 63, 64, 89, 96, 105, 130–133}

Key pollutants	Emission sources	Key health effects
Particulate matter (PM)	PM is a mixture of solid and/or liquid particles suspended in air They have both anthropogenic and natural sources and can be both directly emitted and formed in the atmosphere Human sources, include traffic, road dust, industrial sources (combustion of fossil fuels, metallurgy, ceramics, and others), domestic fuel combustion, and other human activities7 PM can form in the atmosphere as a result of chemical reactions of certain compounds like sulfur dioxide and nitrogen oxides Natural sources, including wildfires, soil dust, and sea salt	Associated with all-cause daily mortality and more highly associated with mortality from respiratory conditions19 Lowered life expectancy20 Asthma symptoms and exacerbation89 Coughing, wheezing, and breathlessness27,39 Impaired lung development in children45 and impaired lung function in adults55–57 Exacerbation of chronic obstructive pulmonary disease (COPD)96
Ozone (O3)	Not emitted directly, but formed as a product of chemical reactions between sunlight, nitrogen oxides (NOx), and volatile organic compounds (VOCs) These primary or ‘precursor’ pollutants can be emitted from various sources, including traffic, power plants, refineries, chemical plants, and other sources130	Emphysema and decreased forced expiratory volume over one second (FEV1)105 Asthma symptoms and exacerbation89 Allergic responses with co-exposure to allergens37
Nitrogen dioxide (NO2)	Formed in high-temperature combustion processes, including power plants, traffic, and off-road vehicles131	Decreased lung function63,64 Allergic responses with co-exposure to allergens37
Sulfur dioxide (SO2)	Human sources include combustion of sulfur-containing fuels (such as coal) in power plants and other industrial process, metal extraction, and heavy vehicles132 Natural sources, including volcanic eruptions	Eye and upper airway irritation1 Alterations to lung function, loss of smell, headaches, dizziness, and decreased fertility133
Traffic-related air pollution (TRAP)	Combustion of diesel and gasoline in motor vehicles Significant sources include roadways, especially those with high traffic density	Decreased lung function63,64 Asthma symptoms and exacerbations89

Particulate Matter –

The term particulate matter (PM) describes the mixture of solid and/or liquid particles suspended in air, which may or may not be visible. These particles are generated through mechanical or chemical processes and can be either directly emitted or can form through chemical reactions in the air. For example, PM can be generated from wildfires, combustion of fossil fuels (e.g., oil, gasoline, diesel), industrial sources, as well as from the suspension of road dust and soils. PM is often classified by the size fractions that determine the pattern of capture, deposition and transport in the lung, and thus directly affects the extent of human exposure and related health effects. For example, PM₁₀ refers to particles that are smaller than 10 microns in diameter and PM_2.5 refers to particles smaller than 2.5 microns in diameter. Both of these fractions are considered inhalable, with the smallest particles, such as PM_2.5 or smaller fractions having a higher likelihood to be deposited deep in the lung. A recent systematic review⁷ summarized the literature that has estimated source apportionment of particulate matter, and found that globally 25% of urban ambient PM_2.5 is generated by traffic, 15% by industrial activities, 20% by domestic fuel burning, 22% from unspecified sources of human origin, and 18% from natural dust and salt. Similarly, utilizing data from a national network of PM_2.5 monitors with chemical speciation, Thurston et al.⁸ identified the major PM_2.5 sources in the U.S. as (in no particular order) motor vehicle traffic, metals industry, crustal/soil particles, steel industry, coal combustion, oil combustion, salt particles and biomass burning. While motor vehicle emissions were ubiquitous, the relative contribution of these sources varied significantly by region.

While significant progress has been made in reducing PM_2.5 in the U.S., exposure disparities across economic and racial lines are notable. A 2018 analysis of PM-emitting facilities in the United States showed that those living in poverty had 1.35 times higher burden than did the overall population, and that black populations had a 1.54 times higher burden than did the overall population^9,10. A recent study focused on ambient monitoring data in Massachusetts showed that racial disparities in population-weighted concentrations increased over time, although overall exposures have decreased during the same period. Due to the effects of urbanization, differences in motor vehicle fleets, fuel usage patterns and other factors, the global exposure picture is troubling. A 2018 assessment showed that 95% of the world’s population lived in areas where ambient PM_2.5 levels exceeded the World Health Organization 10 μg/m³ (annual average) guideline¹¹.

It has long been known that the size and composition of airborne particles can strongly influence exposure and the observed patterns of health effects¹². Another fraction — ultrafine particles (UFP), defined as particles smaller than 0.1 microns in diameter — have been suggested as an important component of airborne particles that may be mechanistically responsible for some health effects¹³. While ultrafine particles are not regulated (like PM_2.5 and other particulate matter fractions), the health effects of these exposures remain an active and important area of investigation.

Ozone –

Ozone, a key component of smog, is not emitted directly, but rather is formed in the atmosphere through complex series of photochemical reactions involving two other classes of pollutants: oxides of nitrogen (NOx) and volatile organic compounds (VOCs). In addition to its health effects, ozone is known to affect agricultural output and damage materials. Due to the photochemical origins of ozone, large urban areas located in warmer climates are more likely to experience high ozone levels. Ozone hotspots are frequently located downwind of emission sources, due to the timescales of the underlying chemical reactions.

NO₂ –

Nitrogen dioxide (NO₂) is formed during high temperature combustion and is both relevant for its direct effects on health as well as its role as a precursor of ozone. In urban areas, the most significant contributor to the levels and patterns of nitrogen dioxide exposure is traffic. Power plants and other industrial sources that burn fossil fuels are also major emitters of NO₂ (and other oxides of nitrogen). Personal exposures to nitrogen dioxide are influenced by these ambient sources, as well as indoor combustion sources, such as emissions from gas stoves.

SO₂ –

When burned, sulfur-containing fuels, such as coal, can release significant quantities of sulfur dioxide. While SO₂ can be released naturally (e.g. volcanoes), most emissions are anthropogenic, from power plants, pulp and paper production, smelter and steel mill operations, and other industrial operations¹⁴. Historically, the focus on controlling SO₂ emissions was based on its presumed contributions to acid rain, and not health effects.

TRAP/diesel –

Given the range of pollutants released from gasoline- and diesel-powered vehicles and the potential range of health effects, it has been convenient to refer to this pollutant mix as traffic-related air pollution, or TRAP. This designation is aligned with the large body of evidence that shows a consistent pattern of health effects associated with being exposed to high traffic density or living close to major roadways. Numerous exposure-focused studies have documented the influence of roadways on the concentration gradients for several air pollutants near these sources¹⁵.

The ability to estimate human exposure to ambient pollutants has evolved substantially over the past several decades. The primary measurement direct measurement devices for population-based pollution research have been central monitoring sites that are able to measure real-time and filter-based particle and gas composition in the local environment. However, sophisticated modeling that incorporates land use, green space, and other factors that affect the local exposure profiles have greatly enhanced the precision of these measures and ability to extrapolate from central monitors to discrete nearby locations. The use of satellite imagery to further enhance predictive models has led to accurate ground estimates as small as 1km across large portions of the U.S. More recently, the availability of low-cost sensors allows for more fine-scale or personal assessment of exposure to pollutants released by traffic and other urban sources. For example, recent studies reveal the small-scale variation of air pollution at the neighborhood level, and the potential associations with health^16,17.

Health effects

Population health

Air pollution health effects are seen on a population scale in both healthy and vulnerable subjects. The World Health Organization estimates that ambient pollution is responsible for 4.2 million premature deaths annually¹⁸. Several studies in the developed and developing world have consistently demonstrated a higher risk of all-cause mortality in people exposed to high levels of pollutants. Liu and colleagues from the Multi-City Multi-Country (MCC) Collaborative Research Network recently reported on the effects of daily particulate exposure with daily mortality among 652 cities from 24 countries or regions¹⁹. Daily mortality increased 0.68% for each 10 μg/m3 increase in PM_2.5. A recent study incorporating data from counties across the US from 1999 to 2015 observed excess PM_2.5 was responsible for approximately 30,000 premature deaths, lowering the estimated national life expectancy by 0.15 years²⁰. In counties where PM_2.5 was reduced over the 15-year period, so did mortality. Highlighting these health effects, changes in emissions as a result of the U.S. Clean Air Act and its amendments over a 20 year period from 1980 – 2000 revealed that a 10 μg /m³ improvement in PM_2.5 resulted in mean increased life expectancy of greater than 7 months across 51 US cities, which accounted for 15% of improved longevity overall^5,21. These findings are consistent with other cohort studies over the same time period^22,23. In 2011, the U.S. Environmental Protection Agency (EPA) estimated that improved PM exposure would result in 230,000 adult lives saved by 2020²⁴. Most notably, the dose-response of the relationship between particulate exposure and mortality is fairly consistent across concentration ranges, even at ambient levels below national and international thresholds^19,20.

Respiratory specific mortality is an even higher individual risk. In the MCC data investigated by Liu et al, the corresponding increase in daily mortality from respiratory events was 0.74% for each 10 μg /m³ increase in PM_2.5, higher than both all-cause and cardiovascular mortality attribution¹⁹. Respiratory mortality is driven by chronic obstructive pulmonary disease (COPD) and lung cancer, for which the estimates of respiratory mortality from the Global Burden of Disease study are >800,0000 persons and 280,000 in 2015, respectively². However, in contrast to these provocative mortality data, a recent prospective study with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE) found no significant association of air pollution exposure with non-malignant respiratory mortality among 1559 deaths from 307,553 subjects across 16 cohorts²⁵.

Pollutant transport to the respiratory tree

The size of the particulate and the solubility of the pollutant dictate the type of symptoms that are induced by pollutant exposure. Generally speaking, large particles are filtered by impaction in the upper airway and natural cleaning mechanisms in the nose (nasal hair and turbulent flow) and upper airway. Particle sizes 10 microns and above tend to be deposited in the upper airway and may cause nasal congestion and/or mucous membrane irritation of the eye. PM_2.5 is small enough to reach the small airways and deposit as deep as the alveolar space. For this reason, PM_2.5 is most highly associated with lower respiratory tract diseases, including asthma and airway infections.

Ultrafine particles freely cross the alveolar capillary membranes and can be transported to all organ systems. For gaseous pollutants, tissue specificity depends more on solubility profile. For example, water soluble pollutants, such as sulfur dioxide, cause eye and mucous membrane irritation in the upper airway. NO₂ and O₃ are less soluble and therefore penetrate deeper into the lower respiratory tract and lung¹. However, it is important to recognize that real-world encounters with ambient pollutants are largely with pollutant mixtures that may contain a variety of particle sizes and gaseous components. Many studies have attempted to disentangle the effects of different pollutants in multipollutant models, but this is complicated by the number of contaminants and the variety of elemental components^26,27 that contribute to particle mass at different levels.

Mechanism of biological effects

Mechanistic studies to determine how air pollution affects human health have uncovered several plausible pathways²⁸, including oxidative stress and damage, innate²⁹ and adaptive immunologic/inflammatory responses, allergic sensitization and Th2 airways inflammation, alteration of epigenetic loci that influences airways development, and direct effects on neuromuscular function of the airways.

Air pollution exposure may cause a variety of inflammatory changes in the airways which depend on the type of pollutant exposure, elemental composition of the particles and concurrent exposures. Additionally, host factors may play a significant role in the type of the inflammatory response. The inflammatory response to naturally occurring pollutant mixtures and co-exposure to other environmental factors are inherently difficult to systematically study due to the countless variables that would need to be accounted, so inferences are drawn from carefully designed single and co-exposure cell, animal and human studies. Perhaps the most ubiquitous response to air pollution exposure found in human studies has been the association with airways and lung injury via oxidative stress^30,31 mechanisms which increase neutrophilic airway inflammation. Controlled human exposure studies have demonstrated increased levels of inflammatory cells, primarily neutrophils, but also mast cells and lymphocytes, along with increased inflammatory mediators, such as IL-8 and IL-13 in healthy volunteers^32,33. Gene variants in the glutathione pathway have been shown to influence the effect of ambient pollutant exposure on lung function in children^34,35, further supporting the role of oxidative stress as a mechanism in the adverse health effects of pollution exposure.

At-risk populations of patients with underlying asthma and atopy have found increased allergic responses, such as nasal and airway eosinophilia in response to exposure³⁶. Moreover, studies of co-exposure of NO₂ or PM with allergens has found these pollutants to have an adjuvant effect on allergic inflammatory response. Fine particles may be important conduits in which adherent allergens may reach the lower respiratory tract or cause epithelial disruption due to oxidative stress³⁷.

Additionally, diesel exhaust particles, a major component of urban pollution, have been shown to affect the vagal afferent nerves in in vitro and in vivo models by depolarization of the vagus nerve via airway c-fiber afferents, which could lead to respiratory symptoms by a direct neurostimulatory effect on airway smooth muscle³⁸.

Respiratory symptoms

These biologic mechanisms affect respiratory symptoms in both general and vulnerable populations. In studies involving general populations of children and adults, exposure to particulate pollution has been associated with regular cough, wheezing and breathlessness^27,39 which improve with reduction of pollutant levels⁴⁰. A few case-control studies in children and adults have demonstrated higher rates of non-infectious conjunctivitis and conjunctival irritation associated with urban pollutant exposure^41,42. Moreover, chronic exposure to air pollutants have been associated with dry eye disease across populations^43,44.

Alteration of lung function

Chronic exposure to ambient pollution has been linked to impaired lung growth in children and progressive lung function decline in adult populations. Rice and colleagues evaluated chronic pollutant effects on early lung function development in a large birth cohort study and found that both proximity to roadway and home address estimates of black carbon (BC) and PM_2.5 in the first seven years of life was associated with low forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁) without significantly impacting the ratio of FEV₁/FVC⁴⁵. These data suggest that early life exposure to pollutants affects lung growth in a restrictive pattern rather than airway obstruction. In adolescence, the effects are similar. Perhaps the most demonstrative examples are from the California Health Study which demonstrated across three distinct time periods the association of ambient NO2, PM_2.5 and BC with poor lung function in children^46,47. While the most significant effects were reported for FEV₁, the effect on FVC and maximal mid-expiratory flows were similarly reduced. Importantly, for children who moved from high exposure locations to lower exposures, there was a significant improvement in lung function⁴⁸, highlighting that intervention on an individual level can alter long term lung growth. These findings extend to the prenatal period in which maternal exposure is associated with lower lung function in the child, as well as preterm birth⁴⁹, which itself is associated with poor lung function outcomes⁵⁰. These data suggest that perhaps alteration in DNA methylation is responsible for altered lung formation rather than direct effects of airway inflammation⁵¹. However, these associations have not been found in all cohorts⁵². The summation of the prenatal and pediatric findings are particularly salient as more and more data supports that long term lung function trajectories are determined in childhood^53,54.

In adults, several longitudinal studies have demonstrated exposure to particulate pollutants are associated with lower lung function in cross-sectional and longitudinal analyses^55–57. Moreover, across repeated measures, the Normative Aging Study found higher annual BC concentration was associated with accelerated rate of decline in FEV₁ and FVC for elderly men living in Boston, MA USA⁵⁵. Results from studies documenting the improvement in lung function in concert with decreased ambient PM add more convincing evidence of the causal effect of long term pollution on lung function outcomes^58,59. The SAPALDIA study, a Swiss population-based study sampling over 9000 adults, demonstrated a 10 μg/m³ decrease in PM₁₀ concentration was associated with a 9% decrease in annual FEV₁⁵⁸.

Ambient pollution and respiratory disease

The effects of ambient pollutant exposure on respiratory symptoms and lung function in the general population are amplified in vulnerable populations of adults and children with existing lung disease. Moreover, for many chronic lung diseases, ambient exposure to particulates and gaseous pollutants have been implicated in the inception of the disease process. In the following sections, we detail the relationship of ambient pollution exposure to the inception and exacerbation of chronic lung diseases, focusing primarily on asthma and COPD, which represent the most common non-cancer lung diseases of childhood and adulthood. Figure 2 illustrates respiratory diseases affected by ambient air pollutants.

Figure 2.

Respiratory diseases affected by ambient air pollutants. Schematic of respiratory diseases affected by ambient pollutant exposure. COPD: chronic obstructive pulmonary disease; ARDS, acute respiratory distress syndrome; ILD, interstitial lung disease; CF, cystic fibrosis.

Asthma

Asthma inception

The relationship between air pollution and the development of asthma has been found in population studies across all age groups. Prenatal exposure to ambient pollution may lead to epigenetic modifications that can be transmitted from mother to child in a nongenomic hereditary manner⁶⁰. The Asthma Coalition on Community, Environment and Social Stress (ACCESS) project, an urban pregnancy cohort, found that exposure to BC and PM_2.5, particularly in the second trimester were associated with infantile wheeze and childhood asthma, especially for boys⁶¹.

The Southern California Children’s Health Study identified home and school air pollution as a significant contributor to incident asthma in kindergarten and first grade students who were asthma and wheeze-free at the start of the study⁶². Similarly, a Swedish birth cohort found that TRAP and NO₂ encountered in the first year of life had significant effects on lung function later in childhood and adolescence^63,64. While a longitudinal European study incorporating multiple birth cohorts found no association between childhood air pollutant exposure and asthma prevalence⁶⁵, the vast majority of studies from the developed world support the relationship^66–71. Moreover, a population-based study including over 14,000 children from prospective birth cohorts in Germany, Sweden and the Netherlands extended the findings from childhood asthma measured primarily during early childhood to adolescents. They found a significant association of NO₂ and BC (measured as PM_2.5 absorbance) at the birth address with higher odds of incident asthma up to age 14–16 years⁷². Overall, these findings 1) demonstrate that long term associations persist between early life pollutant exposure and asthma, and 2) add confidence to the association at an age when asthma is more reliably diagnosed. The breadth of pediatric data strongly supports the relationship between ambient pollution and the inception of asthma in childhood across regions of the world and racial/ethnic differences, with a suggestion that early life exposures are the most important with different studies identifying differential effects of gender, allergic sensitization and family history of atopy that may modify the relationship.

Fewer data are available for adult onset asthma^73,74. A study by Bowatte et al. identified that in the Tasmanian Longitudinal Health Study there was a significant association between home NO₂ exposure or living within 200m from a major road and current wheeze and asthma⁷⁴. The highest risk group had the null genotype of GSTT1, suggesting that lack of antioxidant activity may be a susceptibility factor for developing airways disease and thereby highlighting the role of an oxidative stress mechanism in explaining harm from pollutants. Aside from the association with the inception of adult asthma, exposure to ambient pollution may influence the development of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS), which is noted to have higher morbidity and lung function decline than either condition alone. The prospective Canadian Community Healthy Survey study identified an almost 3-fold higher incidence of developing ACOS in those residing in locations with higher cumulative PM_2.5 and 31% higher in areas of higher O₃⁷⁵.

Asthma morbidity

Human controlled exposure studies in subjects with allergic asthma have shown both increased airway hyperresponsiveness to subsequent allergen challenge⁷⁶ and reduced lung function after exposure to ambient pollutants at levels encountered in routine urban life⁷⁷. The lung function deficits were accompanied by elevated markers of neutrophilic airways inflammation and acidification.

Epidemiologic studies extend these findings to demonstrate consistent alterations in lung function, increased symptoms and emergency healthcare services use in relation to short term increases in ambient pollutant exposures, primarily those included in TRAP, ozone, NO₂ and particulate matter⁷⁸. Children with asthma enrolled in the Childhood Asthma Management Program (CAMP) were found to have decreased indices of lung function and heightened airways reactivity with higher ambient exposure to CO, O₃ and NO₂ without evidence of treatment effect from inhaled steroids⁷⁹. We similarly found a direct relationship between elevated levels of NO₂ and airflow obstruction on spirometry in a cohort of inner city school children exposed to NO₂ in their school classroom⁸⁰. Notably, these affects were not driven by atopy and there was no relationship with fractional exhalation of nitric oxide (FeNO), so they appear independent of typical allergic asthma triggers.

Emergency department (ED) visits for pediatric asthma have been highly associated with spikes in ambient pollution in urban environments^81,82; this relationship is potentially stronger in asthmatic patients with premature birth or from low income and Latino populations^83,84. Time series analyses confirm increased emergency room visits for children and young adults with asthma exacerbations in concert with elevations in ambient pollutants⁸⁴. While it is difficult to differentiate individual pollutants from pollutant mixtures, ozone appears to have the most potent effect on asthma exacerbations⁸⁵ and is consistently found to be associated with ED visits^86,87. In a study assessing asthma exacerbations presenting to emergency departments across Seoul, Korea, multiple triggers were assessed in time series analysis, stratified by age (infant, preschool children, school-aged children, adults and elderly (60 years or older))⁸⁸. The most provocative association for asthma morbidity was air pollutant exposure, measured as individual gaseous or particle pollutants, which exceeded the effect of viral infection or environmental allergens. Moreover, in each age stratification, 7-day O₃ exposure had the highest relative risk of asthma exacerbation, greater than any allergen, weather or viral factor. In summary, pollutant exposures, including particles, gases (ozone and NO2, primarily) and TRAP are strongly and consistently associated with increased asthma symptoms, lung function decline, and exacerbations of asthma across all ages⁸⁹.

COPD

COPD inception

COPD is the second most common chronic respiratory disease in adults worldwide, affecting more than 170 million people, but has a disproportionately high rate of associated morbidity and mortality⁹⁰. Cigarette smoking is the predominant etiology for the development of COPD; the mechanisms responsible likely mirror those for pollutant toxicity, however the evidence for causality between ambient pollution and COPD development is limited. Exposure to higher levels of ambient pollution is associated with accelerated loss of lung function in population based studies^55,56. In parts of China, extremely high chronic exposures to PM have been found to have similar odds of COPD prevalence as smoking⁹¹; however this association is observed at PM levels greater than 5-fold higher than the World Health Organization recommended average annual exposure⁹². Large epidemiologic studies have been less consistent in identifying the relationship between air pollution and incident COPD. Initial COPD hospital admission over a 10-year period in a prospective Danish cohort of 53,000 subjects was associated with 35-year mean NO₂ level at home residence⁹³. However, a subsequent large English⁹⁴ study with over 800,000 subjects did not find an association and an analysis of European cohorts included in the ESCAPE (European Studies on Chronic Air Pollution Effects) project found positive but non-significant associations between COPD incidence and prevalence with air pollution measure⁹⁵. When using the GOLD criteria to define COPD, there was a significant association with traffic intensity near the home and suggested that female and never-smoker subgroups may be more strongly affected⁹⁵.

The association of ambient pollution with exacerbation of COPD is much more consistent. A recent meta-analysis by Li and colleagues report a 3.1% increase in COPD related hospitalization and 2.5% increase in COPD mortality for each 10 μg/m³ increase in daily PM_2.5 exposure⁹⁶. In Chile, COPD ED admissions increase by up to 19% in association with increased pollutants by an interquartile range⁹⁷.

Several panel studies of patients with COPD reporting person-level outcomes have demonstrated variable associations with air pollution and COPD morbidity. Several studies have demonstrated increased symptoms and exacerbations^98–100 while the effects on lung function parameters^101,102 are less consistent⁹⁸. A large East London cohort with COPD identified a significant increase in symptoms with pollutant exposure and non-significant trends for exacerbations associated with local ambient pollutant exposure in East London¹⁰³. Even moderate exercise in high traffic areas may reduce the benefits of exercise in patients with COPD¹⁰⁴.

Perhaps the most convincing evidence of the relationship of exposure with disease progression comes from a recent longitudinal cohort from the Multi-Ethnic Study of Atherosclreosis (MESA) and Lung Studies. In this study, investigators found significant associations between ambient pollutant exposure and increases in percent emphysema measured on chest computed tomography (CT) scans over a 10 year period¹⁰⁵. Concentrations of O₃, PM_2.5, NOx and BC, while only O₃ and NOx at follow-up, were significantly associated with the 10-year change in percent emphysema. O₃ was also significantly associated with decrease in FEV₁ over the 10-year time period.

Other respiratory disorders

While the majority of air pollution respiratory literature focuses on asthma and COPD, it is important to highlight a few respiratory conditions in which there is evidence suggesting the influence of ambient air pollution: lung cancer, acute respiratory infection, acute respiratory distress syndrome (ARDS), and interstitial lung disease (ILD). Cancer incidence and cancer mortality are also both associated with exposure to high levels of ambient air pollution. The International Agency for Research on Cancer estimates that between 3–5% of lung cancer cases are attributable to ambient air pollution. The independent effect of pollution on lung cancer mortality is estimated at greater than 62,000 per year².

A recently emerging body of evidence links ambient pollution exposure to risk of ARDS after trauma, an association that suggests pollutant exposure confers respiratory vulnerability in otherwise healthy adults such that a non-respiratory event that stresses the respiratory system can be overwhelming. Reilly and colleagues found that among 996 critically ill patients with acute trauma, both short and long term exposures with ambient pollutants were highly associated with development of ARDS¹⁰⁶. These exposure levels were largely within acceptable ranges per U.S. and European Union air quality standards. The findings were mirrored in a separate cohort of critically ill patients with a specific risk associated with ozone exposure at their home location¹⁰⁷.

Several studies have documented the increased risk of respiratory infection associated with air pollution exposure. The odds of acute lower respiratory tract infections, particularly bronchiolitis, following short term elevations in particulate matter increase by 7–15%^108,109 and even higher for infants born preterm. Short term increases in air pollution have been associated with acute respiratory infection emergency visits and hospitalization in children and adults^110–112.

Globally, increased levels of indoor and ambient pollutants are risk factors for pneumonia across the ages^113,114. For patients with cystic fibrosis, a genetic disease of dysfunction chloride transport which leads to airways inflammation and chronic and acute infection, exposure to ambient pollution is significantly associated with respiratory exacerbations^115–117 and decline in FEV₁¹¹⁵.

While the full narrative on environmental and social determinants is unfolding, some early analyses suggest that COVID-related outcomes are related to ambient air pollution. Recently published studies from both China¹¹⁸ and Italy¹¹⁹ have demonstrated significant relationships between regions of high ambient particle and gaseous pollution and rates of COVID-19 infection. In a cross-sectional study using county-level U.S. data¹²⁰, COVID-related mortality was highest in locations where long-term air pollution concentrations have been highest, adjusting for some key area-level risk factors, such as population size, age distribution, and population density. A similar study in the UK¹²¹ showed association between COVID mortality and ambient levels of nitrogen oxides and ozone.

The development of interstitial lung diseases (ILD) from exposure to occupational or intense environmental exposures have been well documented for conditions such as hypersensitivity pneumonitis, silicosis, asbestosis, and other pneumoconioses. More recently, outdoor air pollution has emerged as a plausible contributor to ILD¹²². Gaseous pollutants, O₃ and NO₂ have been associated with idiopathic pulmonary fibrosis (IPF) exacerbations^123,124, while PM has been associated with decline in lung function¹²⁵ and mortality¹²⁶. In a longitudinal study by Johannson and colleagues, with weekly symptom and spirometry measures over 40 consecutive weeks, air pollution was associated with lower lung function across the study period, but not short-term variations in lung function¹²⁷.

How clinicians can approach pollution and respiratory health

The summation of basic science, human exposure panel studies, cohort and large epidemiologic research overwhelmingly supports both the health risks to humans from exposure to ambient air pollution at levels encountered in industrialized and developing countries, alike. The risks are even higher for vulnerable populations with underlying chronic lung diseases, such as asthma and COPD. So how does the clinician coerce the breadth of research findings into daily practice? This, too, can be addressed on many levels. As the source apportionment of harmful environmental contaminants are derived largely from the burning of fossil fuels for industry, home and transportation uses, efforts to promote curtailing these practices should be encouraged. Supporting local, regional and national policies to encourage clean energy production and utilization and regulations to minimize emissions of pollutants may lead to improved air quality.

Alterations in personal use, such as minimizing gas and oil dependency in favor of renewable sources of energy for home (solar) and personal transportation (electric vehicles, public transportation, cycling and walking) can minimize the personal contribution to environmental pollution.

Healthcare providers have a unique relationship with patients with chronic disease. The office visit serves to assess and manage the individual’s physical disability but also offers a discrete opportunity to offer guidance on minimizing harmful exposures. One such publicly available tool providers can utilize for anticipatory guidance for patients is the air quality index (AQI). AirNow is a program by the U.S. EPA that is the national repository for real-time air quality data derived from federal ambient sampling sites for ozone and particle pollution with coverage of all 50 states, 6 Canadian provinces and 24 U.S. national parks¹²⁸. The AQI is presented in a color-coded graphic to represent the air quality rating and levels of health concerns, specifically identifying conditions that may affect sensitive populations¹²⁹ (Figure 3), and can be accessed by website, social media feed, and iPhone and Android apps. For individual patients, this daily information and forecasting of air quality can help provide advanced warning for adverse conditions for which the patient will want to avoid being outside and consider using an air cleaning device indoors.

Figure 3.

Schematic of Air Quality Index. From U.S. EPA’s AirNow Program. From U.S. EPA’s AirNow ProgramAir Quality Index (AQI) Basics. Available at: https://airnow.gov/index.cfm?action=aqibasics.aqi. Accessed February 11, 2020; with permission.

Conclusion

Air quality is an important influence on human health and disease. Our understanding of these relationships are limited by the complex interactions between exposure dynamics (e.g., pollutant mixtures, concentrations, the duration and intensity of exposure) and personal characteristics (e.g., age at exposure, underlying disease, genetic predisposition). While the adverse respiratory effects of air pollutants encountered in the outdoor environment presented in this article highlight the negative impact of pollutants on chronic disease and lung function growth and decline, it is important to note that human exposure to air pollution is not so neatly compartmentalized – sources of pollutants are ubiquitous in the indoor and outdoor environment and mixing of ambient and indoor air occurs constantly. Nevertheless, there are clear risks that poor ambient air quality presents to the development and exacerbation of chronic lung disease, especially COPD and asthma. Clinicians should be aware of the health effects of these environmental factors, as well as the publicly available resources to monitor them, in order to provide optimal guidance for their patients.

Synopsis:

Globally, exposure to ambient air pollutants is responsible for premature mortality and is implicated in the development and exacerbation of several acute and chronic lung disease across all ages. In this article, we discuss the source apportionment of ambient pollutants and the respiratory health effects in humans. We specifically discuss the evidence supporting ambient pollution in the development of asthma and COPD and acute exacerbations of each condition. Practical advice is given to healthcare providers in how to promote a healthy environment and advise patients with chronic conditions to avoid unsafe air quality.

Key points:

• Ambient air pollution is emitted primarily as a result of fossil fuel combustion and atmospheric chemical reactions

• Ambient air pollution exposure is responsible for premature mortality due to its effect on multiple organ systems, particularly the respiratory and cardiovascular system

• Outdoor pollutant exposure is highly associated with impaired lung development and accelerated lung function decline

• Outdoor air pollution is a potent modifiable risk factor for exacerbations of asthma, COPD, and acute bronchopulmonary infections