Allergens And The Indoor Environment

For more than 5,000 years, observers have recorded episodes of disease and demise that today are recognized as allergic reactions. For example, the death of King Menes of Memphis in about 3000 B.C. was the result either of anaphylaxis from the sting of a hornet or of being trampled by a hippopotamus. (A question arises because hornet and hippo share the same ancient Egyptian word.) During the sixteenth, seventeenth, and eighteenth centuries, reactions were noted (mostly to foods) that were surely allergic in nature, and some surprisingly intuitive observations were made regarding cause and effect. During this period, cats, dogs, horses, feathers, and many foods were suspected of causing asthma. In the early nineteenth century, it was recognized that pollen caused "hay fever" and that dust from beaten carpets produced similar symptoms. The first experimental challenges with pollen apparently were done by Kirkman in 1835, followed by Blackley's extensive investigations into both allergy and aerobiology in the 1870s (Blackley, 1873).

More recently, much progress has been made in recognizing specific causes of asthma and hay fever and in defining the mechanisms by which symptoms are elicited. Yet in spite of increasing knowledge of the mechanisms of allergic disease and of the agents that cause sensitization and symptoms, we have modified indoor environments in ways that may contribute significantly to exposure to these agents and to the development of allergic disease. For example, we have adopted central heating on a broad scale, which means that we heat all parts of our houses, even when they are not occupied. By the late 1960s and 1970s it became obvious that much energy was wasted in houses and other buildings owing to excessive heat transfer through surfaces such as walls, ceilings, and windows or through "cracks." This waste inspired a federally sponsored campaign to make houses and other buildings both better insulated and "tighter." Insulation may not directly affect the levels and kinds of allergens in the indoor environment (as long as it remains dry), but decreased ventilation encourages their accumulation and may increase relative humidity, leading to conditions that favor the growth of biological allergen sources (e.g., microbes and mites).

Other twentieth-century amenities have also contributed to increased allergen exposure. The invention and widespread use of the vacuum cleaner have been followed by the practice of installing wall-to-wall carpeting in homes, schools, hospitals, and offices, despite the fact that the vacuum cleaner is probably not effective for removing skin scales, mites, and excess moisture from carpeting. In fact, vacuum cleaning is quite effective in dispersing and suspending allergens and other particles in the air. Heating, ventilating, and air-conditioning (HVAC) systems, which have become widespread in this country, can also create problems in terms of indoor allergens. On the one hand, HVAC systems allow windows to remain closed, filter out outdoor particulate material, and decrease relative humidity, thus lowering the risk of microbial and mite contamination. On the other hand, if air-conditioning units are not maintained properly, they can be sources of microbial contamination and have caused more than one major epidemic of infectious disease (Fraser et al., 1977). In addition to these factors, pets in the home are a major source of allergens and can play a large role in sensitization and allergic disease (Mathison et al., 1982; Ohman et al., 1977; Reed and Swanson, 1987; Swanson et al., 1989). Thus, lifestyle changes have influenced indoor air pollution both positively and negatively. Overall, indoor air quality is better than it was in the Middle Ages, when straw was used as a floor covering, sanitation was nonexistent, and burning fuels created a smoky environment. In modern times, however, homes and buildings still harbor the potential for severe allergic problems.

Over the past 25 years, a steady increase in our knowledge of the biological sources (sensitizing agents) that give rise to immunological sensitization has allowed us to identify specific health risks and to establish methods for measuring some of the indoor agents that are thought to cause hypersensitivity disease (i.e., "allergies"). For most agents, it is clear that exposure creates a risk, but insufficient data are available to propose threshold or risk levels. For a few sensitizing agents, it has been possible to propose specific levels of exposure that constitute a risk for sensitization and symptom development (Platts-Mills and Chapman, 1987). Most research on indoor air quality, however, has focused on the same pollutants that are found in outdoor air (nitrogen oxides, carbon monoxide, etc.) and a few other nonbiological agents that are either relatively easy to measure (e.g., asbestos, radon) or that have stimulated major controversy (e.g., environmental tobacco smoke). Very little research has been directed toward the health effects, prevalence, or relative risks of allergens, toxins, and volatile irritants of biological origin in indoor air.

The major sources of indoor allergens include house dust mites, molds, and animal dander. These and other potential sources of allergens are the focus of this report and are covered in detail in the chapters that follow. Also emphasized are several specific allergic diseases of the upper and lower airways: rhinitis, asthma, and hypersensitivity pneumonitis. Before proceeding to this discussion, however, several concepts and definitions are described that will be useful to an understanding of the material that follows. Readers are also encouraged to consult the glossary, which follows the references at the end of the main text of the volume.

Concepts and Definitions

Allergy, generally speaking, is the state of immune hypersensitivity that exists in an individual who has been exposed to an allergen and has responded with an overproduction of certain immune system components such as immunoglobulin E (IgE) antibodies (defined below). More specifically, common use of the term allergy usually refers to a type I hypersensitivity reaction (the type I reaction is also called the anaphylactic type or immediate type of allergic reaction). It is the common type of allergic reaction caused by IgE antibody and results in the common allergic diseases such as hay fever, allergic asthma, allergic urticaria, and the less common but potentially fatal anaphylactic reaction. About 40 percent of the population have IgE antibodies against environmental allergens, 20 percent have clinical allergic disease, and 10 percent have significant or severe allergic disease.

Gell and Coombs (1968) classified hypersensitivity reactions into four major types, according to the immune mechanisms involved (see Table 1-1). For the purposes of this report (and unless noted otherwise), the term allergic reaction means the immediate hypersensitivity response that occurs when a sensitized individual is exposed to an allergen, that is, a type I, IgE-mediated reaction. Although these reactions against indoor allergens are our primary focus, some attention is also given to allergic diseases that operate through different mechanisms, for example, hypersensitivity pneumonitis—a disease that involves IgG antibodies and reactive lymphocytes. Chapter 4 describes the mechanisms of the immune function in technical detail.

TABLE 1-1

Four Types of Immunologic Reactions to Indoor Allergens that Cause Pulmonary Disease in Humans.

There are two major components of the immune system that respond to allergens: antibodies, which are specific proteins of the immunoglobulin E (IgE) type, and mast cells, which carry receptors for IgE and release chemicals such as histamine. The initial phase of the immune response, known as sensitization, sets up the mechanisms for an allergic reaction (Figure 1-2).

FIGURE 1-2

Hypersensitivity and IgE-mediated allergy. (A) Upon initial exposure to an allergen, there will be no overt manifestations of allergic disease because the patient is nonsensitized. However, this allergen will initiate an immune response that results in (more...)

During sensitization (in the case of airborne allergens, this occurs in the airways or on the skin), the immune system of a susceptible person encounters an allergen in the form of an antigen (a substance that stimulates the production of an antibody). The system responds by producing IgE specific to that antigen¹—that is, an IgE that will recognize and react with that specific antigen when they meet again. During the sensitization process, the antigen-specific IgE that is produced attaches to receptors on mast cells²—completing the sensitization process. When the "sensitized individual" is exposed again to the allergen, the IgE on the mast cells binds the antigen, triggering the mast cells to release histamine and other chemicals from their cytoplasm. These chemicals interact with surrounding tissues, producing inflammation and the typical allergic reaction. IgE antibody production can last for many years, sensitizing the mast cells. Thus, for example, someone who had an allergic reaction to penicillin as a child could still be allergic to the drug as an adult.

Another important term is atopy. Atopy is generally defined as the state of having one or more of a defined group of diseases (allergic rhinoconjunctivitis, allergic asthma, and atopic dermatitis) that are caused by the genetic propensity to produce IgE antibodies to environmental allergens (predominantly from pollens, molds, dust mites, animals, and foods) encountered through inhalation, ingestion, and possibly skin contact. Although everyone produces some IgE, people with a genetic predisposition to allergy (i.e., atopy) produce significant quantities of it.

For epidemiological surveys, atopy is sometimes defined differently, that is, solely by the presence of IgE antibodies to one or more allergens—whether or not clinical disease is present. The population identified by this definition is considerably larger than that defined by disease because a sizable number of asymptomatic persons have such antibodies (this condition is known as asymptomatic atopy).

Thus, an atopic individual is defined differently in different settings and by different researchers as either a person with a particular disease described under atopy or a person with IgE antibody (i.e., positive skin tests). It is obviously important, therefore, that the context and use of the term be well defined in its particular applications and settings. In discussing the published literature in this report, the meaning of the term will correspond to that used in the study being considered.

Scope And Organization Of The Report

In addressing the tasks described earlier in the chapter, the committee used the following guidelines to define the scope of its deliberations. First, it focused on airborne allergens, although contact allergens (e.g., cosmetics) and food allergens are also in the home (the second major focus). A second major focus in the scope was the residential environment; the broad topic of industrial/occupational allergens was deemed to be beyond the scope of this report and was not covered in depth. Some attention is given, however, to allergens that are found in nonindustrial work sites such as office buildings, hospitals, and schools. Similarly, some attention is given to selected nonbiological chemicals that have been shown to be allergenic and that are found in residential or nonindustrial work sites (e.g., trimellitic anhydride and isocyanates). Primarily, however, the report focuses on airborne allergenic agents of biological origin.

In-depth consideration of multiple chemical sensitivity (MCS) reactions was excluded from the scope of this report because of a lack of data showing immune mechanisms. As stated in a recent NRC report (NRC, 1992a, p. 138), "there is insufficient evidence to ascribe an immune etiology to this disorder." For information on the topic of MCS the reader is directed to the recently published proceedings of a workshop and compilation of individually authored papers (NRC, 1992b).

The remaining seven chapters of this volume present the committee's findings, conclusions, and recommendations on several aspects of the problem of indoor allergens. Chapter 2 discusses the magnitude and dimensions of allergen-caused disease, and Chapter 3 presents a detailed discussion of allergen sources and their distribution. Chapter 4 describes the mechanisms of immune function. A discussion of test methods, with particular attention to their applicability, reliability, and interpretation appears in Chapter 5. Chapter 6 discusses the assessment of exposure and risk. The report concludes with an examination in Chapter 7 of engineering control strategies and the role of education in Chapter 8.

In preparing this report, the committee identified and developed a list of research agenda items and 15 priority recommendations. The recommendations focus primarily on the need to improve awareness and education, and as such are also relatively inexpensive and easy to implement compared to the research agenda items. The research agenda focuses on the longer term, more expensive, and more technical aspects of fundamental research and data collection.

Although cost-benefit analyses were beyond the scope of the committee's charge in conducting this study the committee's findings have been separated into recommendations and research agenda items, as described above, based on relative ease of implementation and estimations of associated costs. Policy development and further priority setting, however, should be based on investigations of the probable costs and benefits of the various strategies for prevention and control. The cost analyses should include both direct and indirect costs (i.e., medical costs as well as lost work), and benefits should include a full assessment of the effects on improving the quality of life and on reducing morbidity and mortality.

All of the committee's recommendations and research agenda items are compiled in the Executive Summary. In the body of the report they are presented in their individually relevant chapters and chapter sections.

Footnotes

1

Specific IgE can be assayed in vivo by skin testing or in vitro by such assays as radioallergosorbent test or enzyme-linked immunosorbent assay.

2

Mast cells are present throughout the body but occur at the highest concentrations in areas that are exposed to the outside world (i.e., the skin and linings of the nose, lungs, and gastrointestinal tract).