To the Editor: Building-related illnesses include a variety of recognized disease entities that are characterized by objective clinical findings potentially related to specific exposures in the indoor environment.1 Examples include allergic rhinitis, asthma, hypersensitivity pneumonitis, Legionnaire's disease, and humidifier fever.2-4 A number of microorganisms, including many species of bacteria and fungi, are well established as potential etiologic agents of building-related illnesses; these illnesses may be classified as being allergic, infectious, or related to a toxic or inflammatory reaction.5 The recent article by Hodgson et al (Hodgson MJ, Morey P, Leung W, et al. Building-associated pulmonary disease from exposure to Stachybotrys chartarum and Aspergillus versicolor. J Occup Environ Med. 1998;40:241-249) addresses the issue of whether exposure to mycotoxins in an indoor environment is related to illness among building occupants. We agree with the authors that this is an important public health issue, but we disagree with the authors' conclusions that a "mycotoxin-induced effect is the most likely explanation" of the health problems discussed in the article.
We recognize the difficulties of performing adequate clinical and epidemiologic evaluations of large groups of people, particularly in a setting such as that described by Hodgson et al. However, because of the lack of objective evidence supporting an increased prevalence of pulmonary illness among building occupants, the lack of any information demonstrating actual exposure to mycotoxins, and the limited evidence from the literature suggesting that mycotoxins are related to illness in the indoor environment, in our opinion the authors' conclusion that a mycotoxin-induced effect is the most likely explanation for the observed pulmonary findings among building occupants in this study should be questioned.
Published accounts concerning human health effects related to potential exposure to mycotoxins have been case reports involving agricultural settings and/or the ingestion of contaminated foodstuffs.6-9 The relevance of these case reports to fungal growth in the indoor environment is unclear. Stachybotrys chartarum, one of the fungi identified by Hodgson et al, is one of many fungi that produces a class of mycotoxins called trichothecenes.10,11 Reports of stachybotryotoxicosis (mycotoxicosis related to Stachybotrys exposure), occurring in animals and humans, have come primarily from Eastern Europe and Russia, in areas where stachybotryotoxicosis was enzootic in horses.10,12 Human illnesses were reported to include dermatitis, bloody rhinitis, cough, and severe upper respiratory tract irritation. Cases of stachybotryotoxicosis related to occupational exposure have been reported to occur among workers at farms, cotton-seed oil plants, grain elevators, and facilities used for reprocessing moldy grain, malt grain-processing facilities, textile mills using plant fibers, and bindertwine factories.10 In those reports, the illnesses were characterized as a "general intoxication," including a variety of chest and upper respiratory tract symptoms and fever, as well as dermatitis and (in some cases) leukopenia. Recovery was reported to be rapid after cessation of exposure, and re-exposure resulted in much more serious sequelae.10 These cases of mycotoxicosis, concerning persons in agricultural or industrial environments, may have involved exposures to fungi and their products in concentrations that can be assumed to be much higher than those experienced by persons in most indoor environments.
Several studies are frequently cited (by Hodgson et al and other investigators) as evidence that adverse health effects or symptoms are related to indoor exposure to mycotoxins.13-16 None of these studies provide any objective evidence of clinical illness clearly related to mycotoxin exposure. One cited study16 reported findings from a group of persons working in a water-damaged office building contaminated by Stachybotrys. The primary finding was that, compared with workers in another building, persons in the building contaminated with Stachybotrys reported an increased prevalence of lower respiratory tract, dermatologic, eye, and constitutional ("flu-like") symptoms. Also, there were statistically significant differences between work locations in results of tests for white blood cell count, the proportion of mature T-lymphocyte cells (CD3%), and natural killer cell count. However, persons working in the most heavily contaminated areas (basements) had elevated cell counts and percentages, compared with those working on another floor of the same building. In addition, the clinical significance of the reported laboratory differences (such as CD3% of 75.66, 72.9, and 73.65 among controls, ground-floor occupants, and basement occupants, respectively) is unclear. Antibody testing of occupants of the problem building revealed no evidence of increased exposure to any specific fungi. No exposure to mycotoxin was demonstrated.
In another cited study,14 five occupants of a home reported a variety of symptoms, including cold and flu symptoms, sore throats, diarrhea, headaches, dermatitis, patches of hair loss, and fatigue. The clinical descriptions of the illnesses were incomplete, and no medical diagnostic information was presented. In the home, a cold-air return duct and an area of wood fiberboard were contaminated with Stachybotrys. When the mold was cleaned up, the family members' symptoms reportedly resolved. The authors inferred that mycotoxins from the mold were responsible for the symptoms. Even if some or all of the reported symptoms were related to the occupants' presence in the home, it is just as reasonable to infer that an allergenic response to the fungi (or some other [unidentified] factor[s]) were responsible for some or all of the reported symptoms.
In 1994, an investigation of 10 cases of acute pulmonary hemorrhage and hemosiderosis among infants was reported.17,18 A case-control study determined that case patients were more likely to be male, more likely to have a close relative who also coughed up blood while living in the same home, and more likely to live in a home in which a guardian reported water damage during the six-month period preceding the illness.19 Air sampling revealed that the quantity of fungus, including Stachybotrys atra (chartarum), was higher in the homes of the case infants than in those of controls.18 No systematic evaluation of water damage in these homes was reported. The air sampling was done using an "aggressive" sampling strategy (purposely stirring up potential contaminants in the homes),20 which is unlikely to be representative of actual exposures to fungi. The investigators presented limited evidence indicating the presence of mycotoxins in ceiling tiles and wall coverings.
In the current study, Hodgson et al have limited ability to "describe the spectrum of disease" among occupants of the subject buildings. The use of several undefined case definitions makes interpretation of the reported symptoms and pulmonary function tests difficult. Lack of data concerning comparison groups also limits interpretation and raises the question of whether the comparison groups were appropriate. The authors report that 17 of 47 self-selected individuals had some clinical evidence of pulmonary disease, but they do not report results of similar testing among "unexposed" office workers. The authors compare symptoms among occupants of the building of concern with those of occupants of other buildings but do not provide adequate information to compare response rate, demographic factors, smoking status, or job duties between the occupants of the study and comparison buildings. These factors are known to influence the prevalence of reported symptoms among building occupants.21,22 In addition, without some means of assessing exposure at the level of the individual or groups of individuals, we have no way of knowing whether the reported symptoms are related to mycotoxin exposure. The results of this study's limited antibody testing add no support to the hypothesis that the building's occupants had biologically significant exposure to fungi.
It is our personal opinion that there is currently no clear evidence documenting that mycotoxins cause health effects among building occupants. The presence of excessive fungal growth in a building is an indicator of inadequate building design, construction, and/or maintenance. The basis for, timing of, and extent of the remediation of a contaminated building are beyond the scope of this discussion; important factors to consider regarding remediation would include the extent of building contamination, the fungal biodiversity, and the frequency and severity of documented health effects among building occupants. Persons who have symptoms potentially related to an indoor environment should be clinically evaluated and, if indicated, removed from exposure to the offending agent(s) until that exposure is reduced or eliminated. If fungal exposure is thought to be a factor, close follow-up with the treating clinician and others will likely be needed as there are currently no "acceptable" limits of fungal growth in the indoor environment;23 given that fungi are ubiquitous, all potential sources of fungal exposure (including the home) would also need to be evaluated. It is clear that health problems potentially related to the indoor environment, including those potentially associated with exposure to fungi or fungal products, need further evaluation using appropriate environmental, medical, and epidemiologic tools.24
Elena Page, MD, MPH
Douglas Trout, MD, MHS
Hazard Evaluations and Technical Assistance Branch; National Institute for Occupational Safety and Health; Cincinnati, OH
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