Clinical Experience and Results of a Sentinel
Health Investigation Related to Indoor Fungal Exposure
Eckardt Johanning,1 Paul Landsbergis,2 Manfred Gareis,3 Chin S. Yang,4 and Ed Olmsted5
1Mount Sinai School of Medicine, New York, New York USA; Eastern New York Occupational and Environmental Health Center, Albany, New York USA; 2Cornell University Medical College, Mount Sinai School of Medicine, New York, New York USA; 3Federal Meat Research, Microbiology and Toxicology, Kulmbach, Germany; 4P&K Microbiology Services, Inc., Cherry Hill, New Jersey USA; 5Olmsted Environmental Services, Inc., Garrison, New York USA
Study Group Selection and
Health Symptoms Survey
Sentinel Case Example
We investigated the environmental conditions inside the apartment and compared them to outside conditions and a reference apartment inside the same building that did not have visible evidence of moisture and fungal problems (healthy adult occupant). In addition to the index case, the brother (subject B; 21 years of age) and the mother (subject C; 50 years of age) were studied because they reported symptoms, although less severe. Subject A (who had lived since birth in the apartment) and subject C spent most of a typical day inside, whereas subject B was only in the apartment during the night. The family was removed from the contaminated apartment and retested after a period of 8 weeks (pulmonary function and T-lymphocyte flow cytometry) and again after 4 months (lymphocyte flow cytometry). There were never any pets in the apartment. The apartment building had a known history of cockroach and rat infestation.
Fungal Exposure Sampling
Cockroach Antigen Sampling
Dust mite or other animal antigens were not measured. (This was a winter period and no household animals were present.) Other chemical or organic compounds were not measured because the industrial hygienist did not observe any unusual presence or use of household chemicals. An indoor asbestos and lead screening was negative.
Review of Clinic Records
The analysis of clinically recorded health symptoms and organ complaints of patients with a history of indoor fungal exposures showed a high prevalence (> 50% of all respondents) of symptoms of upper and lower airways, eyes, and central nervous system. Children also showed a high prevalence of symptoms, although the absolute percentage rate was slightly lower than that of adults (Table 1, Figure 1). Compared to the office workers with health problems associated with fungal exposure and the nonexposed controls, children appeared to complain slightly more about upper airway problems (symptoms related to rhinitis, sinusitis, laryngitis) and slightly less about lower airway problems (symptoms related to bronchitis, asthma, or pneumonitis). Skin, eye, and central nervous system complaints were present in more than 40% of respondents, with similar high proportions for the adults. Excessive physical and mental fatigue (fatigue) was reported by about one-third of the children interviewed and by about half the adults (54%). The rate of preexisting and diagnosed allergy in patients was less than 20% and lower than in the comparison groups. The higher prevalence of symptoms among patients and exposed office workers relative to nonexposed controls was not likely due to group differences in age, gender, or smoking, as groups were similar on these potential confounders (except, of course, for the younger ages of children).
Figure 1. Health survey: children vs. adults. For explanation of office workers and controls, see text.
Five percent of the children had any evidence of specific IgE antibodies to tested fungal allergens (except S. atra), 9% had an IgE reaction (borderline values), and none had an elevated IgG (> 40 mcg/mL) to S. atra. None of these children had a specific antibody reaction to cockroaches. Complete lymphocyte and other immunoglobulin analysis were available for only five children and are not reported here. On the basis of the review of available industrial hygiene data, about 90% of the children had verifiable exposure to higher-than-normal indoor levels of primarily Penicillium and Aspergillus spp., and at least 41% of the children had documented exposure to S. atra.
Sentinel Case Example
After leaving the apartment, all subjects reported a marked improvement and a partial resolution of their health problems. Less frequent and severe cough episodes, less chest discomfort, and fewer breathing problems, headaches, fatigue, and flulike symptoms were noted. Pulmonary function improved in all three subjects (Table 2) and the lymphocyte enumeration measured 8 and 16 weeks after removal (Table 3) appeared to show some minimal improvement in some parameters. The index case had a PWM and CON mitogen response abnormality during the exposure period (data not shown). The results of the T-lymphocyte function (mitogen proliferation) tests performed 16 weeks after removal were normal in all subjects. These results and the lack of clinically significant viral or bacterial infections after removal from exposure indicate only a minor remaining immunodeficiency, which could be explained by the known preexisting genetic abnormality.
Inside the apartment, approximately 70-100 m2 of surface area (walls, ceilings, around the window air conditioning unit, the doors, and window frames) were covered with a blackish-colored growth. Airborne fungal counts (viable and nonviable) were significantly higher (10-200 ) than the outside or the control apartment used as a reference (Table 4). Predominant indoor airborne fungi were Cladosporium, Aspergillus, Penicillium, and S. chartarum. Bulk samples taken from the problem apartment showed a high concentration of S. chartarum, A. versicolor, and Cladosporium. All bulk samples taken from the home (bedroom, bath, and kitchen) were toxic to highly toxic in the MTT screening test.
Cockroach allergen Bla g 1 in sampled floor dust was considered high, based on the classification by the National Cooperative Inner-City Asthma Study, although the maximum concentration in the Inner-City Asthma Study was 1,190 U/g dust [median 8 U/g) (21)]. No pesticide toxins were detected inside the apartment.
The symptom survey of children evaluated in our specialty clinic indicates a high rate of morbidity related primarily to the upper airways, skin and mucous membranes and, to a lesser degree, lower airways. In all cases we confirmed that these children had all been living in indoor environments with high levels of fungi, often species not normally found indoors or in such concentrations compared to the outside air (i.e., S. chartarum, A. versicolor, Trichoderma). Our results are in agreement with a number of previous studies. A recent review of the literature investigating the association of wheeze and cough and damp or mold found that the adjusted odds ratio for an increased risk of children was generally in the range of 1.5-3.5 (22). The high rate (about two-thirds) of central nervous system problems among children from moldy homes suggests a complex exposure-associated morbidity reaction with a pathologic pathway that cannot readily be explained by atopy or allergy (IgE-mediated). The health complaints summarized by organ system were similar for children compared to adults, although the absolute percentage rate of complaints was slightly lower for children. The rate of reported symptoms was higher than that of a nonexposed adult control group in almost all categories except for a previous diagnosed history of allergy. None of the queried children had evidence of an allergy to cockroaches, which has been described as an important predictor of environmental-associated asthma (21). On the basis of our assessment of the clinical cases, morbidity related in time and place to indoor fungal exposure appears to be widespread in environments with a history of flooding, water leaks, moisture problems, and ventilation defects that resulted in intense fungal growth on interior building materials or furniture.
Differences were not analyzed for statistical significance because of methodological issues and limitations such as small sample size and different time and location of measurements. The response variations and group differences may be due to selection bias, biologic differences, or survey limitations (e.g., children were less used to questionnaire formats, were unfamiliar with interview techniques, or were assisted by parents).
Only 2 children and 13 adults had positive (abnormal) laboratory findings for the presence of IgE- and IgG-specific fungal antigens. In this small sample, neither the presence of positive antigen findings nor a fungal exposure history showed a statistically significant association with symptoms. The small number of subjects with abnormal laboratory findings (only 5 children had undergone complete lymphocyte testing) did limit the statistical power of analysis of group differences in laboratory findings. The differences in laboratory test results may be related to a variety of factors including the differences in exposure duration, latency, timing of laboratory testing relative to exposure and testing, and temporary medical treatment effects. A study of a larger number of children with similar exposure (children in kindergarten or schools) that included testing of biologic markers at the same time would be beneficial for epidemiologic studies. Presently there is not a reliable mycotoxin biomarker available for clinical screening studies. Therefore, clinicians rely on indirect laboratory effects measures such as T-lymphocyte responses and immunoglobulins counts. Advances in immunology, laboratory, and diagnostic methods may ease clinical diagnosis in the future.
In the case example investigation, a key factor was the reported history of variability of health complications depending on the indoor environment, i.e., the dramatic health improvement away from the fungal exposure inside the apartment. We presented this case example because it appears to demonstrate that such fungal exposure can significantly aggravate and complicate pre-existing immunological disease. The exposure was not only affecting the index case but also the brother and mother who shared the apartment with her but had no history of genetic abnormalities. Inside the apartment we identified very high levels of fungi indoors, with a predominance of Cladosporium and toxigenic S. chartarum. The presence of airborne S. chartarum in indoor environments is considered by experts to be highly uncommon in normal buildings and unacceptable from a public health perspective. The MTT cytotoxicity tests showed that all samples taken from the girl's home environment had toxic metabolites (such as trichothecene) in the fungal materials. The fungal mass (spores) would have become airborne when disturbed.
Blood lymphocyte changes effecting the T-lymphocyte differentiation and subpopulation proportion were measured as in previous studies (11,23). Changes of the T-lymphocyte population were demonstrated in in vitro and in vivo studies but remain difficult to interpret on an epidemiological level because of only very small differences and variations in observed trends. In our case example, some lymphocyte parameters showed improvement after exposure cessation, but these may be within laboratory and normal daily variations. Only the index case had genetic evidence of a deletion of 22q11.2, confirming a velo-cardio-facial syndrome (DiGeorge variant). Cockroach antigen (Bla g1) exposure, although present in high concentration, did not result in measurable allergies in any of the apartment occupants. On the basis of available data and the observed health improvement with exposure cessation, we concluded that indoor fungal exposure was the probable contributing cause of the health problems associated with living in this apartment. Some other unidentified agents or conditions may have also contributed to the improved outcome, although we think this is very unlikely under the circumstances. Studies of health outcomes related to bioaerosol exposure appear more complicated than monoagent chemical exposure studies because several biologic components (i.e., ß-glucans, microbial volatile organic compounds, endotoxins, allergen, mycotoxins) may have independent or combined effects.
It is our clinical experience that symptoms associated with mold exposure tend to resolve with exposure avoidance and symptomatic treatment. In some individuals, symptoms may last several weeks to months after exposure control and in some rare cases may not be reversible at all. A highly increased sensitivity with recurrent fungal exposure has been noted by some individuals. These variations in the postexposure periods may be related to differences in the exposure duration, intensity, and particular conditions (different fungal species), the biologic differences of the immune reaction of exposed individuals, and the type of medical intervention or treatment.
Children with preexisting, significant immunological weaknesses and defects are at increased risk and should be protected from unnecessary fungal exposure. Long-term benefits of such intervention (secondary prevention) and related health indicators should be studied more systematically. Fungal exposure in indoor environments should be included in future environmental respiratory and immunologic disease studies, in addition to already known indoor pollutants. It is necessary for the physician examining a child with complex respiratory problems, allergy, nervous system disorders, and perhaps other organ system problems, to inquire about problems in the home such as chronic water leaks, extensive interior condensation, flooding, and especially visible fungal growth on interior building materials. In many cases, effective fungal exposure control and avoidance may be all that is needed to achieve a significant improvement in the child's health.
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