History

Air pollution has posed a threat to human health since the advent of fire, 500,000 years ago. Evidence of soot in prehistoric caves indicates that early humans were exposed to high levels of indoor air pollution. Outdoor pollution began to rise as populations grew and clustered in cities. During the Industrial Revolution, there was a dramatic increase in coal use by factories and households. The resulting smog caused significant morbidity and mortality, particularly when combined with stagnant atmospheric conditions. During the Great London Smog of 1952, heavy pollution for 5 days caused at least 4000 excess deaths (Figure 80-1). This episode highlighted the relationship between air pollution and human health and, together with other episodes, led to clean-air policies in Europe and in the United States. Over the next several decades, with improvements in the regulatory framework, air quality in the developed world steadily improved. Even as energy consumption and greenhouse gas emissions have increased, pollutants that are toxic to humans have been better controlled. Nevertheless, 186 million Americans, or 60% of the population, still live in counties with levels of air pollution higher than U.S. Environmental Protection Agency (EPA) standards (Figure 80-2). Air pollution also continues to be a growing problem in cities and households of the developing world.

Figure 80-1 Weekly mortality in greater London, October 1952 to March 1953; SO₂, oxygen saturation.

(Modified from Bell ML, Davis DL: Reassessment of the lethal London fog of 1952: novel indicators of acute and chronic consequences of acute exposure to air pollution, Environ Health Perspect 109(suppl 3):389–394, 2001.)

Figure 80-2 Counties designated as “nonattainment areas” for EPA National Ambient Air Quality Standards (NAAQS) of various pollutants, including particulate matter, ozone, sulfur dioxide, carbon monoxide, and lead.

(From US Environmental Protection Agency Green Book, 2011. www.epa.gov/oaqps001/greenbk/mapnpoll.html.)

Composition of Air Pollution

Many different substances are considered “air pollutants,” which typically exist in combination in the environment; these include particulate matter (PM), carbon monoxide (CO), ozone (O₃), nitrogen oxides (NOx), sulfur oxides (SOx), and volatile organic compounds (VOCs). The composition varies by season and regions, and the chemistry, state, and size of a pollutant influence the resulting health effects (Figure 80-3). Although CO has specific toxicity affecting oxygen transport, many pollutants appear to cause disease by triggering injury through inflammation and oxidative stress. Physiologic effects can be confirmed by experimental studies, but health impacts of air pollution on populations can be difficult to attribute to a single pollutant because they often share sources and vary together. A multipollutant approach to understanding health effects is becoming more common. Nevertheless, this section discusses some of the physiologic effects of individual pollutants before a description of the health outcomes seen with exposure to air pollution.

Figure 80-3 Physiologic effects of air pollutants on the respiratory tract.

(Modified from Beckett WS: Occupational respiratory diseases, N Engl J Med 342:406–413, 2000.)

Particulate Matter

Among air pollutants, PM is most consistently associated with increased mortality effects at ambient exposure concentrations regularly encountered today. Although PM can be formed by a wide variety of natural and man-made processes, one of the largest sources of PM pollution is through combustion of biomass and fossil fuels. PM is composed of organic and inorganic compounds that vary greatly in size (Figure 80-4). Fine PM (<2.5 µm) has the most well-recognized health effects, and the ultrafine PM fraction (<0.1 µm) may be especially important. Larger PM is filtered and trapped in the proximal respiratory tract, but fine particles can penetrate deep into the lung, where they are efficiently deposited, cause local effects, and may be systemically absorbed.

Figure 80-4 Size classification of particulate matter with reference to common structures; RBC, red blood cell; PM, particulate matter.

(Modified from Brook RD, Franklin B, Cascio W, et al: Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association, Circulation 109:2655–2671, 2004.)

The composition of PM also influences its health effects. The mechanism of PM toxicity in the lung is still being elucidated but is likely multifactorial and can include impaired ciliary function, damage to epithelial cells, inflammation, and oxidative stress. Neutrophils and macrophages phagocytize the poorly soluble particles and initiate inflammatory cascades. PM also causes oxidative stress by generating reactive oxygen species (ROS) on the surface of particles that may then cause cellular effects. Inflammation and oxidative stress apparently provoke cardiovascular disease through atherosclerosis, thrombogenesis, vasoconstriction, and reduced heart rate variability (Figure 80-5).

Figure 80-5 Mechanism of cardiovascular disease from exposure to air pollution.

(From Mills NL, Donaldson K, PW Hadoke, et al: Adverse cardiovascular effects of air pollution, Nat Clin Pract Cardiovasc Med 6:36–44, 2009.)

Epidemiologic studies have associated changes in PM with respiratory symptoms, respiratory tract infections, impaired pulmonary function, asthma exacerbations, chronic obstructive pulmonary disease (COPD), cardiovascular events, cerebrovascular accident (CVA, stroke), lung cancer, and all-cause mortality.

Ozone

The stratospheric ozone layer is a normal part in the Earth’s atmosphere that absorbs high-frequency ultraviolet (UV) rays and protects us from their damaging effects. In contrast, ground-level ozone is an air pollutant, which has harmful respiratory and cardiovascular effects. Ground-level O₃ is largely the result of UV photolysis of NOx and VOCs (products of vehicular and industrial combustion). Inhaled O₃ reacts with biomolecules to form free radicals, which trigger proinflammatory and prooxidative mediators. Increased neutrophils, eosinophils, and inflammatory cytokines have all been noted in bronchoalveolar lavage (BAL) fluid in response to O₃ exposure. Exposure to even very low levels of O₃ leads to airway inflammation and bronchoconstriction. Clinically, exposure to O₃ causes exacerbation of asthma and COPD, impaired pulmonary function, and increased respiratory symptoms, and it has been associated with increased mortality. The effects of O₃ are further potentiated by exposure to PM.

Sulfur Dioxide

Combustion of sulfur-containing fuels, including coal and petroleum, produces sulfur dioxide (SO₂), a highly water-soluble gas that is readily absorbed in the mucosa of the eyes and upper respiratory tract. SO₂ is a strong irritant that leads to local inflammation. SO₂ can also bind to organic PM and affect the distal airways. SO₂ increases vascular distention, mucosal edema, smooth muscle contraction, and intraairway secretions. Lung function in healthy individuals is relatively resistant to the effects of considerable doses of SO₂ (5 ppm), but even lower doses (e.g., <1 ppm) elicit acute and substantial bronchoconstriction in some asthmatic patients. Although SO₂ causes multiple respiratory symptoms, it does not seem to be independently responsible for air pollution–related mortality.

Nitrogen Dioxide

Nitrogen dioxide (NO₂) is formed during the combustion of fossil fuels, predominantly at power plants and in vehicles. Being relatively insoluble, NO₂ is not significantly absorbed by proximal mucosa. Instead, NO₂ travels to the more distal airways, where it reacts with water in the respiratory tree to create nitric acid. HNO₃ causes both local and systemic inflammation. Acutely, this can lead to bronchospasm. NO₂ is generally less potent than other pollutants and is likely to have its most harmful effects by acting in synergy with these other compounds. Although high levels of indoor NO₂ can increase susceptibility to viral infection, this has not been observed with outdoor levels of NO₂ pollution. In epidemiologic research, NO₂ concentrations are often considered a surrogate for exposure to traffic-related air pollution; thus the relationship of NO₂ with disease in these studies is probably caused by other pollutants that share exposure profiles.

Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) include a number of organic molecules that are found in biomass and fossil fuels or are formed in their combustion. Use of these fuels aerosolizes PAHs along with other VOCs. Although there are many different types of PAH, small and lipophilic PAHs are the most readily absorbed in the respiratory tract. The effects of each PAH species depends on its underlying composition and structure. Many PAHs are irritants to respiratory mucosa. Others, such as benzo[a]pyrene, one of the carcinogens first described, and the dioxins, are mutagenic and carcinogenic, with special concern regarding cancer of the mouth, nasopharynx, larynx, and lung.

Outdoor Air Pollution