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Air Pollution and Primary Care Medicine

Author: Jefferson H. Dickey MD


Introduction

"Air pollution" encompasses a diverse array of anthropogenic chemical emissions including gaseous combustion products, volatile chemicals, aerosols (particulate), and their atmospheric reaction products. Indoor air has its own hazards and is discussed in a separate chapter. Pollutants, exposure, and sources will be discussed first, followed by health effects, diagnostic considerations, and management.

Atmospheric chemistry of air pollution has recently been reviewed.1

Pollutants, Exposure, and Sources

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.

TABLE 1: CITIES AND COUNTIES WITH HIGHEST RECENT AIR POLLUTION LEVELS

Ozone Particulate Carbon Monoxide

Glendora, Los Angeles Co, CA

Crestline, San Bernardino Co, CA

Redlands, San Bernardino Co, CA

San Bernardino, San Bernardino, CA

Azusa, Los Angeles Co, CA

Fontana, San Bernardino Co, CA

Perris, Riverside Co, CA

Upland, San Bernardino Co, CA

Rubidoux, Riverside Co, CA

Pasadena, Los Angeles Co, CA

Howell Co, MO

Power Co, ID

Phoenix, Maricopa Co, AZ

Philadelphia, Philadelphia Co, PA

Whitefish, Flathead Co, MT

Salt Lake City, Salt Lake Co, UT

Calexico, Imperial Co, CA

Henderson, Clark Co, NV

Teller Co, CO

El Paso, El Paso Co, TX

Lynwood, Los Angeles County, CA

Calexico, Imperial Co, CA

Fairbanks, Fairbanks North Star Borough, AK

Hawthorne, Los Angeles Co, CA

Star Borough, AK

Denver, Denver Co, CO

Spokane, Spokane Co, WA

Las Vegas, Clark Co, NV

Weirton, Hancock Co, WV

Phoenix, Maricopa Co, AZ


The Clean Air Act (CAA) stipulates that the EPA administrator promulgate NAAQS which protect the most sensitive members of the population with an adequate margin of safety; asthmatics are specifically designated as a sensitive subgroup. In addition, the CAA amendments of 1990 began the process of regulating hazardous air pollutants (HAPs, "air toxics"). The most useful source of information on air pollution levels over the last decade and current regulatory issues is the EPA Office of Air and Radiation web sites.23 http://www.epa.gov/airsweb/monvals.htm, http://www.epa.gov/airlinks/

Ozone (O3)

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.

This section will 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 driven by 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. Information sources about state and local ozone levels are listed in the resource section at the end of this chapter.

Particulate

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 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 oxides, metals, nitric acid, ammonium salts, acid aerosols, 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. Information sources about state and local particulate levels are listed in the resource section at the end of this chapter.

Carbon Monoxide

About 12 million persons lived in areas exceeding the NAAQS for carbon monoxide (CO). CO is formed by incomplete combustion of carbon containing fuels. Local accumulation in heavy traffic is the most important source for community ambient exposure. Indoor levels are generally low in the absence of strong indoor sources, but intrusion from outdoor sources can occur.

Sources of Community Carbon Monoxide exposure:

  • Inside passenger car, commuting 5 ppm
  • Proximity to busy roads, intersections 15 ppm
  • Parking areas 4 ppm
  • Traffic tunnels 5 - 42 ppm

Other important contributors to CO exposure include traffic volume, traffic speed, winter season, motor vehicle density, age composition of the fleet, emissions standards for the fleet and vehicle characteristics (CO intrusion problem), community combustion of oil, gasoline, coal, wood, and use of lawn mowers, chain saws, space heaters, and charcoal. Recent EPA AIRS (Aerometric Information Retrieval System) data found peak community exposures to be generally 15-25 ppm for an 8 hr average and 25-35 ppm for 1 hour averages.

Smokers typically have COHb levels of 5-6%. Setting aside tobacco and indoor sources, the relationship between ambient CO concentrations and blood levels is largely determined by duration of exposure and ventilation rate; the latter is roughly correlated with workload. Older US National Health and Nutrition Examination Survey biological monitoring data shows mean wintertime carboxyhemoglobin (COHb) {in the general population}to be about 1.2%, with 3-4% of population above 2%. For example, during heavy labor in a busy traffic tunnel with CO levels of 42 ppm, the COHb would reach about 5% in 90 minutes. Risk groups include commuters, smokers, persons working in traffic. Persons with cardiac and pulmonary disease are most vulnerable; symptoms such as dyspnea and angina may develop at COHb levels of 3-4%.

Sulfur Dioxide (SO2)

Sulfur Dioxide (SO2) gas is formed during the combustion 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.

Nitrogen Dioxide (NO2)

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.

Air Toxics

Toxic air pollutants is the term applied to certain volatile organic chemicals, pesticides, herbicides, metals, and radio nuclides. This section highlights selected pollutants, emission sources, and information sources; these may be regulated in the 1990 Clean Air Act (Section 112), subject to emissions reporting in the Toxics Release Inventory (TRI)4 http://www.epa.gov/tri/ and http://www.rtk.net/www/data/tri_gen.html), or subject to evaluation through the National Toxic Inventory (NTI). The Toxics Release Inventory (TRI), published by the U.S. EPA and mandated by the Emergency Planning and Community Right-To-Know Act, is a valuable source of information about toxic chemicals that are being used, manufactured, treated, transported, or released into the environment. The NTI, which includes air toxics sources not covered by the TRI, is not required by the CAA, but is maintained by the US EPA to assist in many program areas. The NTI reveals small point sources ("area sources", especially consumer and commercial solvent use) to account for 31 percent of U.S. toxic emissions, mobile (transportation) sources account for 39 percent, and point (major fixed) sources account for 30 percent. Lead is regulated by EPA within the NAAQS. Ambient lead concentrations have decreased substantially since removal of lead from US gasoline; nonetheless, 4.5 million Americans live in communities which do not meet the NAAQS for lead. These are mostly located in the vicinity of nonferrous and ferrous smelters, battery manufacturers, and other stationary sources of lead emissions.

TABLE 2: COMMUNITY TOXIC AIR POLLUTANT SOURCE CATEGORIES5
http://www.epa.gov/ttn/uatw/mactscc.txt

  • fuel combustion
  • non-ferrous metals processing
  • ferrous metals processing
  • mineral products processing
  • petroleum and natural gas production and refining
  • organic liquids and gasoline distribution
  • surface coating processes
  • waste treatment and disposal
  • agricultural chemicals production
  • fibers production processes
  • food and agriculture processes
  • pharmaceutical production processes
  • polymers and resins production
  • production of organic and inorganic chemicals
  • halogenated solvent and dry cleaning operations
  • chromium electroplating
  • chromic acid anodizing
  • commercial sterilization facilities
  • others

Recent reviews67 aid the assessment of potential community exposures; for most volatile organic compounds, indoor concentrations generally exceed those outdoor. Actual ambient exposure may be dominated by proximity to primary sources. Significant personal exposures may also arise through automobile transit, solvent use, wood burning, barbecuing, and smoking. Polycyclic aromatic compounds and mutagenic heterocyclic amines8 may be distributed in the environment adsorbed to aerosols.

TABLE 3: COMMUNITY SOURCES OF SPECIFIC AIR TOXICS 

benzene driving and personal activities associated with vehicles, pumping gasoline, direct and indirect tobacco exposure, lawnmowers and other small household combustion engines, household solvents and cleaners, art and hobby supplies, and glues
1,3-butadiene proximity to industrial sites and gasoline vapor
formaldehyde combustion of hydrocarbons from incinerators and vehicle exhaust
styrene industrial processes, especially the petrochemical industry, vehicle exhaust, incineration, and other combustion
tetrachloroethylene (perchloroethylene) waste disposal sites and dry cleaning establishments
polychlorinated dibenzodioxins and polychlorinated dibenzofurans industrial sources (chemical synthesis and processing, manufacture of pesticides), combustion sources (incineration: municipal, hazardous wasted, sewage sludge, hospital waste, metal reclamation), diffuse sources (automobile exhaust, private home heating, cigarettes, accidental fires [PCB transformers, PVC fires, warehouse fires], waste sites, dry cleaning establishments, and pulp bleaching.
polycyclic aromatic compounds7 biomass combustion, wildfires, fireplaces, internal combustion engines, municipal solid waste incineration, and cigarette smoke
mutagenic heterocyclic amines diesel-exhaust particles, cigarette smoke, cooking fumes, rain water, sewage water, incineration-ash and soil8

Nonoccupational exposures to pesticides may occur during both agricultural and lawn and garden spray operations; pesticide application may not be limited to the target, but may drift or be subject to over spray. Subsequent to application, pesticides may volatilize and disperse downwind. Groundwater, surface water and soil may become contaminated, and food may be directly or indirectly contaminated. Indoor air may be contaminated both from indoor application and contamination from outdoor sources. Downwind drift may occur from both public land and recreational area (golf courses and park) maintenance and insect control. General population exposure has been well documented, with residues of pesticides and metabolites found in blood, urine, breast milk, fat tissue, and other tissues. Some of this exposure derives from living in proximity to agricultural areas.9

Incinerators10

Particulate and gaseous emissions from municipal solid waste incineration depend on the waste stream composition and incinerator engineering and operation, but typically include heavy metals (Hg, Pb, As, Cd. Cr, Mn, Ni, Sb, Se, Zn, V), polychlorinated dibenzodioxins, dibenzofurans, and polycyclic aromatic hydrocarbons, in addition to acid gasses and oxides of nitrogen, sulfur, and carbon. Batteries, florescent light bulbs, magazine dyes, papers, plastics are sources of metals; lead and cadmium are emitted mostly in the particulate fraction, while mercury is more in gaseous form. Incinerator ashes contain high concentrations of metals. Chlorine and fluorine are emitted as acid gasses, and contribute to halogenated aromatic organic compound formation. Proximity to incinerators has been associated with local lead soil distribution; the association of dioxin exposure with incinerators is less consistent. The major route of dioxin ingestion is in animal fat foods (milk, eggs, animal flesh), although plant deposition and inhalation contribute small amounts. Dioxins have also contaminated herbicides widely sprayed along highways and railroad right-of-ways. Nonetheless, cows milk may be more contaminated with dioxins near municipal solid waste incinerators11, a recent ecological study found stomach and lung cancers to be elevated in communities near municipal solid waste incinerators in Great Britain11. This preliminary and unconfirmed finding is an outcome of concern in light of parallel cancer elevations in a study of MSW workers12. Increasing attention is being paid to dioxin and mercury emissions from medical waste incinerators.13 14 15 http://www.epa.gov/ttn/uatw/hmiwifs.html) Exposure to metals16 and dioxins may also occur from hazardous waste incinerators.


Health Effects

Perhaps the two most important recent reviews of air pollution health effects were by the American Thoracic Society17 18 and Brunekreef and others19.

Ozone / Health Effects

Ozone / Overview of Condition

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 are concomitant.

Ozone / Pathophysiology

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 / Symptoms

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.

Ozone / Pulmonary Function

Pulmonary function is variably impaired. DLCO 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.

TABLE 4: PULMONARY FUNCTION RESPONSE TO VARIOUS OZONE EXPOSURES 20

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 sthmatics and non-asthmatics non-specific bronchial hyper responsiveness
1 hour @ 120 ppb asthmatics specific bronchial hyper responsiveness (conflicting evidence)21 22
3 hours @ 250 - 400 ppb asthmatics specific bronchial hyper responsiveness (convincing evidence)23

Ozone / Susceptible Populations

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.

Ozone / Course and Complications

As noted above, different individuals can have very different reactions to the same ozone exposure. Typically symptoms will increase gradually over several hours and then subside within a day or two, though a more rapid onset has been described. Spirometric declines may be less marked after repeated exposures over 3 to 5 days, but methacholine hyper responsiveness does not seem to abate. In some, there is increased susceptibility to allergen triggers, and macrophage dysfunction may predispose to bacterial respiratory infection. Epidemiologic evidence suggests that the incidence of clinical illness varies with not only the ozone air pollution levels, but probably with other air pollutants as well. Meta-analysis of time series studies suggests that for each 50 ppb increase in peak ozone levels, hospitalization rates increase 6-10% for asthma, pneumonia, and chronic obstructive pulmonary disease. Ozone air pollution episodes have been associated with increases in emergency department use from 8 - 15% (New Jersey) to 43% (Mexico City). Chronic exposure to ozone pollution has been associated with de novo development of chronic lung disease, with mild pulmonary fibrosis and modest increases in small airway obstruction.

Particulate / Health Effects

Particulate / Epidemiology / Weight of Evidence

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 Size, Chemistry, and Pathophysiology

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.24 Persons with obstructive pulmonary disease (smokers, asthmatics, and patients with small airway disease or COPD) have greater distal airway deposition of particles, and this effect is inversely and well correlated with predicted FEV1.25

A robust epidemiologic data set associates PM10 with adverse health effects.17 19 26 27 28 29 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.30 31 32 33 34 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.35

Particulate / Clinical Syndrome

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 study30 and the American Cancer Society cohorts34 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 methodologies36, and with the several meta-analyses of the time series studies.26 29 37 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.38-40

META-ANALYSIS OF PARTICULATE HEALTH EFFECTS (for a 10 mcg/m3 increase in PM10, a relatively small difference in exposure) 17 37

  • 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,35 (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.


Other Criteria Pollutants

Carbon Monoxide / Health Effects

The health effects of carbon monoxide (CO) are thought due to decreases in the oxygen carrying capacity of blood and to disruption in cytochrome function. Some evidence, though controversial, suggests acceleration of atherosclerosis. Low level animal exposures have been associated with fetal developmental and mortality effects. In humans, symptoms of low level exposure begin with headache, fatigue, and flu-like symptoms. (Reports have appeared in the lay press of ultimately fatal cases of carbon monoxide poisoning missed because the "flu like illness" was accompanied by a fever). Risk groups include smokers and those with coronary artery disease (CAD), peripheral vascular disease, and COPD.

Adverse cardiac effects include decreased exercise capacity, and in persons with CAD, shorter exercise time before developing ST changes and angina (COHb levels of 2-4%), and arrhythmias (levels of 6%). Individuals with COPD have decreased ventilatory elimination of CO, and suffer earlier symptoms and reductions in exercise tolerance. Neurologic manifestations include changes in visual and auditory perception, psychomotor function, dexterity, vigilance, and time interval discrimination.

Epidemiologic studies have increasingly link ambient CO exposure with hospitalization for cardiovascular disease. As with other pollutants, problems with these studies include poor individual exposure assessment and confounding co-pollutants. However, these associations have been seen in multiple cities, down to very low levels of CO exposure. Recent studies have also suggest an association of ambient CO levels with hospitalization rates for congestive heart failure.41 42

Sulfur Dioxide (SO2) / Health Effects

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.43

Nitrogen Dioxide / Health Effects

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.44 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.


Diesel and Automobile Exhaust / Health Effects

Diesel exhaust contributes to ambient sulfur oxides, ozone precursors, and aerosols, seems to contribute to chronic respiratory morbidity and mortality, and probably contributes to the cancer risk of urban air pollution. Mutagenic and carcinogenic compounds (such as PAHs) are adsorbed to diesel soot.

Diesel clearly causes cancer in rats (but not hamsters), and the mechanism may be chronic inflammation, hyperplasia, multifocal fibrosis, and macrophage particle clearance overload.45 Diesel may be a co-carcinogen, and extrapolation of risk from laboratory animals is perilous. Diesel has been demonstrated to modulate the immune response, acting as an adjuvant in the specific IgE response, and augmenting non-specific IgE production and inflammatory cytokine synthesis, up regulating the atopic state, increasing eosinophil degranulation, and increasing the inflammatory respiratory response to allergen. Non-specific IgE augmentation has been associated with increased odds of asthma.[Sunyer, 1996 #809] Some vapor phase constituents cause bronchoconstriction.

In humans, occupational case control and cohort studies have found a small but generally consistent association of prolonged exposure to high diesel concentrations, when adjusted for cigarette smoking, with a relative risk (RR) of lung cancer incidence of 1.4 to 1.7 in the best studies. While most studies have problems with exposure assessment, wide confidence intervals, and low effect magnitude,46 (http://www.epa.gov/ncea/diesel.htm) a recent meta-analysis47 of over twenty studies examining occupational exposure to diesel exhaust, confirmed a statistically significant RR of 1.33 for lung cancer, again with adjustment for cigarette smoking.

Heavy exposure to diesel is clearly associated with pulmonary inflammation, with some evidence of increased incidence of respiratory symptoms (cough, phlegm, and wheezing) and small work shift pulmonary function decrements; heavily exposed cohorts may have elevated risks of mortality from chronic lung disease (chronic obstructive lung disease and respiratory infection).46

Community studies (many of them well controlled for important confounders) have found living, going to school, or working in proximity to high traffic density, to be associated variously with asthma, chronic bronchitis, and allergic rhinitis. Important variables seem to be traffic density, truck traffic density, and distance to the roadway. Many other roadway related factors may contribute, including combustion related particles, road dust, nitrogen oxides from non-diesel engines, tire particle aerosols, and other volatile organic compounds.


Air Toxics (Hazardous Air Pollutants)

Air Toxics / Health Effects / Asthma

Increasing attention is being paid to the potential for urban air toxics to exacerbate asthma,48 through induction of specific or non-specific airway hyper reactivity, or of reactive airways dysfunction syndrome (RADS). Individual hypersensitivity to specific substances may play a role, such a case where a person sensitive to ampicillin suffered a delayed allergic response after visiting a town where ampicillin is manufactured. Similarly, asthma epidemics in Barcelona, Spain have been traced to atmospheric distribution of soybean antigen during shipping port cargo transfers,49 34 requiring engineering source controls. Other emissions of concern include metals (cadmium, chromates, cobalt, nickel sulfate, platinum compounds), asthmogenic chemicals (maleic and phthalic acid anhydrides), aldehydes (acetaldehyde, acrolein, formaldehyde), polyisocyanates, hydrazine, methyl isocyanate, phenylenediamene, and styrene), and irritants (chlorine, hydrofluoric and hydrochloric acids, toluene diisocyanate, hydrazine, SO2, acetic acid, phosgene, phosphine, and ammonia).

Community exposure to toluene diisocyanate (TDI) has recently been documented in a North Carolina neighborhood in proximity to a polyurethane foam manufacturing plant. ATSDR (Agency for Toxic Substances and Disease Registry) detected TDI in ambient air in a residential area near the facility at levels as high as 29 parts per billion (ppb). Some residents who lived near the facility reported health effects that they attributed to emissions from the plant, and approximately 9% of tested persons living near the plant tested positive for antibodies to isocyanates, two thirds of which could not be explained by other potential sources of exposures.50 http://www.cdc.gov/epo/mmwr/mmwr_wk.html

Air Toxics / Health Effects / Non-Respiratory

Air toxics reach the general population by direct pulmonary assimilation, by regional ecological bioaccumulation and subsequent ingestion in food (including fresh water fish and human breast milk), and insidiously through global distribution and bioconcentration. Air toxics may cause or promote cancer and other serious health consequences, including respiratory, immune, nervous systems, birth defects, and reproductive effects. Toxics of greatest concern include mercury51 http://www.epa.gov/ttn/uatw/112nmerc/mercury.html, dioxins52 http://www.epa.gov/ordntrnt/ORD/health/index.html, and other persistent organic pollutants53 (http://action.psr.org/popsmon.pdf). Some air toxics can cause death or serious injury if accidentally released in large amounts.54


Diagnosis

Diagnosis of respiratory illness related to ozone, NOx, PM, SO2, diesel, and air toxics is clinical and presumptive, based on a history of elevated community pollutant levels, especially in combination with prolonged exposure outdoors with elevated workloads. Soft clues include an association with typical symptoms (ocular and upper respiratory irritation, chest pain, shortness of breath, cough, wheezing, nausea, malaise, headache), and signs (conjunctival and upper respiratory inflammation, pulmonary inflammation or infection, wheezing, prolonged expiratory phase). The chest pain associated with ozone exposure is characteristically exacerbated during inspiration and relieved during expiration, resulting in a decreased tidal volume. FEV1, FVC, and DLCO may be reduced, and methacholine responsiveness may be increased.

Differentiation from other common causes of respiratory illnesses is not well defined, and several etiologies may contribute to an individual's illness. Similarly, atmospheric concentrations of multiple pollutants often fluctuate simultaneously, making precise etiologic differentiation rarely practical.

Asthma

Asthma is an inflammatory disease with episodic symptoms of airflow obstruction, at least partial reversibility of airway obstruction, diagnosed after reasonable exclusion of alternative diagnoses. The NIH/NHLBI Guidelines for the Diagnosis and Management of Asthma,55 http://www.nhlbi.nih.gov/nhlbi/lung/asthma/prof/asthhc.htm provide details on diagnosis and management of asthma. Environmental considerations in asthma include different classes of exposure substances and scenarios of exposure. Environmental substances to be considered in asthma pathogenesis include specific sensitizers, irritants and non-specific sensitizers, and adjuvants. Relevant exposure scenarios include ambient air pollution, building related indoor contamination, occupational exposures, and in utero exposures (tobacco smoke).

Specific sensitization is associated with asthma with latency and may result from a constitutional predisposition combined with a sufficient exposure over time to either biological materials (molds, pollens and plant materials, insect and animal materials, possibly viruses), or non-biologic specific sensitizers (isocyanates, colophony, acrylates, persulfate salts/senna, reactive dyes, amino alcohols, metals [chromium, aluminum, platinum, nickel, cobalt], and pharmaceuticals). Asthma without latency may result in reactive airways dysfunction syndrome after a single exposure to a high concentration of a strong irritant gas, vapor or fume.[Brooks, 1995 #28] Non-specific sensitizers increase the susceptibility of asthmatics to specific triggers, and include oxidant and irritant gases (ozone, sulfur dioxide, and nitrogen dioxide), and possibly viruses. Finally, adjuvants non-specifically upregulate the immune response, resulting in augemented responses to the specific allergens. Examples include diesel exhaust particles, carbon black, pyrene, and second hand smoke (ETS). The mechanism by which particulate air pollution aggrevates asthma is not certain.

While ozone causes symptoms, inflammation, reversible airways obstruction, and hyper responsiveness, ozone pneumonitis differs in that pulmonary restriction occurs and susceptibility to infection may be increased. Diesel, in addition to contributing SO2, NOx, particulate, and ozone precursors, augments the specific asthmatic IgE response, and some volatile components trigger asthma responses directly.

TABLE 5: DIFFERENTIAL DIAGNOSIS OF ASTHMA

infants and children viral infections or bronchiolitis, foreign body in airways, tracheal abnormalities, cystic fibrosis, bronchopulmonary dysplasia, heart disease
adults COPD, pulmonary embolism, drugs (ACE inhibitors, beta-blockers, others), Churg Strauss syndrome, pulmonary eosinophilic infiltrates, allergic bronchopulmonary aspergillosis
all ages allergic rhinitis, sinusitis, gastroesophageal reflux and aspiration, laryngeal and vocal cord dysfunction, heart disease and congestive heart failure, airways tumors, aspirin sensitivity

Diagnostic patient evaluation includes spirometry (pre- and post- bronchodilator may demonstrate at least 12 % or 200 ml reversibility in FEV1, or an FEV1/FVC ratio of less than 65%). Consideration should be given to measureing flow volume loops, lung volumes, and diffusion capacity to rule out upper airway obstruction (inspiratory flow limitation), restrictive lung disease such as hypersensitivity pneumonitis (decreased DLCO and lung volumes), and COPD (decreased DLCO). Great interindividual variability exists in vulnerability to air pollution related pulmonary compromise. Peak flow meters may demonstrate a 20% difference during or subsequent to different exposure scenarios, and may be a useful method to assess environmental aggrevants.

Exposure related responses may be immediate (<1 hour), delayed (2 to 8 hours), or nocturnal. Recommendations that measurements be performed four times a day up to every two hours may need to be tempered with the observation that adherence with the diagnostic regimen may be poor. Symptom diaries may useful, but 15% of asthma patients, 25% of elderly patients, and some patients with near fatal asthma fail to perceive significant declines in FEV1. Non-specific bronchial provocation testing (methacholine, histamine, cold air, exercise) may identify asthmatic and non-asthmatic persons who develop bronchial hyper responsiveness during and after air pollution episodes.

TABLE 6: ASTHMA MANAGEMENT GUIDANCE BASED ON PEAK FLOW READINGS (percent predicted maximum).

green zone: >80% take medications as usual
yellow zone: 50-80% immediate use of short acting bronchodilator, discuss need for additional medications with health care provider
red zone: <50% immediate use of short acting bronchodilator, immediately contact physician for instructions or proceed to the nearest emergency room

Other tests and evaluation to consider include chest xray, allergy testing, ENT evaluation, and evaluation of gastroesophageal function.

Chronic Obstructive Pulmonary Disease and Chronic Bronchitis

TABLE 7: COPD DIAGNOSTIC CONSIDERATIONS

DEFINITIONS / one or more of: 1. chronic cough with excess mucus secretion and sputum production

2. dyspnea and wheezing with infections or after exposure to irritants

3. distension of the distal airways and destruction of alveolar septa

4. airway inflammation and bronchospasm

GAS EXCHANGE 1. mildly reduced PO2; possible polycythemia

2. low, normal, or elevated PCO2

LUNG FUNCTION abnormalities may include: 1. decreased flow rates: may show no reversibility, some acute reversibility, or some reversibility with chronic corticosteroid treatment

2. decreased diffusion capacity

3. increased residual volume

CHEST XRAY hyperinflation or increased bronchovascular markings

Illnesses and mortality associated with chronic obstructive lung disease are increased during air pollution episodes. The mechanism is not clear, but epidemiologic studies implicate particulate, ozone, and sulfur dioxide; the precise responsible species has not been identified.

Coronary Artery Disease

The diagnosis of symptoms and signs related to carbon monoxide rely on a history compatible with carbon monoxide exposure in association with typical signs and symptoms (headache, flu-like symptoms, angina, cardiopulmonary compromise, EKG changes, arrhythmias, and arterial blood gas carboxyhemoglobin elevation). Pulse oximeters will display misleadingly high hemoglobin saturations; arterial blood gas analysis is necessary to determine the relative contributions of oxyhemoglobin and carboxyhemoglobin.


Treatment

Treatment of air pollution related cardiopulmonary disease related to air pollution is pharmacologic and behavioral.

Treatment / Pharmacology

Physicians should consider annual influenza vaccination in persons with chronic lung or heart disease.

Definitive data do not exist to recommend pharmacologic treatment of air pollution related cardiopulmonary disease which diverges from established guidelines for asthma, COPD, congestive heart failure, and coronary artery disease. However, some tentative suggestions from the literature may be useful.

SO2: Bronchoconstriction related to SO2 is generally well prevented by nedocromil, zafirlukast, theophylline, and beta-2-adrenergic agonists.

OZONE: Animal studies find atropine to partially prevent increases in airway resistance, indomethacin to partially prevent increases in airway resistance, not to prevent increases in alveolar protein exudation, and to partially prevent increases in mortality after challenge with bacterial aerosol. Chlorpheniramine partially prevents increases in airway resistance, and cromolyn partially prevents increases in airway resistance and declines in DLCO.

Some human observations find albuterol to mostly fail to block the ozone induced spirometric declines, increases in symptoms, and increase in bronchial reactivity, while other observations find albuterol to be effective preventing spirometric decline. Indomethacin, however, results in substantially less spirometric decline, but has negligible effect on bronchial responsiveness. INDOMETHACIN (AND OTHER NON-STEROIDAL MEDICATIONS, INCLUDING ASPIRIN) CAN CAUSE SERIOUS, EVEN FATAL, REACTIONS IN SOME ASTHMATICS. EXTREME CAUTION IS ADVISED.

Antioxidants are being actively investigated as agents which may prevent consequences of oxidation in the airways.

PARTICULATE: Spirometric changes after particulate exposures are generally small; information can be culled from epidemiologic studies which find that asthmatics tend to use bronchodilators more during PM air pollution episodes, however, this treatment generally fails to mitigate declines in peak flow rates.

CARBON MONOXIDE: See the chapter/section on carbon monoxide. For the relatively low dose exposures experienced in urban traffic, evaluate for angina and congestive heart failure, monitor for arrhythmias, consider administration of oxygen and treat underlying coronary artery disease.

Treatment / Behavioral Approaches

Behavioral approaches can be characterized as individual, administrative, or societal. Individual avoidance of exposure derives from identifying potential exposures, and avoiding prolonged outdoor exertion during significant air pollution episodes. Behavioral recommendations should especially be focused on those most at risk, including the elderly, those who work or exercise outdoors, and those with underlying heart and lung disease. See the web sites for information on historical criteria pollutant exposure levels, daily summertime ozone predictions and readings, air toxics emissions inventories and potential community source list. Local patterns of particulate air pollution exacerbations can be inferred from observations of geographic susceptibility to weather temperature inversions, trapping of stagnant air masses, proximity to strong sources (industrial and roadway), being downwind from urban plumes, and historic EPA data. Ozone levels tend to be higher especially after several hot, sunny, stagnant days. Regional ozone air pollution warning systems are being developed. (Table 8).

Ozone and particulate levels (attributable to outdoor air pollution) are lower indoors, although fine particles, thought responsible for many of the serious health effects, penetrate indoors more efficiently than larger particles. Ozone levels are about 30% lower indoors when windows and doors are open and 80% lower when they are closed.

Administrative guidelines are suggested by the American Conference of Governmental Industrial Hygienists (ACGIH) concerning duration and load of labor outdoors during ozone air pollution episodes. The higher the workload, the higher the air pollution levels, the shorter the recommended duration of outdoor labor. The ACGIH guidelines assume active workers to be "less likely to include individuals with risk factors that would make them particularly susceptible to the effects of ozone" and fail to consider synergistic effects of pollutants and heightened sensitivity to allergens. Nonetheless, ACGIH TLV draft document finds acceptable 8 hour ozone exposures to 0.1 ppm with light work, 0.08 ppm with moderate work, and 0.05 ppm with heavy work.

Societal approaches to reducing air pollution levels include advances in energy, transportation, and industrial technology and policy and changes in patterns of energy use and population growth. During air pollution episodes individuals should limit driving and postpone errands; if driving is necessary, use the newest vehicle; arrange shared rides to work or take mass transportation; avoid use of gas powered yard equipment; refuel cars after 7 PM. Recent significant public health successes include dramatically reducing community lead levels (removal from gasoline), declines in carbon monoxide (automobile engine and gasoline modifications), declines in volatile organic compound emissions during gasoline distribution and retailing (fuel vapor recovery), declines in aerosol levels in the northeast (implementation of Clean Air Act and joint US / Canadian acid rain agreements), and recent promulgation of new EPA NAAQS for ozone and particulate. These historic successes and hopes for future gains are largely the result of continuing basic science and epidemiologic research , and the determined public advocacy for political and regulatory action.


Table 8: Sources of Information on Local Ozone Air Pollution Levels

Ozone air pollution data is available on the internet and from local hot lines. The EPA is constructing web access to current air pollution data at http://www.epa.gov/airnow/

Updated information on air pollution hotlines can be obtained from the American Lung Association at: 800-LUNG-USA. The Boston area hotline is: 800-882-1497.

Internet sites with daily ozone air pollution data include:


Table 9: Air Quality Standards

The US EPA sets NAAQS in an attempt to protect the general population from air pollution. The American Conference of Governmental Industrial Hygenists (ACGIH) develops guidelines to assist in control of health hazards in the workplace. The former carry weight of law; the latter do not.

NITROGEN DIOXIDE (3 ppm = 5.6 mg/m3)

US EPA 0.053 ppm (annual arithmetic mean)

ACGIH 3 ppm (TWA)

OZONE

US EPA 0.08 ppm (8 hours) 0.12 ppm (1 hour)

ACGIH (complex; incorporates workload, duration, and air concentration; see "BEHAVIORAL APPROACHES")

PARTICULATE (PM2.5)

US EPA 15 µg/m3 (annual mean) 65 µg/m3 (24 hour)

PARTICULATE (PM10)

US EPA 50 µg/m3 (annual mean) 150 µg/m3 (24 hour)

SULFUR DIOXIDE

US EPA 0.03 ppm (80 mcg/m3; annual average) 0.14 ppm (365 mcg/m3; 24 hour)

ACGIH 2 ppm (TWA) 5 ppm (ceiling)

CARBON MONOXIDE

US EPA 9 ppm (10 mg/m3; 8 hour) 35 ppm (40 mg/m3; 1 hour)

ACGIH 25 ppm (TWA)


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