Indoor and Outdoor Air Pollution

What every physician needs to know:

Exposure to indoor and outdoor air pollutants may increase an individual’s risk for morbidity and mortality from a variety of different conditions in multiple organ systems. These exposures cause and/or exacerbate respiratory diseases and diseases in other organ systems. Air pollution may also cause sensory irritation and decrease well-being through, for example, loss of visibility.

Ambient air pollution arises from both natural and human-derived sources. Air pollution has likely had adverse health effects throughout history due to natural occurrences such as volcanic eruptions and wildfires. In the modern era, burning fossil fuels, electric power generation, home heating, and motor vehicle transport has greatly increased emissions and pollution exposure. The importance of ambient air pollution was first appreciated in the 20th century, when cars, trucks, and other vehicles created “smog,” or photochemical pollution and when public health crises arose from periods of intense pollution such as the London “killer fog” in 1952.

Recent unprecedented growth of urban areas forming “megacities” on multiple continents has led to enormous concentration of emissions from sources including massive fleets of motor vehicles, electric power generation, heating, and industry, which combine to produce remarkable and sustained air pollution events. Rarely, events such as the collapse of the World Trade Center have created short-term intense levels of outdoor air pollutants with recognized health effects.

There has also been increasing recognition that the problem of air pollution extends to indoor environments. In low-income countries, exposure to smoke from biomass fuel combustion is widespread and typically occurs at high concentrations. Poor residents of high-income countries may experience indoor pollution due to biomass fuel burning. More commonly in high-income countries, indoor pollutants are generated by human activities and released from materials used for construction and furnishings. These indoor pollutants are often maintained at unhealthy concentrations by building designs that seal them in with limited exchange of indoor air with outdoor air.

Several factors related to specific pollutant characteristics and patterns of exposure determine the likelihood of injury from inhalation of indoor or outdoor air pollutants.

Pollutant Characteristics

Uptake of gases: Penetration into and retention within the respiratory tract of gaseous pollutants vary widely, depending on the physical properties of the gas (e.g., solubility), the concentration of the gas in the inspired air, the rate and depth of ventilation, and the extent to which the material is reactive.

Highly water-soluble gases, such as formaldehyde and SO2, are almost completely extracted in the upper airways. Removal of less water-soluble gases like NO2 and O3 is much less complete, and these gases may penetrate to the distal airways and alveoli. Exercise augments penetration of gases into the lung parenchyma and the total dose of pollutants delivered to the airways.

Particle deposition and retention: Deposition of particulate pollutants depends on several factors, including the particles’ aerodynamic properties (primarily particle size), airway anatomy, and breathing pattern. Particles >10 μm in diameter are filtered out in the nose and nasopharynx, while particles <10 μm tend to be deposited in the tracheobronchial tree. Deposition in the alveoli is maximal for particles <1-2 um in diameter, while particles <100 nanometers (ultrafine particles) can deposit throughout the respiratory tract. Removal of particles from the larger airways occurs by the mucociliary apparatus within hours of deposition. Clearance from the deep lung by alveolar macrophages is much slower requiring days to months.

Personal Exposure

Definitions of concentration, exposure, and dose are fundamental to considering the effects of air pollution. Concentration is the amount of material present in the air. For the respiratory tract, exposure is the amount of time spent in contaminated air; exposure is given units of concentration x time. Dose is the amount of material that enters the body. A biologically effective dose is the amount of material that must reach the target site, i.e., alveoli, for injury to occur. Total personal exposure is the relevant index of exposure, which refers to the time-weighted average pollutant concentration in the microenvironment in which a person spends time. For example, a relevant microenvironment for high particulate exposure would be an office in which smoking is permitted.

Studies indicate that residents of most high-income countries spend most of their time indoors so that exposure to many pollutants occurs indoors. Data in a number of countries showed that people spend an average of 65-75% of their time inside their homes and >90% of their time indoors. Even so, time spent outdoors may be the predominant determinant of exposure for some pollutants, such as ozone, especially for people who exercise outdoors and receive an augmented dose of ozone to their lungs because of the increased ventilation associated with exercise.


Outdoor air pollution

Outdoor air is polluted with a dynamic mixture of pollutants from both natural and manmade sources. The nature of the mixture depends primarily on the mix of sources and their operations and on meteorology. The mixture includes primary pollutants like nitrogen oxides and primary particles, which come directly from their sources, and secondary pollutants like ozone and secondary particles, which are formed through chemical and physical transformations in the atmosphere. These pollutants are variably classified based on their characteristics and sources. One commonly used classification is based on Section 108 of the Clean Air Act, which covers “criteria pollutants” (particulate matter, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and lead). Among these, particulate pollutants and ozone receive the greatest focus and have the most extensive health data. In addition to criteria pollutants, 189 “toxic air pollutants” are recognized, including carcinogens and irritants.

For public health and particularly for persons with cardiopulmonary disease, exposure to particulate matter and ozone at levels associated with adverse health effects is common. Particulate matter in urban air is typically a heterogeneous mixture classified into 3 size ranges based on diameter: the ultrafine range (<0.10 microns in diameter), the fine range (<2.5 microns in diameter), and the coarse range (between 2.5-10 microns in diameter). The ultrafine particles, which reflect fresh combustion, are in highest numbers near roadways, where they come from vehicles. Much of the mass in the fine range is attributable to secondary particles. The coarse mode particles in urban areas are comprised of dust, tire debris, bioaerosols, and other materials.

Ozone is an indicator of oxidant pollution formed through sunlight-driven photochemistry that involves nitrogen oxides and hydrocarbons. Concentrations vary across the day based on traffic, sunlight, and weather. Photochemical pollution now affects much of the US, particularly sunny and warm areas.

For both inhaled particles and ozone, oxidative injury with local and systemic consequences is the key mechanism of injury. Particulate matter in urban air typically has carcinogens among its components. Decades of epidemiologic research link these air pollutants to adverse respiratory effects, including exacerbation of chronic lung diseases such as asthma, COPD, and cystic fibrosis, and reduced lung function. At very high concentrations of particulate matter, excess deaths have been well-documented, particularly among those with cardiopulmonary disease. Although the major entry of air pollution is via the respiratory tract, air pollution has extensive effects in multiple organ systems. Literature links particulate matter to increased cardiovascular morbidity and mortality, including myocardial infarctions, arrhythmias, congestive heart failure, hypertension, and stroke. Emerging evidence also links particulate matter exposure with pulmonary malignancies, adverse birth outcomes, childhood respiratory disease, diabetes, deep venous thrombosis, and neuropsychiatric disease. As a consequence, epidemiologic studies document increased short- and long-term mortality associated with particulate matter at levels present over the last several decades.

Short-term ozone exposure is associated with multiple health effects including increased asthma and COPD exacerbations, hospital admissions and deaths. Acute but reversible reduction of lung function is well documented from experimental exposures. Long-term ozone exposure is linked to increased cardiovascular and respiratory mortality in multiple epidemiologic studies.

Indoor air pollution

There are myriad forms and sources of indoor pollution, including combustion (tobacco smoke, stoves, fireplaces, and wood stoves), household products, construction materials, biologic agents (e.g., microbes, pets), off-gassing from water, and soil gas. In particular, soil gas is the origin of most indoor radon. These agents cause disease through diverse mechanisms, inflammation and irritation, immune responses, carcinogenesis, and effects on the central nervous system. The spectrum of adverse respiratory consequences is broad and includes upper airway symptoms, causation and exacerbation of asthma, hypersensitivity pneumonitis, and lung cancer.

Many potential toxins exist in indoors (Figure 1), and several have been well characterized in the literature. Examples of agents associated with acute or chronic toxicity from inhalation include wood smoke, biological agents, radon, second-hand cigarette smoke, and formaldehyde.

Figure 1.n

Occupational and Environmental Disorders with Borders

Wood Smoke

Environmental Sources of Exposure

In North America, use of a wood stove as a primary or secondary heat source is common and can lead to intermittent high levels of indoor particulate matter and endotoxin. In developing countries, use of wood, coal, and other biomass fuels for cooking, heating, and lighting leads to extremely high exposure levels of indoor toxicants. Additionally smoke from household burning of biomass fuel contributes to ambient air pollution and can infiltrate into neighboring non-wood stove households.

Mechanism of Injury

The toxicology of some components of wood smoke, such as benzo[a]pyrene, other polycyclic organic compounds, and nitrogen oxides, has been well studied. These components can produce inflammation and oxidant injury and act as carcinogens. Some studies investigating experimental exposure to wood smoke as a complex mixture have demonstrated increases in oxidative stress, inflammation, and coagulation factors, however results have been inconsistent and more research is needed to better characterize the toxicology and mechanism of injury from wood smoke.

Spectrum of Respiratory Disorders Associated with Exposure

Most epidemiology on the health effects of wood smoke is derived from studies in developing countries, where intense smoke exposure results from cooking fires in poorly ventilated dwellings. Studies indicate increases in acute respiratory infections, decreased lung growth and development, asthma, COPD in women non-smokers, lung and non-respiratory malignancies, and chronic respiratory morbidity in children and adults from exposure to wood smoke. There is growing recognition of the major impact of household air pollution from solid fuel combustion on worldwide deaths and global burden of disease.

Biological Agents

Environmental Sources of Exposure

Indoor allergens and microbes, the principal biologic agents in indoor air pollution relevant to human health, have diverse sources. Some of the most severe and prevalent indoor biologic pollution arises from the growth of microorganisms or mold on surfaces that are wet or moist. Indoor levels of allergens and microbes may be increased by accumulation of materials like human/animal dander and growth of fungi and bacteria on interior surfaces or air conditioning systems. Other common indoor allergens include those from house dust mites and cockroaches. Indoor pollen derived almost entirely from outdoor plants, and fungus spores from outdoors may also enter the indoor environment in air filtration systems or on people, animals, or objects that move from outdoors to indoors.

Mechanism of Injury

Biologic agents cause upper and lower respiratory infections, immunologic responses, and inflammation. Although considerable attention has focused on the effects of allergic responses to fungi, these organisms also cause non-allergic responses. Some species of fungi, including some molds, are capable of producing mycotoxins and volatile and semi-volatile compounds, and the health effects of inhalation of these compounds remains unclear. Non-allergic responses that may occur include neurotoxicity, immunotoxicity, sensory irritation, and dermal toxicity.

Spectrum of Respiratory Disorders Associated with Exposure

A wide spectrum of disease is associated with biologic agents. Bacteria may result in upper or lower respiratory infections that range from acute bronchitis to pneumonia. Exposure to fungi from indoor mold and damp environments can cause pulmonary infections, hypersensitivity disorders such as hypersensitivity pneumonitis and allergic bronchopulmonary aspergillosis, asthma symptoms, bronchial reactivity, and allergic fungal rhinosinusitis. Allergy symptoms or worsening of asthma symptoms may occur as a result of exposure to common indoor allergens.


Environmental Sources of Exposure

Radon, a colorless/odorless gas, originates from the decay of naturally occurring uranium-238. Present in soil gas, it enters homes through openings in basements and around foundations, drawn in by the pressure gradient that a structure creates across the ground. The concentration depends on local geology, including the porosity of the earth and the concentration of radium, the precursor of radon. In some places, radon may also be present in high concentrations in water and off-gassed during use of water. Radon is a well-documented occupational carcinogen that causes lung cancer. Underground mines can be contaminated by very high concentrations of radon, as in uranium mines.

Mechanism of Injury

Radon decays into a series of particulate radioactive progeny, two of which are alpha-particle-emitting polonium isotopes. Alpha particles, which have high mass and high energy, can create ionization tracks across cells that damage DNA. Lung cancer caused by radon is attributed to the traversal of basal cells in the respiratory epithelium by alpha particles emitted by the polonium progeny that have been deposited in the airways. Because the energy of the alpha particles does not depend on concentration, the risk of lung cancer associated with radon varies directly with the exposure; there is no threshold below which there is no risk.

Spectrum of Respiratory Disorders Associated with Exposure

Risk for lung cancer is the major concern for the population exposed to radon. However, in heavily exposed underground miners, there is some indication that radon exposure contributes to fibrosis; it has also been examined as a cause of non-respiratory cancers but the findings have been inconsistent. The epidemiologic evidence shows that radon causes lung cancer in both those who smoke and those who have never smoked, and there is evidence of a synergy between smoking and radon in causing lung cancer. Radon has not been definitively linked to any particular histologic type of lung cancer; however, observations in underground uranium miners showed an unexpectedly high frequency of small-cell carcinoma.

Secondhand Cigarette Smoke

Environmental Sources of Exposure

Secondhand smoke (SHS) refers to the mixture of diluted sidestream cigarette smoke and exhaled mainstream smoke that is inhaled by non-smokers in indoor environments. SHS is a complex dynamic mixture of gaseous and particulate components that changes as it is diluted and as various chemical transformations occur. The concentration of SHS depends on the number of smokers in the room and their pattern of smoking, the level of exchange of the indoor air with outdoor air, and on removal mechanisms, including surface deposition and filtration. In modern buildings with central air-handling units, SHS from one space may be distributed to others.

Mechanism of Injury

SHS is a rich mixture that includes agents that can cause symptoms and disease through diverse mechanisms including irritation, inflammation, and carcinogenesis. SHS includes many agents classified as carcinogenic by the World Health Organization’s International Agency for Research on Cancer, along with oxidant species that can contribute to carcinogenesis through nonspecific mechanisms.

Spectrum of Respiratory Disorders Associated with Exposure

Diverse respiratory effects have been linked to SHS exposure in children and adults. The first epidemiologic studies on SHS were directed at lower respiratory illnesses in infants and young children. Subsequently, a lengthy list of adverse effects of SHS exposure in children has been identified including risk of lower respiratory tract illnesses, middle-ear problems, exacerbation and possibly causation of asthma, and reduced lung growth. In 1981, two epidemiologic studies showed increased risk for lung cancer associated with SHS in those who had never smoked. Now both lung cancer and coronary disease are causally associated with SHS in those who have never smoked. SHS is also a well-established cause of eye and upper-airway irritation.


Environmental Sources of Exposure

Formaldehyde is a natural product in some foods and is naturally present in the body as a metabolic intermediate. It is a widely used chemical and component of materials used in homes and furnishings as well as a component of SHS. Formaldehyde has been of particular concern in indoor environments where high concentrations have been documented: homes insulated with improperly cured urea-formaldehyde foam insulation and in poorly ventilated mobile homes and trailers with formaldehyde-emitting particle board and plywood. Formaldehyde levels were found to be high in many US Federal Emergency Management Agency trailers following Hurricanes Katrina and Rita. It is also present in outdoor air, where major emission sources include power plants, incinerators, refineries, manufacturing facilities, and automobiles.

Mechanism of Injury

Formaldehyde has a simple one-carbon chemical structure and has been linked to both non-malignant and malignant health outcomes. For non-malignant effects, key mechanisms include triggering of irritant receptors and nonspecific inflammation. For carcinogenesis in the respiratory tract, two mechanisms may be relevant: genotoxicity and regenerative cellular proliferation resulting from cytotoxicity, particularly for nasal tumors.

Spectrum of Respiratory Disorders Associated with Exposure

Diverse respiratory effects have been investigated in relation to inhaled formaldehyde. Of these, irritation is a well-established consequence. The evidence is less certain for other respiratory outcomes e.g., reduction of lung function and causation/exacerbation of asthma. In workers with high levels of exposure, formaldehyde exposure has been linked to cancers of the nose, nasal cavity, and nasopharynx.

Are you sure your patient has had exposure to indoor or outdoor air pollutants? What should you expect to find?

With few exceptions (e.g., hypersensitivity pneumonitis and carbon monoxide poisoning) air pollution does not cause “signature” diseases. Rather, air pollution contributes to the general burden of respiratory diseases, making contributions significant from a public health perspective. In particular, air pollution commonly contributes to episodic exacerbation of existing disease, especially cardiopulmonary disease, or contributes to progression of existing disease. Risk assessment methods are used to calculate the contributions of various pollutants to the public health burden. These estimates address population-level effects but are not informative as to which individuals have been harmed by air pollution. For example, indoor radon is estimated to be the second leading cause of lung cancer in the US, contributing to ~20,000 deaths annually.

One syndrome, “sick-building syndrome,” has been associated with indoor environments that are unhealthy because of indoor pollution, temperature, humidity, and other factors. Respiratory symptoms may be a component of the nonspecific syndrome, which is diagnosed on the basis of symptoms and the temporal link of its occurrence to presence in the triggering environment.

Beware: there are other diseases that can mimic exposure to indoor or outdoor air pollutants.

Not applicable.

How and/or why did the patient develop a condition related to indoor or outdoor air pollutants?

Not applicable.

Which individuals are at greatest risk of developing a condition related to indoor and outdoor air pollution?

In the US, the Environmental Protection Agency, states, and municipalities carry out extensive monitoring of the key pollutants, particularly the criteria pollutants. These data show that levels are highest in major urban areas, and fine-scale studies show that exposures can be particularly intense along major roadways. Individuals likely to have higher exposures tend to live in inner cities and close to industrial sources. Because people who live in these areas tend to be of lower socioeconomic status, they are also more likely to have lower quality housing and higher exposures to indoor air pollution. The term “vulnerability” has been used to refer to this potential for higher exposures, while “environmental inequity” or “environmental injustice” refers to the higher exposures for those who are less advantaged.

By contrast, susceptibility refers to a higher risk for developing disease or other adverse outcomes at a particular exposure than that of those who are not susceptible. Broad groups considered as susceptible include infants and elderly, persons with chronic cardiopulmonary disease, and those with other chronic diseases, such as diabetes. An important question concerns the differences in susceptibility to the health effects of air pollution between similarly exposed individuals. Research is in the process of addressing genetic determinants of susceptibility.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

Few lab tests are specifically relevant, with the exception of tests for exposures that have specific biomarkers: carboxyhemoglobin for CO, blood lead level, and antibody screens for hypersensitivity pneumonitis. As for exposure to tobacco smoke in indoor air, the level of cotinine, a nicotine metabolite, can be measured in saliva, blood, and urine, but this measurement is largely for research purposes.

While not a “lab test,” inexpensive passive devices can readily measure indoor concentrations of radon. The Environmental Protection Agency recommends measurement of indoor radon for most homes and in some jurisdictions, it has become required with the sale of a house.

What imaging studies will be helpful in making or excluding the diagnosis?

Not applicable.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of a condition related to indoor or outdoor air pollution?

Since air pollution commonly acts by exacerbating existing respiratory diseases, studies to determine the severity and change in physiological abnormality may be helpful. However, pulmonary function studies are generally not helpful for detecting the specific contribution of air pollution to the process except following discrete exposure to high levels of pollutants.

What diagnostic procedures will be helpful in making or excluding the diagnosis?

Not applicable.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis?

Not applicable

If you decide the patient has a condition related to indoor or outdoor air pollution, how should the patient be managed?

Controlling the health effects of indoor and outdoor air pollution requires strategies oriented toward both populations as a whole and individual patients.

Patient-oriented Strategies

At the individual level, efforts should be made to limit personal exposure of susceptible groups during periods of elevated ambient pollution. It is important for the provider to recognize if the patient falls into one of these groups. Ideally the patient may wish to be aware of pollution levels in the community, using information conveyed from local media or air quality apps. Modifying time-activity patterns to limit time outside during significant pollution represents the most effective strategy to reduce exposure. Those susceptible to air pollution should remain indoors during pollution episodes. During air pollution events, affected individuals should discontinue vigorous outdoor exercise, as exercise increases the dose of pollution delivered to the respiratory tract. In the setting of very high levels of pollution (above EPA standards) even healthy individuals should consider exercising indoors. Summertime ozone presents a distinct pattern of exposure, often with low levels in the morning and high levels in the later part of the day, often coinciding with periods of high traffic congestion. Exposure may be reduced by encouraging exercise in the early morning during periods of high daytime ozone.

Susceptible individuals, especially those with asthma or COPD, should be reminded about medication adherence during pollution episodes. Medication use should follow the usual clinical indications, and regimens should not be adjusted because of the occurrence of pollution. Patients should have an action plan in the event of increased symptoms during pollution episodes.

Traditionally, the use of masks to reduce individual exposure during pollution episodes has not been recommended and commonly available surgical masks have no benefit. However, there is recent data suggesting that high efficiency masks (N95) may reduce particulate exposure and physiologic responses in susceptible individuals walking outside during high level pollution episodes. More research is required to better define the role for this intervention. Masks have no role in protection against ozone. There has been increasing interest in the use of indoor air filters. High efficiency particulate air (HEPA) filters can be effective for improving indoor air quality, and have been shown to have health benefits for children with asthma. However, more research is needed to establish effectiveness for other at-risk individuals.

Community-oriented Strategies

The EPA developed an Air Quality Index (AQI) that provides descriptors of air quality and guidelines for cautionary statements. The actions taken when “alert levels” are reached or anticipated include issuing public health advisories. The EPA’s recommendations are used by local air pollution agencies in preparing daily air quality summaries to be disseminated to the media.

Pulmonologists may be faced with community issues that range from building-related issues to the effects of local sources, such as power plants and manufacturing facilities. Exposure to environmental pollutants may disproportionately affect disadvantaged communities, and the term “environmental justice” is used to address inequities between poorer and more well-to-do communities. Since these inequities are often complex issues that exceed the expertise of the local physician, guidance from public health and environmental agencies should be sought.

What is the prognosis for patients managed in the recommended ways?

Not applicable.

What other considerations exist for patients?

Not applicable