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Allergen sampling in the environment

Allergen sampling in the environment
Author:
Robert G Hamilton, PhD, DABMLI, FAAAAI
Section Editor:
Peter S Creticos, MD
Deputy Editor:
Anna M Feldweg, MD
Literature review current through: Feb 2022. | This topic last updated: Dec 03, 2021.

INTRODUCTION — Avoidance of allergens remains a cornerstone in the management of patients with allergic diseases. However, many allergens, such as those associated with dust mites, other insects, and animal danders, are ubiquitous in the environment and cannot be entirely avoided. Therefore, effective avoidance measures should be tailored to the specific allergens that are important for a particular patient. The clinician should also focus on environments that can be altered (ie, indoor spaces) and those in which the patient spends significant time. In this context, allergen sampling of the environment may be clinically useful.

This topic will discuss the identification of allergens, indications for allergen sampling, and methods for sampling and measuring allergens, with a focus on aeroallergens in the indoor environment. Indicators of quality testing methods that the clinician can use to identify an appropriate testing laboratory are also discussed. Testing of individuals to determine sensitivity to specific allergens and measures to reduce indoor allergen exposure are presented elsewhere. (See "Overview of skin testing for allergic disease" and "Allergen avoidance in the treatment of asthma and allergic rhinitis".)

IDENTIFICATION OF ALLERGENS — An allergen is a natural substance that is generally innocuous to most people, but when introduced into a genetically predisposed individual, elicits the formation of immunoglobulin E (IgE) antibodies specific to that substance. These allergen-specific IgE antibodies bind to IgE receptors on the surface of the individual's mast cells and basophils. When the subject is re-exposed to that allergen, the allergen binds multiple IgE molecules on the cells' surface, generating activation signals. Mast cell and basophil activation results in the release of an array of inflammatory mediators that precipitate the symptoms of allergic disease. Approximately 20 percent of the population has inherited the ability to become allergic, ie, produce increased amounts of IgE against a specific (usually) proteinaceous substance. The individual's environment then influences the specific allergies they develop.

The identification of clinically important allergens in an environment begins by obtaining clinical histories from affected individuals who, when exposed to a given substance, develop similar signs and symptoms that are known to represent IgE-mediated allergic disease. This process is undertaken when new allergens are suspected in a population. In the past few decades, several new allergens have been identified in the general population, such as Asian ladybugs and stink bugs, and new occupational allergens are regularly identified among manufacturing workers.

Making the connection between symptoms and a specific exposure is most straightforward when allergic symptoms appear shortly after exposure (eg, anaphylaxis following ingestion of peanuts, severe rhinitis or asthma following grass cutting). In contrast, allergens to which people are chronically exposed are much more difficult to identify. As an example, it took several decades to identify the dust mite as the primary source of allergenic material in house dust [1]. In addition, allergen dose and route of exposure also affect the clinical presentation [2]. Allergens that are inhaled or injected usually cause more immediate symptoms compared with those that are ingested.

Once the association between symptoms and a specific exposure is made, blood is collected from these individuals and serum is analyzed to detect any allergen-specific IgE as an indicator of sensitization. In some cases, an extract of the suspect allergenic material can be used in its naturally occurring form to skin test the patient. The goal of this diagnostic allergy work-up is to verify that the individual is sensitized and thus has an IgE-mediated hypersensitivity that may be driven by particular allergens in his/her environment. This process allows effective planning of environmental sampling, targeting of allergen testing, and eventual selection of methods for environment remediation.

To determine what component(s) of the suspect allergenic material is acting as the allergen, a bulk quantity of the substance is then collected and solubilized, usually by soaking it in a physiologic saline solution. Although seemingly crude, this simple technique mimics the conditions that are present when the material contacts a mucous membrane. The resulting extract generally contains a complex mixture of proteins, carbohydrates, and lipids, which can be analyzed using a number of physical, chemical, and immunologic laboratory techniques. Most (not all) allergens are proteins or contain proteins. Protein components are separated based upon their size or net charge. Some can be bound to paper for detection by IgE antibodies from the symptomatic patient(s) serum using Western blotting or isoelectric focusing immunoblotting.

Sera from symptomatic patients are then applied to the allergen-containing blots to determine which components of the allergenic substance bind patients' IgE. This process results in identification of allergens based upon molecular weight and/or isoelectric point. Protein sequencing may then be performed to get the precise primary structure [3]. In addition, advanced analytical methods such as two-dimensional electrophoresis and immunoblotting; liquid chromatography-high resolution mass spectrometry and multiple reaction monitoring mass spectrometry are being used to more precisely identify complex environmental allergens such as those presence in clinically important molds (Alternaria) [4], insects (cockroach) [5], and rodent excretions (mice) [6]. The processes used in the production of allergens for diagnostic testing and treatment are similar and are discussed in more detail separately. (See "Allergen extracts: Composition, manufacture, and labeling".)

When new allergens are identified, information about their taxonomic, biochemical, molecular, and/or genetic characteristics are submitted to the Allergen Nomenclature Sub-Committee (ANSC) of the World Health Organization/International Union of Immunological Societies (WHO/IUIS) Nomenclature Committee. The ANSC is an international network of experts who review submissions of newly-recognized allergens, assign names to them, and maintain the Allergen Nomenclature Database (ANDB). As of late 2021, the database contained 1036 allergens, 106 of which had been submitted in the preceding three years [7]. Other comprehensive allergen databases include:

Allergome: A comprehensive collection of data of on allergens and allergen sources.

AllergenOnline: A peer-reviewed database of allergen sequences for prediction of the allergenicity of proteins.

The Structural Database of Allergenic Proteins (SDAP): A list of allergen sequences, structures, and epitopes linked to bioinformatics tools for sequence analysis and comparison.

The Immune Epitope Database (IEDB): The largest repository of T cell, B cell, and major histocompatibility complex protein epitopes, including epitopes of allergens.

The Allergen Family Database (AllFam): A listing of allergens classified into families of evolutionarily-related proteins using definitions from the Pfam protein family database [8].

The 2021 Diagnostic Allergen Database (DADB [CLSI-IL/A-37]): A database of allergen codes currently used by manufacturers of IgE assays, along with the common names, Latin names, and allergen grouping. Lists all the commercially available allergen extracts and molecules in use in clinical immunology laboratories worldwide as reagents in diagnostic IgE antibody serology autoanalyzers [7].

Another technique for screening for novel allergens within a known allergenic substance involves creating a complementary DNA (cDNA) library from the substance, which is then screened with serum IgE antibodies from a population of people allergic to the substance [9]. One example involves the creation of "AllerScan," a programmable phage display system that is used to characterize the binding specificities of anti-allergen IgG and IgE antibodies in serum against thousands of allergenic proteins from hundreds of organisms found in the environment at peptide resolution [10]. Verification of allergenicity then requires expression of the suspected allergen (eg, in Escherichia coli) and confirmation of allergenicity by in vitro activation of effector cells (eg, IgE-bearing basophils) from individuals who are known to manifest objective allergic symptoms following a challenge with the substance.

Determining the importance of an allergen within a population — The overall importance of a given allergen within a population of allergic patients is determined by the percentage of individuals who produce IgE antibody against it [11]. These determinations are made using study groups of patients who are allergic to a given allergen source (eg, cats). To be designated as a "major" allergen, over 50 percent of subjects who are sensitized to the source need to have IgE antibodies that detect that specific allergen. As an example, feline uteroglobin (Fel d 1) is the major allergen in cat dander and is detected by IgE in the sera of 60 to 90+ percent of cat-allergic patients, depending on whether cat allergen extract or recombinant Fel d 1 is used as the allergen source for testing [12].

Clinicians and patients sometimes wonder if an important indoor or outdoor allergen could have been overlooked. The approach described above should detect the majority of clinically relevant allergens provided the following requirements are met:

The environmental sample collected needs to be representative of all relevant environments in which the exposure is occurring, and it needs to contain the allergen(s) of interest.

The method of allergen extraction should mimic how the allergenic material normally contacts the human body (eg, isotonic extraction of aeroallergens typically absorbed into mucosa of the lung or an acidic solvent extraction that resembles gastric fluid to accurately identify allergens that are absorbed in the stomach after ingestion of a food).

The analytical method (eg, Western blot analysis, isoelectric focusing and/or mass spectroscopy) used to identify proteins that bind IgE needs to be analytically sensitive, accurate and able to discriminate components based on their size, charge or tryptic peptide profile.

The individual serum or pooled sera used to probe the extracted allergen needs to be collected from a population of patients who have unequivocal symptoms to the allergen source being investigated.

Identifying the relevance of an allergen to a specific patient — Testing for the presence of IgE antibodies against various allergens is part of the diagnostic work-up of allergic rhinitis, allergic asthma, and several other allergic disorders. Following a detailed clinical history and physical examination, tests for allergen-specific IgE are performed. These usually consist of in vivo skin tests or provocation tests or in vitro immunoassays based on enzyme-linked immunosorbent assay (ELISA) technology [13]. A number of chip based immunoassays such as the ISAC or ALEX2 Macroarray have also been developed for simultaneously detecting IgE antibodies in a patient’s serum to over 100 molecular allergens in a single analysis [13]. Patients who have demonstrable IgE to a specific allergen are said to be sensitized to that allergen. The diagnosis of various allergic diseases is presented separately. (See "Overview of skin testing for allergic disease" and "Diagnostic evaluation of IgE-mediated food allergy", section on 'In vitro testing' and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis".)

It is critical that the patient be evaluated for allergic disease by in vivo testing to the suspected allergen or in vitro IgE antibody testing before any environmental sampling and allergen testing is considered. This process allows for more effective targeting of the potential offending allergen sites in the analysis phase. In other words, if an individual is not allergic to a particular allergen, then there is no need to consider remediation of the patient’s environment for that allergen specificity. Also, it maximizes the probability of success in resolving the patient's health concerns using environmental remediation techniques to eliminate the allergen source. (See 'Indications for indoor aeroallergen analysis' below.)

Identifying novel allergens — New allergens emerge periodically. In some cases, the source is relatively obvious, such as the Asian ladybug (Harmonia axyridis), which has become prominent in the United States. This insect can infest homes and buildings during cool weather and can trigger rhinitis and asthma in certain individuals. The link between infestation and allergic symptoms was apparent to both patients and clinicians.

Allergens that are not visible or intuitively obvious may only be revealed by a lengthy investigative process involving epidemiologists and laboratory immunologists. The emergence of latex allergy in the early 1990s illustrates this process. At the time, natural rubber latex (Hevea brasiliensis) was used in gloves, catheters, and other medical items and was not known to be an allergenic material. Anaphylaxis was reported in six patients at one institution following barium enema examinations, one of whom died [14]. Initially, barium was thought to be the culprit. However, careful investigation of materials from various items used in the implicated procedures revealed that proteins from latex catheters, gloves, and raw latex could bind IgE antibody in serum from affected patients. One patient volunteered to be skin tested to extracts of the latex products and demonstrated immediate positive results, further confirming latex as the cause. It took many years before all of the principal latex allergens were identified. Products containing natural rubber latex are known to contain at least 15 potent allergenic proteins. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis" and "Latex allergy: Management".)

Another illustration involves the detection of a food allergen (casein from cow's milk) in the padding of a kickboxing glove. A young girl with a severe milk allergy experienced life-threatening anaphylaxis involving cardiac arrest immediately following initial use of a new pair of gloves. Natural rubber latex was initially suspected as the allergen source, but the culprit was ultimately found to be milk protein used as filler in the padding of the gloves. The glove was dissembled and its various parts directly extracted in buffered saline. This was followed by analysis using the IgE antibody and glove extract-based competitive inhibition immunoassay [15] and subsequently Western blot analysis using the girl's serum as an IgE antibody source. Casein protein from cow's milk was identified in the padding of the glove and it was shown to be aerosolized when the glove was used in punching [16].

SOURCES OF AEROALLERGENS — The principal outdoor aeroallergens are pollens released from grasses, trees, and weeds, as well as outdoor molds. The main indoor aeroallergens are released from dust mites, fur-bearing animals, and insects (eg, cockroaches), and selected molds. The table contains a summary of the major categories of known allergens (table 1). Allergens are also found in drugs, venoms, foods, parasites, consumer products (eg, latex balloons, boxing gloves), and a variety of occupational materials, although these are not discussed here. Assessing mold in the environment is discussed separately. (See "Assessment of mold in the indoor environment".)

Outdoor aeroallergens — The presence and relative level of various pollens and mold spores in outdoor air is determined by a network of pollen-counting stations dispersed around the United States, usually in or near major cities [17]. Typically, a cascade or suction impactor device (Rotorod or Burkard sampler) is used to sample the air at daily or weekly intervals. Technical limitations of these methods include the following:

"Pollen and mold counts" are retrospective and represent an integrated measure of pollen and mold spores in the air over the previous 24 hours. However, by the time a pollen or spore count is tabulated and reported, the actual pollen or mold content in the air may have changed significantly because levels of each pollen and spores are highly dependent on weather conditions and they can fluctuate dramatically over short periods of time.

Routine pollen counts are variable in their specificity. The standards defined by the National Allergy Bureau (Aeroallergen Network of the American Academy of Allergy, Asthma & Immunology) request that a center report actual raw numbers for major categories of aeroallergens or report levels as low/medium/high. As an example, if an overall level for all pollens is the only information provided, without individual analyses of tree, grass, and weed pollens, then the information may be misleading for some allergic patients. For instance, on a spring day when grass pollen is high and pollen counts are reported as "high," a person sensitized to ragweed (a late summer/fall allergen) may be minimally symptomatic and may be confused by the report of high counts. Knowing the patient's specific sensitivities is helpful both in educating the patient (eg, environmental control, knowing when to initiate medicines prior to the relevant allergen season) and in considering allergen immunotherapy, if indicated.

Indoor aeroallergens — The principal indoor allergens that induce upper and lower airway allergic symptoms are released by dust mites, fur-bearing pets and rodents, insects (eg, cockroaches and Asian ladybugs), and molds [18]. In addition, pollen and outdoor animal allergens and molds can be transported into the home or school to varying degrees. For each type of allergen, there are indicator allergens (usually the major allergen) that can be measured in reservoir/surface dust samples. The level of these indicator aeroallergens can be used to identify an environment that places a sensitized individual at risk for upper and/or lower airway allergic symptoms [19,20].

Allergen levels can be influenced by many factors, including the building structure, the type of heating and cooling systems, the season, temperature and humidity, pets in and around the environment, furniture and carpeting [21,22], and the number of residents.

Dust mites — The term "house dust mite" refers to four species of arachnid mites that commonly populate homes: Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermatophagoides microceras, and Euroglyphus maynei [1]. Dust mites live and breed in mattresses, carpets, and upholstered furniture, where they absorb water from the air and eat skin and dander shed from humans and animals. Fecal pellets and decaying body parts from these mites contain potent allergens, such as group 1 and 2 allergens from D. pteronyssinus (Der p 1 and 2) [23]. Another major allergen, Der p 23, was identified in 2013. Der p 23 is a protein found in the lining of the midgut of D. pteronyssinus, as well as on the surface of fecal pellets, which can become airborne upon excretion and was recognized by immunoglobulin E (IgE) antibodies from 74 percent of dust mite-allergic patients in one large study [9].

Fur-bearing animals — A variety of domesticated animals including cats, dogs, guinea pigs, hamsters, rabbits, rats, and mice produce dander, saliva, and urine that contain allergens.

The domestic cat (Felis domesticus) releases a potent allergen (Fel d 1) from its sublingual mucous salivary glands and hair root sebaceous glands [24]. Fel d 1 adheres to fibers in carpets and upholstered furniture and to respirable dust particles from 2 to 10 microns in size. Levels of Fel d 1 are used as an indicator of cat allergen burden in house dust. Even pet-free homes and classroom environments have low basal levels of cat and dog allergens, as the allergens are transported into the area on the clothing of people who have household pets [25].

The domesticated dog (Canis familiaris) also releases allergenic proteins from its hair and dander [26]. While both common and breed-specific dog allergens have been reported, Can f 1 is the major cross-reactive dog allergen that is used as an indicator for dog allergen burden in house dust.

Mouse and rat allergens have been detected in the air and surface dust of urban homes. Mus m 1 [6] and Rat n 1 are used as indicator allergens for mouse and rat allergens, respectively, in indoor environments [27]. Larger pets, such as goats, geese, chickens, ducks, cows, and horses are typically kept outdoors, but they can produce allergens that can be tracked into the home. Assays are not available for monitoring the presence of these allergens in household surface dust.

Cockroaches — Of the 50 varieties of cockroach, the German (Blattella germanica) and American (Periplaneta Americana) cockroaches are of particular concern as sources of allergens in homes. Levels of group 1 and 2 German cockroach allergens (Bla g 1 and, Bla g 2) are used as indicator allergens [28]. Potent allergens are released from the saliva, fecal material, secretions, cast skins, and dead bodies of cockroaches. The kitchen, dining room, and other areas of the home where food is consumed remain principal locations for cockroach allergen exposure. Reduced exposure to cockroach allergen can be accomplished by confining eating to the kitchen and dining room, putting non-refrigerated items in tightly sealed plastic containers, and removing the garbage on a daily basis. Moreover, frequent vacuuming, damp-mopping of hard floors, and routine cleaning of countertops and other surfaces reduce potential cockroach allergen exposure. Cockroach allergen exposure is most problematic in urban and tropical areas, in which high densities of cockroaches are maintained.

INDICATIONS FOR INDOOR AEROALLERGEN ANALYSIS — Allergen sampling can be costly and it is often performed prematurely. It is rare for standard air quality assessments performed in workplaces or other public buildings to assess aeroallergens in a comprehensive way, with the possible exception of mold (because public awareness of mold contamination is high compared with that of other aeroallergens). In many cases, it is appropriate that initial air quality assessments focus on factors other than allergens, since many patients' symptoms result from inadequate ventilation or exposure to common indoor irritants. (See "Building-related illness and building-related symptoms", section on 'Building factors'.)

Typically, if an employee complains of a chronic cough or bad odor confined to an area of the building, an initial evaluation will involve review of ventilation in that building, particulate counts, environmental temperature and humidity measurements, and crude mold evaluations.

Before any formal sampling and laboratory analysis of dust from an environment is contemplated, the affected individual must be confirmed to have allergic disease (eg, allergic asthma, allergic rhinitis, or conjunctivitis) to that particular allergen specificity [29]. (See "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Tests for allergy' and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis".)

Not uncommonly, a patient suspects he/she has an allergy to something in the home or workplace but is not sure and has not been evaluated by a clinician (usually an allergy or pulmonology specialist) who can diagnose an allergic disorder. If this evaluation has not taken place, then indoor aeroallergen analysis of the problematic environment is premature and likely to be an ineffective use of time and money.

Once allergic disease is confirmed, an initial inspection of the environment should be performed to identify any obvious signs of allergen contamination. Are cat, dog, mouse, or rat droppings evident? Are there dead cockroaches present? Is there high humidity, a musty odor, or visual evidence of water damage? All these signs are readily and inexpensively detected by the individual's eyes or nose. Oftentimes, the nose can detect mold contamination that is not visually obvious, because it is embedded in the wall.

If initial inspection reveals a possible source of allergens, the next step is reasonable efforts at remediation.

If remediation fails to improve symptoms, then a formal aeroallergen analysis of the environment is appropriate.

A formal aeroallergen analysis of an environment is most useful for individuals who continue to suffer from allergic or asthmatic symptoms following reasonable efforts at remediation. The analysis can uncover unexpected sources of allergen exposure (eg, epidermal allergen from the pets next door or a rodent or cockroach infestation). Alternatively, it can be useful as formal documentation to counter school or workplace claims of a clean environment when a student or worker continues to experience allergic symptoms [30]. The most common concern in these settings is mold infestation after a water leak.

As a general rule, aeroallergen measurements outside of research settings are most likely to be clinically helpful when all of the following criteria are met:

The patient spends significant time in the environment.

The patient has symptoms consistent with IgE-mediated allergic disease (asthma, rhinoconjunctivitis).

The patient is sensitized to relevant indoor allergens that can be measured using the techniques available.

The environment can be altered if a problem is found.

ENVIRONMENTAL SAMPLING METHODS

Indoor aeroallergen analysis — Outside of research, indoor aeroallergen analysis is usually performed to evaluate a patient with allergic respiratory symptoms, such as allergic asthma or allergic rhinoconjunctivitis. Homes represent the principal location of most indoor aeroallergen exposure. Workplaces and schools are generally less problematic, since they are constructed in a manner with less carpet and upholstered furniture, which simplifies cleaning. However, early learning and daycare centers where carpet, stuffed toys, bedding, and upholstered furniture are present can be problem areas for allergen exposure [22,30].

Allergens are distributed on particles in both the air and settled dust. An initial evaluation of the indoor environment often begins with a "global" airborne or surface particulate (dust) specimen that is collected from all of the principal living and working areas of the building where the individual spends considerable time and where symptoms are consistently noted. This composite dust specimen represents a survey of the entire space in question, and it can usefully identify the principal source of a gross aeroallergen problem at minimal expense. The collection of a composite sample addresses the concern of allergen heterogeneity among the different rooms in the living space [18].

As a result of low concentrations of allergens, sampling from air using cyclone (eg, Burkard sampler), impactors (eg, rotorod) and filter samplers has been historically problematic [31]. A newer technology involving ionic propulsion with a high air flow rate [32] has improved airborne allergen sampling efficiency [33]. However, the most rigorous specimen collections continue to involve reservoir dust sampling that can be performed by the homeowner using commercially available dust collection kits. They come with specific written instructions, often prepared by an industrial hygienist. The homeowner, who knows where the most time is spent in the environment, is often best at collecting dust specimens in the home, using the directions provided. Industrial hygienists have some experience but no special certification by any agency in the collection of dust specimens. Reservoir dust collectors (eg, sock filters, wipes, dust stream collectors) [31] that fit on the end of a standard household vacuum are available from testing laboratories. If a dust collection kit is purchased directly by the homeowner (online, for example), care should be taken to ensure that the kit efficiently collects particles down to 1 micron in size.

If the global dust specimen analysis identifies an allergen source, then evaluation of individual rooms within the environment may be useful. This depends, in part, on the type of heating and cooling system present. Forced air tends to circulate allergens among all rooms and minimizes the utility of individual room analysis, while baseboard heating systems tend to preserve regional hot spots of allergens near their source.

Dust specimen processing — Once collected, the specimen is sent to a laboratory that specializes in environmental allergen testing. Dust specimens can contain debris, such as food crumbs, synthetic fibers, and soil, hair, plant, and insect parts, so the sample is first processed by passing it through a 50 mesh metal sieve (50 wires/inch, each with a 0.009 inch diameter). This allows particles smaller than 250 microns to be collected on a waxed filter paper. Next, 100 milligrams of fine dust are extracted in 2 mL of physiologic extraction buffer (phosphate buffered saline containing a carrier protein, such as 1 percent bovine serum albumin). Extraction is rapid, with more than 99 percent of the allergen being solubilized within one hour. However, for convenience, extractions are typically conducted overnight with gentle agitation. In quality laboratories, the extract is filter-sterilized through a 0.22 micron filter and frozen at -20°C (-4°F) or lower until analyzed.

LABORATORY ANALYSIS OF ALLERGEN LEVELS — Certain training and expertise are required for a laboratory to provide aeroallergen testing.

Laboratory certification — Clinicians seeking a laboratory to perform aeroallergen analysis can take several steps to ensure that the laboratory is able to provide reliable results. A quality laboratory should provide the requested information without reservation.

Verify that the laboratory is credentialed by the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) by inspection and accreditation by the College of American Pathologists or the American Industrial Hygiene Organization. This certification ensures that the director of the laboratory and the technical staff have received the appropriate education and training to perform these tests properly.

Request a copy of the procedures for reservoir dust collection, processing, extraction, and analysis to ensure that the laboratory procedures are logical.

Request a copy of two past dust mite, cat, or dog allergen assays and the Levey-Jennings Quality Control chart to ensure consistency between assay runs for each of the allergens. The purpose of this request is verification that the laboratory has established a system to assess their assay reproducibility over time.

Assays — The laboratory should use validated enzyme-linked immunosorbent assays (ELISAs), such as two site immunoenzymetric assays or multiplex assays [34,35]. These assays involve a capture antibody that binds allergen from the extracted surface dust and an enzyme-labeled detection antibody that binds to a different epitope on the same allergen molecule. A particle-based multiplex assay has been validated for the simultaneous measurement of multiple dust mite, pet, insect, and rodent epidermal allergens using a small sample volume.

Reagents should be verified to be specific for the major allergens in dust mite (eg, Der p 1 and 2, Der f 1 and 2), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1 and 2), mouse (Mus m 1), and rat (Rat n 1). Indoor Biotechnology is the primary commercial source for aeroallergen reagents. It provides monoclonal antibodies and qualified allergen standards, and most laboratories which perform aeroallergen testing in the United States purchase reagents from this company. Assays for food allergens, such as peanut, are being used to assess the allergen levels required to promote prevention and subsequent detection of these allergens in the indoor spaces (eg, planes, homes) [36].

Quality control and proficiency testing — No national proficiency testing program exists for monitoring the quality of aeroallergen measurements across clinical laboratories that provide these services. Internal laboratory quality control and inter-laboratory proficiency testing is voluntary. Only one large program, called the "Healthy Homes Project," has instituted a clinical laboratory proficiency testing program in which a common dust is provided to the laboratory periodically, and analytical results are monitored over time by participants.

Despite the lack of organized oversight, at least one study found that there was acceptable accuracy and precision in a sampling of eight experienced commercial, academic, and municipal laboratories that were measuring dust mite allergens using ELISA-based technologies [37].

TARGET LEVELS OF INDOOR ALLERGENS — In general terms, the lower the level of allergen in the environment, the lower the risk of allergic symptoms [38]. Complete avoidance of indoor allergens is not achievable in most cases, so studies have attempted to define desirable target levels [39]. These levels can only estimate tolerable levels for subgroups of patients, since the level that is tolerated by a given individual is obviously dependent upon his/her sensitivity.

Dust mite allergens — In limited studies of dust mite-sensitive children with asthma, levels >2000 micrograms per gram of surface reservoir dust of indicator allergen (eg, Der p 1, Der p 2, Der f 1, or Der f 2) were associated with increased risk of sensitization, and levels >10,000 micrograms were associated with an increased risk of allergic symptoms [18,38,39].

Cat and dog allergens — For both cat (Fel d 1) and dog (Can f 1) allergen, levels >8000 to 10,000 and >80,000 nanograms per gram of fine dust, respectively, have been identified as targets above which there is an increased risk for allergic sensitization and symptoms, respectively [18,38,39].

Other allergens — No target levels have been identified for indicator allergens of mouse, rat, or cockroach that signify an environment that is a potential problem for an atopic individual who is sensitized to these allergens. Instead, any detectable level of Bla g 1 and Bla g 2 (eg, higher than 1 unit/gram) is considered indicative of a home that places a sensitized individual at risk for allergic symptoms. Rodent and cockroach exposure can be particularly problematic for children with asthma who live in urban areas [40].

Molds — Assessment of mold in the indoor environment is reviewed in detail separately. (See "Assessment of mold in the indoor environment".)

SUMMARY AND RECOMMENDATIONS

Allergens of clinical importance are identified through an investigative process that begins when a link is made between allergic symptoms and a specific exposure. Suspect substances are collected from the environment, processed in the laboratory to release proteins and other components, and tested with sera from patients to determine what components react with the patients' immunoglobulin E (IgE) molecules. This same process is repeated whenever a new allergen emerges. (See 'Identification of allergens' above.)

Outside of research settings, allergen sampling is most often performed to evaluate indoor spaces, as most people spend the majority of their time indoors, and these environments can be altered if a problem is found, unlike outdoor environments. The principal indoor allergens that induce upper and lower airway allergic symptoms originate from dust mites, fur-bearing pets and rodents, insects (cockroaches), and molds. (See 'Sources of aeroallergens' above.)

Aeroallergen sampling is likely to be clinically useful only if the patient has allergic rhinitis, rhinoconjunctivitis, or asthma, is known to be sensitized to the allergens included in the assessment, and has persistent symptoms despite already taking reasonable measures to reduce known allergen sources. (See 'Indications for indoor aeroallergen analysis' above.)

Aeroallergen sampling is performed on physiologic extracts of dust from the patient's living space, which is filtered to remove debris and used in a series of enzyme-linked immunosorbent assays (ELISAs) that detect the major allergens of the important indoor allergens. Specific questions about Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) accreditation and quality control measures can help clinicians identify appropriate laboratories. (See 'Environmental sampling methods' above and 'Laboratory analysis of allergen levels' above.)

Levels of major allergen above which the patient is at increased risk for symptoms have been identified for dust mite, cat, and dog. (See 'Target levels of indoor allergens' above.)

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  10. Monaco DR, Sie BM, Nirschl TR, et al. Profiling serum antibodies with a pan allergen phage library identifies key wheat allergy epitopes. Nat Commun 2021; 12:379.
  11. Burbank AJ, Sood AK, Kesic MJ, et al. Environmental determinants of allergy and asthma in early life. J Allergy Clin Immunol 2017; 140:1.
  12. Grönlund H, Saarne T, Gafvelin G, van Hage M. The major cat allergen, Fel d 1, in diagnosis and therapy. Int Arch Allergy Immunol 2010; 151:265.
  13. Hamilton RG, Hemmer W, Nopp A, Kleine-Tebbe J. Advances in IgE Testing for Diagnosis of Allergic Disease. J Allergy Clin Immunol Pract 2020; 8:2495.
  14. Ownby DR, Tomlanovich M, Sammons N, McCullough J. Anaphylaxis associated with latex allergy during barium enema examinations. AJR Am J Roentgenol 1991; 156:903.
  15. Hamilton RG. Allergen-specific human IgE antibody based analysis of food. In: Handbook of food allergen detection and control, Flanagan S (Ed), Woodhead Publishing, London 2014.
  16. Hamilton RG, Scheer DI, Gruchalla R, et al. Casein-related anaphylaxis after use of an Everlast kickboxing glove. J Allergy Clin Immunol 2015; 135:269.
  17. Pollen count information is available through the website of the American Academy of Allergy, Asthma, and Immunology. www.aaaai.org/nab (Accessed on August 23, 2010).
  18. Hamilton RG. Assessment of indoor allergen exposure. Curr Allergy Asthma Rep 2005; 5:394.
  19. Hamilton RG, Eggleston PA. Environmental allergen analyses. Methods 1997; 13:53.
  20. Ahluwalia SK, Matsui EC. Indoor Environmental Interventions for Furry Pet Allergens, Pest Allergens, and Mold: Looking to the Future. J Allergy Clin Immunol Pract 2018; 6:9.
  21. Becher R, Øvrevik J, Schwarze PE, et al. Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review. Int J Environ Res Public Health 2018; 15.
  22. Salo PM, Wilkerson J, Rose KM, et al. Bedroom allergen exposures in US households. J Allergy Clin Immunol 2018; 141:1870.
  23. Thomas WR, Smith WA, Hales BJ. The allergenic specificities of the house dust mite. Chang Gung Med J 2004; 27:563.
  24. Leitermann K, Ohman JL Jr. Cat allergen 1: Biochemical, antigenic, and allergenic properties. J Allergy Clin Immunol 1984; 74:147.
  25. Bollinger ME, Eggleston PA, Flanagan E, Wood RA. Cat antigen in homes with and without cats may induce allergic symptoms. J Allergy Clin Immunol 1996; 97:907.
  26. de Groot H, Goei KG, van Swieten P, Aalberse RC. Affinity purification of a major and a minor allergen from dog extract: serologic activity of affinity-purified Can f I and of Can f I-depleted extract. J Allergy Clin Immunol 1991; 87:1056.
  27. Matsui EC, Simons E, Rand C, et al. Airborne mouse allergen in the homes of inner-city children with asthma. J Allergy Clin Immunol 2005; 115:358.
  28. Arbes SJ Jr, Sever M, Mehta J, et al. Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation results. J Allergy Clin Immunol 2004; 113:109.
  29. Gold DR, Adamkiewicz G, Arshad SH, et al. NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and childhood asthma-implications for home environmental intervention in asthma prevention and management. J Allergy Clin Immunol 2017; 140:933.
  30. Permaul P, Phipatanakul W. School Environmental Intervention Programs. J Allergy Clin Immunol Pract 2018; 6:22.
  31. Raulf M, Buters J, Chapman M, et al. Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology & Air Pollution. Allergy 2014; 69:1280.
  32. Gordon J, Reboulet R, Gandhi P, Matsui E. Validation of a novel sampling technology for airborne allergens in low-income urban homes. Ann Allergy Asthma Immunol 2018; 120:96.
  33. Gordon J, Detjen P, Nimmagadda S, et al. Bedroom exposure to airborne allergens in the Chicago area using a patient-operated sampling device. Ann Allergy Asthma Immunol 2018; 121:211.
  34. Luczynska CM, Arruda LK, Platts-Mills TA, et al. A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p I and Der f I. J Immunol Methods 1989; 118:227.
  35. Earle CD, King EM, Tsay A, et al. High-throughput fluorescent multiplex array for indoor allergen exposure assessment. J Allergy Clin Immunol 2007; 119:428.
  36. Hindley JP, Filep S, Block DS, et al. Dose of allergens in a peanut snack (Bamba) associated with prevention of peanut allergy. J Allergy Clin Immunol 2018; 141:780.
  37. Pate AD, Hamilton RG, Ashley PJ, et al. Proficiency testing of allergen measurements in residential dust. J Allergy Clin Immunol 2005; 116:844.
  38. Platts-Mills TA, Ward GW Jr, Sporik R, et al. Epidemiology of the relationship between exposure to indoor allergens and asthma. Int Arch Allergy Appl Immunol 1991; 94:339.
  39. Platts-Mills TA, Chapman MD, Pollart SM, et al. Establishing health standards for indoor foreign proteins related to asthma: dust mite, cat and cockroach. Toxicol Ind Health 1990; 6:197.
  40. Sheehan WJ, Rangsithienchai PA, Wood RA, et al. Pest and allergen exposure and abatement in inner-city asthma: a work group report of the American Academy of Allergy, Asthma & Immunology Indoor Allergy/Air Pollution Committee. J Allergy Clin Immunol 2010; 125:575.
Topic 13525 Version 15.0

References

1 : The history of the finding of the house dust mite.

2 : Clinical laboratory assessment of immediate-type hypersensitivity.

3 : Amino acid sequence of Fel dI, the major allergen of the domestic cat: protein sequence analysis and cDNA cloning.

4 : The Allergen: Sources, Extracts, and Molecules for Diagnosis of Allergic Disease.

5 : Measurement of German cockroach allergens and their isoforms in allergen extracts with mass spectrometry.

6 : Diversity and complexity of mouse allergens in urine, house dust, and allergen extracts assessed with an immuno-allergomic approach.

7 : Newly defined allergens in the WHO/IUIS Allergen Nomenclature Database during 01/2019-03/2021.

8 : Navigating through the Jungle of Allergens: Features and Applications of Allergen Databases.

9 : Natural Evolution of IgE Responses to Mite Allergens and Relationship to Progression of Allergic Disease: a Review.

10 : Profiling serum antibodies with a pan allergen phage library identifies key wheat allergy epitopes.

11 : Environmental determinants of allergy and asthma in early life.

12 : The major cat allergen, Fel d 1, in diagnosis and therapy.

13 : Advances in IgE Testing for Diagnosis of Allergic Disease.

14 : Anaphylaxis associated with latex allergy during barium enema examinations.

15 : Anaphylaxis associated with latex allergy during barium enema examinations.

16 : Casein-related anaphylaxis after use of an Everlast kickboxing glove.

17 : Casein-related anaphylaxis after use of an Everlast kickboxing glove.

18 : Assessment of indoor allergen exposure.

19 : Environmental allergen analyses.

20 : Indoor Environmental Interventions for Furry Pet Allergens, Pest Allergens, and Mold: Looking to the Future.

21 : Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review.

22 : Bedroom allergen exposures in US households.

23 : The allergenic specificities of the house dust mite.

24 : Cat allergen 1: Biochemical, antigenic, and allergenic properties.

25 : Cat antigen in homes with and without cats may induce allergic symptoms.

26 : Affinity purification of a major and a minor allergen from dog extract: serologic activity of affinity-purified Can f I and of Can f I-depleted extract.

27 : Airborne mouse allergen in the homes of inner-city children with asthma.

28 : Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation results.

29 : NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and childhood asthma-implications for home environmental intervention in asthma prevention and management.

30 : School Environmental Intervention Programs.

31 : Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology&Air Pollution.

32 : Validation of a novel sampling technology for airborne allergens in low-income urban homes.

33 : Bedroom exposure to airborne allergens in the Chicago area using a patient-operated sampling device.

34 : A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p I and Der f I.

35 : High-throughput fluorescent multiplex array for indoor allergen exposure assessment.

36 : Dose of allergens in a peanut snack (Bamba) associated with prevention of peanut allergy.

37 : Proficiency testing of allergen measurements in residential dust.

38 : Epidemiology of the relationship between exposure to indoor allergens and asthma.

39 : Establishing health standards for indoor foreign proteins related to asthma: dust mite, cat and cockroach.

40 : Pest and allergen exposure and abatement in inner-city asthma: a work group report of the American Academy of Allergy, Asthma&Immunology Indoor Allergy/Air Pollution Committee.