National Academies Press: OpenBook

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

Chapter: 5 Medical Testing Methods

« Previous: 4 Mechanisms of Immune Function
Suggested Citation:"5 Medical Testing Methods." 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.
×

5
Medical Testing Methods

Methods to determine the effects of indoor allergens can be divided into two general categories: patient testing and environmental testing. Patient testing evaluates the health status of an individual (clinical) or population (epidemiological). Environmental testing characterizes environments with respect to sources of allergens, dissemination factors, ambient concentrations, and human exposure. Data from both kinds of testing can be used to direct treatment, control, and prevention of allergic disease. This chapter discusses common approaches to patient testing including the medical history, skin tests, in vitro serum tests, and evaluations of pulmonary function. Chapter 6 discusses environmental testing and the assessment of exposure and risk.

MEDICAL HISTORY AND DIAGNOSIS

History

A common dictum in allergy practice is that the patient's medical history is the primary diagnostic test. Laboratory studies, including skin and in vitro tests for specific immunoglobulin E (IgE) antibodies, have relevance only when correlated with the patient's medical history. Furthermore, treatment should always be directed toward current symptomatology and not merely toward the results of specific allergy tests. Several authors of current allergy textbooks reiterate these points:

Suggested Citation:"5 Medical Testing Methods." 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 selection of appropriate diagnostic tests is fully dependent on the clinical history presented by the patient in question. It therefore follows that diagnostic tests should be ordered only after a careful history and physical examination have been obtained" (Kaplan, 1985).

  • "The degree of success that will be achieved in the treatment of a patient's allergies will be proportional to the exactness of the history obtained" (Weiss and Rubin, 1980).

  • "It is of utmost importance to begin with a thorough, perceptive general medical history…. If the general history suggests an allergic disease, one must ascertain what factors are important in producing the difficulty of the individual patient. The history is the major approach in making this assessment, and the most important clinical skill to be learned in evaluating allergy patients is to acquire facility in asking discerning questions so that logical deductions can be made about the cause of the patient's difficulty" (Korenblat and Wedner, 1984).

  • "The purposes of the medical evaluation are to establish the diagnosis, to estimate the severity of the illness, to determine responses to previous treatment, to identify possible complications, and thus to guide appropriate further management. A thorough medical history is the most helpful tool in achieving these objectives in the field of allergy" (Bierman and Pearlman, 1988).

In spite of universal agreement about the primary importance of a patient's allergy history, the same textbooks from which these quotations were taken (and others) devote little or no space to this topic (Tables 5-1 and 5-2). Furthermore, review of the allergy literature reveals no discernible research on the subject.

Allergists use a variety of methods to obtain a history, including (1) an open-ended, nondirected question-and-answer session, (2) a series of questions ordered according to a formal protocol to ensure completeness, (3) a structured questionnaire history completed by the physician, or (4) a structured questionnaire history completed by the patient. Many allergists use a combination of these methods.

The use of particular history formats or questionnaires depends on the purpose of the examination—for example, whether it is the clinical evaluation of an individual patient or an epidemiological study of a general or selected population (e.g., that of a particular building, factory, or industry). A commonly used format for evaluating a patient's medical history contains the following eight components:

  1. Chief complaint—This includes (a) the reason for the patient's visit, such as referral from a primary physician, need for treatment of a current problem, potential need to avoid an allergen (e.g., penicillin, cat), or disability evaluation, and (b) a concise definition of the symptom or complaint

Suggested Citation:"5 Medical Testing Methods." 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 5-1 Textbooks of Clinical Immunology

Textbook

Publisher

Total Pages

Allergy Pages

Clinical Evaluation Pages

History Pages

Parker, C.W., Clinical Immunology (2 vols.), 1980

Saunders

1,438

248

0

0

Graziano, F.M., and Lemanske, R.F., Clinical Immunology, 1989

Williams & Wilkins

310

103

0

0

Freedman S.O., and Gold, P., Clinical Immunology (2nd ed.), 1976

Harper & Row

620

133

0

0

Lockey, R.F., and Bukantz, S.C., Principles of Immunology and Allergy , 1987

Saunders

335

214

26

Lockey, R.F., Allergy and Clinical Immunology, 1979

Medical Examination Publishing Co.

1,175

588

9

3

Altman, L.C., Clinical Allergy and Immunology, 1984

G.K. Hall

473

268

0

0

Samter, M., Immunologic Diseases (2 vols., 4th ed.), 1988

Little, Brown

2,044

267

0

0

Stites, D.P., and Terr, A.I., Basic and Clinical Immunology (7th ed.), 1991

Appleton & Lange

794

64

½

for which the patient is seeking treatment, preferably in the patient's own words.

  1. Present illness—A complete description of current symptoms, including severity and duration. Questions such as the following should be answered:

  • Do symptoms vary seasonally, monthly, weekly, or diurnally? Or are they randomly intermittent?

  • What is the relationship of symptoms to location, such as in the home, at work, and while traveling?

Suggested Citation:"5 Medical Testing Methods." 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 5-2 Textbooks of Allergy

Textbook

Publisher

Total Pages

Clinical Evaluation Pages

History Pages

Kaplan, A.P., Allergy, 1985

Churchill Livingstone

692

0

0

Lessof, M.H., Allergy: Immunological and Clinical Aspects, 1984

Wiley

464

0

0

Beall, G.N., Allergy and Clinical Immunology, 1983

Wiley

326

0

0

Korenblat, P.E., and Wedner, H.J., Allergy: Theory and Practice, 1984

Grune & Stratton

512

13

5½ (plus 5-page questionnaire)

Lawlor, G., and Fischer, T.J., Manual of Allergy and Immunology: Diagnosis and Therapy, 1981

Little, Brown

409 (plus 13 appendixes)

10

1½ (plus ½-page questionnaire)

Klaustermeyer, W.B., Practical Allergy and Immunology, 1983

Wiley

209

25

Weiss, N.S., and Rubin, J.M., Practical Points in Allergy (2nd ed.), 1980

Medical Examination Publishing Co.

211

4½ (appendix)

Middleton, E., et al., Allergy: Principles and Practice (2 vols., 3rd ed.), 1988

C. V. Mosby

1,597

0

0

Bierman, C.W., and Pearlman, D.S., Allergic Diseases from Infancy to Adulthood (2nd ed.), 1988

Saunders

787

6

3

Patterson, R., Allergic Diseases (3rd ed.), 1985

Lippincott

825

20

9 (plus 2-page questionnaire)

Suggested Citation:"5 Medical Testing Methods." 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.
×
  1. Patients should be asked about known precipitants (e.g., dust, animals, weather). If symptoms occur in discrete attacks, the allergist should ascertain the frequency of attack, and ask the patient to describe in detail a typical or recent episode. The description of the present illness should also include a list of all current medications and the duration of their use, as well as the efficacy of symptomatic medications. The practitioner should address specific efforts made by the patient to avoid certain allergens and the efficacy of such avoidance.

  2. Past allergy history—In assessing this component, the practitioner reiterates questions about the patient's present illness but directs them toward other allergic manifestations that are either no longer occurring or not related to the current evaluation. In addition, he or she should specifically ask the patient about known allergies to foods, drugs, vaccines, and insect bites or stings. Results of past allergy testing and immunotherapy are also informative. Because of regional differences in both indoor and outdoor aeroallergens, a chronological listing of the patient's places of residence should be compared with a history of symptoms.

  3. Current and past medical history, including review of systems—This is necessary because of the possible effect of other diseases on allergy, and vice versa. In addition, pregnancy may alter certain allergic manifestations.

  4. Family history of allergy—The allergy history and general health of immediate family members should be determined.

  5. Occupational history—This portion of the evaluation seeks clues to work-related sources of allergens that may explain a patient's illness. In cases evaluated for work disability, this step must include a complete list of all occupations in which the patient has engaged, including employer, location, and job description.

  6. Social history—This set of questions may reveal a symptomatic role for psychosocial factors and "substance" use (tobacco, drugs, alcohol).

  7. Environmental history—This is a unique feature of the allergy history. It describes specific features of the patient's indoor and outdoor environments and the effects of specific environmental agents on symptoms. It also serves as the basis of recommendations for allergen avoidance. Table 5-3 details appropriate information regarding the patient's environmental history.

Conclusion and Recommendation

In spite of universal agreement on the primary importance of a patient's allergy history, very little space in medical textbooks is devoted to the topic, and no standard exists for collecting appropriate information. A standardized, validated allergy-history questionnaire would be useful in both clinical and research settings.

Suggested Citation:"5 Medical Testing Methods." 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 5-3 Environmental History for Indoor Aeroallergen Exposure

1. Home: Location_______________________________________________

Age________Years of Residence________Construction_______________

Heating/cooling system_________________________________________

Filter type_______________Frequency of change____________________

Indoor plants________________________________________________

Bedroom: Carpeting type____________________________Age________

Carpet pad__________________Furniture_________________________

Mattress type________________________Age______Dust cover_______

Pillow(s) type________________________Age______Dust cover_______

Quilt or comforter_________________________________Age_________

Living room: Carpeting__________________________Pad_____________

Family room: Carpeting__________________________Pad_____________

Basement: Flooring_____________________________Dampness_________

2. Animals and Birds

Dog(s): No.______ Years______ In or out________

Cat(s): No.______ Years______ In or out________

Others: No.______ Years______ In or out________

Bird(s) No.______ Years______ In or out________

3. Work: Employer_________________________________Years__________

Occupation___________________________________________________

Effect on symptoms_____________________________________________

4. Hobbies:______________________________________________________

Effect on symptoms________________________________________________

5. Exposure

Allergens

Irritants

House dust

Auto exhaust

Other dust

Diesel fumes

Mold, mildew

Gasoline

Feathers

Pesticides

Cats

New carpet

Dogs

Perfumes

Horses

Paints

Chickens

Cleaners

Birds

Solvents

Rats

Smoke

Mice

Newsprint

Guinea pigs

Others

Rabbits

 

Suggested Citation:"5 Medical Testing Methods." 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.
×

Research Agenda Item: Develop, test, and validate a standardized allergy-history questionnaire for use in multi-center studies.

Physical Examination

The physical examination should be thorough enough to rule out other causes for the patient's symptoms. Because allergic diseases may be episodic, the physical examination should be performed during a period of allergen exposure when objective signs of allergy can be seen. Negative results from a physical examination performed during a period of allergen avoidance does not mean that the patient does not have an allergy.

Daily Diaries

Daily diaries are sometimes necessary in cases in which the diagnosis is not clear from the history. They allow ongoing symptoms to be recorded and correlated with observed environmental exposures, ingested food, medication use, and other factors. Diaries can also be used in conjunction with such functional measures as the pulmonary peak flow rate (see the discussion later in this chapter). Clinical trials of medications or immunotherapy and studies of occupational asthma have used such diaries extensively and to good advantage. The literature indicates several specific uses that have been made of them. For example, daily diaries have been used to study the acute effects of environmental factors (Cohen et al., 1972; Finklea et al., 1974a,b; Lawther et al., 1970; Lebowitz et al., 1985; McCarroll et al., 1966; Quackenboss et al., 1989a; Schoettlin and Landau, 1961; WHO, 1982; Zagraninski et al., 1979). There have also been some efforts at partial standardization of diaries (Finklea et al., 1974a; WHO, 1982; Zagraninski et al., 1979) and validation for symptom and medication usage (Lebowitz et al., 1985; Zagraninski et al., 1979).

Daily diaries for use in surveys of morbidity (e.g., to estimate the prevalence of specific diseases) were developed, tested, and used in the early 1950s. They have higher reporting levels than standard health history questionnaires and may provide better information about minor health events. Diaries are especially useful for accurate reporting of acute episodes and disability (Allen et al., 1954; Laurent et al., 1972; Mooney, 1962; Muller et al., 1952; Peart, 1952; Verbrugge and Depner, 1981). Because symptom recording occurs soon after symptom development, recall is at a maximum, resulting in more comprehensive health information about the individual. Diaries compare favorably with interview surveys in response rate, segment completion rate, and low attrition. Physician visits reported in diaries are generally quite accurate, except for unusual events (e.g., x-rays only) or as part of

Suggested Citation:"5 Medical Testing Methods." 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.
×

general nonresponse (Marquis, 1978). Thus, diaries may provide important information with great accuracy for certain clinical research studies.

The format for diaries must be established on a case-by-case basis to obtain the information needed for the specific purpose of the study. Population studies that require statistical analyses may mandate simplified reporting at specified times of particular symptoms on a yes/no basis or by using a severity scale; clinical evaluation of an individual patient may be better served by open-ended narrative descriptions. Within a household, a daily diary can be completed by each adult and by one adult for all children. The data should include (1) symptoms selected from a list, (2) medication usage, (3) activity, (4) disability, and (5) physician visits.

For analysis, symptoms can be aggregated into sets (e.g., irritant, allergic, asthmatic, acute respiratory illness, nonspecific). Other information can also be aggregated—for example, (1) days of restricted activity ("unable to do usual activities"), (2) days of disability ("unable to work, go to school …"), and (3) days requiring physician or emergency room visits (as well as days requiring increased medication usage). In addition, acute respiratory symptoms such as irritative, infectious, or allergic responses can be tracked for periods of 2 or more weeks and then repeated in a different season of the year or at selected regular intervals to measure the reliability of findings and to study the effect of seasonal or other environmental exogenous stimuli.

SKIN TESTS

Allergen skin testing has been a primary diagnostic tool in allergy since the 1860s. Skin tests, in and of themselves, are not diagnostic of allergic disease but provide evidence of immunologic sensitization. These tests are of particular value in deciding on, and undertaking strategies to avoid exposure to indoor allergens that are causing allergic symptoms (NHLBI, 1992).

A positive skin test is the culmination of a number of events that begin with the interaction of the allergen with IgE on the surface of cutaneous mast cells, as described previously in this report. This interaction is followed by the release of chemical mediators such as histamine, which then exert their effects on the skin by causing the blood vessels to dilate and the plasma to leak into the tissue. Neuronal axon reflexes are also involved.

The characteristic skin reaction consists of a "wheal" produced by the leakage of fluid into the skin and a surrounding area of redness ("flare") produced by the dilated blood vessels—the "wheal and flare" response. Thus, the skin test is not simply a test for the presence of specific IgE antibodies; it also involves the sensitivity of the mast cell and the biological effect of the chemical mediators on tissue. The size of the reaction is related to several factors including the amount of allergen injected, the

Suggested Citation:"5 Medical Testing Methods." 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.
×

degree of sensitization of the cutaneous mast cells and their ability to release histamine, and the reactivity of the skin to the mediators released (H. S. Nelson, 1983). The advantages of skin testing are its simplicity, rapidity of results, low cost, and high sensitivity; however, skin tests can be subject to abuse through inappropriate use or overuse. Table 5-4 presents a comparison of some in vivo and in vitro methods for the diagnosis of IgE-mediated allergic disease.

Major Methods

Two major skin testing methods are commonly used: the skin prick or puncture test and the intradermal test. In the prick method, a drop of allergenic extract is applied to the skin, and the skin is pricked with a needle through the drop. A number of devices are commercially available for testing using this method (Demoly et al., 1991). The most commonly used skin prick method is to introduce the tip of a stylette or a 27 (or smaller) gauge needle into the epidermis at a 15- to 20-degree angle through the drop of test allergen and then to lift up until the tip of the needle pops loose. Alternatively, lancets or solid needles are often used.

One concern about the skin prick method is the possible transfer of allergens from one test site to another if the needle is not properly wiped off

TABLE 5-4 Comparison of Two In Vivo Skin Tests (Prick and Intradermal) with In Vitro Tests (RAST or Equivalent) for Diagnosing IgE-Mediated Allergic Diseasea

 

In Vivo Skin Tests

 

In Vitro (Specific IgE)— RAST or Equivalent

Parameter

Skin Prick

Intradermal

Sensitivity

Good

Excellent

Fair-good

Specificity

Good

Poor-fair

Excellent

Safety

Excellent

Good

Excellent

Reproducibility

Good

Good

Excellent

Convenienceb

Excellent

Good

Fair

Cost

Excellent

Good

Fair

NOTE: RAST, radioallergosorbent test.

a Ratings are based on the assumption that the procedures are done by well-qualified personnel using properly standardized reagents and adequate quality control.

b Convenience is a composite of efficiency and ease of testing, lack of discomfort, and rapid availability of test results.

SOURCE: Adapted from Van Arsdel and Larson, 1989.

Suggested Citation:"5 Medical Testing Methods." 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.
×

between each test. This problem can be avoided by using a fresh needle for each test site. Another potential area of difficulty involves placement of the allergens: if they are too close, overlapping reactions cannot be separated. It is therefore recommended that the extracts be placed at least 2 cm apart.

Infection and bleeding can lead to false-positive results. Likewise, insufficient penetration of the skin by the puncture instrument may lead to false-negative results. (This problem is more likely to occur with plastic devices [Bousquet, 1988].) Skin prick tests are applicable to children as young as 1 month of age if clinical indications are present. Use of the test usually requires allergen concentrations of 1:10 to 1:20, weight/volume. Skin prick tests pose an extremely low risk for the development of systemic anaphylactic reactions or fatalities.

In intradermal testing, allergenic extracts are diluted in a buffered saline solution containing 0.3 percent human serum albumin as a stabilizer. Volumes of 0.01 to 0.05 ml are injected intradermally. As noted above, individual, unitized syringes should be employed for each skin test to avoid any risk of contamination from syringes with removable needles that have been used repeatedly (Shulan et al., 1985). Solutions containing less than 1 percent glycerine may be used for skin testing; concentrations greater than this amount may induce nonspecific reactions.

Because a small but definite risk of anaphylaxis and fatalities exists with intradermal testing (Lockey et al., 1987), skin prick tests should be conducted prior to any such testing. In addition, patients who are suspected of having allergic disease but who have a negative skin prick test may be candidates for intradermal testing because intradermal testing is more sensitive. Properly conducted negative intradermal skin tests virtually exclude the presence of specific IgE antibody.

Scratch or abrasion methods should probably be abandoned (Van Arsdel and Larson, 1989). These tests have poor reproducibility because of the variable amount of allergen introduced into the skin. False-positive reactions may occur if bleeding is induced; there is also a risk of systemic allergic reactions (Guerin and Watson, 1988).

Variables and Controls

Several variables can affect the size of the cutaneous reaction. The magnitudes of both allergen and histamine reactions vary over different parts of the body. The upper and midback are more reactive than the lower back. The back is more reactive than the forearm. The ulnar side of the arm is more reactive than the radial. The wrist area is less reactive than the space in front of the elbow (H. S. Nelson, 1983). There is also some variability in skin test responsiveness at different times of the day. At 7 a.m., the reaction to allergen and histamine is less than that in the late

Suggested Citation:"5 Medical Testing Methods." 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.
×

afternoon and early evening. The age of the individual undergoing testing also influences the size of the skin test response. Young infants have wheals and flares that are smaller in diameter than those in adults. In addition, skin test reactivity declines after age 60.

The reproducibility of epicutaneous skin testing, particularly that using a skin prick test, depends on the degree of pressure applied to the skin. Medications can significantly affect the skin test response. For example, antihistamines and tricyclic antidepressants must be discontinued for at least 4 to 5 days before testing occurs (I. L. Bernstein, 1988). Some long-acting antihistamines such as astemizole (Hismanal®) may interfere with skin test results for up to 6 weeks. Long-term use of high-potency topical steroids also decreases skin test reactivity. Oral corticosteroids at doses of up to 30 mg a day for 1 week do not suppress the allergic skin test response.

Because skin tests may be affected by a number of factors, positive and negative controls should be applied. Some general recommendations for skin testing procedures are summarized in Box 5-1.

Shortcomings and Precautions

One of the major difficulties with reproducibility of skin test responsiveness is the lack of standardized reagents. Certain indoor allergenic extracts (e.g., dust mite and cat) now contain standardized amounts of major allergens, and further efforts at standardization are under way for other allergens. Because extracts often become less potent over time when stored under warm conditions, refrigeration is important. The addition of glycerine to skin prick test reagents enhances their stability, as does the use of

BOX 5-1 Allergy Skin Test Procedures

  1. Avoid antihistamines and tricyclic antidepressants for 4 to 5 days prior to testing. Long-acting antihistamines e.g., astemizole (Hismanal®) should be avoided for 4 to 6 weeks prior to testing. Topical corticosteroids applied to the test site can reduce the response when used for several weeks. Topical, nasal, inhaled, or systemic corticosteroids have no effect on the skin test response.

  2. Appropriate positive (histamine or codeine phosphatase) and negative (diluent) controls should be used.

  3. The forearm or upper back skin are appropriate test sites.

  4. Appropriately trained personnel and equipment to treat systemic anaphylaxis should be available.

Suggested Citation:"5 Medical Testing Methods." 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.
×

human serum albumin for the more dilute solutions used for intradermal testing.

Because of safety issues involved in allergy skin testing, tests should never be performed unless properly trained personnel and emergency equipment to treat systemic reactions are available. In particular, patients receiving beta-adrenergic-blocking agents for treatment of hypertension or heart disease should be advised of this risk, because they are less likely to respond to epinephrine in the case of anaphylaxis. Skin testing should be avoided in these patients until a substitute treatment can be found (Executive Committee, American Academy of Allergy, 1989).

Interpretation of Results

The methods for interpreting skin tests are not well defined. It is known that an immediate skin test response to histamine reaches a peak at about 8–10 minutes; for agents such as codeine that act directly to cause histamine release from mast cells, peak response comes at 10–15 minutes, whereas allergens elicit responses in 15–20 minutes. At the time of peak response, the diameter of the wheal and flare is measured; sometimes a permanent record is obtained by outlining the size of the reaction with a pen and then blotting the marks onto cellophane tape, which is stored on paper.

Generally, a wheal 3 mm or greater in diameter is considered a positive test using the skin prick method. However, a grading system has been established (Bousquet, 1988) in which erythema (redness of the skin) and a wheal of less than 5 mm in diameter is a negative test. A 2+ reaction is a 5- to 10-mm wheal with 21–30 mm of erythema; this size response is often elicited by histamine control. A 3+ reaction is a 5- to 10-mm wheal with pseudopods and erythema of 31–40 mm. A 4+ reaction is a wheal of 15 mm or greater within any pseudopods and erythema of 40 mm or more. Other investigators have found that if a control site is completely negative, wheals of 1–2 mm with flare and itching are likely to represent a positive response. Although these reactions indicate immunologic sensitization, they do not necessarily indicate the presence of clinically relevant allergic symptoms.

From 2 to 8 percent of individuals with no personal history of allergy or respiratory disease exhibit positive skin test responses with intradermal testing. These positive tests may indicate the presence of specific IgE antibodies but not the presence of clinical allergy. A true false-positive test occurs as a result of irritant reactions; in the case of intradermal testing, it may be produced by the so-called splash response when air is injected into the skin. Occasionally, a false-positive reaction is the result of nonspecific enhancement, through the axon reflex, from a nearby strong allergic reaction. For this reason, skin tests should be placed at least 2–5 cm apart, and the positive histamine control should be at some distance from the allergen test

Suggested Citation:"5 Medical Testing Methods." 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.
×

sites. False-negative skin test results are usually due to poor quality, low potency, or lack of stability of the extracts used for testing. Most commercially available extracts exhibit wide variability in the concentration of allergens. Unrefrigerated extracts lose potency rapidly. Stabilizing agents such as glycerine or human serum albumin can improve this situation.

Correlation with Other Tests

Skin tests have been correlated with other tests for diagnosing allergic disease. A reasonably good correlation seems to exist between a strongly positive skin prick test and specific IgE assay by radioallergosorbent test (RAST) (see the discussion in the section below, ''In Vitro Diagnostic Tests"). Similarly, a negative skin prick test and negative RAST also correlate well (H. S. Nelson, 1983). Small reactions to skin prick tests are less frequently associated with a positive RAST. Intradermal tests that are positive with high concentrations of allergens are only occasionally associated with a positive RAST (H. S. Nelson, 1983).

Patients may have positive skin prick tests before they develop allergic symptoms, and the tests may be predictive of future symptoms. In patients with negative histories and negative skin prick tests, the diagnosis of allergic disease can usually be excluded if the extract is of high quality.

Conclusions and Recommendations

A major unknown in skin testing is the identity of the more prevalent allergens involved in many indoor exposures. Studies to characterize these allergens are important for the development of reliable diagnostic reagents. Additional research is needed to identify, characterize, and standardize indoor allergenic extracts used for diagnostic testing.

Research Agenda Item: Develop standardized, well-defined indoor-allergen reagents for skin tests that can be used in clinical diagnosis and research studies.

Despite some relatively minor shortcomings, the value of skin testing has been well established over the past century. When correlated with an appropriate clinical history, skin prick tests often are a useful way of screening for the presence of allergic disease. Using appropriate positive and negative controls, intradermal testing can be used to demonstrate low levels of sensitization when allergy is clinically suspected. However, studies are necessary to determine the optimal concentrations and methods for skin testing and to address the relationship between defined skin test reactions and disease.

With respect to the specificity and sensitivity of skin tests within a

Suggested Citation:"5 Medical Testing Methods." 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.
×

population, more research is needed to determine the predictive values of both skin prick and intradermal tests. Moreover, the doses and criteria for positive skin tests used for such studies need further definition, together with criteria to define the relationship of a positive skin prick test to the wheal area or erythema that appears.

Recommendation: Encourage the development and use of improved standardized methods for performing and interpreting skin tests.

For safety reasons, appropriately trained personnel and adequate equipment need to be available to treat possible adverse systemic reactions.

IN VITRO DIAGNOSTIC TESTS

Confirmation of the diagnosis of an allergic reaction resulting from a given agent generally requires some immunologic test that demonstrates a specific antibody response to the agent. For allergic rhinoconjunctivitis and most allergic asthma, demonstration in vivo or in vitro of specific IgE would be appropriate. For hypersensitivity pneumonitis, in vitro demonstration of either specific immunoglobulin or specific cell-mediated immunity, or both, would be acceptable. Although allergic asthma is IgE mediated, the immunopathogenesis of non-IgE-mediated asthma has not been elucidated; thus, the appropriate corroborative immunologic tests are unknown. The exact role of cell-mediated immunity and T cell activation in asthma also has not been defined. Therefore, the role of assays to detect specific cell-mediated immunity or T cell activation in asthma is unclear.

An immunologic response to an agent is not sufficient to diagnose an allergic disease caused by that agent. Such a response means only that a prior sensitizing exposure to the agent or a cross-reacting agent has occurred. Diagnosis of a hypersensitivity disease such as allergic rhinitis requires a compatible clinical syndrome in addition to the appropriate specific immunologic response.

Several in vitro tests are available for use in clinical practice and research. These include a variety of serum antibody tests and tests of cell-mediated immunity. These tests are discussed below, along with the importance of reagent quality, the diagnostic value of the tests, and the importance of quality control.

Serum Antibody Tests

Several investigators have reported on in vitro tests for estimating IgE directed against an allergen. A widely used immunoassay is the RAST, in which the allergen is bound to a solid phase and then incubated first with patient serum and then with radiolabeled antihuman IgE (Adkinson, 1986).

Suggested Citation:"5 Medical Testing Methods." 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 number of radiolabeled antihuman IgE molecules that bind to the allergen is indicative of the amount of specific IgE in the patient's serum. If antibody is not present in excess in the serum, however, or if there is competing allergen-specific antibody of another isotype, interference can occur.

The enzyme-linked immunosorbent assay (ELISA) is analogous to RAST except for the detection system (Voller and Bidwell, 1986). In the case of ELISA, the antihuman IgE is conjugated to alkaline phosphatase, which catalyzes a colorimetric change proportional to the level of serum-specific IgE. The same interferences described above for RAST can occur with ELISA. In addition, false positives may occur in both assays if the serum has a high total level of IgE resulting in nonspecific binding of IgE with the allergen being tested. Several other immunoassays for specific IgE have been reported but are not widely used.

By using antihuman antibody directed to other immunoglobulin classes, such as antihuman IgG, ELISA can be used to demonstrate specific isotypes other than IgE. The clinical significance of such antibodies in asthma, however, is not clearly apparent. In cross-sectional studies of asthma and hypersensitivity pneumonitis, the presence of specific IgG has been interpreted as a biological marker of exposure (Biagini et al., 1990; Lushniak et al., 1990). There is also evidence, especially following immunotherapy with allergens, that antibody of a non-IgE isotype can be protective and prevent exposed individuals from manifesting IgE-mediated clinical sensitivity (Cooke et al., 1935).

In patients with hypersensitivity pneumonitis, precipitin assays can be used to demonstrate high titers of specific antibody. The most commonly employed assay of this type is the double-immuno-diffusion method of Ouchterlony (A. M. Johnson, 1986). In this assay, center and circumferential wells are cut in agar; sera are then placed in the circumferential wells, and the allergen is placed in the center. A precipitin band will form between the serum and the allergen wells if precipitating antibody, usually class IgG, is present in the serum. If a test serum is next to a positive control serum, researchers can determine whether the antibodies in the two sera recognize the same allergens, different allergens, or a combination; this judgment is based on the pattern of the precipitin lines, which show complete identity, nonidentity, or partial identity, respectively. Because commercial preparations of most hypersensitivity pneumonitis allergens are poorly standardized, the use of positive and negative control sera is critical. False-negative test results can also occur if a zone of equivalence (where precipitin lines form) is not obtained because of improper allergen concentration. Other techniques, including ELISA and the ammonium sulfate precipitation method of Lidd and Farr, have also been used as immunoassays for the evaluation of hypersensitivity pneumonitis (Lidd and Farr, 1962; Zeiss et al., 1977).

Suggested Citation:"5 Medical Testing Methods." 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.
×

Tests of Cell-Mediated Immunity

Specific cell-mediated immunity can be evaluated by several methods (Fink et al., 1975; Stankus et al., 1982). In the lymphocyte transformation assay, the patient's lymphocytes are incubated with an allergen, and DNA replication is measured by tritiated thymidine incorporation. Other assays of cell-mediated immunity include production of mediators or cytokines, or messenger RNA for cytokines by sensitized lymphocytes that have been incubated with the putative agent. Although assays for detecting specific cell-mediated immunity may be more specific for hypersensitivity pneumonitis, they are generally regarded as research assays and are not usually performed in evaluations of patients or populations with hypersensitivity diseases.

Test Reagents

ALLERGENS

Ideally, the test reagents used in immunodiagnostic assays of allergic disease should be standardized extracts, the allergen contents of which are well characterized. Efforts to produce such reagents are in early stages of development. There are several requisites for allergen standardization and characterization that differ depending on whether the allergen is a complete protein allergen or a low-molecular-weight (LMW) chemical that requires conjugation to an autologous protein (Bush and Kagen, 1989; Butcher et al., 1989). Most protein allergens have not been standardized or characterized. To standardize an extract that contains protein allergens, the source of the allergen should be identified, as should the extraction procedures used, including time, temperature, extraction fluid, and method of filtration (Bush and Kagen, 1989). For many extracts the source is known, but the biochemical composition is not, although numerous procedures exist for such characterization. Properties that are useful for evaluation include total protein content, molecular weight distribution, isoelectric points of individual components, and allergenic composition. Protein content can be measured by techniques such as the biuret method (Kabat and Mayer, 1967) and the ninhydrin assay (Richman and Cissell, 1984). Using a variety of gels, column chromatography can determine molecular weight distribution. Isoelectric focusing can be used to ascertain the isoelectric points of individual components (Marcus and Alper, 1986). Numerous in vitro and in vivo assays are available for assessing such properties as immunologic or allergenic composition of an extract, including quantitative cutaneous endpoint titration (Norman, 1986), immunoblotting (Thorpe et al., 1988), RAST inhibition (Helm et al., 1988), leukocyte histamine release (Siraganian and Houk, 1986), and immunoelectrophoresis (Price and Longbottom, 1986).

Suggested Citation:"5 Medical Testing Methods." 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 availability of recognized reference preparations, particularly in lyophilized form, would be of obvious value (Platts-Mills and Chapman, 1991). The International Union of Immunologic Societies (IUIS) in the World Health Organization has developed several reference preparations. The Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration has also developed or sanctioned some preparations. They differ from the IUIS preparations, however, in character and unitage. In short, there are no universally agreed upon reference standards, methods of characterization, or assignment of unitage.

Because LMW chemicals are not complete allergens, they generally require conjugation to a carrier protein before they can be used in immunoassays (D. I. Bernstein and Zeiss, 1989). It is, of course, important to determine whether chemical protein linkage has occurred and the range of epitope density that has been defined, since the latter is known to determine the allergenicity of a chemical-protein conjugate. Any of a variety of techniques may be appropriate: free amino group analysis (Snyder and Sobocinski, 1975), spectrophotometric analysis (Zeiss et al., 1980), or gas chromatography (D. I. Bernstein et al., 1984). Thus, a reagent can be optimally prepared by selection of epitope density. The same uncertainties of characterization and standardization outlined above for complete protein allergens also exist for chemical-protein conjugates.

ANTIBODIES

Currently, there is no central serum bank or sharing of serologic reagents, and controls tend to be obtained by individual laboratories. In addition to reference allergen preparations, reference sera, reference serum pools, or reference monoclonal antibodies of known specific antibody content would be useful as positive controls in immunoassays.

Diagnostic Value of In Vitro Tests

The value of a laboratory test for diagnosing a given condition in a given population is judged by its sensitivity, specificity, and positive predictive value (Galen, 1986). These qualities of in vitro tests for the presence of IgE specific to common inhalant allergens have not been accurately determined. Evaluations of these tests would be useful before embarking on any large epidemiological studies of putative indoor allergens that cause allergic reactions. Among certain indoor allergens, such as various species of dust mite, cross-reactivity 1 of allergens is known to occur. To what

1  

 The interaction of an antigen with an antibody formed against a different antigen with which the first antigen shares closely related or common antigenic determinants. The effect is to reduce the specificity and sensitivity of the test method.

Suggested Citation:"5 Medical Testing Methods." 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.
×

extent this occurs in general with indoor allergens is not well established. In reports comparing in vivo and in vitro testing, however, in vivo testing (e.g., skin tests) has been found to be more specific (Johansson and Foucard, 1978; Wide and Bennich, 1967).

Almost all symptomatic hypersensitivity pneumonitis patients have positive precipitins against the inciting agent; however, a significant proportion of exposed, asymptomatic individuals (15–40 percent) also have positive precipitins (Pepys and Jenkins, 1965; Wilson et al., 1981). The sensitivity of the precipitin assay thus approaches 90 to 100 percent; the specificity is approximately 60 to 85 percent. These figures apply only when the inciting agent is identified and an antigen is available for in vitro testing. Cellular assays such as lymphocyte stimulation studies have been reported to result in fewer clinical false-positive results with consequent specificity of approximately 95 percent (Hanson and Penny, 1974). Virtually all symptomatic individuals also have positive cellular assay results; thus, the sensitivity of such tests approaches 100 percent. In addition, there is an epiphenomenon of patients with inflammatory lung diseases such as sarcoid or idiopathic pulmonary fibrosis who may have precipitins against common inhalant allergens.

Quality Control

Quality control of immunoserologic testing is similar but not identical to quality control for other diagnostic tests (Taylor, 1986). Moreover, it is unlikely that these criteria are universally followed; therefore, comparability of results from various laboratories should not be assumed. Periodically, a laboratory should assess inter- and intra-assay variability. Positive sera of known value and negative sera should also be assessed periodically. A standard curve is generally employed for quality control; the results of the assessments should fall within a certain range on the curves.

As new immunoassays are developed and reported, certain properties of the tests must be evaluated. These include specificity, parallelism, interassay variability, intra-assay variability, and comparability of tests to those results obtained from a recognized immunoassay.

Conclusions and Recommendations

The accuracy of any immunodiagnostic test is highly dependent on the characteristics of the test reagents, in particular, the allergen reagent. Standardization and characterization of allergen reagents used for immunodiagnostic tests are imperative. There are a variety of characterization methods and unitages that could be used. Similarly, the existence and characterization of control antibody, whether polyclonal or monoclonal, would be valuable for standardization and quality control of immunodiagnostic tests. Ideally, minimal

Suggested Citation:"5 Medical Testing Methods." 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.
×

standards for quality control should be devised for labs reporting results of tests to detect specific immunologic responses to indoor allergens.

Once the above are instituted, the specificity, sensitivity, and positive predictive value of immunodiagnostic tests could be determined for use in major epidemiological studies or to determine specific immunologic responses of individuals to indoor allergens. In addition, the degree of cross-reactivity of antibody developed in response to a given allergen could be determined by cross-inhibition with other allergens. It would be important to assess these factors prior to embarking on any large epidemiological studies. There are also several unclear aspects of the immunopathogenesis of allergic disease that need elucidation in order to define the role of various tests (e.g., tests of specific cell-mediated immunity in asthma). Further immunopathogenic studies of non-IgE-mediated asthma and cellular studies in all types of immunologic asthma will be required to clarify these issues.

Future studies in the development of in vitro diagnostic tests should include the following:

Research Agenda Item: Identify selected allergens of potential research usefulness, and prepare pure reference standards for the development of immunoassays, including those that can be used in large scale epidemiological studies.

Research Agenda Item: Develop and assess immunoassays for new allergens, including low molecular weight allergenic chemicals, that can be used for research and for the diagnosis of allergic disease.

PULMONARY FUNCTION TESTS

Applications and Methodological Challenges

Pulmonary function tests are well-established, practical methods that are widely used in the evaluation and monitoring of diseases due to indoor allergens. One of the major shifts in clinical practice recommendations is the suggestion that peak flow meters be widely used for outpatient self-monitoring of asthma (NHLBI, 1991). However, objective measurements of respiratory status have been available for decades.

The clinician must choose among an array of possible pulmonary function tests. Table 5-5 shows the types of practical questions that may be answered using pulmonary function tests, and which tests will address these questions. All diagnoses are made using pulmonary function tests as one part of a complete clinical evaluation. Patient cooperation and maximal effort are essential for valid test results. Proper training of pulmonary function technicians, supervision of the testing facility by a knowledgeable

Suggested Citation:"5 Medical Testing Methods." 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 5-5 Choosing Lung Function Tests for Use in Clinical Medicine and Research

Question

Test Method

Does my patient meet the objective criteria

for a diagnosis of asthma?

 

(1) Variable airflow obstruction

▪ An obstructive pattern on spirometry with an immediate positive bronchodilator response (15 percent improvement in FEV1)

or

▪ Peak flow variability with serial measurements.

or

▪ Variable airflow obstruction with repeated spirometry

(e.g., methacholine or histamine)

or

(2) Bronchial hyperreactivity

▪ Positive response to nonspecific challenge

Is my patient improving with asthma treatment?

▪ Reduced bronchial hyperreactivity

▪ >10 percent improvement in FEV1 or peak flow

▪ Reduced diurnal variation in peak flow

Does my patient have hypersensitivity pneumonitis?

▪ Reduced spirometry

▪ Reduced diffusing capacity

▪ Reduced lung volumes

Is my patient becoming ill in his/her home?

▪ Peak flow measurements with prolonged time in and out of the home

Could the reduction in lung function in my patient be due to a problem (disease) other than asthma?

▪ Spirometry

▪ Lung volumes

▪ Diffusing capacity

Why is my patient so short of breath with exercise?

▪ Spirometry and diffusing capacity

and

▪ If symptoms are unexplained by these tests, then perform exercise testing

What is the clinical value of histamine or methacholine challenge testing? (See Cockroft and Horgreave, 1990.)

▪ Excluding or confirming a diagnosis of asthma

or

▪ Diagnosis and management of occupational asthma

or

▪ Assessing the severity of asthma and monitoring asthma treatment

NOTE: Lung function tests are to be used in conjunction with a clinical evaluation.

Suggested Citation:"5 Medical Testing Methods." 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.
×

professional, and attention to quality assurance generally result in high-quality tests (Enright, 1992).

Diseases such as asthma and hypersensitivity pneumonitis, which are caused by indoor allergens, are characterized by decrements in lung function that vary over time (Fink et al., 1971; Hodgson et al., 1987; Jacobs et al., 1989; Kawai et al., 1984; Lopez and Salvaggio, 1988). The variability occurs in recognizable patterns, yet is highly diverse among individuals (Perrin et al., 1991). This feature poses important challenges for clinical and epidemiological studies. Chief among these challenges is the requirement for repeated measures of pulmonary function and the need to assess the magnitude and pattern of variability in the test result. Clinicians must also develop practical schemes to monitor variations in lung function.

Pulmonary function tests have many applications in clinical medicine and research related to indoor allergens (Table 5-6). The appropriate choice of pulmonary function test depends on the requirements of the specific application.

Spirometry

Spirometry, the most reliable and commonly used pulmonary function test, measures the characteristics of a forced expiratory maneuver (ATS, 1991; Gold and Boushey, 1988). To perform this test, subjects are instructed to take in as deep a breath as possible, to seal their lips around the

TABLE 5-6 Applications of Pulmonary Function Tests

Application

Clinical Practice

Clinical Studies

Epidemiological Studies

Diagnosis

Evaluate the effect of sensitization

X

 

 

Identify specific diseases

X

X

X

Assess disease severity

X

X

X

Suggest causal relationships*

X

X

X

Demonstrate causal relationships*

X

X

 

Treatment

Evaluate the response to therapy Medication

X

X

X

Environmental modification/allergen modification

X

X

X

Impairment/disability evaluation

X

 

 

Disease incidence or prevalence

 

 

X

* Suggestion or demonstration of causal relationships usually requires serial measurements of pulmonary function coupled with challenge testing or a change in environments.

Suggested Citation:"5 Medical Testing Methods." 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 5-7 Coefficients of Variation (percentage) for Spirometric Measurements of Different Subject Groups

Subject

Slow VC

FVC

FEV1

FEF25–75%

Normal

3

5

7

13

Obstructed

 

11–14

14

18

NOTE: VC, vital capacity (maximal volume of air exhaled from the point of maximal inhalation); FVC, forced vital capacity (total volume of air exhaled); FEV1, volume of air exhaled in 1 second; and FEF25–75% , forced expiratory flow between 25 and 75 percent of forced vital capacity.

SOURCE: ATS (American Thoracic Society), 1987.

spirometer mouthpiece, and then to blow out as hard and as fast as they can for at least 6 seconds or until instructed to stop. The spirometer measures changes in volume as a function of time (a volume-based system) or changes in airflow as a function of time (a flow-based system) and plots the tracing on an x–y axis. The results of each tracing are described as volume exhaled in 1 second (FEV1), the total volume exhaled (FVC, forced vital capacity), and the percentage of the total volume exhaled in 1 second ([FEV1/FVC] × 100). Subjects repeat the maneuver until three acceptable tracings are obtained. Criteria for acceptable tracings have been established by the American Thoracic Society. One important criterion is that the technician must judge that the patient has exerted a maximal effort. The best value of three acceptable efforts is taken as the actual measurement.

To be a valid measure of lung function, reproducibility criteria must be met. Reproducibility criteria state that the best and the second-best FEV1 and FVC should be within 5 percent or 100 cc, whichever is greater (ATS, 1987). However, the use of these standards may tend to produce underestimates of pulmonary function changes in worker populations, because those with the most disease are the least likely to produce acceptable curves. Diseased workers producing nonreproducible or unacceptable spirometry results would be deleted from the study and thus would not be identified as having disease. This example of "ascertainment bias" has been discussed more extensively by Eisen (1987). Studies summarized in Table 5-7 have quantitated reproducibility in spirometric measurements across days and weeks (ATS, 1991; Lebowitz et al., 1987). Less precise measurement could lead to more variability over time; conversely, stringent quality assurance can result in coefficients of variation below 6 percent for repeated spirometry, even for subjects with obstructive lung disease (Enright et al., 1991).

Spirometry results are compared to published reference values, and presented as percent predicted derived from cross-sectional population-based

Suggested Citation:"5 Medical Testing Methods." 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 (Crapo et al., 1981; Knudson et al., 1983; Morris et al., 1971). Predicted values depend on an individual's height, age, and sex. Tall, young men have the greatest predicted lung function. When an individual's actual function is below predicted values, the magnitude of the abnormality may be described according to various schemes such as that presented in Table 5-8 (Engelberg, 1988).

Spirometry interpretation characterizes the type of abnormality that is present. Typically, asthma is characterized by airflow obstruction, meaning that a disproportionate decrease in FEV1 relative to FVC exists and peak flow rates are reduced. Hypersensitivity pneumonitis is characterized by a reversible restrictive pattern; that is, FEV1 and FVC are reduced in parallel, and peak flow rates may be unchanged despite significant drops in other measures of lung function. Exceptions to these generalizations, however, are well recognized. In asymptomatic or mild asthma, lung function may fall within the normal range. In more severe asthma, symmetric reductions of FEV1 and FVC occasionally occur and may be misinterpreted as restrictive lung disease. Measurement of lung volumes (see below) will show an increased total lung capacity and air trapping. Clinical evaluation using bronchodilators may also result in improvement. The use of flow rates is helpful in limited circumstances and requires more careful interpretation (ATS, 1991). Spirometry may be repeated after administration of bronchodilators; improvement in pulmonary function indicates the presence of reversible airway obstruction, a characteristic feature of asthma.

Spirometry interpretation includes determining whether lung function has changed over time. Comparison with previous tests by the same subject

TABLE 5-8 American Medical Association/American Thoracic Society: Description of Respiratory Impairment

Parameter

None

Mild

Moderate

Severe

FVCa

≥80

60–70

51–59

≤50

FEV1

≥80

60–79

41–59

<40

FEV1/FVC

≥70

50–69

41–59

<40

DLCOb

≥80

60–79

41–59

<40

or

 

 

 

 

VO2maxc ml(kg · min)

>25

20–25

15–20

<15

a Predicted values of FVC are from Crapo and Morris, 1981; Crapo et al., 1981.

b DLCO, diffusing capacity of the lungs for carbon monoxide.

c VO2max, maximum volume of oxygen exhaled.

SOURCES: Engelberg, 1988; Renzetti et al., 1986.

Suggested Citation:"5 Medical Testing Methods." 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.
×

adds greatly to the validity of spirometry because it narrows the range of expected values. With this approach, normal is defined with reference to the subject's original value instead of defining ''normal" as any value between 80 percent and 120 percent of standard, predicted values which are derived from population studies. In principle, there is a 95 percent certainty of a decline in lung function if the measured fall is 1.65 times the coefficient of variation for repeated studies (Pennock et al., 1981). However, these guidelines are not uniformly applied or accepted. For example, the cotton dust standard of the U.S. Department of Labor defines a 5 percent, or 200 ml, change across a work shift as significant, yet some studies have shown this magnitude of change to be within expected cross-shift variability for some workers (Glindmeyer et al., 1981; Sheppard, 1988a). Enright and others (1991) achieved a confidence interval of 5.9 percent for duplicate spirometry performed (on average) 25 days apart among subjects with mild to moderate airflow obstruction. Intrasubject variability from year to year, as reported by Nathan and colleagues (1979) for more than 1,000 individuals, indicates that most subjects have greater yearly variability than short-term changes (Lebowitz et al., 1982). Roughly speaking, the expected annual decline in FEV1 is 1 percent.

In the clinical setting, a source of potential variability is the use by patients of different laboratories with different equipment and technicians. In theory, of course, these differences should be minimal if proper calibration procedures are used.

For the most effective evaluation of individual pulmonary function, epidemiologists must also designate proper criteria by which to define exposure-response relationships. Lebowitz and colleagues (1987) propose that such criteria represent clinically meaningful—as distinct from statistically significant—responses.

Spirometry equipment is relatively inexpensive, portable, and accessible. It may be transported to work sites and is available in most hospitals and some physician offices. The equipment is sturdy and usually retains precision. Spirometers are now frequently coupled with computers for automated data calculation. Results appear on a printout or on a computer screen, and sequential tracings are superimposed for ease in assessing reproducibility. "Hard-copy" tracings can also be made and may be required for medicolegal reports.

Extensive efforts have resulted in improved precision for spirometry testing. Table 5-9 shows minimum standards for spirometry equipment that have been established by the American Thoracic Society. Nevertheless, S. B. Nelson and coworkers (1990) found that some commercially available spirometers produced FVC errors as large as 1.5 liters (a 25 percent error) primarily as a result of problems with computer software. Technicians and subjects can be trained to perform the test with precision, accuracy, and

Suggested Citation:"5 Medical Testing Methods." 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 5-9 Technical Standards for Peak Flow Meters and Spirometers

Device

Range of Accuracy

Interdevice Variability

Precision

Reproducibility

Peak flow meters Children

Adults

100–400 liters/min

100–700 liters/min

= 10%

±5%

±10%

5% or 10 liters/min

Spirometers

720 liters/min

≥7 liters

15 seconds

 

±3% or 0.05 liter

5% or 100 cc

NOTE: The test signal for spirometers is the 24 standard waveforms; for peak flow meters, only waveform no. 24 should be used. The waveforms, developed by Hankinson and Gardner, can be used to drive a computer-controlled mechanical syringe for testing actual hardware and software.

SOURCES: ATS (American Thoracic Society), 1987; NHLBI, 1991.

reproducibility. Technician training courses, certified by the National Institute for Occupational Safety and Health, are available throughout the United States. Efforts to standardize spirometry methods (ATS, 1987) and improve technician training have greatly increased precision, which is now adequate for such applications as clinical diagnosis, disease management, evaluating severity of impairment, and for clinical and epidemiological studies. However, this precision is inadequate to allow a demonstration of subtle longitudinal declines in lung function, because the expected rate of decline for an individual is only about 1 percent per year. Conversely, spirometry is a sensitive measure of disease, since reductions can be detected before severe impairment occurs.

Determination of the reversibility of airflow obstruction is made by performing spirometry before and after administration of a bronchodilator. A 15 percent improvement in FEV1 after using a bronchodilator is considered evidence of reversible airflow obstruction.

Peak Flow Measurements

Peak flow measurements are especially useful to patients in asthma self-management. Patients produce peak flow measurements by inhaling as deeply as possible, sealing their lips around the mouthpiece, and briefly exhaling at maximum velocity. The tube is attached to a measuring device that records the maximum flow rate achieved during exhalation. Patients then read the result and manually record it on a paper record. Patients perform 3 efforts, and the best value is taken as the actual measurement.

Suggested Citation:"5 Medical Testing Methods." 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.
×

Peak expiratory flow occurs within the first second of a forced expiratory maneuver. Maximum flow occurs within the first few hundred milliliters of volume expired from total lung capacity and is volume and effort dependent. To measure peak flow accurately, the exhalation must begin at maximum inspiration and must be performed with maximum effort. In contrast to spirometry, there is no requirement for a prolonged smooth exhalation, which is an advantage for asthmatics. (Asthmatics often cough immediately following a forced expiratory effort, which can interfere with attempts to obtain acceptable spirometry.) Reduced peak expiratory flow is considered a valid measure of airflow obstruction, and it correlates well with FEV1.

Peak flow meters are lightweight, compact, inexpensive ($15–$50) instruments that are small enough to be carried in a purse or coat pocket. Hospitals use peak flow meters for bedside monitoring of asthma severity and response to bronchodilators. Current asthma management guidelines recommend daily home monitoring of peak flow using a peak flow meter (NHLBI, 1991). Peak flow measurements are used extensively in clinical trials of asthma therapy.

Efforts are proceeding to improve peak flow meters. The European Respiratory Society and the American Thoracic Society are developing standards for their construction and use. In addition, peak flow meters with a computer chip to allow recording of the time of peak flow effort should be on the market soon. This innovation will increase the cost of peak flow meters but will be a significant advantage for clinical studies.

The accuracy of peak flow meters varies among models. Table 5-9 shows technical standards suggested by the National Asthma Education Panel of the National Heart, Lung, and Blood Institute (NHLBI, 1991). Deficiencies in commonly used meters are outweighed by their benefits (Lebowitz, 1991; NHLBI, 1992). Although a flow range of 0–720 liters per minute has been recommended, some units are highly inaccurate within this range. Nevertheless, peak flow meters are invaluable for correlating changes in respiratory obstruction with a variety of activities and events experienced by the patient.

Current guidelines suggest that peak flows should be reproducible within 5 percent or 10 liters per minute (NHLBI, 1991). Reproducibility of peak flow measurements using mini-Wright peak flow meters was determined by having 10 subjects perform 30 forced expiratory maneuvers. Coefficients of variation ranged from 2 to 14 percent (Lebowitz et al., 1982). Significant training effects were seen during the first 2 days of a fortnight's study, and Quackenboss and colleagues (1991b) excluded these data from consideration in an epidemiological study. Measurement by standard and mini-Wright peak flow meters has been found to be stable over 6 months (Morrill et al., 1981; Van As, 1982). This stability over time may be more important

Suggested Citation:"5 Medical Testing Methods." 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.
×

than absolute accuracy, given that the usual application for peak flow involves an assessment of serial changes in peak flow in the same subject over time (Van As, 1982).

Interpretation of peak flow variability is best performed by visual inspection of a graph that plots peak flow over time. Computer-based algorithms for interpreting peak flow measures have been shown to be no better than the "eyeball" method for diagnosing work-related asthma (Perrin et al., 1992).

Detection of Airway Hyperreactivity

Bronchial hyperreactivity, a cardinal feature of asthma, is measured as follows. Patients perform initial spirometry, and the resultant FEV1 is defined as the baseline value. The patient then inhales saline, followed by increasing concentrations of an agonist such as methacholine or histamine, or a stimulus such as cold air or a distilled water aerosol. After each provocation, spirometry is repeated and FEV1 is determined for that dose. The test is stopped when a predetermined reduction in lung function is achieved or the maximum dose is administered. Exercise testing is also used occasionally to measure bronchial reactivity. Typically the test ends when a 20% reduction in FEV1 or a 35 percent reduction in specific airway conductance has occurred, and a provocative dose is calculated.

The challenge method and type of data recorded differ among laboratories (Chai et al., 1975; Chatham et al., 1982a). Some record the concentration of agonist at the endpoint, whereas others record the cumulative dose. The percent decrease in FEV1 (targeted as a positive end point) ranges from 10 to 40 percent, with a 20 percent decrease being most common. Popa and Singleton (1988) attempted to determine which of the current provocative doses for histamine optimally separates normal from asthmatic subjects. They concluded that new normative data for diagnostic provocation were needed because of a high misclassification rate using current methods. Inhalation challenge testing with methacholine, histamine, distilled water, exercise, etc., is commonly termed non-specific challenge testing to distinguish these from specific allergen challenge testing. However, each of these chemical and physical agents act on different bronchial receptors and therefore reflect different aspects of non-specific bronchial hyperreactivity. Furthermore, animal studies indicate that inherited hyperreactivity to these agents is transmitted at distinct genetic loci (Levitt et al., 1990).

Despite recognized limitations, testing for airways reactivity is widely used because it is a practical test which has great utility in clinical medicine and research. Asthmatics as a group develop reductions in lung function with provocation at much lower doses than do non-asthmatics. The considerable within-subject overlap in hyperreactivity to methacholine, histamine

Suggested Citation:"5 Medical Testing Methods." 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.
×

and distilled water challenges means that each of these agents is widely used. Increased reactivity has been described in non-asthmatics, particularly in first degree relatives of asthmatics, cigarette smokers, people with allergic rhinitis, and some apparently normal individuals. In general, asthmatics are the most reactive (i.e., require the smallest concentration of agonists to effect a reduction in lung function). The risk of bronchial reactivity increases with increasing skin test reactivity (Burrows and Lebowitz, 1992; Lofdahl and Svedmyr, 1991). In asthmatics, the degree of reactivity correlates with other measures of disease severity. People with allergic rhinitis demonstrate an intermediate level of reactivity. A high proportion of cigarette smokers with airflow obstruction demonstrate increased airways reactivity, but the population distribution of airways reactivity among smokers without airflow obstruction is unknown at present.

Data from Pattemore and colleagues (1990) show a 24 percent prevalence of frequent wheezing in children with normal airway responsiveness and a lack of current asthma symptoms in 41 percent of people with hyperresponsiveness. This has led some to criticize the utility of measurement of methacholine or histamine responsiveness in clinical practice. Cockroft and Horgreave (1990) disagree, and point out that when spirometry is normal, methacholine and histamine hyperresponsiveness is a sensitive measure of abnormal airway function that correlates closely with the presence and degree of variable airway obstruction.

Cockroft and Horgreave (1990) specifically identify three areas of clinical utility for histamine and methacholine inhalation tests:

  1. Exclusion or confirmation of a diagnosis of asthma, especially if the presentation is atypical.

  2. Diagnosis and follow-up of occupational asthma.

  3. Assessment of the severity of asthma and monitoring of asthma treatment.

Bronchoprovocation Testing with Specific Allergens

Allergen-specific bronchoprovocation testing is a research tool used to diagnose specific immunologic diseases, identify new etiologic agents, and study the pathogenesis of asthma and hypersensitivity pneumonitis (Chan-Yeung and Lam, 1986; Pepys and Hutchcroft, 1975). Guidelines for allergen challenge have been proposed by the American Academy of Allergy and Immunology (Chai et al., 1975).

The limits of allergen inhalation challenge testing outside of a research setting are several. It is time-consuming and staff intensive, and may not be reimbursable. Patients must be monitored for up to 24 hours to detect and treat late reactions. Potentially toxic reactions must be avoided. When an individual has been removed from exposure to an allergen, several days'

Suggested Citation:"5 Medical Testing Methods." 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.
×

reexposure may be required for a measurable response to occur. Allergen extract in aerosol form is deposited differently in the bronchial system compared with allergen in its natural state.

Allergen challenge has been used in connection with bronchoalveolar lavage, in which a bronchoscope is used to sample the fluid in the alveoli. Bronchial biopsies can also be performed. Demonstration of lymphocytosis in bronchoalveolar fluid can suggest the diagnosis of hypersensitivity pneumonitis (Reynolds, 1988). Beasley and others (1989a) performed specific inhalation challenge with allergen followed by bronchial biopsy and lavage, and, later, histamine challenge. Their studies demonstrated an inverse correlation between the number of epithelial cells in lavage fluid and histamine reactivity.

Despite its limitations, specific inhalation challenge testing will continue to have a unique place in the study of the health effects of indoor allergens.

Lung Volumes

Measurement of lung volumes is useful to help evaluate reductions in forced vital capacity. The usual method (gas dilution) involves breathing a known concentration of an inert gas in a closed-circuit system, followed by measurement of the functional residual capacity (volume in the lungs at the end of a normal breath). Total lung capacity is then determined by summing the functional residual capacity and the inspiratory capacity (determined by spirometry).

Diffusing Capacity Testing

Measurement of diffusing capacity is indicated when the clinician suspects that gas exchange is impaired by the disease process. Diffusion capacity measurements are not necessary in most cases of suspected asthma, but they may be indicated occasionally to exclude interstitial lung disease.

In diffusing capacity testing, the patient inhales a known mixture of an inert (nondiffusible) gas and a readily diffusible gas such as carbon monoxide (ATS, 1987). The exhaled gas is collected and analyzed, and the uptake of carbon monoxide is expressed in ml/min/mmHg. Similarly to spirometry, reference values have been determined by cross-sectional studies; interpretation consists of comparing actual values with reference values and with any previously measured values for the patient. Possible confounding factors are also considered. For example, diffusing capacity may be falsely elevated by conditions that raise the metabolic rate, lung blood volume, or red blood cell count; it may be lowered by the presence of carboxyhemoglobin in the blood or by anemia (Gold and Boushey, 1988). Reference standards

Suggested Citation:"5 Medical Testing Methods." 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.
×

exist for the performance of diffusing capacity testing. As of 1987, however, interlaboratory variability was too great to recommend one set of equations for all laboratories. Rather, laboratories are advised to use internal controls, such as repeated measurements on a normal individual.

Exercise Studies

Exercise pulmonary function studies can be used as part of a clinical evaluation to quantitate exercise-induced bronchoconstriction in asthmatics (Chatham et al., 1982b), and to exclude the diagnosis of asthma in other cases. Often, however, serial peak flow monitoring during normal activities will be sufficient to document exercise-induced asthma. Exercise testing is also used to evaluate an individual with suspected interstitial lung disease. The occurrence of desaturation or a widening alveolar-arterial oxygen gradient suggests significant interstitial disease (Whipp and Wasserman, 1988). Finally, exercise testing can be used as part of the impairment evaluation when symptoms are disproportionate to static lung function due to deconditioning or unrecognized cardiovascular or pulmonary pathology (Engelberg, 1988).

Measures of Upper Airway Function

Measures of upper airway function are primarily used in research settings at present. The one exception is the obtaining of a nasal swab with cytologic examination for the presence and characteristics of inflammatory cells.

For physiologic measurement of nasal airflow (rhinomanometry), the pressure-flow characteristics during panting maneuvers are used to derive nasal airway resistance (Cole, 1982). Ten to 15 percent of patients are unable to perform the maneuver successfully; normal values are problematic because of normal fluctuations in nasal airway caliber. Nasal resistance measures correlate to a variable degree with congestive symptoms. Peak flow measurements of nasal airflow have been made by adapting a standard peak flow meter with a pediatric anesthetic mask (Ahman, 1992). This method is not without its problems or constraints; for example, technical questions remain about whether to record a nasal inspiratory or expiratory maneuver.

Acoustic rhinometry is a new technique that describes the cross-sectional area of the interior of the nose as a function of the distance from the nares. An acoustic pulse is generated, and reflections are recorded by a microphone and analyzed with a computer program using Fourier analysis. Subjects must stop breathing only for approximately half a second; the test is therefore easier to perform than physiological measures of nasal airway

Suggested Citation:"5 Medical Testing Methods." 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.
×

resistance. The technique has been validated by comparison with cadavers and computerized tomography (Hilberg et al., 1989), but much more extensive clinical trials are needed to evaluate this technique for clinical use.

Nasal lavage can be readily performed following nasal inhalation challenge. Analysis of cells, mediators, and proteins can then be conducted to study the pathogenesis of allergic and nonallergic rhinitis (Bascom et al., 1986). However, normal values have not been determined for most measures.

Conclusions and Recommendations

There are simple, reliable measures of lung function that may be used for studying diseases caused by indoor allergens. Indeed, objective measures of respiratory function should be a part of protocols to determine the efficacy of therapeutic strategies for these diseases. Predicted values for pulmonary function fall along a normal distribution curve with 95 percent confidence intervals for FEV1 and FVC of approximately 80–120 percent. The lower limit of variation in population studies for the midlevel expiratory flow rate (FEF25–75) is approximately 60 percent.

Spirometry is limited in its ability to detect impairment of ventilatory function in asymptomatic individuals (Morris et al., 1971) because of the wide range of normal values, even with predicted levels that control for age, sex, and height. Significant inaccuracy can result from errors in spirometry performance, almost all of which lead to underestimation of the true respiratory function. These tests can, however, help to evaluate the effects on an individual of sensitization to specific allergens (J. M. Smith, 1988). They can also help to diagnose respiratory diseases that may be caused or worsened by indoor allergens (Lopez and Salvaggio, 1988; NHLBI, 1991; Woolcock, 1988) and to assess disease severity, which is often critically important in clinical decisionmaking (NHLBI, 1991). Serial pulmonary function testing in the home or workplace can demonstrate causal relationships between the indoor environment and respiratory illness. Serial pulmonary function testing coupled with bronchoprovocation can demonstrate the causal relationship between specific allergens and respiratory responses (Chan-Yeung and Lam, 1986).

In epidemiological studies, measures of environmental factors and of pulmonary function can be evaluated for associations that suggest causal relationships (S. Weiss et al., 1983). Pulmonary function tests may also be used to assess the efficacy of therapy, determine response to treatment, or determine the effect of environmental modification (Ehnert et al., 1991; Platts-Mills et al., 1982). Such tests are required when physicians are asked to determine impairment resulting from a respiratory disease for insurance or benefit systems such as workers' compensation and social security disability

Suggested Citation:"5 Medical Testing Methods." 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.
×

(Engelberg, 1988). Finally, estimates of disease incidence or prevalence often result from epidemiological studies in which pulmonary function tests are used to ascertain disease.

Recommendation: Include pulmonary function tests in epidemiological studies to help improve estimates of disease incidence and prevalence. Because they are portable and can be self-administered, tests that utilize peak-flow measurements are most desirable for this purpose.

One drawback of many pulmonary function tests is that they must be administered by technicians. Peak flow measurements are less reliable but are highly portable, can be self-administered, and are therefore often more sensitive in the diagnosis of asthma.

Recommendation: Include objective measures of respiratory function in experimental protocols designed to determine the efficacy of therapeutic strategies (e.g., pharmacotherapy, environmental modification, avoidance) used to treat respiratory diseases caused by indoor allergens.

Bronchial hyperreactivity is a feature of asthma that correlates with clinical severity and does not require repeated measurement (Boushey et al., 1980). It is unclear, however, whether bronchial hyperreactivity can be correlated with exposure to indoor allergens.

Research Agenda Item: Determine whether changes in bronchial hyperreactivity can be correlated with exposure to indoor allergens. If such a correlation exists, determine how reducing the level of allergens affects bronchial hyperreactivity.

Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 153
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 154
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 155
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 156
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 157
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 158
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 159
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 160
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 161
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 162
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 163
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 164
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 165
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 166
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 167
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 168
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 169
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 170
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 171
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 172
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 173
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 174
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 175
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 176
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 177
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 178
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 179
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 180
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 181
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 182
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 183
Suggested Citation:"5 Medical Testing Methods." 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.
×
Page 184
Next: 6 Assessing Exposure and Risk »
Indoor Allergens: Assessing and Controlling Adverse Health Effects Get This Book
×
Buy Paperback | $95.00 Buy Hardback | $95.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

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.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!