More than 20 million people in the United States are estimated to have asthma. Among children, it is the most common chronic illness. A substantial body of research, including population-based studies of school-aged children and young adults, indicates that the prevalence and severity of asthma have increased dramatically over the last several decades in the United States and many other parts of the world. Furthermore, in the U.S., rates of increase of asthma are disproportionately high among children and African Americans. Although research has suggested that a large portion of the observed racial/ethnic differences in asthma prevalence is explained by factors related to income and level of education, residence in an urban area has been implicated as an important risk factor for all children. Researchers have also found marked differences in the types of asthma triggers found in homes in inner-city areas compared to suburban or rural areas. However, substantial differences in the overall burden of agents which exacerbate asthma have not necessarily been established.
These increases in asthma prevalence and severity have occurred despite general reductions in levels of most air pollutants outside; therefore, many researchers instead point to coinciding changes in the home environment as potentially influential, and possibly more important, factors in determining asthma risk. In particular, housing designs intended to increase energy efficiency, resulting in a decrease in passive ventilation, and the presence of upholstered furnishings and carpeting have all been cited as conditions in the home that have the potential to affect indoor air quality and the prevalence and severity of asthma. Potentially increasing the significance of indoor air exposures as risk factors for asthma, data show children in the U.S. currently spend the overwhelming majority of their time indoors.
The strongest established risk factors for development of asthma are family history of allergic disease and sensitization to one or more indoor allergens. Allergens are proteins with the ability to trigger immune responses and cause allergic reactions (atopy) in susceptible individuals (e.g., those with a family history of allergic disease). They are typically found adhered to very small particles, which can be airborne as well as present in household dust reservoirs (e.g., in carpets and on surfaces). In indoor environments, allergen exposure primarily occurs through inhalation of allergens associated with airborne particles. Common indoor allergen sources include dust mites, cockroaches, animals (domestic animals and pests such as rodents), and mold. Particular allergens identified in animals include proteins found in the urine (for rodents), saliva (for both cat and cockroaches), feces (for house dust mites and cockroaches), and skin flakes or body casing particles (for dog, cat, and cockroach). Conventionally speaking, sensitization to a substance is the development of the potential for an allergic reaction to that substance. Sensitization occurs in susceptible individuals when repeated exposure to an allergen (also called an antigen in immunological science) results in the production of the immunoglobulin E (IgE) antibody. An antibody is a protein that is manufactured by lymphocytes (a type of white blood cell) to neutralize an antigen or foreign protein. An allergic response may result when the individual is again exposed to the substance which caused IgE antibody formation. IgE is a class of antibody normally present in very low levels in humans but found in larger quantities in people with allergies and certain infections. Evidence suggests that it is the primary antibody responsible for the classic allergic reaction (American Academy of Allergy, Asthma and Immunology (AAAI)).
Of the tests used to determine whether an individual is sensitive to an allergen, the skin prick is the most common method. A small amount of allergen is introduced into the skin by making a small puncture through a drop of allergen extract. Swelling occurs if the patient is allergic to the specific allergen. If skin-prick tests are all negative, a physician may use a more sensitive, but less specific intradermal test. Generally, intradermal testing is used to test for allergy to insect stings or penicillin. A blood test, called a RAST (radioallergosorbent) test, may sometimes be used. This is a more expensive method, is generally less sensitive than skin testing, and requires more time for results to be available. It is generally used only when skin tests cannot be performed. Allergen extracts are produced commercially according to Food and Drug Administration (FDA) standards.
Exposure to house dust mite allergens in childhood has been linked to an increase in the relative risk of developing asthma, and numerous other allergens are associated with asthma exacerbation in sensitized individuals. Asthma exacerbation is the onset or worsening of symptoms, such as shortness of breath, cough, wheezing, and chest tightness, in an individual who has already developed asthma. Data regarding critical ages for sensitization are not well defined in the literature. Research does generally support the recommendation that avoidance measures for allergens be introduced before birth or at the earliest possible age in high-risk infants (e.g., those with family histories of allergic diseases, atopic dermatitis in the first three months of life, or sensitizations to specific food allergens in the first three years of life). In the Canadian Childhood Asthma Primary Prevention Study, intervention (which included encouragement of breast feeding as well as environmental measures) began during the third trimester of pregnancy and continued for the first year of life. Environmental measures consisted of (1) dust mite control, including encasement of parents’ and infants’ beds, weekly cleaning of bedding, and treatment of carpeting and upholstery with benzyl benzoate powder and foam, respectively, (2) pet avoidance measures, and (3) avoidance of environmental tobacco smoke. At seven years after birth, the prevalence of pediatric allergist- diagnosed asthma was significantly lower in the intervention group than in the control group (14.9 % vs. 23.0%).
Nonetheless, many questions remain. For example, recent evidence has suggested that high-dose exposure to cat allergen early in life may produce a form of immunologic tolerance to cats, rather than cause sensitization. Furthermore, it has been suggested that avoidance of cat allergens by removing the cat from the family home, especially within a community where many other cats are present (i.e., moderate ambient levels of cat allergen are present), might achieve the opposite of the intended effect for children in the early stages of immune system development (i.e., immunologic tolerance might have occurred at higher exposure levels; sensitization can occur at moderate levels). Additional research is needed to better characterize the complex relationship between pet ownership and asthma. Specifically, intervention studies in which pets are removed from the home may help to determine the effect of animal removal on asthma development.
Another concept, known as the “hygiene hypothesis,” has spawned a number of studies. The hygiene hypothesis suggests that children’s immune systems are not being developed normally at a young age due to a general lack of exposure to infectious agents. Research in the U.S. and Europe has found evidence that exposure to microbial organisms via lifestyle characteristics such as day care attendance, having multiple siblings, and close proximity to farming practices may decrease the risk of atopy and asthma. The inverse relationship between atopy-related illnesses and microbial exposure observed in the studies above is by no means universal, however. Celedon et al. (2003) found that the protective effect of day care attendance was only observed in children without maternal history of asthma. Other research casts doubt over the hygiene hypothesis in its entirety. Results of the International Study of Asthma and Allergies in Childhood showed that there was not a lower prevalence of asthma in some underdeveloped countries (i.e., countries with poor hygiene and high infection rates) compared with those in the developing world. It is possible, however, that children in developing countries are exposed to different sensitizing agents, thereby changing their risk level and subsequent expression of disease. After extensive review of studies investigating the relationship between the number of siblings in a family and allergic disorders, Karmaus and Botezan (2002) concluded that the hygiene hypothesis failed to explain inconsistent study results.
Research also indicates that other factors can exacerbate asthma symptoms, such as respiratory tract infections, bacterial endotoxins, indoor pollutants (environmental tobacco smoke, nitrogen oxides/indoor combustion products, formaldehyde, phthalates, VOCs, pesticides), outdoor pollutants that penetrate the indoor environment (sulfur oxides, ozone, particulate matter), cold air, obesity, exercise, and the presence of wood burning stoves and fireplaces. These substances act by an irritant mechanism which sets off the body’s inflammatory response as opposed to the allergic mechanism described above. In the case of bacterial endotoxins, the relationship between exposure and asthma symptoms is difficult to characterize. Some studies have associated endotoxin with asthma exacerbation, while others have noted that endotoxin exposure may have a protective effect early in life. Michel et al. (1996) found that the presence of endotoxin in house dust was significantly related to the severity of asthma symptoms in individuals sensitized to the dust mite. Thorne et al. (2005), using cross-sectional data from 831
U.S. homes in the National Survey of Lead and Allergens in Housing, found that endotoxin
levels in settled dust were significantly related to diagnosed asthma, asthma symptoms in the past year, current use of asthma medications, and wheezing, but not allergy. The relationships were strongest for dust on bedroom floors and bedding, they were observed in adults only, and they indicate that “endotoxin exposure worsens symptoms in adults, regardless of whether an individual has allergies or not.” A study of children in rural Germany, Austria, and Switzerland, however, produced quite different results. In these areas, researchers found that children from
farming households who are routinely exposed to high levels of environmental endotoxin were observed to have a significantly decreased risk of hay fever, sensitization to six common aeroallergens, atopic wheeze, and atopic asthma. This effect was seen in children from both farming and nonfarming households, indicating that even low levels of exposure to endotoxin may protect against atopic diseases in early life.
The few studies focusing on asthma in elderly persons indicate that it is a significant problem for this population group, that much of the cause of morbidity may be sensitivity to indoor allergens, and that the pattern of sensitivity appears to be similar to that reported in children and young adults in urban areas of the United States.