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Indoor Allergens: Assessing and Controlling Adverse Health Effects (1993)

Chapter: 3 Agents, Sources, Source Controls, and Diseases

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Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

3
Agents, Sources, Source Controls, and Diseases

The indoor environment contains many allergens that can be airborne. They derive from various organic and inorganic sources and may be inhaled as particles, vapors, or gases. Chemically, most are proteins, but low-molecular-weight (LMW) reactive chemicals in industrial settings have also caused allergy. Indoor allergens can be derived from the outside, from the structure or furnishings of a building, or from the humans, animals, and plants within it. Similarly, microbiological aerosols can originate in outside air or in sources within the building.

Biological sources of allergens are surprisingly diverse: they range from domestic animals that shed allergen-containing particles to such sources as food substances dropped on the floor, fungi growing on walls or under carpets, plant materials brought into the house, microorganisms within the air-conditioning system, and a variety of arthropods (in particular, the house dust mite) that may grow within the structure of the house or in the furniture (Table 3-1). Homes, apartment buildings, schools, offices, hospitals, stores, and factories each have unique features that affect the types and quantities of allergens that are present. The major allergenic protein molecules—and in some cases, even the allergenic epitopes—have been identified and characterized in the case of house dust mites, cats, dogs, and certain fungi.

DUST MITE, COCKROACH, AND OTHER ARTHROPODA

House dust (called house dust because most studies have focused on houses—but it also occurs in schools, offices, and other buildings) is made

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

up of fibers from carpets and furniture, grit and sand particles, human skin scales, and food debris. This mixture is combined with allergens from domestic animals, insects, and a variety of microscopic arthropods, bacteria, algae, and fungi growing within the house and other buildings. In addition, air coming into these buildings can carry pollen and molds from outside that then become part of the dust. Because the occupants of a house are inevitably exposed to house dust, any source of foreign protein in the dust is a potential cause of sensitization. Skin testing of patients with asthma or rhinitis initially utilized extracts made from dust collected from their own house (i.e., autologous dust; Kern, 1921); now, however, commercial extracts of house dust are widely used for diagnosis and immunotherapy. In 1980 the U.S. Food and Drug Administration (FDA) estimated that at least 10 million injections of "house dust" extract were administered annually in the United States.

Until 1967, house dust allergenicity was attributed to animal dander, insects, and fungi (Spivacke and Grove, 1925; Vannier and Campbell, 1961). In that year, however, Voorhorst and his colleagues in the Netherlands observed large numbers of mites in dust samples and demonstrated that dust

TABLE 3-1 Biological Sources of Allergens in Houses

Acarids

Fungi*

Dust mites

Dermatophagoides pteronyssinus

Dermatophagoides farinae

Euroglyphus maynei

Blomia tropicalis

Storage mites

Inside

Multiple species including

Penicillium, Aspergillus, Rhizopus, Cladosporium (growing on surfaces or wood)

Spiders

Outside

Entry with incoming air, multiple species

Insects

Pollens

Cockroaches

Blattella germanica (German)

Periplanetta americana (American)

Blatta orientalis (Oriental)

Derived from outside

Other

Crickets, flies, beetles, fleas, moths, midges

Sundry

Horsehair in furniture, kapok

Food dropped by inhabitants

Domestic Animals

Rodents

Cats, dogs, ferrets, skunks, horses, rabbits, pigs

Wild: mice, rats

Pets: mice, gerbils, guinea pigs

* Fungal spores may contain very little allergen and may require germination to produce significant exposure.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

mites of the genus Dermatophagoides were a major source of house dust ''atopen" (Voorhorst et al., 1967). They also developed techniques for growing mites in culture, which made it possible to produce extracts commercially for skin testing. Most patients with positive skin tests to house dust have specific immunoglobulin E (IgE) antibodies to dust mite allergens (Johansson et al., 1971). Sensitization thus can be detected either by skin tests or measurement of serum IgE antibodies.

Dust mite sensitivity was found to be strongly associated with asthma by J. M. Smith and colleagues (1969) and Miyamoto and coworkers (1968). Indeed, in some countries (e.g., Brazil, Australia, New Zealand, Japan, the Netherlands, Denmark, and England), sensitivity to dust mites appears to be so common among young asthmatics that other sources of indoor allergens are relatively unimportant (see Arruda et al., 1991; Clarke and Aldons, 1979; Sears et al., 1989; and Sporik et al., 1990). In dry climates, however, such as in northern Sweden and central Canada, and in high-altitude areas (e.g., Colorado), mite growth is poor and domestic animals predominate as the major source of indoor allergens. Humidity enhances the growth of mites in carpets, mattresses, and other household items (Korsgaard, 1983a). In some inner-city areas, cockroach debris or rodent urine may be the dominant sources of allergens in house dust (Bernton et al., 1972; Hulett and Dockhorn, 1979; Kang et al., 1979; Twarog et al., 1976). Many different protein sources thus contribute to house dust allergenicity (see Table 3-1).

Heavy exposure to house dust can give rise to sneezing in anyone, and it has been suggested that endotoxins or other substances in dust can be directly toxic. The association between exposure to house dust and diseases such as asthma, chronic rhinitis, and atopic dermatitis, however, has been shown only in individuals who have developed hypersensitivity. The symptoms produced by house dust allergens in sensitized (i.e., allergic) individuals include asthma, perennial rhinitis, and atopic dermatitis. For each disease the symptoms range from severe to very mild; moreover, some individuals, despite their having IgE antibodies, suffer no discernible symptoms. In some cases, the correlation between exposure to a specific indoor allergen and symptoms is obvious; certainly, many individuals who are allergic to cats experience the rapid onset of symptoms on exposure to cat allergens. In contrast, most symptoms related to exposure to house dust are nonspecific and not temporally related to exposure. Thus, in general, it is not possible to distinguish the role of different specific indoor allergen sources solely on the basis of an individual's medical history. Indeed, many patients with asthma are not aware of any other symptoms that would be recognized as allergic. Because their histories are not specific and in many cases exposure to house dust allergens is perennial, understanding the relationship between exposure and disease has required both measurement of exposure and documentation of sensitization.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

Dust Mites as a Source of Indoor Allergens

Many different species of dust mites have been found in house dust, but the predominant ones in most parts of the world belong to the family Pyroglyphidae: Dermatophagoides pteronyssinus, D. farinae, and Euroglyphus maynei. In Florida, Central America, and Brazil (see Hughes, 1976; Van Bronswijk, 1981; Voorhorst et al., 1967; and Wharton, 1976), several species of storage mites and Blomia tropicalis are important sources of allergens. It is probably best to reserve the term dust mites for pyroglyphid mites and to use the term domestic mites to cover any species of mites that are found in houses (Platts-Mills and de Weck, 1989).

Mites are eight-legged and sightless, and they live on skin scales and other debris. They absorb water through a hygroscopic substance extruded from their leg joints and are thus entirely dependent on ambient humidity. In addition, they have a narrow optimal growth temperature range of between 65° and 80° F. As humidity falls, mites will withdraw from surfaces, but even in very dry conditions it may take months for mites in sofas, carpets, or mattresses to die or for allergen levels to fall (Arlian et al., 1982; Platts-Mills et al., 1987).

Mites excrete partially digested food and digestive enzymes as a fecal particle surrounded by a peritrophic membrane (Tovey et al., 1981a). Large quantities of fecal particles are found in mite cultures, and they are a major form of the mite allergen in house dust. The peritrophic membrane probably keeps the particles intact; however, chitin is not waterproof; consequently, allergens elute from fecal particles quite rapidly (Tovey et al., 1981b). Mite fecal pellets are similar to pollen grains in size (10–35 μm in diameter), in the quantity of allergen they carry (i.e., ~0.2 ng), and in their rapid release of proteins.

Dust mites are approximately 0.3 mm in length. Moving mites can be seen by light microscopy, but the great majority of mites in dust are dead and are therefore difficult to identify without separating them from other dust particles (Arlian et al., 1982; Wharton, 1976).

DUST MITE ALLERGENS

The first mite allergen to be purified, D. pteronyssinus allergen I (or Der p I; Chapman and Platts-Mills, 1980), is a 24,000-MW glycoprotein that has been sequenced and cloned; it has sequence homology with papain and functional enzymatic activity (Chua et al., 1988). In 1984, high-affinity monoclonal antibodies to Der p I were reported, opening the door to the development of assay systems that would improve the sensitivity and specificity of measurement (Chapman et al., 1984). A second major allergen (MW 15,000) was first identified in 1985 and has now been fully defined,

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

TABLE 3-2 Defined Indoor Allergens

Allergen

 

Molecular Weight (kDa)

Sequence

Function

Monoclonal Antibodiesa

Assay

House Dust Mite

Group I

Der p I

Der f I

Eur m I

25

25

25

cDNA

cDNA Nucleotide

Cysteine protease

++

++

+

ELISA

ELISA

Group II

Der p II

Der f II

14

14

cDNA

N-terminal

Unknown

++

++

ELISA

ELISA

Group III

Der p III

Der f III

29

29

N-terminal N-terminal

Serine proteases

-

++

RIAb

RIAb

Cat—Felis domesticus

Fel d I

 

35

cDNA

Unknown

++

ELISA

Albumin

 

68

±

RIAb

Dog—Canis familiaris

Can f I

 

27

Unknown

++

ELISAb

Cockroach

Blattella germanica

Bla g I

 

20–25

Unknown

+

ELISAb

Bla g II

 

36

N-terminal

Unknown

++

ELISA

Periplanetta americana

Per a I

 

20–25

Unknown

-

Rodent

Mus musculus

 

19

Protein sequence

alpha-2U-

+

ELISAb

Rattus norvegicus

 

19

cDNA

globulin

+

RIAb

NOTE: kDa, kilodaltons; cDNA, complementary DNA; ELISA, enzyme-linked immunosorbent assay; and RIA, radioimmunoassay.

a "++" Indicates that more than one epitope has been defined.

b Assays in research use.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

cloned, and named Der p II (Chua et al., 1990; Heymann et al., 1989; Lind, 1985).

There are homologous cross-reacting allergens produced by D. farinae (Dandeau et al., 1982; Haida et al., 1985; Heymann et al., 1986; Yuuki et al., 1990); see Table 3-2 for current groupings of allergens. The group II mite allergens show greater than 90 percent sequence homology and are very strongly cross-reacting. They are also relatively stable in relation to heat and pH, but they have no enzymatic activity and their function in the mites is not known. Researchers assume that the group I proteins are digestive enzymes because they are found in glands surrounding the gut and are present in high concentrations in fecal pellets (Tovey, 1982). Currently, simple, sensitive monoclonal antibody-based assays are widely used for quantitating group I allergens (Horn and Lind, 1987; Luczynska et al., 1989). Assays for group II (and also group III) are in development.

COMMERCIALLY AVAILABLE ALLERGEN EXTRACTS

House dust extracts for use either in skin testing or for in vitro assays of IgE antibodies are made from vacuum cleaner bags collected outside the pollen seasons from houses without animals. Other sources for dust (e.g., schools, offices) are not commercially available. The quantity of dust mite allergen in commercial house dust extracts varies from 0.05 to 2.0 µg of Der p I/ml.1 Commercial dust mite extracts can be made from either whole mite culture or from isolated mite bodies. At present, the FDA requires that mite extracts be made from isolated mites. Mites are photophobic; they can be separated by using a light source to "drive" them out of the culture material. Horse dander or human shavings contained in the same media that are used for growing mites may expose recipients of the extract to these proteins. Extracts made from bodies of D. pteronyssinus typically contain 30 µg of Der p I and 20 µg of Der p II.

Insects as a Source of Indoor Allergens

Many insects have been identified as sources of inhalant allergens in case reports or small outbreaks; these include moths, crickets, locusts, beetles, nimitti flies, lake flies, and houseflies (Ito et al., 1986; Kay et al., 1978; Kino et al., 1987; Koshte et al., 1989). Yet the only insect that has been repeatedly recognized as a common source of indoor allergens is the cockroach (Bernton et al., 1972; Kang et al., 1991; Pollart et al., 1989, 1991).

1  

Cat allergen (Fel d I; see later discussion) in house dust extract varies from less than 0.01 to 2 µg of Fel d I/ml; in general, there is no detectable cockroach allergen and little in the way of fungal allergens.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

Sources of insect allergens are diverse and may include skin scales from moths and hemoglobin from lake flies or river flies (Mazur et al., 1987). For domestic cockroaches, fecal material and saliva may contribute to the allergen reservoir, and large quantities of allergen can be washed off the outside of the roach.

DOMESTIC COCKROACHES

The German cockroach Blattella germanica is very common in crowded cities, in the southern United States, and in tropical countries of the world. As early as 1964, Bernton and his colleagues recognized that many patients with asthma who sought treatment at indigent care clinics had skin tests positive for cockroach (Bernton et al., 1964). Positive skin tests have been reported in several urban clinic populations including Boston, New York, Kansas City, Detroit, Chicago, and Washington, D.C. (Call et al., 1992; Hulett and Dockhorn, 1979; Kang et al., 1979). Subsequently, Kang and her colleagues reported positive bronchial provocation and good responses to immunotherapy with cockroach extract (Kang et al., 1979, 1991). In most suburban clinics, few or no patients have positive skin tests to cockroach extracts.

A case-control study of emergency room patients confirmed the significant association of cockroach sensitivity with asthma (Pollart et al., 1989). An unpublished study on cockroach allergen levels in houses in different parts of a town showed that the correlation between cockroach sensitization and asthma was restricted to that part of the town in which cockroach allergen was present in the houses (Gelber et al., in press). Researchers have identified two cockroach allergens, Bla g I (MW ∼ 30 kilodaltons [kDa]) and Bla g II (MW 36 kDa; see Table 3-2), and have developed monoclonal antibodies and assays specific for these allergens (Pollart et al., 1991). Details regarding the sources of these allergens, their cross-reactivity with those derived from Periplaneta americana, and the nature of the particles that become airborne are not well established (Swanson et al., 1985). Cockroach allergen can be found throughout the house, but the highest levels are generally found in kitchens.

Further work is needed to define the nature of insect allergens, the nature of the particles that become airborne, and their role as indoor allergens.

Measuring Exposure to House Dust Allergens

The major outdoor allergens are components of well-defined particles (i.e., pollen grains or fungal spores) that are disseminated by wind and that can be identified microscopically. In contrast, indoor allergens come from a variety of particles that are not naturally airborne and that cannot be identified

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

microscopically. Thus, evaluation of airborne indoor allergens depends on sensitive immunoassays and requires a method for collecting particles. This can be done either with a filter or with a multistage impactor (Solomon and Matthews, 1988; see also the discussion in Chapter 6).

In 1981, Tovey and colleagues (1981b) showed that fecal particles were a major form in which the allergen Der p I becomes airborne and that very little or no (i.e., <1 ng per cubic meter of air) mite airborne allergen was detected in undisturbed rooms (de Blay et al., 1991b; Platts-Mills et al., 1986; Swanson et al., 1989; Yasueda et al., 1989). Furthermore, airborne mite allergen falls rapidly after disturbance. These results support the view that mite allergen is predominantly airborne on particles that are larger than or equal to 10 µm in diameter. The levels found in the air during disturbance depend critically on the form of the disturbance and vary from 5 to 200 ng of Der p I/m3. Assuming that airborne Der p I is carried predominantly on fecal particles, it is possible to estimate the number of particles that become airborne and to an estimate of the number of particles that could enter the lung, since the mean allergen content of the particles is known. Chapter 6 discusses methods of assessing exposure and risk.

Thresholds: The Relationship Between Exposure, Sensitization, and Disease

Voorhorst and his colleagues (1967) found that dust from the houses of symptomatic allergic patients generally had more than 500 mites/g of dust. During the 1980s, further data accumulated demonstrating a dose-response relationship between exposure to mite allergens (or mites) and both sensitization and asthma (Bernton et al., 1972; Kang et al., 1991; Pollart et al., 1989, 1991). From these results, it also appeared that there were levels of exposure (or thresholds) below which the risk of sensitization or asthma was much less. This finding notwithstanding, the results suggest that in areas in which all houses contain high levels of mite allergen, sensitivity to mites is a major risk factor, not only for wheezing but for hospitalization of children with asthma.

Fewer data are available on the levels of exposure associated with sensitization or disease for allergens other than dust mite. However, there are data about the levels of cat allergen present in house dust. Dust from all houses with a cat contains at least 8 µg of Fel d I/g (the levels range as high as 1.5 mg of Fel d I/g). In houses without a cat, levels vary from less than 0.2 µg/g to 80 µg/g; it is thought that this allergen is transported into the houses on the clothes of inhabitants. Levels of cat allergen of less than 1 µg of Fel d I/g of dust appear not to give rise to sensitization or disease.

For cockroach allergen the rarity of sensitization among suburban patients suggests that the levels found in suburban houses (i.e., less than 1

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

unit of Bla g II/g of dust) are insufficient to sensitize individuals. By contrast, the levels found in inner-city houses (i.e., more than 10 units of Bla g II/g of dust) are clearly sufficient to induce sensitization and appear to be associated with asthma (Gelber et al., 1992; Pollart et al., 1991). There is a general misconception that levels of allergen will be (or should be) higher in the houses of patients with allergic disease than in the homes of nonallergic individuals living in the same area. It is equally likely, however, that levels of exposure are similar for individuals with and without allergic disease in a given region and that differences in individual responses are a function of individual susceptibility. It is important to understand the actual findings. (Chapter 2 presents a brief discussion of exposure to allergens as a risk factor for sensitization.)

Because the common allergens are thought to cause or exacerbate asthma by the inhaled route, measurement of inhaled allergen might seem to be the best method for determining exposure (Price et al., 1990; Swanson et al., 1985; Tovey et al., 1981b). There are several reasons, however, why current threshold levels for indoor allergen exposure are based on measurements of allergen in dust collected from carpets, mattresses, sofas, and other such items. First, the quantities that become airborne (commonly, 5–50 ng/cubic meter of air) are too small to measure in epidemiological surveys. Second, the relevance of airborne levels depends on particle size, which is technically difficult to determine. Third, the quantities of these allergens that become airborne in a house depend critically on domestic disturbance. Thus, at present, overwhelming practical reasons exist for basing threshold levels on the measurement of a representative allergen in "reservoir" dust. An index of exposure using these measurements of reservoir dust assumes that they are positively correlated with inhaled exposure. Chapter 6 addresses issues related to assessing exposure and risk and presents a risk assessment for sensitization related to dust mite exposure as an example.

Reducing Exposure to Dust Mites

Reducing exposure to so-called "trigger factors," i.e., factors that trigger an allergic response, has been a standard part of the treatment of allergic disease for many years, and for many years it was normal practice to recommend avoidance measures to patients who had skin tests that were positive for house dust. This practice was strongly supported by the experiments of Storm van Leeuwen (Storm van Leeuwen et al., 1927) and Rost (1932), who demonstrated benefits to patients with asthma and atopic dermatitis, respectively, from living in a "climate chamber."

Until recently, there has been only limited clinical use of avoidance measures in treating allergic diseases associated with dust mite sensitivity, in part because the control measures that were originally proposed were not

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

effective in controlling mite allergens (Burr et al., 1980; Korsgaard, 1982). In addition, several general medical tests have suggested that avoidance measures should be considered in patients who have a certain typical history. As discussed earlier, however, many allergic patients are not aware of an association between dust exposure and their symptoms (particularly the association between dust and asthma or atopic dermatitis). Today, there is considerable evidence that full avoidance (i.e., 95 percent reduction of mite allergen) can be achieved and can reduce both symptoms and bronchial reactivity. For example, moving patients to a hospital room or sanatorium has been consistently effective (Dorward et al., 1988; Ehnert et al., 1991; Platts-Mills et al., 1982; Warner and Boner, 1988); these units generally have very low levels of mites (i.e., less than 20 mites/g of dust) and mite allergen (less than 0.4 µg of Der p I/g). Recently, four controlled studies of the effects of avoidance measures conducted in the homes of patients have found significant improvement in both asthma symptoms and bronchial hyperreactivity (Dorward et al., 1988; Ehnert et al., 1991; Murray and Ferguson, 1983; Walshaw and Evans, 1986).

Avoidance measures can be divided into those for use in the bedroom and those for use in the rest of the house (Box 3-1). In the bedroom, the following have been shown to be effective: covering mattresses and pillows with impermeable covers; washing bedding at 130°F once per week

BOX 3-1 Avoidance Measures for Mite Allergen

A. Bedrooms

▪ Cover mattresses and pillows with impermeable covers

▪ Wash bedding regularly at 130° F

▪ Remove carpets, stuffed animals, and clutter from bedrooms

▪ Vacuum clean weekly (wearing a mask)*

B. Rest of the House

▪ Minimize carpet and upholstered furniture; do not use either in basements

▪ Reduce humidity below 45 percent relative humidity or 6 g/kg

▪ Treat carpets with benzyl benzoate or tannic acid

* There is a temporary increase in potential exposure to allergens associated with the vacuuming process. The net potential for exposure should be reduced by vacuuming, however, and is considerably less than the cumulative effects of not vacuuming. Wearing a mask while vacuuming should help reduce exposure while vacuuming.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

(Miller et al., 1992; Owen et al., 1990); and removing carpets (although Rose and colleagues [1992] have shown that the use of acaricides or tannic acid treatment can also reduce mite allergen). Other control strategies for the bedroom are designed to eliminate sites in which mites can grow and to reduce dust collectors to make cleaning easier. The recent report from NHLBI (1991) is an excellent source of information regarding allergen avoidance. (See also Box 8-1 in Chapter 8.)

Three different approaches are possible for control of mite growth in the rest of the house:

  1. Design the house with polished floors and wooden, vinyl, or leather furniture to eliminate sites where mites can grow.

  2. Maintain indoor relative humidity at below 50 percent (absolute humidity below 6 g/kg). Korsgaard (1983a) has shown that in some areas of the world this can be accomplished by simply increasing ventilation. In other areas, it would be necessary to use air conditioning during the humid months.

  3. Use acaricides to treat carpets or furniture, including pyrethroids (D. Charpin et al., 1990b), natamycin (an antifungal), pirimiphos methyl (Mitchell et al., 1985), and benzyl benzoate (Bischoff et al., 1990). In each case the chemicals are effective in killing the mites, although methods for applying the agents may present problems (de Saint-Georges-Gridelet et al., 1988; Platts-Mills et al., 1992).

Several different chemical treatments (as in approach 3 above) have been shown to achieve 90 percent reduction in allergen levels for a month or more. In addition, 1 or 3 percent solutions of tannic acid have been recommended for denaturing mite allergens (Green et al., 1989). Again, this method achieves a 90 percent reduction of mite allergen, but because tannic acid does not kill mites, the effect is temporary (i.e., approximately 6 weeks to 2 months). Carpets fitted onto unventilated floors—for example, in basements or on the ground floor of a house built on a concrete slab—are particularly difficult to treat. Under these circumstances water can accumulate either because of condensation onto the cold surface of the concrete or because of leakage (either domestic or rainwater from outside). In either case, once the carpet is wet, it will stay wet and become an excellent environment for the growth of fungi and mites.

Avoidance Measures for Other Allergens

For most other allergens, only case reports are available as guidance regarding the clinical effectiveness of avoidance measures. Removal is certainly the logical approach to management for most domestic animals or rodents (Wood et al., 1989); if sensitivity to insects (cockroach or others) is

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

demonstrated, eradication, or moving, is the logical approach in such circumstances. At present, there is little evidence about the effectiveness of eradication measures in reducing insect allergen levels. The recent development of assays for cockroach allergens, however, means that it is now possible to evaluate avoidance measures.

The situation is much more confusing for indoor fungi. No simple assays exist for indoor fungal allergens, and the relationship between spore counts and allergen exposure is not clear. Many spores are not viable, and some allergens may only be expressed once the spore germinates (Arruda et al., 1990; Lehrer et al., 1986). It will be difficult to evaluate proposed procedures to reduce exposure to fungal allergens until accurate assays are available. Even then, evaluation of exposure will not be as simple as for mite or cat allergens. (See Chapter 6 for a discussion of monitoring for indoor fungal allergens.) It is often difficult to tell whether fungal spores come from inside or outside the house, because many species can grow in either environment. Nonetheless, it is reasonable to recommend controlling humidity, removing sites for fungal growth, avoiding basements, and cleaning surfaces with fungicides.

Grass pollen can become a major component of house dust and has been found at high levels in dust from the houses of grass pollen-sensitive patients who present for treatment with asthma (Pollart et al., 1988). Filtering incoming air or keeping doors and windows closed can help control the entry of pollens, although other problems may be created (see Chapter 7).

Conclusions and Recommendations

With most Americans spending the great majority of their time indoors—and most of that in their own houses—it is not surprising that the bulk of inhaled foreign protein is associated with indoor air. The evidence shows that a large proportion of asthmatics are allergic to indoor allergens and that several changes in the way we live indoors may have affected the levels of these allergens. These changes include increased mean temperatures, reduced ventilation (with consequent increased humidity), fitted carpets, and cool-wash detergents which have led to water temperatures for washing bedding that do not kill mites.

Once identified, reducing exposure to allergenic "trigger factors" has been a standard part of the treatment of allergic disease for many years. Since approximately half of existing cases of asthma have been attributed to allergenic factors, it is reasonable to expect that asthmatics who require more than occasional treatment might also have allergies that induce their asthma.

Recommendation: Provide appropriate allergy evaluation of asthmatics who require more than occasional treatment. Where allergic

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

factors are present, ensure that these patients are given specific, practical information about how to reduce their exposure to arthropod and other allergens.

Although most studies investigate asthma (because it is common and can be measured objectively), sensitivity to indoor allergens is also very common among patients with other allergic conditions such as chronic rhinitis and atopic dermatitis. Because the important cause of inflammation that is common for all of these diseases is exposure to allergens, avoidance of the exposure should be the primary anti-inflammatory treatment. Developing realistic avoidance protocols for routine use is a challenge that must not take second place to pharmaceutical treatment.

Research Agenda Item: Conduct detailed studies of physical factors, such as sources and emission rates, that influence the levels of exposure to arthropod and other indoor allergens. These studies should include the effects of (a) protocols for reducing exposure and (b) devices advertised as reducing indoor allergen concentrations. More specifically, test the effectiveness of allergen avoidance protocols on the management of allergic asthma and other allergic diseases using protocols that have been demonstrated to reduce exposure by 90 percent or more. Such protocols should be tested under field conditions and should encompass the socioeconomic, cultural, ethnic, and geographic diversity of these problems in the United States.

The more important question now is the effectiveness of avoidance measures for reducing the development of disease (i.e., sensitization). Specific measures include the use of polished wooden floors and no upholstered furniture in bedrooms and possibly in schoolrooms, keeping pillows and mattresses covered, and using bedding that can be washed regularly in hot water. Other measures, which require further evaluation, include air filtration, chemical treatment of carpets, and dehumidification.

Research Agenda Item: Develop allergen-free products to help reduce the incidence of allergic disease in the general public. The initial objective of this initiative, which should be carried out by the industrial/business sector, would be to provide an aesthetically appealing bedroom with reduced allergen exposure for children under the age of five.

There is considerable evidence that allergen avoidance is an effective means of reducing allergy symptoms. Practical measures to control exposure to mite and other allergens in the house can reduce both the symptoms

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
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and the underlying bronchial reactivity. For example, controlled studies of the effects of avoidance measures conducted in the homes of patients who were allergic to dust mites have shown significant improvement in both asthma and bronchial reactivity. The effects of avoidance measures on an individual's quality of life, however, remain to be determined.

Research Agenda Item: Conduct longitudinal studies to determine whether long-term allergen avoidance has a positive effect on quality of life.

MAMMALS AND BIRDS

Allergic reactions to mammals and birds are frequent and have been recognized as such for many years. An estimated 100 million domestic animals reside in the United States, the most common being cats and dogs (Knysak, 1989), and from one-third to one-half of homes in the United States have a domestic pet. Although a large number of individuals in the population experience allergic reactions to various animals, the exact prevalence of this common problem has not been determined. Skin test reactions to animal extracts are frequent, but the relationship between sensitization as demonstrated by a positive skin test and the frequency of clinical symptoms is unknown. Nonetheless, exposure to domestic pets, particularly cats and dogs, accounts for most of the allergic diseases caused by mammals.

In addition to exposures to animals kept as pets, individuals may be exposed to mammal and bird allergens in occupational settings. Bird allergens can cause not only allergic rhinitis and asthma but also hypersensitivity pneumonitis. Exposure to rodents among laboratory and animal care facility workers often results in sensitization and allergic symptoms. Farmers, veterinarians, animal health care workers, and zookeepers are also at risk. The prevalence of allergic diseases as a result of these occupational exposures is largely unknown.

Animals and birds are not only a source of allergens but may also serve as vectors, introducing outdoor allergens indoors. For example, pets may carry inhalant allergens such as pollens and fungal spores on their coats.

Cats

Cats are among the most common household pets in urban areas. A survey of 16,204 individuals ages 6 to 74 in the United States showed that 2.3 percent had positive skin prick tests to cat dander extracts (Gergen et al., 1987). Thus, extrapolating from these data, from 6 to 10 million Americans are potentially allergic to cats (Luczynska et al., 1990; Ohman and Sundin, 1987). Approximately one-third of the 2.3 percent of people with positive cat dander reactions have cats in their homes.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

Cat allergy is especially apt to cause asthma, and the presence of IgE antibody to cat allergen is a significant risk factor for acute attacks of asthma in patients who seek treatment in emergency rooms (Luczynska et al., 1990). Individual sensitivity to these animals may be exquisite, so that even brief exposure to cats can precipitate severe asthma episodes.

The most important cat allergens are Fel d I and cat albumin. Fel d I is the major cat allergen (Ohman et al., 1973), and it is distributed throughout all breeds of cats. Approximately 80 percent or more of cat-allergic patients have IgE antibody to Fel d I (Duffort et al., 1991). In recent years, the complete amino acid sequence of Fel d I has been determined, the genes encoding the protein have been identified, and several allergenic epitopes have been mapped (Morgenstern et al., 1991).

Commercially available cat extract reagents for skin testing have variable quantities of Fel d I and serum albumin. They are prepared from dander (hair with epithelial scrapings) or whole pelts. The concentration of Fel d I is 10 times greater at the root than at the tip of the hair (C. Charpin et al., 1991). It is produced primarily in the sebaceous gland and to a lesser extent in the basal squamous epithelial cells of the skin. It appears to be stored mainly on the surface of the epidermis and the fur. Because saliva also contains Fel d I, licking and grooming may spread the allergen on the hair. The mean daily production of Fel d I from cats is approximately 3-7 µg (Dabrowski et al., 1990); however, there is day-to-day and diurnal variability in Fel d I shedding from individual cats. Washing the cat provides only temporary relief: the original concentration of Fel d I reappears within 1 month.

Cat-allergic patients develop symptoms rapidly upon entering a house with a cat, which suggests that the allergen is constantly airborne. Indoor air sampling measurements in fact have confirmed this hypothesis. In addition, studies have determined the quantity of Fel d I that will produce a 20 percent decrease in FEV1 (forced expiratory volume at 1 second) in cat-sensitive patients who undergo bronchoprovocation testing. A room containing two live cats has a concentration of Fel d I in this range (Van Metre et al., 1986); however, many cat-allergic individuals will be symptomatic in the presence of even one cat. In a 1988 study by Wood and colleagues, this allergen was found in virtually 100 percent of homes sampled for its presence in settled household dust (Wood et al., 1988). The median level of Fel d I in the dust samples was 90 ng per gram of dust (range: 2–130,000 ng Fed d I/g of dust).

Although there are significant differences in allergen content in homes with and without pets, many homes that normally are without a cat nonetheless contain surprisingly high levels of Fel d I in dust (Wood et al., 1988). These levels vary from less than 2 to 7,500 ng/g of Fel d I/g; it is thought that the allergen is transported into houses on the clothes of inhabitants.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

Levels of cat allergen as low as 2 µg Fel d I/g of dust, commonly observed in houses without cats, may be a risk factor for sensitization to Fel d I (Wood et al., 1988).

The size range of the particles that contain cat allergen is broad. Some are of fairly large aerodynamic size (greater than 10 µm in diameter); in contrast, many particles that carry Fel d I are less than 2.5 µm in diameter and are therefore respirable and capable of penetrating deeply into the lung (Findlay et al., 1983; Luczynska et al., 1990). Luczynska and coworkers (1990) estimated that 10–60 percent of airborne Fel d I in domestic houses is associated with small, respirable particles of less than 2.5 µm in diameter. Modest levels of disturbance of dust such as that created by an electric fan can dramatically increase the airborne concentration of cat allergens. During vigorous vacuum cleaning of rooms with a single cat, levels of up to 212 ng of Fel d I/m3 have been observed (de Blay et al., 1991b). Swanson and colleagues (1985) found that bedspreads on which cats slept contained 2,000–4,000 µg of Fel d I. Therefore, beds, stuffed furniture on which cats sleep, and carpets constitute continuing reservoirs for the contamination of the environment. The adherent properties of Fel d I may be an important aspect of their contaminating capability; thus, walls and other surfaces can also contribute to the reservoir of cat allergen (Wood et al., 1992). Finally, because voided urine from male cats contains Fel d I activity, litter boxes are a source of environmental exposure.

CONTROL MEASURES

The following are several animal allergen avoidance measures for the home:

  1. Remove the animal from the home. Once a cat is removed from the environment, it takes at least 20 weeks from the time of removal for the levels of Fel d I in settled dust to fall to that found in homes without cats (Wood et al., 1989).

  2. Where it is not possible to remove the animal, confine it to certain restricted areas. Animals should be kept out of the bedroom. Washing the animal can also be beneficial.

  3. Steam cleaning of carpets has no benefit over regular vacuuming. However, aggressive measures, including carpet removal, can substantially reduce cat allergen content in settled dust more rapidly.

As an alternative to removing the cat from the environment, control measures with the cat in situ can be employed (de Blay et al., 1991a). For example, in an uncarpeted room, a combination of vacuum cleaning, air filtration with a high-efficiency room air cleaner, and washing of the cat can reduce the airborne allergen exposure level by 90 percent or greater. It

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
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should be noted, however, that the effects of these measures on allergic symptoms have not been evaluated.

Dogs

Dogs are among the most abundant of household pets. The prevalence of clinically significant allergic diseases caused by dogs appears to be less than that for cats; nevertheless, dog sensitivity can be a major cause of allergic symptoms, including asthma, in some persons. In a survey of U.S. citizens ages 6 to 74 who were unselected for allergy, 2.3 percent of the 16,204 individuals surveyed exhibited positive skin prick tests to dog extracts (Gergen et al., 1987). This frequency of sensitization is similar to that reported for cats, although other investigators have found a higher prevalence of cat sensitivity in their study populations (Sears et al., 1989). Differences in reported sensitivity may be due in part to less well-characterized and standardized allergic extracts used in skin testing for the presence of dog sensitivity. Moreover, in many parts of the country, dogs are kept out of doors; those that are kept indoors may be washed at frequent intervals.

The major dog allergens are Can f I and dog serum albumin; Can f I has been purified (de Groot et al., 1991; Schou et al., 1991b). Can f I can be obtained from hair collected by brushing dogs and from dog saliva; very little is available from urine and feces. The allergen has been found in varying degrees among nine dog breeds and among individual dogs (de Groot et al., 1991). In approximately 15 percent of dog-sensitive patients, there are significant differences among the skin test responses to different dog breeds, indicating breed-specific allergens (Lindgren et al., 1988). However, there is no evidence to suggest that there are ''nonallergenic" breeds.

In a study by Lind and others (1987), 63 percent of indoor air samples from 43 homes in the Baltimore, Maryland area indicated the presence of dog allergens. Dog allergen has also been found in buildings, such as schools, in which dogs are not kept, which suggests that the allergen can be transported on clothing. Dust samples from 103 households across the United States contained a range of from 10 to 10,000 µg of Can f I/g of dust in those homes with a dog and from less than 0.3 to 23 µg of Can f I/g of dust in homes without dogs (Schou et al., 1991a). Can f I is a relatively stable molecule and may persist in dust for extended periods of time. Effective control measures to reduce exposure to dog allergens have not been investigated.

Rodents

Rodent allergens are a significant occupational cause of allergic rhinitis and asthma among workers exposed to laboratory animals. In addition,

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
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certain rodents, such as hamsters, gerbils, and guinea pigs, may contribute to household allergen levels because they have become increasingly popular household pets. At least 35,000 individuals are exposed to rodent allergens because they work in scientific investigations or breed and care for rodents. In the United States, approximately 11–15 percent of laboratory workers are allergic to rodents (Slovak, 1987); many who become allergic are forced to seek alternative employment. Fifty-five percent of them are sensitive to two or more species; the majority (37–75 percent) are sensitive to rats, mice, and rabbits, whereas 24–33 percent are sensitive to guinea pigs. Patients with atopy may develop symptoms more rapidly than those without it. Moreover, patients with a family history of allergy and positive skin tests to other environmental allergens may be at risk for the development of asthma (Sjostedt and Willers, 1989). Hypersensitivity pneumonitis resulting from exposure to rodent proteins is rare.

Two major allergens have been found in rat urine, Rat n I (α-2-euglobulin) and prealbumin. Skin testing for both allergens shows an equal degree of frequency in sensitized patients. Euglobulin is a major component of pubertal male rat urine but is barely detectable in the urine of females (Knysak, 1989).

In rat rooms and during disturbance of rat litter, a large portion of the urinary allergen is airborne; particles are approximately 7 μm in diameter. Air sampling measurements during certain laboratory activities have indicated that feeding or cleaning of cages results in levels of 20 ng of Rat n I/m3; injections or handling of the animals results in levels of 13 ng/m3. Lower levels (3.1 ng/m3) are found during surgery or during sacrifice of the animal (Eggleston et al., 1989).

The male rat is capable of releasing high levels (up to 20 ng/min) of airborne urinary allergens (Swanson et al., 1990). Personal sampling devices on 12 sensitized subjects working with rats revealed allergen concentrations that ranged from less than 1.5 to 310 ng/m3; even higher levels were noted during cage cleaning. These subjects experienced nasal symptoms with exposure, and researchers obtained direct evidence for an allergic reaction by finding histamine in their nasal lavage fluids. Five of the 12 subjects also had lower respiratory tract responses with decreases in pulmonary function (Eggleston et al., 1990).

Two major allergens, Mus m I and Ag 3, have been identified as related to mice. Mus m I is a urinary prealbumin; it has been molecularly cloned, and its amino acid sequence was found to share 80 percent homology with Rat n I. Research has noted biochemical differences between urinary proteins from different inbred strains of mice, which may explain why some mouse laboratory workers become sensitized to specific strains. The Ag 3 allergen is found primarily in hair follicles and the stratum corneum, implying that it is found predominantly on the hair and skin of mice. Mus m I has

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

been identified in dust from the walls and air-conditioning filters of rooms in which mice are housed. Airborne allergen concentrations ranging from 1.8 to 825 ng/m3 of air have been detected; concentrations vary with both the number of mice and the degree of work activity in the room (Twiggs et al., 1982). Mouse urinary allergenic protein has been found in air samplings from inner-city dwellings (Swanson et al., 1985), but the effects of this exposure on the health of inhabitants are not known.

Guinea pig allergens are present primarily in the urine. At least two major allergenic components have been identified. Air sampling studies may show varying concentrations of the urinary protein in the air, depending on the number of animals. Most allergenic activity in the air is associated with particles in two size ranges: those less than 0.8 μm in diameter and those greater than 5 μm (Swanson et al., 1984).

Occasionally, hamsters and gerbils may account for allergic symptoms. Positive skin tests to hamster dander extracts have been reported among laboratory workers, and gerbil extracts prepared from serum and hair/epithelium have produced positive skin tests in sensitized patients. Allergens from these rodents have not been characterized further. Even less fully characterized are rabbit allergens. The major known allergen is obtained from fur extracts and saliva (Warner and Longbottom, 1991).

CONTROL MEASURES

Control measures for laboratory workers include the use of protective clothing and appropriate respiratory protection. Source control measures involve placing filter caps on animal cages, increasing the frequency of air exchange (including 100 percent exhaust of the animal room with no recirculation), locating exhaust ducts at floor level, increasing the frequency of removal of animal waste and bedding, and using high-efficiency filters to provide filtered laminar flow air. Because of the high rate of production of rat urinary protein allergens, very high air exchange rates are required to substantially reduce allergen levels in rooms that house a large number of animals (Swanson et al., 1990).

Farm Animals

The prevalence of sensitivity to cattle is unknown; however, two major allergens from cattle with molecular weights of 20 and 22 kDa have been identified (Ylönen et al., 1992). These allergens are derived from cow hair and dander, but the 20-kDa allergen is also found in urine. Immunochemical assays for quantitating cattle allergens in cow-shed air samples have shown concentrations ranging from 137 ng/m3 to 19.8 μg/m3 (Virtanen et

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

al., 1986). In addition to cattle epithelium, other potential allergens in barns include fungi and mites (Campbell et al., 1989).

From 8 to 19 percent of allergic patients react to horse allergens on intracutaneous testing (Solomon and Matthews, 1988); however, clinical sensitivity is not as frequent. Horse-sensitive patients may react to extracts of mule and donkey allergens as well. Allergy to horses is less common now than it was in the early years of this century, but significant exposure still occurs among agricultural workers, racetrack and stable attendants, and avocational riders. Allergens have been identified in horsehair and horse dandruff (Lowenstein et al., 1976).

Many workers in swine confinement areas experience respiratory symptoms that are not mediated by IgE. It is believed that most of these symptoms are due to the irritant effects of nitrogenous waste products from the animals or to endotoxins from gram-negative organisms in feces. Nevertheless, occupational asthma caused by allergy to pig urine has been reported (Matson et al., 1983).

Wild Animals

Occasionally, veterinarians and zookeepers exposed to wild animals may develop allergies. For example, large cats (lions and tigers) have the Fel d I allergen; in addition, allergy to deer and elk has been reported. Allergenic sources from deer include hair, dander, saliva, serum, and urine (Gillespie et al., 1985). Asthma triggered by exposure to monkeys has been reported in primate centers. The allergenic sources of that condition appear to be hair and dander, and possibly saliva (Petry et al., 1985).

Birds

Positive skin test reactions to feather extracts but not fresh feathers are common, a finding that may be explained by contamination from dust mites. The most common sources of exposure to feathers are pillows, comforters, quilts, down-filled clothing, and feather beds. About 20 percent of budgerigar and canary fanciers with allergic rhinitis and asthma have IgE antibodies to allergens found in extracts of the feathers of these birds (Solomon and Matthews, 1988).

Another avian source of allergens is chickens. About 10 percent of workers in egg-processing plants develop asthma (A. B. Smith et al., 1990). The allergens are aerosolized in liquid form or occasionally as dried airborne egg protein.

Avian proteins may cause hypersensitivity pneumonitis (also called extrinsic allergic alveolitis). Several specific terms are in use, including bird fancier's, breeder's, or handler's lung or pneumonitis. Parakeets, budgerigars,

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
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pigeons, turkeys, and chickens have been implicated as causes of these conditions. An estimated 5–20 percent of the 250,000 pigeon breeders in the United States may develop pigeon breeder's lung (Christensen et al., 1975). The hypersensitivity pneumonitis seen in these cases is caused by allergy to proteins in the droppings and sera of the birds; exposure occurs through inhalation of these dried materials. Potentially, contamination of ventilation or air-conditioning systems by bird (especially pigeon) droppings could expose a building's occupants to these allergens, but large-scale outbreaks of hypersensitivity pneumonitis from such a cause have not been reported.

Pigeon serum gamma globulin appears to be the major allergen in pigeon breeder's disease, and ongoing allergen exposure even to minimal levels results in impaired lung function (Rose and King, 1992). The diagnosis of the disease is based on clinical presentation and the presence of IgG precipitating antibodies to the allergen in question. Patients with pigeon breeder's disease may have positive skin tests and IgE antibodies to pigeon serum as well; however, crude extracts often are nonspecifically irritating and therefore not useful for diagnosis. Positive in vitro lymphocyte transformation tests with pigeon allergens can be demonstrated more consistently in symptomatic individuals than in asymptomatic but exposed individuals (Fink, 1988).

Conclusions and Recommendations

One of the difficulties in producing good epidemiological data on allergy is the lack of well-characterized, standardized allergenic extracts for diagnostic purposes. Cat allergens have been well studied, although the role of serum albumin and its overall importance in allergic reactions to cats have yet to be determined. Allergenic extracts that are standardized for the content of Fel d I have appeared only recently. Well-characterized, standardized extracts of dog allergen preparations with known concentrations of Can f I are not available and should be developed. Similarly, there is a limited understanding of the identity and characteristics of many other mammalian and avian allergens. The lack of standardized extracts is partially responsible for the lack of development of immunochemical assays such as monoclonal antibody-based assays for many mammalian and avian allergens. Methods for measuring airborne allergen concentrations are critical for devising and evaluating control measures.

Research Agenda Item: Characterize important allergens from indoor animal sources (e.g., cats, dogs, birds, rodents) more precisely in order to develop standardized allergenic extracts for diagnostic purposes and immunoassays suitable for monitoring exposure.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

Despite an increasing body of knowledge regarding the role of indoor allergen exposure, particularly to mammals, as a cause of asthma, much remains to be learned. The relationship between exposure to indoor pets and the increasing morbidity and mortality of asthma requires further clarification.

Research Agenda Item: Determine the relationship between exposure to indoor pets and the incidence, prevalence, and severity of asthma.

In addition, rodents that infest inner-city dwellings need to be examined as potential risk factors for asthma among individuals exposed to these potent allergens.

Research Agenda Item: Explore the possibility that exposure to rodent populations in inner-city areas may be a risk factor for asthma.

For many allergens, the size of airborne particles and their distribution in the air have not been elucidated and should be studied. Reservoirs of animal and avian allergen exposure and their dissemination through ventilation systems of offices, apartments, and other large buildings likewise require investigation.

Research Agenda Item: Investigate the potential role of mammalian- and avian-allergen- contaminated ventilation systems in the development of allergic disease among inhabitants of apartments, offices, and other large buildings.

Although control measures may reduce airborne concentrations of mammalian and avian allergens, the ability of these approaches to influence symptoms in sensitized patients or to prevent the sensitization of naive individuals requires clarification and study. The use of personal monitoring systems should be useful in making these determinations.

Research Agenda Item: Evaluate the effectiveness of environmental control measures on patient symptoms. This should include assessments of preventing sensitization in the naive individual as well as symptom reduction in those already sensitized.

The epidemiology, diagnostic techniques, and even pathogenesis of hypersensitivity pneumonitis from avian proteins are poorly characterized and require further elucidation. In addition, the risk factors and natural history of the disease are poorly understood and the effects of allergen avoidance remain controversial in the ultimate prognosis of the disease. All of these issues require clarification through further research.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

MICROBIAL ALLERGENS

There are many kinds of microorganisms: viruses, bacteria, fungi, slime molds, algae, and protozoa. With the exception of viruses, each will be discussed below in relation to allergic disease. Viruses will not be considered here because they are obligate intracellular parasites and do not cause allergic environmental disease, although viral infections may exacerbate existing conditions.

The Fungi

Fungi are eukaryotic organisms that have rigid, chitinous cell walls and occupy reservoirs ranging from continuously wet to minimally moist. Fungi compete with bacteria for nutrients and oxygen. They can grow at a low pH level and can kill or inhibit many bacteria by excreting toxic metabolites (antibiotics).

Most organic material can be degraded by at least one fungus, provided that sufficient water is present. The fungi digest their food externally, excreting enzymes into the environment. Some fungi change their pattern of enzyme excretion with a change in food source or with changing environmental conditions.

Fungi reproduce both asexually and sexually and often produce spores by one or both of these kinds of life cycles. The fungal spores are allergenic; that is, responsible for causing allergic responses. Many fungal spores resist drying; they also require specific triggers that initiate germination only under favorable circumstances. Fungi are divided into classes (Oomycetes, Zygomycetes, Ascomycetes, and Basidiomycetes) on the basis of the ways in which their sexual spores are produced. A large group of fungi either has lost the ability to reproduce sexually or the sexual stages have yet to be discovered. These species are classed as Hyphomycetes (asexual spores are produced on naked hyphae) and Coelomycetes (asexual spores are produced within fruiting bodies).

SOURCES AND DISSEMINATORS

Fungi are ubiquitous outdoors, growing on living and dead plants, animals, and other microorganisms. Field crops such as corn, wheat, and soybeans are well colonized with fungi during active growth and especially at harvest (Burge et al., 1991). One group of Basidiomycetes (e.g., members of the genera Coprinus, Pleurotus, Merulius, and Ganoderma) live in the soil or as saprophytes or parasites on plants. These fungi produce macroscopic fruiting bodies that elevate spores into the air (Adams et al., 1968; Cutten et al., 1988; Koivikko and Savolainen, 1988). There are also

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

many fungi that can invade living plant tissue (plant pathogens such as the rusts, smuts, and powdery and downy mildews). Fungal growth and spore dissemination depend on available substrates, season, climate, and human activity such as agriculture.

Stored organic material such as compost, silage, hay, or grain supports the growth of fungi that favor low oxygen levels, dryness, and heat (e.g., Aspergillus fumigatus, A. flavus, Penicillium spp.; Campbell et al., 1989). Their spores become airborne when the moldy stored material is handled.

Spores can penetrate interior environments from outdoors either with ventilation air, or on the surfaces of people, animals, or objects (Pasanen et al., 1989; Su et al., 1992). Air conditioning and mechanical ventilation and filtration, however, allow doors and windows to remain closed, thus preventing entry of most outdoor fungal aerosols (Hirsch et al., 1978; Pan et al., 1992).

Indoors, fungi grow in wet environments such as basements, window sills, and shower stall surfaces (Kapyla, 1985; Verhoeff et al., 1990b). Species of Aspergillus and Penicillium often are dominant indoors (Brunekreef et al., 1990). Some fungi (e.g., Aspergillus versicolor, A. flavus, Wallemia sebi) prefer environments that are relatively dry and will grow at a water activity level of 0.65 (i.e., on substrates that contain 65 percent water) (Kendrick, 1985). The humidity at which hygroscopic materials in dust (including human skin scales) absorb enough water from the air to support the growth of these xerophilic ("dry-loving") fungi is unknown, but it is probably close to from 60 to 70 percent. Other residential substrates that have been attractive to fungi include urea formaldehyde foam insulation, wicker baskets used as plant containers, and carpeting installed in bathrooms (Bisset, 1987; Kozak et al., 1980b).

Fungal spores and other effluents become airborne indoors when disturbed by air movement and normal human activities (O'Rourke et al., 1990). Contaminated air conditioners and humidifiers can actively spray spores, fragments, and dissolved allergens into the air (Baur et al., 1988; Burge et al., 1980; Kumar et al., 1990). Humidifiers that cause water to evaporate into the air are less likely to produce measurable aerosols (Burge et al., 1980), although exposure to such aerosols probably occurs during cleaning.

NATURE OF THE AEROSOLS

The composition of aerosols of fungus-derived particles depends on the abundance and strength of sources, as well as on dissemination factors, mixing, dilution, and particle removal. Natural aerosols are almost always composed of mixed species. In agricultural situations and in indoor environments with actively disseminating reservoirs, aerosols may be monospecific (i.e., containing particles derived from a single fungus species), increasing

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

the risk of exposure to species-specific toxins or allergens and thereby increasing the risk of hypersensitivity pneumonitis. Massive exposure to toxin-producing fungi can occur when moldy organic material is handled. Such exposure can cause exacerbation of allergic disease as well as direct toxic effects such as immunosuppression and cancer (Baxter et al., 1981).

Dose-response data for fungal allergens are unavailable. Standardized protocols for the collection of fungal aerosols are not in wide use, and some of the current methods for quantitation may be unreliable (see Chapter 6). Some studies have reported concentrations of measured viable fungal units (i.e., colony-forming units) in the air of homes that vary over several orders of magnitude both within individual homes, between homes in one community, and between communities (Beaumont et al., 1985; Brunekreef et al., 1990; Su et al., 1992; Verhoeff et al., 1990b).

DISEASES

Of the many different kinds of microorganisms, the fungi are most often associated with allergic disease. Airborne fungal allergens have been implicated in allergic rhinitis/conjunctivitis, allergic asthma, and hypersensitivity pneumonitis. Certain fungi grow saprophytically in the mucous lining of the lungs of patients with allergic bronchopulmonary fungosis or aspergillosis and in the sinuses of people with allergic fungal sinusitis. In addition, conditions favorable to fungal growth correlate positively with respiratory symptom rates as determined by questionnaires (Beaumont et al., 1985; Brunekreef et al., 1989, 1990; Dales et al., 1990; Dekker et al., 1991; Platt et al., 1989; Strachan et al., 1990).

All fungi probably produce allergens that will cause disease with appropriate exposure, although skin test rates vary with allergen sources and the populations chosen for study (Cutten et al., 1988; Giannini et al., 1975; Tarlo et al., 1988). Among people referred for assessment of respiratory atopy, from 1 to 10 percent have positive skin prick tests to one or more fungal allergens (Beaumont et al., 1985). In atopic populations, the percentage of responders can be as high as 27 percent (O'Neil et al., 1988). Skin test reaction rates to fungi in atopic asthmatic patients have been as high as 70 percent (Lopez et al., 1976).

Investigators have measured precipitating IgG antibodies that are specific for soluble allergens of a number of different species of Aspergillus as well as Penicillium, Paecilomyces (Dykewicz et al., 1988), Pleurotus ostreatus (Noster et al., 1976), and Leucogyrophana pinastri (Stone et al., 1989). These antibodies are related to exposure to high levels of small fungal particles, but diseases such as allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal sinusitis (AFS) require additional host factors that are

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

currently unknown. In ABPA, exposure to allergens released from active fungal surface growth in the lung stimulates the production of both IgE and IgG. The relationship between exposure to airborne spores and either initiation of ABPA or the status of ABPA patients is unclear.

NATURE OF THE ALLERGENS

Fungal allergens may be a structural part of the microbial cell, or they may be produced by the cells and released into the environment. The fungal allergens that have been isolated thus far are water-soluble glycoproteins, some of which are enzymes (Baldo and Baker, 1988; MacDonald et al., 1989); some may also be high-molecular-weight carbohydrates (Savolainen et al., 1990). Only a few have been partially characterized (Aukrust and Borch, 1979; Horner et al., 1988, 1989; Pazur et al., 1990; Savolainen et al., 1990).

Crude fungal extracts are complex mixtures of soluble materials from mycelial and spore walls, cytoplasm, and metabolites. These extracts are produced from fungi grown in a liquid medium for 5–15 days; the mixture is then blended and filtered. Sometimes the fungal growth is removed from the liquid by filtration and subsequently ground, dried, and extracted. Residual culture medium is sometimes used as a second kind of preparation (Kauffman et al., 1984).

Batch-to-batch variability in fungal extracts is often greater than variability among different strains, species, or even genera (Burge et al., 1989; Savolainen et al., 1989). For most of the mushrooms and other macrofungi, field collections are usually used to produce allergen extracts. Preliminary studies of the comparative allergen content of spores, fruiting body tissue, mycelium, and spent culture medium demonstrate both similarities and differences. Variability in allergen content (determined by radioallergosorbent tests inhibition; see Chapter 6) has been observed in the same kinds of mushrooms collected from different sites and, to a lesser degree, from the same site at different times (Liengswangwong et al., 1987). Studies on cross-reactivity of allergens extracted from different taxa of fungi (Baldo and Baker, 1988; De Zubiria et al., 1990; O'Neil et al., 1988; Shen et al., 1990; Weissman, 1987) have not generally documented batch and strain variability within each species.

There are few reports of experimental human challenges with fungal allergens. Licorish and others (1985) provoked immediate and delayed asthma using Alternaria whole-spore challenges, but they produced only an immediate response with spore extracts. Lopez and coworkers (1989) induced positive bronchial challenges with basidiospores. For some fungi, possibly because the actual allergens are enzymes associated with germination, it may be necessary for a living unit to begin growth on the respiratory tract mucosa before allergen exposure occurs (Savolainen et al., 1990).

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

The Bacteria

Bacteria are prokaryotic microorganisms that lack many of the subcellular structures found in fungal, plant, and animal cells. They are usually single celled and reproduce by simple division. Most bacteria are saprophytes and require a source of complex carbon compounds (i.e., nonliving organic material); they decay substrates both aerobically and anaerobically. In general, bacteria require more water for active growth than the fungi and are usually the dominant organisms in water reservoirs with a pH of greater than 7. Some bacteria form spores that are extremely resistant to environmental stressors.

Many organic substrates can be degraded by bacteria, which form biofilms on surfaces that are continuously wet. Biofilm ecosystems also support the growth of algae, protozoa, and fungi. The bacteria are classified by cell shape, staining properties, spore production, metabolic characteristics, and the human diseases they cause.

SOURCES AND DISSEMINATORS

Bacteria occupy a wide range of reservoirs both outdoors and indoors. Gram-negative bacteria often predominate in outdoor reservoirs on living leaf surfaces and are able to survive at least brief periods of transit in the air. A wide variety of bacteria can be found in soil and in natural bodies of water. Some Bacillus species and the thermophilic actinomycetes (e.g., Faenia rectivirtigula, Thermoactinomyces spp.) will grow only at temperatures between 45° and 60° C. They are found mainly in environments that have become warm from insolation, geothermal conditions, or self-heating.

Outdoor bacteria become airborne with the disturbance of substrates—for example, with the movement of air or rain or with human activity, especially activities related to farming and refuse handling. Indoor reservoirs that allow growth and dissemination of allergenic bacterial aerosols include water-containing appliances such as portable humidifiers, large humidification systems, organic material stored or accumulating indoors, cooling fluids in machining plants, and other such moist areas. Bacillus species tend to accumulate in house dust. Thermophilic organisms occupy indoor reservoirs such as humidifiers attached to heating systems, refrigerator drip pans, evaporative cooler media, clothes dryer exhausts, and other such places characterized by organic material, water, and warm temperatures. Air movements, inadvertent human activity, and activities that allow direct handling of contaminated material (e.g., in removal or cleaning procedures) are common dissemination factors for indoor bacteria.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×
NATURE OF THE AEROSOLS

Similar to the fungi, the composition of bacterial aerosols depends on the abundance and strength of sources, on dissemination factors, and on factors that act directly on the aerosol such as mixing, dilution, and particle removal. Outdoor bacterial aerosols usually are dominated by gram-negative leaf surface bacteria such as Pseudomonas species (Nevalainen et al., 1990). Aerosols near such sources as cooling towers may contain more exotic organisms such as Legionella pneumophila , the agent of Legionnaires' disease. Indoors, where environmental sources are absent, the bacterial aerosol consists primarily of gram-positive cocci that inhabit human skin and respiratory tract secretions (Nevalainen et al., 1990). When gram-negative rods become dominant in indoor air, it can be assumed that they have been emitted from an environmental (rather than human) reservoir. Concentrations of bacteria that constitute a significant risk for sensitizing or provoking human allergic reactions are unknown.

DISEASES

Exposure to bacterial allergens has been associated with work-related asthma, hypersensitivity pneumonitis, humidifier fever, and a disease resembling allergic bronchopulmonary fungosis. Symptoms classified as humidifier fever have been attributed to gram-negative bacterial aerosols, although it is not clear whether the disease results from exposure to endotoxin alone or from exposure to the adjuvant characteristics of endotoxin acting in conjunction with other allergens (Hood, 1989; Polla et al., 1988). Endotoxin causes some of the symptoms related to infections (i.e., fever, chills) and can cause the same symptoms when large quantities of the organisms (or large amounts of toxin) are inhaled.

Like the fungi, bacteria secrete enzymes that can act as allergens, and these enzymes are being found in an increasingly broader range of products and locations. For example, Bacillus species are being used to produce proteases that are added to laundry detergents for stain removal. When initially introduced, aerosols of these enzymes were implicated in outbreaks of hypersensitivity pneumonitis among workers who manufactured these detergents. In this unusual case, a threshold limit value was established in relation to the risk of an allergic disease, and ventilation controls that now allow enzyme-containing products to be manufactured without apparent risk of hypersensitivity pneumonitis have been introduced. Enzymes and spores from gram-positive bacilli and the thermophilic actinomycetes have been implicated in epidemics of hypersensitivity pneumonitis and work-related asthma (I. L. Bernstein, 1972; Dolovich and Little, 1972; C. L. Johnson et al., 1980; Perelmutter et al., 1972; Wiberg et al., 1972).

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×
NATURE OF THE ALLERGENS

Crude extracts of the thermophilic actinomycetes commonly associated with hypersensitivity pneumonitis are produced in a manner similar to that described for the fungi. They are used in double-diffusion assays to evaluate the presence or absence of specific IgG antibodies (precipitins).

Protozoa

The protozoa are microscopic animals that occupy reservoirs similar to those of the bacteria. Intact protozoa are generally too large to remain in the air for long periods of time, although occasionally they cause infection of the eye and brain when introduced into the eye or respiratory tract in large droplets (e.g., those produced by hot tubs). Some protozoa in indoor water reservoirs excrete allergenic material that can become airborne if droplets form. Acanthamoeba polyphaga and Naegleria gruberi allergens have been associated with humidifier fever and work-related asthma (Finnegan et al., 1987).

Algae

The algae are plantlike organisms with rigid, cellulosic cell walls; for the most part, they live in aquatic environments. Vegetative cells of the microscopic algae can be relatively abundant in outdoor air near bodies of water that support luxuriant algal growth (Schlicting, 1969). They have been reported to cause IgE-mediated allergy, but this question has not been well studied (Mittal et al., 1979).

Slime Molds

The slime molds (Myxomycetes) are microorganisms that do not fit well into such classifications as ''plant" or "animal." They are motile amebae during part of their life cycle, but at another juncture they become immobile and produce spores that are indistinguishable from those of some fungi. These small but visible organisms occupy niches in the environment that are similar to those of some fungi (e.g., on damp organic material), and their spores form a small part of the outdoor aerosol. There is some evidence that these spores are sensitizing (Giannini et al., 1975; Santilli et al., 1990).

Environmental Control

Environmental control strategies are intended to reduce airborne concentrations of allergens. Several current strategies and methods are designed

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

either to prevent or remove the contamination of indoor air with microbial allergens. The discussion below addresses these issues briefly; additional information is presented in Chapter 7.

PREVENTION

To prevent the contamination of indoor air by microbial aerosols, the penetration of outdoor aerosols must be reduced, and growth in indoor reservoirs must be eliminated. Keeping indoor environments physically separated from outdoors (by keeping doors and windows closed) and using mechanical ventilation and air conditioning are effective ways to control penetration. Water must not be allowed to accumulate, particularly, in ventilation systems; in addition, airborne water vapor must be kept to a minimum. Relative humidity should be maintained below 60 percent to prevent absorption of water by hygroscopic materials and to avoid condensation on cool surfaces. The effectiveness and utility of biocides (used either on surfaces or incorporated into fabrics or paint) have not been clearly established (see Chapter 7).

SOURCE CONTROL

Vacuum cleaning removes some fungus spores from carpeting, but it probably also reintroduces them into the air, either through the action of the beater in the cleaner or through the bag. High-efficiency particulate arresting (HEPA) filters or release of air and dirt directly to the outdoors, as is the case in central vacuum systems, will reduce such contamination. Wet cleaning of carpeting probably removes some microorganisms (Wassenaar, 1988a), but unless drying is rapid, the added water may spur the growth of those that remain. Water reservoirs associated with portable humidifiers can be cleaned each day and treated with a biocide every third day to maintain relatively low bacterial levels in the reservoir. However, the biocides must be removed before the humidifier is operated.

Biocides are usually used in commercial systems (sumps of machining fluid, spray humidification systems, etc.). For example, aldehydes and quaternary amine compounds have been used to control fungal growth (Kapyla, 1985). These kinds of compounds are clearly irritating, may also be sensitizing, and can also enter the air conveyance system. Reducing the amount of biocide in order to minimize risk to the occupants, however, can result in concentrations that are too weak to prevent the growth of all organisms. Biocide usage can also result in changes in the kinds of organisms in reservoirs rather than in a significant decrease in the total number of organisms. The multiple risks of exposure to fungi and biocides must be carefully balanced.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×
DUCT CLEANING

Duct cleaning involves loosening and removing dirt in ventilation system ductwork. Whether this practice has any effect on exposure to respiratory allergens (either positive or negative) has not been adequately investigated. Chapter 7 discusses duct cleaning in greater detail.

AEROSOL CONTROL

Aerosol control methods may offer some relief in the presence of continuing sources of specific microbial pollutants. Local exhaust that removes pollutants before they can circulate through room air is one of the best options. Machining fluid and bacterial enzyme aerosols have been controlled in this way. Circulating room air through either a central or console air cleaner can reduce particle levels to a steady state that depends on source strengths, dissemination rates, and the rate at which particles are removed by the cleaner. If a HEPA filter is used, all particles larger than 6 μm in size will be removed from the air that passes through the filter. If active sources (e.g., large dust mite populations, active fungus growth, cats) are present, it is likely that dispersal rates will exceed removal rates to a degree and that a steady state will eventually be achieved.

Other modes of aerosol removal depend on electrostatic precipitation and on devices that charge particles so that they become attached to environmental surfaces. The latter devices are not advisable for use with allergens because disturbance of the collecting surfaces (e.g., carpeting, upholstered furniture, walls) will reaerosolize the particles.

Conclusions and Recommendations

Overall, the fungus-associated allergies have been the least well-studied. Little data is available on the distribution of airborne fungal products, dynamics of human exposure, nature of the allergens, factors influencing the quality of skin test and immunotherapy materials, and the basic nature of fungus-related allergic disease.

Research Agenda Item: Initiate and conduct studies to determine the relative etiologic importance, geographic distribution, and concentrations of airborne fungus material associated with indoor allergy.

Fungi grow indoors in damp environments such as basements, window sills, shower stall surfaces, and in dust. Fungal spores and other effluents become airborne indoors when disturbed by air movement and normal human activities. The composition of aerosols of fungus-derived particles

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

depends on the abundance and strength of sources as well as dissemination factors, mixing, dilution, and particle removal.

Research Agenda Item: Investigate the dynamics of fungal colonization of indoor reservoirs and emission of allergens from these sources. The results of such research should permit the risks associated with indoor fungal growth to be evaluated.

Exposure to fungal spores (and possibly other fungal antigen-carrying particles) can produce both IgE-mediated disease (e.g., asthma) and hypersensitivity pneumonitis while other allergens (e.g., dust mite, pollen) produce only the IgE-mediated diseases. It is not clear why or under what conditions fungal particles can have this dual effect.

Research Agenda Item: Study the differences between fungal and other allergen-carrying particles that control the development of hypersensitivity pneumonitis as opposed to IgE-mediated asthma.

CHEMICALS

Low-molecular-weight (LMW) chemical agents have been found to cause immunologic disease primarily in the industrial setting but not generally in the office, school, or residential setting. Nevertheless, a variety of household products may contain immunogenic agents such as reactive chemical anhydrides in epoxy resins and isocyanates in bathtub refinishing agents. In addition, chemical allergy in the industrial setting serves as a model for improving our understanding of allergy mechanisms. More than 150 LMW chemical agents have been reported to cause allergic reactions such as asthma and hypersensitivity pneumonitis (Table 3-3; Butcher et al., 1989; Grammer et al., 1989). As industrialization increases and new agents are introduced, the number of chemicals that cause such allergic reactions is likely to increase. Allergic contact dermatitis to these and other chemicals is another type of allergic response found in industrial settings and an important cause of occupational disease; however, it will not be discussed here.

It has been estimated that in industrialized countries 2 percent of asthma is occupationally related (Salvaggio, 1979). The prevalence of occupational asthma varies with the particular chemical. For example, more than half of all workers exposed to platinum salts became sensitized (Cromwell et al., 1979). Among workers exposed to trimellitic anhydride (TMA), approximately 20 percent developed sensitization (Zeiss et al., 1983), whereas approximately 5 percent of toluene diisocyanate (TDI)-exposed workers developed positive inhalation challenge at levels of less than 20 parts per billion (NIOSH, 1978).

For some industries, studies have estimated the prevalence of allergic

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

TABLE 3-3 Examples of Chemical Allergens and Indoor Sources

Agent

Source

Reference

Antibiotics

Hospitals, pharmaceutical facilities

Davies et al., 1974, 1983

Other drugs: piperazine, alpha-methyldopa, cimetidine, endofluorane anesthetic

Hospitals, pharmaceutical facilities

Butcher et al., 1989

Metal salts: nickel, platinum, chromates

Platinum processing and nickel or chromium plating plants

Block and Chan-Yeung, 1982; Cromwell et al., 1979; Dolovich et al., 1984; Malo et al., 1982; McConnell et al., 1973; Novey et al., 1983; Pepys et al., 1972, 1979; Pickering, 1972

Anhydrides

Facilities that manufacture curing agents, plasticizers, or anticorrosive coatings

D. I. Bernstein et al., 1982, 1984; Grammer et al., 1987; Topping et al., 1986; Zeiss et al., 1977

Isocyanates

Facilities that produce or apply paints, surface coatings, or polyurethane foam

Baur and Fruhmann, 1981; Butcher et al., 1977, 1979, 1980

Ethylenediamine

Buildings in which shellac or lacquer are used

Gelfand, 1983; Lam and Chan-Yeung, 1980

Azo-dyes

Facilities that manufacture or use dyes

Park et al., 1991; Slovak, 1981

reactions to a given chemical among workers. In other instances, estimates have been developed for the number of workers exposed to chemicals such as TMA (20,000 workers) and TDI (50,000-100,000 workers). However, for many chemicals and many industries the number of exposed workers and the prevalence of allergic disease are not known and have not been studied. In many cases, there have been high employee turnover rates in jobs in which workers may develop allergic reactions to chemicals. For example, high turnover rates have been found among platinum workers as a result of respiratory sensitization (Roberts, 1951). In another study of the electronics industry, many of the workers who left their jobs cited respiratory

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

disease as the reason (Perks et al., 1979). Moreover, occupational diseases are generally underreported (I. L. Bernstein, 1981; NRC, 1987a). Although the annual incidence of work-related disease is believed to be approximately 20 per 100 population, one study (Discher et al., 1975) found that only 2 percent of illnesses were actually reported in employers' logs.

Allergic Diseases Caused by LMW Chemicals

The diseases caused by allergic reactions to LMW chemicals are similar to those caused by other, larger (i.e., high-molecular-weight, or HMW) allergens. More specifically, allergic diseases related to LMW chemicals include allergic rhinitis and conjunctivitis, hypersensitivity pneumonitis, asthma, late respiratory systemic syndrome (LRSS), and hemorrhagic pneumonitis. Scientists assume that chemicals act as allergens by forming haptens (covalently coupling) at multiple sites on the surface of a host carrier protein, which could be in the serum, airway, epithelium, or blood cells. Allergic rhinitis or allergic conjunctivitis, or both, may occur as a result. Allergic asthma can be immediate in onset, delayed, or both (Fink, 1982). The hypersensitivity pneumonitis that occurs as a result of exposure to chemicals in the workplace is generally of the acute type. LRSS is a related disease characterized by cough, chills, fever, and myalgias 4 to 12 hours after exposure (Zeiss et al., 1977). Workers with LRSS have high levels of antibody against TMA conjugated with human proteins such as human serum albumin (TM-HSA).

Another disease, hemorrhagic pneumonitis, is caused by immunologic reactions to chemicals such as TMA (Zeiss et al., 1977) and TDI (Table 3-4). For example, after significant exposure in a TMA-sensitized individual, a hemorrhagic pneumonitis and anemia known as pulmonary disease anemia (PDA) syndrome may occur (Patterson et al., 1978). These workers have very high levels of antibody against TM-HSA and very high levels of TMA exposure, usually from hot fumes. The anemia is likely to be an immune-mediated hemolytic type, probably because reactive chemicals like TMA couple easily with cells (they react readily with cell surface proteins). This process results in type II immunologically mediated cytotoxicity, a condition that cannot occur with complete allergens such as foreign proteins because they cannot react covalently with cell surface proteins (Patterson et al., 1979). There have also been reports of hemorrhagic pneumonitis without anemia caused by TDI (Patterson et al., 1990).

Chemical Agents That Cause Allergic Disease

A variety of pharmacologic agents have caused asthma among hospital and pharmaceutical workers when airborne dust is inhaled. Numerous antibiotics,

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

TABLE 3-4 Characteristics of Syndromes Related to Inhalation of TMA

Characteristic

Rhinitis and Immediate-Type Asthma

LRSS

Pulmonary Disease-Anemia

Irritant Syndromes

Latent period (duration of exposure prior to onset of symptoms)

Weeks to months of work exposure

Weeks to months of work exposure

Weeks to months of work exposure

Occurs on first high-work dose exposure

Onset of symptoms

after work exposure

Immediate (minutes)

4–12 hours

Progressive with further work exposure

Variable, depending on exposure

Degree (type) of exposure

TMA dust (mild) or fumes

TMA dust (moderate) or fumes

TMA fumes (heavy)

Fumes or dust (great)

Skin tests (TM-HSA)

Positive immediate-type

Negative

Not done

Negative

Total antibody to TM-HSA

Present

High

Very high

Variable

IgE to TM-HSA

Present

Absent

Absent

Absent

NOTE: TMA, trimellitic anhydride; LRSS, late respiratory systemic syndrome; TM-HSA, trimellitic anhydride-human serum albumin.

SOURCE: Zeiss et al., 1982.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

including penicillin, sulfa, and spiramycin, are known to induce specific IgE, positive skin tests, and asthma (Davies and Pepys, 1975; Davies et al., 1974). Other pharmacologic agents including cimetidine and alpha-methyldopa can cause asthma on an immunologic basis, that is, as a result of an antigen being recognized by specific antibody or sensitized cells (Butcher et al., 1989).

Metal salts of nickel, platinum, and chromates can cause rhinitis, conjunctivitis, or asthma (Block and Chan-Yeung, 1982; Cromwell et al., 1979; Dolovich et al., 1984; Malo et al., 1982; McConnell et al., 1973; Novey et al., 1983; Pepys et al., 1972, 1979; Pickering, 1972). Positive skin tests, specific IgE, and positive bronchial challenges have all been reported. Exposure occurs in processing or plating facilities. Some investigators believe that sensitization to platinum is virtually universal, given a large enough exposure.

Acid anhydrides are used as curing agents in the manufacture of epoxy resins. Exposure may occur in a variety of industries including those that manufacture curing agents, plasticizers, or anticorrosive coating agents. In addition to allergic rhinitis, conjunctivitis, and asthma, two other allergic reactions or diseases, LRSS and PDA, described above, may result from TMA. Other anhydrides, including phthalic anhydride and tetrachlorophthalic anhydride, have also caused asthma (D. I. Bernstein et al., 1982; Topping et al., 1986).

Isocyanates are used to produce a number of products including paints, surface coatings, and polyurethane foam. They are also found in some home improvement products such as refinishing agents. In contrast to people who react to TMA, many individuals affected by isocyanates do not have specific IgE or positive skin tests (I. L. Bernstein, 1982). Isocyanate asthma is a major cause of LMW chemical-induced asthma, but to date, the mechanism (i.e., allergy versus nonimmunologic sensitivity) is unknown. In addition to asthma, reports have linked isocyanates with hypersensitivity pneumonitis and an immunologically mediated hemorrhagic pneumonitis (Patterson et al., 1990).

Research has shown that ethylenediamine induces asthma in individuals exposed to shellac or lacquer (Gelfand, 1983; Lam and Chan-Yeung, 1980). Positive skin tests and positive bronchial responses, both immediate and delayed, have been reported. Azo-dyes, such as azodicarbonamide, can also cause asthma (Park et al., 1991; Slovak, 1981). These studies describe positive skin tests and changes in pulmonary functions after a work shift. Exposure to such chemicals may occur in plants that manufacture or weigh dyes.

Formaldehyde is a chemical that is often found at very low levels in homes, offices, and schools and at higher levels in workplaces that use the substance. Asthma is sometimes reported following gaseous formaldehyde

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

exposure; bronchial provocation studies are usually negative but on occasion they may be positive (Hendrick and Lane, 1977; Nordman et al., 1985). Two studies that investigated immunologic sensitization reported negative challenges even in those individuals with specific IgE to formaldehyde (Dykewicz et al., 1991; Grammer et al., 1992). Thus, immunologically mediated asthma resulting from formaldehyde exposure has yet to be proved. Other volatile organic chemicals such as toluene and turpentine can act as irritants but are not specific sensitizers.

Exposure and Risk

Various air sampling and personal monitoring techniques are used to measure chemical exposures (Eller, 1984), but they are not without limitations. For example, intermittent samples may not reflect an individual's actual exposure because of variations in the exposure levels of the chemical. In addition, only a few allergenic chemicals such as TDI and TMA have threshold limit values (TLVs) set by the American Conference of Governmental Industrial Hygienists (ACGIH, 1986) or permissible exposure limits (PELs) set by the Occupational Safety and Health Administration (OSHA; CFR, 1991).

TLVs and PELs are generally established to help prevent chemical toxicity among workers. Thus, they may have no relevance to levels of chemicals that may sensitize an individual or provoke allergic responses and that may be many orders of magnitude below toxic levels. Very few studies report threshold levels for human exposure to chemicals that elicit allergic responses, and those that do describe exposure concentrations present them only as estimates. A Japanese study of 41 workers exposed to two enzymes and three antibiotics showed that the incidence of occupational allergy was correlated with the frequency and concentration of exposure to allergens (Chida, 1986). In other studies, approximately 50 TMA workers were evaluated in a facility that reduced worker exposure over time by improved ventilation, work practices, and respiratory protection. The levels of antibody in workers decreased with decreasing exposure to TMA (Boxer et al., 1987; Grammer et al., 1991b). In a study of isocyanate workers, the group with the highest exposure had the highest prevalence of positive antibody (Grammer et al., 1991a). In a study of 500 workers at a TMA manufacturing facility, five categories of exposure were identified (Zeiss et al., 1992). Only workers in the highest exposure categories developed specific antibody and allergic reactions to TMA.

In contrast to human studies, estimates of exposure in animal models are considerably more accurate. Studies have reported a concentration-dependent immunologic response in a guinea pig model of TDI asthma (Karol, 1983) and a threshold concentration and concentration-immunologic

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

response relationship in a rat model of immunologic TMA disease (Zeiss et al., 1989). It is likely that such relationships also exist in humans, but there are no data to illuminate such linkages. (Quantitative exposure data from animal experiments may not necessarily translate to humans.)

Other than exposure, risk factors for the development of sensitization to a given chemical have not been defined. In studies of risk factors for development of sensitization to chemicals such as TDI, atopy and airway hyperreactivity were either not predictive or only weakly so (I. L. Bernstein, 1982; Chester and Schwartz, 1979; Nicholas, 1983).

Control by Avoidance and Exposure Reduction

Although some of the control measures used in industrial settings may not be directly applicable to the indoor air environment, the model of reduced exposure that results in reduced sensitization rates is applicable to indoor aeroallergens. Prospective studies of TMA workers (Grammer et al., 1991b; Zeiss et al., 1983, 1992) have reported that serial immunologic studies are useful in predicting which individuals are likely to develop immunologically mediated disease. With careful monitoring, those workers who develop specific antibody can be removed from exposure at the onset of any allergic symptoms. Alternatively, if the development of disease seemed very likely, the worker could be relocated at the onset of serologic positivity. In TMA workers, there is evidence that development of specific antibody is predictive of allergic disease, but this finding has not been confirmed in a definitive manner in populations of workers exposed to other chemical allergens.

The timing of removal from exposure relative to disease onset is important. Some data suggest that early removal of workers who develop asthma as a result of chemical exposure will allow most of them to return to normal pulmonary function. In contrast, asthma tends to persist among workers who have had the disease for several years before they are removed from exposure (Chan-Yeung, 1990). This is especially true for workers who already have abnormal pulmonary function.

With respect to reducing exposure, there is evidence that decreasing airborne concentrations of a chemical such as TMA reduces disease prevalence (Boxer et al., 1987; Chan-Yeung, 1990). As outlined earlier, other evidence in animals and in humans suggests the existence of environmental exposure concentration thresholds and environmental concentration exposure-immunologic response relationships. If these thresholds and relationships could be defined for chemical allergens, reducing exposure could be the best approach to preventing allergic disease caused by these substances. Exposure reduction measures would include improved ventilation, work practices, and protective equipment.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

Conclusions and Recommendations

Many of the protein allergens have long been recognized, but a lengthening list of newly recognized allergenic chemicals is developing. Allergic diseases caused by these chemicals can differ from those caused by protein allergens in terms of symptoms, mechanisms of action, and appropriate treatment. The diseases can differ also in terms of etiology and exposure, i.e., often occurring at the work site. A better understanding of these differences will assist in the formulation of improved measures of prevention and treatment.

Research Agenda Item: Determine the types of allergic diseases caused by reactive allergenic chemicals, their prevalence rates, and the mechanisms responsible for the resulting airway reactions.

A body of knowledge about chemical allergens is available, but many areas have not been well studied. Other chemicals besides those already reported to cause allergic reactions may provoke responses. Thus, as new chemicals are introduced, the list of agents that elicit allergic reactions is likely to grow.

Research Agenda Item: Identify the risk factors, such as a specific immunologic response, that are predictive of the development of chemically induced sensitization or allergic disease, and as soon as possible after their introduction, determine the sensitizing potential of new chemical entities. This knowledge will facilitate the development of primary and secondary preventive strategies.

The allergic rhinitis, conjunctivitis, and asthma that arise from exposure to chemicals appear to be due to classic immunologic reactions. However, late respiratory systemic syndrome (LRSS) and immunologic hemorrhagic pneumonitis occur only in response to chemical exposures and are not the result of response to the usual protein allergens; the mechanisms of immunologic damage in these two cases are not entirely known. The mechanism of non-IgE-mediated isocyanate asthma is also unclear.

Research Agenda Item: Determine the disease mechanisms of chemically induced LRSS, of immunologic hemorrhagic pneumonitis, and of non-IgE-mediated isocyanate asthma. Appropriate in vitro or in vivo models should also be developed.

LMW reactive allergenic chemicals can cause immunologic sensitization and consequent allergic reactions. At a minimum, hundreds of thousands of U.S. workers are exposed to chemicals that can form haptens with airway proteins and induce allergic diseases. The goal of reducing the

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

incidence and severity of allergic disease caused by chemical exposure is achievable, although it may not be possible to prevent all such disease.

Research Agenda Item: Determine the number of workers exposed to allergenic chemicals in various industrial and non-industrial settings and the prevalence of allergic disease resulting from such exposure. Populations in close contact with reactive allergenic chemicals and highly potent sensitizers would be logical candidates for study.

For those individuals who develop allergic disease from exposure to chemicals, it is important to determine their long-term prognosis. In particular, if immune responses that are predictive of allergic disease can be identified, and reduced exposure can be shown to result in resolution of disease (and disappearance of immunologic sensitization), then reduced exposure may represent the most practical approach for preventing allergic disease arising from chemical exposure.

Research Agenda Item: Conduct dose-response studies in humans to determine both the relationship between allergen concentration and immunologic response, and a threshold environmental exposure concentration for sensitization.

In addition to studies of the threshold concentrations necessary for sensitization, thresholds for elicitation of allergic reactions to chemicals once sensitization has occurred also require study. Such thresholds exist but vary markedly from individual to individual, as shown by bronchoprovocation tests performed with high-molecular-weight allergens. This is probably also the case with chemical allergens, but the issue has not been systematically studied. If threshold concentration levels do exist but are highly variable, and in some cases very low, the only practical way to manage sensitized individuals is to terminate the exposure.

PLANTS AND PLANT PRODUCTS

It is well known that plants produce substances, materials, or products that are allergenic in humans. The best understood are pollen from trees, grasses, and weeds and the oils or resins from the leaves of poison ivy and poison oak. Airborne pollen can produce allergic rhinitis or asthma, or both, in the susceptible atopic population. The oils from poison ivy can produce allergic contact dermatitis; susceptibility is not limited to atopic individuals. Pollen production is seasonal and varies in quantity, depending on geographic location and climatic conditions. Local pollen production also varies annually, depending on weather conditions.

Outdoor pollen can enter the indoors with ventilation air and can also

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

be transported indoors on people and their clothing as well as on pets. Clothing that was previously hung outdoors to dry is another source of pollen. Studies have shown that indoor pollen concentrations can be quite high during the pollen production season (O'Rourke et al., 1990; Platts-Mills et al., 1987; Pollart et al., 1988). Reports of indoor pollen concentrations have ranged from 0 to 5.5 million pollen grains per gram of house dust (O'Rourke and Lebowitz, 1984). Elevated concentrations of pollen in indoor air are found under open window conditions (in one case 600 grains per cubic meter in a room) (O'Rourke et al., 1989). These high airborne pollen concentrations are rare, but 30 pollen grains per cubic meter are not uncommon. Since people spend a majority of their time indoors (NAS, 1981; Quackenboss et al., 1991a,b), over 20 pollen grains can be inhaled in a typical household each day (on average, over all seasons). During the spring, when average outdoor pollen concentrations approach 400 grains per day, indoor exposure can approach 40–80 grains per day (O'Rourke, 1989).

Indoor plants are commonly found in office or school environments and in the home. Most are grown for their green foliage and accommodate low light or a lack of direct sunlight. As such, most do not flower in these environments and therefore are not pollen sources. Indeed, most plants grown indoors are not highly allergenic. Nevertheless, as more plants are used indoors, especially in large numbers in office settings, those considered not allergenic or only slightly allergenic may need to be reexamined. For example, Axelsson and colleagues (1987b, 1991) report that the leaves of Ficus benjamina (weeping fig) can produce airborne IgE-mediated rhinitis and asthma. They estimate that the risk of sensitization among truly atopic individuals is 6 percent. Hausen and Schulz (1988) report on a woman who developed conjunctivitis, rhinitis, and asthma from the nectar secretions of an ornamental plant, Abutilon striatum (flowering maple). Ford and co-workers (1986) report the development of IgE antibodies to pollen allergens from Parietaria judaica, an outdoor allergenic member of the nettle family found in the Mediterranean region but not likely to be found indoors.

Most recent reports in the literature regarding allergic reactions to indoor plants involve contact dermatitis produced by airborne allergens. Plants provoking such reactions include Allium (garlic), chlorophora (iroki; Fernandez de Corres et al., 1984, 1985), Chrysanthemum , citrus, Coleus (Van Hecke et al., 1991), common ferns (Geller-Bernstein et al., 1987), Compositae (daisy), Frullania (Pecegueiro and Brandao, 1985), lichens, Lilium (lily), Pelargonium (geranium), Philodendron, Pinus (pine), Platycodon grandiflorum (balloon flower; Nagano et al., 1982), Primula (primrose), Typha latifolia (cattail), and Umbelliferae (family name for parsley, carrots, coriander, etc.). Because many of these studies report the effects of mixtures of houseplants and garden plants, it is difficult to determine which house or indoor plants are truly allergenic.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

The types of plants grown in the home will frequently differ from those grown in the office or workplace, in that the home gardener may well experiment with different types of plants grown in different locations at various times of the year (e.g., growing herbs in an indoor window box with a southern exposure). Similarly, home gardeners with a greenhouse may grow a wide variety of allergenic plants. Although there is only limited knowledge of the extent of allergic disease from allergenic indoor plants, it seems logical to assume that if increased use is made of indoor plants that are pollen producers, atopic individuals may find indoor environments as unpleasant as the outdoors during the traditional pollen season. In addition, indoor blooming patterns are sometimes manipulated to be different from outdoor ''normal" seasonal patterns.

Plant Products

In addition to the plants themselves, plant materials such as Psyllium and latex can be brought indoors in a variety of consumer products. Psyllium is a grass from India used as a fiber and bulk supplement for bowel control. There are reported cases of severe anaphylactic reactions among workers who produce this product, as well as among those who use it. Airborne exposure to the product can also produce allergic reactions among susceptible individuals during use in the home.

Plant sources of allergens that have been shown to produce asthma in selected occupationally-exposed populations are presented in Chapter 2 (Table 2-4). Some of these plant materials can be present in residential and other indoor environments because of the activities of the occupants. Whether they will pose a hazard to the occupant depends on many factors including the amount of airborne exposures. Dried flowers are another example of a potentially allergenic product that can be brought indoors.

LATEX

Latex allergy has recently received substantial attention because of increasing reports of its occurrence and its potential, in certain individuals, to produce life-threatening anaphylactic reactions. The latex (or sap) of the Havea brasiliensis plant is the source of natural rubber (cis-1,4-polyisoprene). Although rubber production yields a product that is 93–95 percent polyisoprene, the final product may be as much as 2–3 percent protein by weight (Windholz et al., 1983). The protein component of the latex contains allergens that are responsible for numerous recent reports of latex allergy. Exposure occurs by direct contact or by inhalation of dust or powder that is often used for packaging. Patient reactions to latex have ranged from contact urticaria to systemic anaphylaxis. Persons at increased risk include patients with congenital

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

problems of the spinal cord (e.g., myelomeningocele), patients with recurrent bladder catheterizations, or any patient with a history of rash, swelling, or itching after blowing up balloons, wearing rubber gloves, or using other latex-containing products. On rare occasions, latex condoms can cause allergic reactions.

Most cases of allergy to latex are mediated by IgE antibodies. However, because of varying source materials, the heterogeneity of immune response, and a variety of test methods, the identities of the specific protein allergens remain to be determined (Jones et al., 1992).

Case reports of latex allergy began to appear in the literature in 1979 (Nutter, 1979). Most early reports were of contact urticaria (Forstrom, 1980; Meding and Fregert, 1984; Nutter, 1979); reports of allergic rhinitis (Carrillo et al., 1986), anaphylaxis (Axelsson et al., 1987a; Slater, 1989; Turjanmaa et al., 1984), and asthma (Seaton et al., 1988) followed. Occupational asthma related to latex hypersensitivity has also been described; the response has been attributed to inhalation exposure to cured latex during the inspection and packaging of finished gloves (Tarlo et al., 1990). Fisher (1987) has also reported contact urticaria and anaphylactoid reaction as a result of exposure to cornstarch surgical glove powder. Swanson and colleagues (1992) support the conclusion that dust from latex gloves is a significant occupational aeroallergen, reporting 28 medical center employees diagnosed with rhinitis or asthma caused by exposure to dust from latex gloves.

In addition to health care workers and manufacturers, children with spina bifida are at increased risk for latex allergy, and credible evidence supports an IgE-mediated mechanism (Slater, 1989; Slater et al., 1990a, 1991; Spanner et al., 1989; Turjanmaa, 1987). One prospective study reported that 5 out of 12 spina bifida patients (41 percent) have IgE antibody specific for rubber proteins (Slater et al., 1990a). Another report suggested that IgE titers to latex allergen might be due to parenteral exposure to latex surgeon's gloves during primary closure of the meningomyelocele and that early initial exposure and frequent reexposures may predispose children with spina bifida to rubber allergy (Slater et al., 1990b).

Recent episodes of fatal and life-threatening anaphylaxis have made it increasingly urgent to identify the specific allergen(s) responsible for these reactions (Kelly et al., 1991). Jones and others (1992) and Turjanmaa and colleagues (1988) have reported large variations in the latex allergen content of gloves from different manufacturers; powder-free gloves were significantly less allergenic in this survey. Slater and Chhabra (1992) reported that all patients with latex-specific IgE had antibodies to a 14-kDa peptide present in an extract made from nonammoniated latex; many sera recognized a 20-kDa peptide as well. They concluded that current data are insufficient to identify definitively the major allergen(s) and suggested that

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

studies of latex extract would be useful in further characterizing the immune response to natural rubber.

With recent increases in the production and use of latex gloves and other rubber products, clinical sensitivity may be more common than in previous years, and the regulatory, research, and medical communities are responding accordingly. A current regulatory review by the FDA may result in relabeling of latex products—including latex gloves, condoms, catheters, dental dams, and enema kits—to highlight the risks of latex hypersensitivity. The FDA has already issued a Medical Alert (MDA91-1, March 29, 1991) containing recommendations to health professionals regarding the use of latex products. The American College of Allergy and Immunology has also issued interim guidelines on latex allergy.

As noted by Slater (1989), and others, and described in the medical alert and guidelines, patients with a history of rubber-induced allergic reactions, as with all life-threatening allergy, should practice avoidance as the main form of treatment. Health care workers should use nonrubber gloves when treating these patients, and appropriate care should be taken to avoid exposing latex-sensitive patients to either direct or aerosolized contact (e.g., from the cornstarch dust used in packaging latex gloves). It has also been suggested that latex allergen may be carried on syringe needles from the rubber stoppers of multiuse vials (Silverman, 1989).

Finally, it is important that sensitive individuals be recognized prior to surgery so that proper precautions can be taken to avoid latex exposure and minimize the potential for experiencing the associated adverse reactions. In addition to allergen avoidance strategies, some authors believe that latex-sensitive patients should be premedicated according to protocols for the prevention of anaphylactic reactions in surgery (Bielory and Kaliner, 1985; Greenberger et al., 1985; Lasser et al., 1987).

CONCLUSIONS AND RECOMMENDATIONS

Indoor plants are commonly found in offices, schools, and the home. Although most indoor plants do not produce aerosols of allergen-containing particles, as more plants are used indoors, especially in large numbers in office settings, the risk of exposure to plant allergens increases.

Research Agenda Item: Assess the significance of workplace exposures to indoor plants, including the contribution to the overall magnitude of indoor allergic disease.

Latex allergy has recently received substantial attention because of increasing reports of its occurrence and its potential, in certain individuals, to produce life-threatening anaphylactic reactions. In addition to health care

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
×

workers and manufacturers, children with spina bifida are at increased risk for latex allergy.

Research Agenda Item: Conduct research to further characterize the immune response to natural rubber. This effort should include studies of the incidence and prevalence of natural-rubber-related allergic disease.

Suggested Citation:"3 Agents, Sources, Source Controls, and Diseases." Institute of Medicine and National Research Council. 1993. Indoor Allergens: Assessing and Controlling Adverse Health Effects. Washington, DC: The National Academies Press. doi: 10.17226/2056.
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More than 50 million Americans, one out of five, suffer from hay fever, asthma, and other allergic diseases. Many of these conditions are caused by exposure to allergens in indoor environments such as the house, work, and school--where we spend as much as 98 percent of our time.

Developed by medical, public health, and engineering professionals working together, this unique volume summarizes what is known about indoor allergens, how they affect human health, the magnitude of their effect on various populations, and how they can be controlled. The book addresses controversies, recommends research directions, and suggests how to assist and educate allergy patients, as well as professionals.

Indoor Allergens presents a wealth of information about common indoor allergens and their varying effects, from significant hay fever to life-threatening asthma. The volume discusses sources of allergens, from fungi and dust mites to allergenic chemicals, plants, and animals, and examines practical measures for their control.

Indoor Allergens discusses how the human airway and immune system respond to inhaled allergens and assesses patient testing methods, covering the importance of the patient's medical history and outlining procedures and approaches to interpretation for skin tests, in vitro diagnostic tests, and tests of patients' pulmonary function.

This comprehensive and practical volume will be important to allergists and other health care providers; public health professionals; specialists in building design, construction, and maintenance; faculty and students in public health; and interested allergy patients.

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