Abstract and Introduction
Stachybotrys chartarum is one of several species of filamentous fungi capable of producing mycotoxins under certain environmental conditions. In some observational studies, the growth of this toxigenic mold in the indoor environment has been implicated as a cause of building-related illness. Following reports of a cluster of cases of pulmonary hemosiderosis and hemorrhage associated with exposure to Stachybotrys, public health measures have been recommended which have far-reaching implications. Although the hazards associated with exposure to some mycotoxins have been well studied, the health risks from environmental exposure to Stachybotrys remain poorly defined. The purpose of this review is to critically evaluate the current body of epidemiologic knowledge regarding Stachybotrys and to increase physician awareness regarding this emerging environmental health issue.
Fungi are ubiquitous in the environment and are well known for their potential to stimulate an immune response in sensitive individuals. In addition to their allergenic potential, some filamentous fungi are known to produce mycotoxins (by-products of fungal metabolism), which show a variety of biologic effects in animals and humans. Much of what is currently known about exposure to mycotoxins has emerged from veterinary science. The toxic effects from mycotoxins produced by Stachybotrys chartarum (also known as S atra; Figure 1) were first reported in the 1920s in Russia, when researchers reported severe morbidity and mortality in cattle and horses that ingested hay contaminated with this mold. Clinical observations included severe skin and mucous membrane inflammation, bleeding disorders, diarrhea, and upper and lower respiratory tract disorders.
Under certain growth and environmental conditions, Stachybotrys may produce several different mycotoxins, including a class known as trichothecenes. The trichothecenes are potent inhibitors of DNA, RNA, and protein synthesis, and have been well studied in animal models because of concern about their potential misuse as agents of biologic warfare. Yellow Rain attacks in Southeast Asia during the 1970s were allegedly associated with the use of aerosolized trichothecenes; however, the evidence to support these claims remains poorly substantiated in the scientific literature. Recent experimental animal studies have reported severe intra-alveolar, bronchiolar, and interstitial inflammation in mice that were exposed via an intranasal route with trichothecenes. In contrast to toxicity from direct inhalation of Stachybotrys spores, simulated environmental conditions with extensive surface growth of toxigenic Stachybotrys and high air flow have not produced significant pulmonary toxicity in exposed mice. This observation may be related to the physical properties of Stachybotrys; it produces spores in a slimy mass that are unlikely to become airborne without dry conditions. In addition, the production of mycotoxin by Stachybotrys is dependent upon the environmental conditions of its growth. On some building materials and growth substrates, Stachybotrys has not demonstrated biologic toxicity or mycotoxin production.
In the United States, reports of human health effects associated with exposure to Stachybotrys have been limited to case reports and case-control investigations.[11,12] The first case report described the experience of a group of individuals occupying a water-damaged home in which Stachybotrys was isolated. Individuals complained of multiple symptoms including headache, sore throat, diarrhea, fatigue, dermatitis, and depression. Upon removal from the environment and remediation of the water damage, these health effects subsided. A medical evaluation of the affected individuals was not described in this report. The authors concluded that exposure to trichothecenes was responsible. This report is frequently cited in investigations and public health statements describing the human health hazards of exposure to Stachybotrys.
In the past several years, case-control studies of occupational exposure to Stachybotrys in water-damaged building environments have generated much controversy. In one of these investigations, significant differences in self-reported symptoms (chronic fatigue, dermatologic, constitutional, and lower respiratory tract) between cases (n=51) and controls (n=21) were attributed to exposure to Stachybotrys and other atypical fungi. The study design did not include an evaluation for water damage or the presence of these fungi in the work or living environments of control subjects. Speculation that exposure to Stachybotrys produced immune dysfunction in cases was based on observations that cases had a lower proportion of mature T-lymphocyte (CD3) cells than controls (74% vs 76%, respectively), a finding that was statistically significant. The clinical significance of this finding remains difficult to interpret, and could have been affected by laboratory as well as individual daily variation. More important, this observation was the only one of over 20 hematologic and immunologic comparisons made between cases and controls that was found to be statistically significant, an observation that could be explained by chance. In another case-control study, which concluded that exposure to Stachybotrys and other toxigenic fungi was responsible for various pulmonary diseases (including asthma, interstitial lung disease, and "emphysematous-like" disease) among office workers in a water-damaged building, no reliable biomarkers of exposure to Stachybotrys or radiographic findings correlating with the self-reported pulmonary symptoms were present.
Perhaps the most significant publication implicating Stachybotrys in human disease was a report of a cluster of cases of pulmonary hemosiderosis and hemorrhage among infants living in water-damaged buildings in Cleveland. Ten cases were identified by active surveillance, and environmental and other risk factors were compared with risk factors for 30 age-matched controls. In all cases of pulmonary hemorrhage, water damage had occurred in the infant's home within the previous 6 months, a strong and significant association. Infants exposed to environmental tobacco smoke (ETS) were nearly 8 times as likely to have pulmonary hemorrhage, while infants with higher concentrations of Stachybotrys in their homes were 1.6 times as likely. Based on these findings, public health authorities recommended prompt cleanup and disposal of all moldy materials in water-damaged homes. This has been followed by policy statements and guidelines regarding the toxic effects of indoor molds, which emphasize the need to eliminate water problems and reduce the growth of indoor molds.
A review of the environmental data collected in the investigation of the Cleveland cluster raises more questions than answers. In that report, environmental samples for fungi were obtained from 12 case homes, although subsequent publications on the same cluster of cases reported data from only 9 homes. Despite the fact that controls outnumbered cases by more than a factor of 2, the reported number of environmental samples for mold were virtually equal between the 2 groups. The presence of Stachybotrys spores in air samples was measured by 2 mycologists, who agreed on its presence, absence, or possible presence in only 56% of the samples. In 81% and 91% of air samples obtained in case and control homes, respectively, the measured concentration of Stachybotrys was below the level of detection, making the mean concentration of fungi an unreliable estimate of exposure. The results of surface sampling (using growth media selective for Stachybotrys) revealed that 43% of control homes had detectable surface contamination with Stachybotrys, an observation that contradicts the frequently cited reference that this mold is not commonly encountered in the indoor environment. Despite active surveillance and aggressive clinical management of the cases of acute pulmonary hemorrhage, neither Stachybotrys nor mycotoxins were isolated from specimens taken from these infants.
Beyond the issues of error in measurement and information bias inherent in any case-control investigation, the issue of confounding is particularly relevant to the Cleveland cluster, where exposure to ETS was much more strongly associated with pulmonary hemorrhage than exposure to Stachybotrys. This is very important, given that in many case homes, infants were exposed to multiple smokers on a regular basis. Despite these observations, investigators involved in the Cleveland cluster have dismissed the suggestion that exposure to ETS may be a primary risk factor for pulmonary hemosiderosis and hemorrhage, concluding instead that ETS may play a secondary role to toxigenic fungi in triggering pulmonary hemorrhage. To support this assertion, the authors cite their observation that the association between ETS and pulmonary hemorrhage failed to achieve statistical significance. A closer evaluation of the data initially reported in the MMWR, however, clearly shows that neither the strong association between ETS and pulmonary hemorrhage (odds ratio 7.9, 95% confidence interval 0.9-70.6) nor the weak association between Stachybotrys and pulmonary hemorrhage (odds ratio 1.6, 95% confidence interval 1.0-30.8) was statistically significant.
In the case of ETS, the lack of statistical significance could easily be attributable to the small sample size in this investigation, as well as the qualitative (not quantitative) methods used to assess exposure. With the observed differences in exposure to ETS between cases (90%) and controls (53%) in the Cleveland cluster investigation, twice the number of case subjects would have been needed to detect a statistically significant difference in exposure to ETS between groups. Given the evidence that smoking has been associated with pulmonary hemosiderosis, as well as the known toxicity of ETS to infants and neonates, the importance of ETS as a risk factor for pulmonary hemosiderosis and hemorrhage continues to be underemphasized and misinterpreted in the pediatric literature, which remains primarily focused on toxigenic fungi.
Despite fundamental epidemiologic questions that remain unanswered regarding Stachybotrys, the past several years have seen a remarkable public health response to this issue. The detection of Stachybotrys in the indoor environment has led to the closure of office buildings and schools, and has prompted highly publicized class-action litigation against building owners. An industry of industrial hygienists specializing in the assessment and remediation of indoor molds has emerged, and their services are recommended by expert panels, although there is currently no evidence-based consensus on what measures should be undertaken to reduce the risk of disease. Given the ubiquitous nature of fungi in the environment and the observation that certain species of common indoor fungi (such as Alternaria and Penicillium) have been identified as mycotoxin producers, the issue of toxigenic mold exposure is certain to pose challenges to physicians until further research can clarify current controversies.
© 2000 Medscape
Cite this: Stachybotrys chartarum: Current Knowledge of Its Role in Disease - Medscape - Feb 29, 2000.