Mold Claims - Allergic And Other Hypersensitivity Reactions

Atopic Individuals and Common Allergies

Unfortunately, in some individuals the acquired immune system is genetically predisposed to develop exaggerated responses to common, harmless environmental exposures. These people, said to be “atopic,” generate a class of specific antibodies (so called IgE antibodies) in response to these common environmental factors. These immune responses are called “immediate hypersensitivity reactions,” “Type I allergic reactions,” or – most commonly – “allergies.” Burns, L.A., et al., Toxic responses of the immune system 355-402 in Casarett and Doull's Toxicology -- The Basic Science of Poisons(C.D. Klaassen et al., eds.) (McGraw-Hill, New York 1995); Evans, R., III Epidemiology and natural history of asthma, allergic rhinitis, and atopic dermatitis 1109-1136 in Allergy -- Principles and Practice, Vol. II (E. Middleton, Jr. et al., eds.) (Mosby – Year Book, Inc., St. Louis, MO 1993).

Common inhaled environmental triggers for allergic reactions include animal dander, feathers, insect proteins from body parts, grasses, pollens and molds. Foods, medications, and insect stings may be additional triggers. Atopic individuals tend to have allergic reactions not just to one environmental factor but generally have allergic responses to a number of them. For these people, reactions to inhaled allergens (antigens) can vary from relatively mild irritation of the eyes and nose to severe congestion and breathing difficulties including allergic asthma. In the extreme, an immediate hypersensitivity reaction can be life-threatening.

Of the molds that commonly grow indoors, Penicillium and Aspergillus species are the most important as allergens. However, outdoor molds such as Cladosporium and Alternaria are generally more abundant and more important than indoor molds in causing allergic airway disease. When mold spores and plant pollens are abundant in outdoor air, they may also be found at high levels in the indoor air. See Horner, W.E. et al., Fungal allergens,Clin. Microbiol. Rev. 8(2):161-179 (1995); Solomon, W.R. and Platts-Mills, T.A.E., Aerobiology and Inhalant Allergens 367-403 inAllergy : Principles and Practice(E. Middleton, Jr. et al., eds.) (Mosby Co., St. Louis 1998).

Depending on methods used, estimates vary as to how common fungal allergies are. At least 30% of the population may be atopic, and 20% is affected by allergic diseases such as asthma and rhinitis (runny nose), with 10% of these individuals having severe allergic disease. Skin prick tests and in vitro tests for allergic antibodies provide accurate information as to the presence of allergic antibodies to fungal and other allergens. The prevalence of fungal allergies as determined by these methods is highly variable with reactions occurring in 3% to 91% of the population, depending on the exact population studied and the source of the challenge material used. See Evans, supra note 1; Horner et al., supra note 2.

Uncommon Allergic Syndromes


1. Allergic Bronchopulmonary Mycosis and Allergic Fungal Sinusitis

Antigen – antibody interactions are also involved in the uncommon allergic syndromes “allergic bronchopulmonary aspergillosis” Fungi other than Aspergillus are now recognized to cause this condition in the lungs, so the term “allergic bronchopulmonary mycosis” has been suggested to replace “allergic bronchopulmonary aspergillosis.” and “allergic fungal sinusitis.” The number of fungal organisms recognized as being involved in allergic fungal sinusitis is increasing, but Aspergillus and Curvularia are the most common genera. , Specific diagnostic criteria have been established for both allergic bronchopulmonary mycosis and allergic fungal sinusitis. In these conditions, the fungi actually grow within the patient's airways (either the lungs or the sinuses). These individuals generally have airway damage from previous illnesses or other conditions that impair normal drainage. That poor drainage provides a site at which fungi can grow within the body without actually invading adjacent tissues. Such fungal colonization is without adverse health consequence unless the subject is also allergic to the specific fungus that has taken up residence. In that case there can be ongoing allergic reactions to fungal substances being released directly into the body.

See, e.g., Cockrill, B.A. and Hales, C.A., Allergic bronchopulmonary aspergillosis, Ann. Rev. Med. 50:303-316 (1999); deShazo, R D. and Swain, R.E., Diagnostic criteria for allergic fungal sinusitis, J. Allergy Clin. Immunol. 96(1):24-35 (1995); Greenberger, P.A. Allergic bronchopulmonary aspergillosis, allergic fungal sinusitis, and hypersensitivity pneumonitis, Clin. Allergy Immunol. 16:449-468 (2002); Greenberger, P.A. and Patterson, R., Diagnosis and management of allergic bronchopulmonary aspergillosis, Ann Allergy 56(6):444-448 (1986); Katzenstein, A. L. et al., Allergic Aspergillus sinusitis: a newly recognized form of sinusitis, J. Allergy Clin. Immunol. 72(1):89-93 (1983); Schubert, M.S., Fungal rhinosinusitis: diagnosis and therapy, Curr. Allergy Asthma Rep. 1(3):268-276 (2001); Schubert, M.S. and Goetz, D.W.,Evaluation and treatment of allergic fungal sinusitis, I. Demographics and diagnosis, J. Allergy Clin. Immunol. 102(3):387-394 (1998); Slavin, R.G., Allergic bronchopulmonary aspergillosis, Clin. Rev. Allergy 3(2):167-182 (1985); Zhaoming, W. and Lockey, R. F., A review of allergic bronchopulmonary aspergillosis, J. Investig. Allergol. Clin. Immunol. 6(3):144-151 (1996).


2. Hypersensitivity Pneumonitis

Unrelated to immediate hypersensitivity (allergic) reactions, hypersensitivity pneumonitis or “extrinsic allergic alveolitis” is a much more severe lung condition that results from an exaggerated immune response involving a different class of immunoglobulins. The scientific evidence suggests that this immune response is limited to intensive occupational exposures or rarely home animal protein (birds particularly) or bacterial (not mold) exposures.
Development of hypersensitivity pneumonitis requires both very high blood levels of specific immunoglobulin proteins and inhalation exposure to very large quantities of foreign antigens. The inhaled antigens and their specific immunoglobulin antibodies interact to produce an intense local immune reaction.
If the exposures continue, hypersensitivity pneumonitis can progress to a disabling fibrotic lung disease. Most cases of hypersensitivity pneumonitis result from occupational exposures to high levels of organic dust that includes plant debris, fungi and bacteria; but it has also been attributed to pet birds, humidifiers and heating, ventilation, and air conditioning (HVAC) systems. In the latter two exposures, the predominant organisms responsible for hypersensitivity pneumonitis are thermophilic Actinomyces, which are not molds but rather are filamentous bacteria that grow at high temperatures.

Fink, J. and Zacharisen, M.C. Hypersensitivity Pneumonitis 994-1004 in Allergy: Principles and Practice(E. Middleton, Jr. et al., eds.) (Mosby Co., St. Louis 1998); Greenberger, supra note 7; Lacey, J. and Crook, B., Fungal and actinomycete spores as pollutants of the workplace and occupational allergens, Ann. Occup. Hyg. 32(4):515-533 (1988).

Changes in Scientific Testing


Immunoglobulin antibodies classically were detected in tests that involved diffusion in flat sheets of agar gel into which holes, or “wells,” have been punched. Concentrated extracts from sources suspected of causing allergies (e.g., animal dander, bird droppings, mold samples) were placed in a row of wells from which antigens can diffuse through the gel. Antibodies could have been incorporated into the gel itself, or blood serum from the patient would be placed in a row of wells parallel to those containing suspected antigen sources. If a specific antigen encountered its corresponding specific antibody in the gel, a reaction took place that was visible as a “precipitin” band in the gel. These traditional tests were highly specific but relatively insensitive; i.e., they did not detect small immunoglobulin levels. (The traditional tests do, however, remain useful in diagnosing hypersensitivity pneumonitis where high levels of immunoglobulin antibody are found.) See Homburger, H.A. and Katzmann, J.A., Methods in laboratory immunology –Principles and interpretation of laboratory tests for allergy 554-72 in Allergy –Principles and Practice, Vol. I (E. Middleton, Jr. et al., eds.) (Mosby – Year Book, Inc., St. Louis, MO 1993).

New immunoglobulin tests called “solid phase immunoassays” are faster, easier to perform and more quantitative than the older gel diffusion tests. The new tests are also more sensitive and can detect low immunoglobulin levels, much lower than can be detected in gel diffusion tests.

Elevated immunoglobulin levels in the new solid phase immunoassay tests have less diagnostic value than do elevated levels in traditional gel diffusion tests because many people may have elevated levels of a specific immunoglobulin such that the more precise newer tests give “false-positive” results, i.e., such results indicate some previous exposure to the corresponding specific antigen but do not indicate hypersensitivity pneumonitis or other disease. Because an estimated 5% of the normal population has immunoglobulin levels above reference values for any one tested material, a panel of tests against a series of mold or other antigens has a high probability of producing a false-positive result. Thus, solid phase immunoassay tests should not be used to screen for mold exposure unless there is a pre-existing clinical suspicion for hypersensitivity pneumonitis.See id.; see also California DHS, Misinterpretation of Stachybotrys Serology (2000) (May 5, 2002); Fink and Zacharisen, supra note 8; Flaherty, D.K., et al., Multilaboratory comparison of three immunodiffusion methods used for the detection of precipitating antibodies in hypersensitivity pneumonitis, J. Lab. Clin. Med. 84(2):298-306 (1974).

The Potential Link to Mold