Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Environmental Triggers of Asthma
Environmental Factors

Learning Objectives

Upon completion of this section, you will be able to

• identify five indoor triggers of an acute asthma episode,
• identify five outdoor triggers of an acute asthma episode, and
• describe the impact of occupational exposures on adult asthma prevalence.

Introduction

Asthma can be triggered and exacerbated by exposure to many environmental factors. The American Academy of Pediatrics has recently published a book about childhood environmental health problems, which states: "Avoiding environmental allergens and irritants is one of the primary goals of good asthma management" (AAPCEH 2003).

Medical and nursing education programs often fail to fully incorporate environmental questions and an exposure history into asthma management. A recent study reported that, although over half of practicing pediatricians surveyed had seen a patient with health issues related to environmental exposures, fewer than 1/5th were trained in taking an environmental history (Kilpatrick et al. 2002).

This Case Study focuses on allergens (pollen, mold, animal dander, insect parts, and some chemicals) and irritants (smoke, dust, gas or diesel fumes, and chlorine) which can trigger or exacerbate an asthmatic attack in individuals with increased airway hyper responsiveness.

Models of Effect

How an environmental pollutant may affect asthma severity (IOM 2000).

• The pollutant might act as an inciter or trigger, leading to an asthma attack in an individual with hyper-responsive airways.
• The pollutant can exacerbate preexisting airway inflammation, leading to increased airway hyper-responsiveness, which may persist after exposure ends.
• The pollutant might augment or modify immune responses to inhaled antigens or intensify the effect of other pollutants in the respiratory tract.

Evidence of Effect

The importance of allergies and allergens in triggering and exacerbating asthma is supported by several studies. Key findings include the following.

• Sensitization to indoor allergens and the spores of outdoor molds is a risk factor for the development of asthma in children and adults.
• In children and adults, sensitive to indoor allergens, the severity of asthma symptoms may vary with the level of exposure.
• Reduction of exposure to house-dust mites has produced improved Pulmonary Function Tests (PFTs) and reduction in airway inflammation and hyper-responsiveness in sensitive children and adults (Nelson 2000; Frew 2003a; Simpson and Custovic 2004).

Taken together, these studies make a strong argument for the importance of allergen and irritant exposure as aggravating factors in asthma in both children and adults. The findings reinforce the importance of the identification and treatment of these exposures.

Indoor Air Pollution

In industrialized countries, adults and children often spend most of their time indoors (Schwab et al. 1992). Exposure to indoor air pollutants may have a more important effect on childhood asthma than may exposure to outdoor air pollutants (IOM 2000; Etzel 2003).The primary indoor air pollutants associated with asthma exacerbation include (AAPCEH 2003; Jones 2000)

• biologic allergens (dust mites, cockroaches, animal dander, mold, etc.),
• environmental tobacco smoke (ETS),
• irritant chemicals and fumes, and
• products from combustion devices.

Biologic Allergen Overview

Biologic allergens can be found throughout the home, school, and work environments—although concentrations of dust mites, cockroaches, and animal dander allergens (pets, mice, rats) vary with geographic location. However, dust mite allergen, mold, and cat and dog allergens can be found in most homes, including homes where there are no pets at present (Togias 2003; Weinberger 2003; Nelson 2000).

Dust Mites

Sensitization to house dust mites is an important risk factor for asthma exacerbations and the development of asthma. The dust mite grows optimally at warm temperatures and with humidity greater than 50% in cloth-covered objects such as soft toys, upholstered furniture, bedding, mattresses, and carpets (Sporik et al. 1990; Platts-Mills et al. 1995; Duffy et al. 1998).

Cockroaches

Cockroach allergens also may increase a child’s risk of developing asthma (Etzel 2003). Cockroach droppings may be one of the most underappreciated allergens in the indoor environment. A 36% cockroach sensitization rate has been reported in inner-city asthmatic children. Children with asthma and cockroach allergy who are exposed to cockroach allergens have more wheezing, missed school days, emergency room visits, and hospitalizations than nonsensitized or nonexposed children (IOM 2000; Rosenstreich et al. 1997).

Cats

Exposure to cats is causally related to asthma exacerbations among many children with asthma (IOM 2000). The severity of allergic reactions to cats is greater than reactions to other common domestic pets. More than 6 million U.S. residents have allergies to cats, and up to 40% of atopic patients demonstrate skin test sensitivity (Wood and Eggleston 1993). However, recent studies have shown that the presence of a cat in the house may decrease the risk of developing asthma (Platts-Mills et al. 2001; Nafstad et al. 2001).

Other Animals

Dogs, rodents, birds, and other furry or feathered animals in the home may contribute in varying degrees to the animal allergens within the home. Dogs may have breed-specific allergens, and are less uniformly allergenic than cats (Lindren et al. 1988). Rodent allergens can come from pets or pests in the home. Birds and feathers have been suggested as allergenic; however, it may be that the dust mites associated with feathers (including feathers in pillows and clothes) are the culprits (IOM 2000).

Molds

Exposure to molds may lead to allergic sensitization and may exacerbate asthma or allergic rhinitis (Pope et al. 1993). At least 60 species of molds have spores thought to be allergenic (Burge 1989). Species of particular concern are

• Penicillium,
• Aspergillus,
• Cladosporium, and
• Alternaria.

On exposure to these species, nasal congestion, runny nose, sneezing, conjunctivitis, lacrimation, wheezing, chest tightness, and shortness of breath may occur. Among patients studied, children are the most sensitive to mold allergens (Etzel 2003).

Environmental Tobacco Smoke (ETS)

Exposure to environmental tobacco smoke (ETS) is a risk factor for asthma attacks in children (AAPCEH 1997). Children with asthma and whose parents smoke have more frequent asthma attacks and more severe symptoms (Weitzman et al. 1990; Martinez et al. 1992; Murray and Morrison 1993). There is clear evidence of an association between exposure to environmental tobacco smoke and the development and exacerbations of asthma. Exposure to ETS also places children at increased risk for sinusitis, otitis media, and bronchiolitis (IOM 2000; Tager et al. 1993).

Combustion Devices

Improperly used or malfunctioning heating devices are a major source of combustion pollutants indoors. Possible sources of contaminants include

• gas ranges, especially if used for home heating;
• improperly vented fireplaces;
• inefficient or malfunctioning furnaces;
• stoves burning wood, coal, or other biomass; and
• unvented or improperly vented kerosene or gas space heaters.

The combustion products from these devices include

• carbon monoxide (CO),
• nitrogen dioxide (NO₂),
• particulate matter, and
• sulfur dioxide (SO₂).

Although CO is a major health concern, it is not an irritating gas and is not likely by itself to exacerbate asthma. In combination, these combustion products will often exacerbate asthma symptoms (AAPCEH 2003).

Chemical Fumes

Some building materials and home furnishings off-gas formaldehyde (US EPA 1994). Formaldehyde may exacerbate asthma in some infants and children (Krzyzanowski et al. 1990). At sufficient concentrations in the air, cleaning products such as chlorine and ammonia may also trigger reactions.

Miscellaneous Allergens

Latex may cause an allergic response either by direct contact or by inhalation of latex particles. Symptoms range from skin eruption to bronchospasm and anaphylaxis. Gloves, balloons, condoms, and various types of sporting equipment may trigger allergic responses around the home (Landwehr and Boguniewicz 1996).

Outdoor Air Pollution

For the last several decades, high levels of outdoor air pollution have been associated with short-term increases in asthma morbidity and mortality (AAPCEH 1993; Ostro et al. 2001; Tolbert et al. 2000). Specific exposures to outdoor plant allergens such as organic dusts from castor beans, soybeans, and grains dramatically illustrate this relationship (Etzel 2003). Ambient hazardous air pollutants, as well as industrial releases of aldehydes, metals, isocyanates, and others have been shown to cause and trigger asthma (Leikauf et al. 1995). In some communities, hazardous air pollution is associated with noxious odors, and odors can exacerbate symptoms among some people with asthma (Shusterman 1992).

Air pollution has been implicated as one of the factors responsible for the dramatic increase in asthma incidence in recent years. (Salvi 2001) Clinicians should be aware of the common (criteria) air pollutants that may affect asthmatic patients. The National Ambient Air Quality Standards (NAAQS) are set for six criteria pollutants:

• ozone (O₃),
• SO₂,
• NO₂,
• CO,
• lead,
• particulate matter <10 microns (PM₁₀) and particulate matter <2.5 microns (PM_2.5).

The standards are designed to protect the health of all susceptible groups, including asthma. The Air Quality Index (AQI, Table 2) provides standardized means of communicating health information associated with daily ambient levels of ground-level O₃, SO₂, NO₂, CO, PM₁₀, and PM_2.5. (See Appendix 1) For any reported index value greater than 100, the U.S. Environmental Protection Agency (EPA) determines the index number daily and reports the highest of the index figures, the critical pollutant, and the specific groups sensitive to the pollutant (US EPA 1999).

Ozone

Some children with asthma (and some children without asthma) have decreases in lung function after exposure to ozone. In the United States, a large fraction of ambient O₃ is the product of photochemical reactions between various nitrogen oxides (NOx), volatile organic chemicals (VOCs) and ultraviolet light. Most of the health effects research on O₃ has focused on the short-term effects, such as reductions in FEV1 and forced vital capacity (FVC). Levels of O₃ are usually greatest on hot summer days and tend to peak in the late afternoon (Etzel 2003; Avol et al. 1985; Spektor et al. 1991).

SO₂

Because of its high solubility, SO₂ mainly irritates the upper airway. The nasal mucosa effectively removes most inspired SO₂ during breathing at rest. Deep penetration to the lung mucosa may occur during moderate exercise. SO₂ has a dose-response association with bronchoconstriction. The amount of SO₂-induced bronchoconstriction is dependent on the level of pre-existing hyper-responsiveness and exercise of the individual. A person without asthma can tolerate a higher concentration of SO₂ before developing symptoms. The bronchoconstrictor response develops within minutes of exposure and resolves within an hour after exposure ends (Ware et al. 1986; Koenig et al. 1990).

NO₂

In contrast to the other pollutants, NO₂ is both an indoor and outdoor air pollutant. Indoor sources of NO₂ include

• malfunctioning gas stoves,
• furnaces,
• fireplaces, and
• kerosene space heaters.

Most NO₂ health effects are believed to be due to long-term, low-level outdoor exposure. Like the other air pollutants, NO₂ increases bronchial responsiveness during exercise. NO₂ decreases lung function in people with asthma who are exposed to concentrations above 0.3 ppm, although there is not a clear dose-response relationship. Short-term exposure to high concentrations of NO₂ induces terminal bronchiolar changes and diffuse alveolar injury. Such high concentrations are generally seen only in accidental exposure, as might occur within confined spaces or in an occupational setting (Etzel 2003; Avol et al. 1985; Shima and Adachi 2000).

PM₁₀ and PM_2.5

Particulate matter is a mixture of solid particles and liquid droplets. Particulate matter <10 microns (PM₁₀) is the respirable portion of particulate matter that results in lower airway exposure (AAPCEH 2003). PM₁₀ is the standard measure of particulate air pollution used worldwide. Studies suggest that asthma symptoms can be worsened by increases in the levels of PM₁₀, which is a complex mixture of particle types. PM₁₀ has many components and there is no general agreement regarding which component(s) could exacerbate asthma. However, pro-inflammatory effects of transition metals, hydrocarbons, ultrafine particles and endotoxin—all present to varying degrees in PM₁₀—could be important (Donaldson et al. 2000).

Particulate matter <2.5 microns (PM_2.5) is referred to as “fine-particle pollution.” Sources of PM_2.5 include

• industrial and residential combustion,
• vehicle exhaust,
• forest and vegetation fires, and
• atmospheric reactions between gases ( SO₂ and NO_x) and VOCs.

PM_2.5 penetrates deeper into the lung than does PM₁₀, potentially causing greater adverse health effects (AAPCEH 2003; Schwartz and Neas 2000). Several recently published community epidemiologic studies associated adverse effects when PM_2.5 formed a significant portion of the particulate exposure, even though PM₁₀ air concentrations were below NAAQS. Medication use, hospital admissions, and the number of emergency room visits (seen primarily with elderly patients and individuals with cardiopulmonary disease) increased under those conditions (Ware et al. 1986; Dockery et al. 1989).

Traffic-Related Pollutants and Diesel Exhaust

Exposure to motor traffic emissions can have a significant effect on respiratory function in children and adults. Studies show that children living near heavily traveled roadways have significantly higher rates of wheezing and diagnosed asthma (Ciccone et al. 1998). Epidemiological studies suggest that diesel exhaust may be particularly aggravating to children (Brunekreef et al. 1997). A child riding in a school bus may be exposed to as much as 4 times the level of diesel exhaust as one riding in a car (NRDC 2001).

Work-Related Asthma

The most common occupational respiratory disease in many developed countries is work-related asthma. Approximately 15%–25% of adults with asthma may have work-related asthma (i.e., both occupational asthma that is caused by conditions at work and work-aggravated asthma) (Balmes 2003; Wagner 2006; Henneberger 2007). The two types of occupational asthma are distinguished as shown below.

• Allergy-induced asthma arises after a latency period that is necessary for acquiring sensitization.
• Irritant-induced asthma develops because of acute high-level exposure to irritant materials, and may be due to repeated irritant exposures (Malo and Chan-Yeung 2001; Liu 2002; Holla et al. 2002; Gautrin 2006).

Asking an adult asthma patient whether their symptoms improve when away from work and worsen during periods at work is a simple but direct means of detecting potential cases of work-related asthma. Some occupational sensitizers and irritants, such as cleaning agents, epoxy glues, hairdressing products, are also found outside the workplace and may be relevant in non-occupational asthma (Tarlo 2003). However, exposure to these agents in occupational settings will often be more frequent and/or more intense than in non-occupational settings (Friedman-Jimenez et al. 2000).

There are well over 300 agents reported to cause occupational asthma (Malo and Chan-Yeung 2006), and an equal or greater number of agents and conditions at work can aggravate existing asthma. Numerous workplace biologic allergens can cause asthma, including natural rubber latex in medical care settings and animal allergens in research laboratories and veterinary offices. A wide range of airborne dusts, gases, fumes, and vapors can cause dose-related symptoms in individuals exposed to them in the workplace. Among the chemicals associated with occupational asthma, the acid anhydrides have been signal agents for study because of their inherent and complex biological activity and the wide range of associated occupational airway disease seen in exposed workers in various occupational settings (Zeiss 2002). In addition to traditional “dirty” workplaces, offices and other non-industrial indoor work environments can pose a risk for asthma. In 2004, the Institute of Medicine concluded that sufficient evidence exists for associating the presence of mold or other agents in damp buildings to nasal and throat symptoms, cough, wheeze, and asthma symptoms in sensitized asthmatics (IOM 2004). Since this review was published there has been further work indicating that exposure to damp indoor environments and mold can lead to the development of asthma (Cox-Ganser 2005; Jaakkola 2005).

Based on surveillance for work-related asthma in the United States during 1993-1999, the most common putative agents, in decreasing order, are

• miscellaneous chemicals,
• cleaning materials,
• mineral and inorganic dust,
• indoor air pollutants,
• pyrolysis products,
• isocyanates,
• solvents,
• hydrocarbons,
• polymers, and
• welding exposures (NIOSH 2003).

Diisocyanates are the leading identified cause of occupational asthma worldwide (Johnson et al. 2004; Wisnewski 2006).

A number of reports indicate that occupational exposure in health care workers to natural rubber latex can elicit symptoms of rhinoconjunctivitis, with or without asthma, in selected individuals who are sensitized (Fish 2002). Further research is needed to determine whether upper airway responses to occupational exposures indicate or predict lower airway responses (Christiani 2006).

Key Points

• A wide range of indoor and outdoor allergens and irritants can exacerbate asthma.
• Household exposures to dust mites and cockroach allergens, and the irritant effects of environmental tobacco smoke, contribute significantly to asthma morbidity.
• Occupational asthma may be caused by allergens or irritants in the work environment.

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