Subsequently, a controlled exposure study was conducted with eight school employees who had shown increased histamine release to P. chrysogenum. Short-term exposure to high doses of P. chrosygenum and Trichoderma harzianum spores did not result in more mucous membrane or general symptoms than placebo. However, exposure to a high concentration of fungal spores for a short period may not accurately capture the effects of long-term exposure to low or moderate doses. One should emphasize that clinical data have only demonstrated a value of IgE antibodies against allergens as a predictor of whether health effects are observed. Although several studies have claimed that fungi are involved in sinus disease, such data do not clearly indicate environmental molds and suggest that recovered mold in cultures is primarily secondary to overgrowth from the use of broad-spectrum antibiotics. Often, such claims of sinus disease and mold are not even accompanied by appropriate sinus imaging. Interestingly, studies of children attending the same schools indicated that levels of culturable fungi in floor dust were significantly associated with symptoms in boys only . Specifically, mold exposure increased the risk of eye irritation, headache, concentration problems, and dizziness. Similarly to the adult population, the strongest associations with symptoms were observed for factors other than mold exposure—particularly recent airway infection, hay fever, and psychosocial factors. As part of the BASE study funded by the US EPA, repeated measurements of culturable fungi in air, floor dust, and chair dust were obtained over a period of 1 yr in 21 offices in four office buildings in Boston . In addition to work environment and personal factors,dry rack for plants a group of unidentifiable fungi in chair dust was significantly associated with nonspecific symptoms in a multivariate analysis.
Fungal concentrations in chair dust also predicted upper respiratory symptoms as well as work environment and personal factors. Few studies have examined the association between SBS symptoms and aero-allergens by measuring exposure directly at the workstation of each participant rather than at a single site or a few sites within a building. One such study found that symptoms of the upper and lower respiratory system were not associated with total culturable fungi, but they correlated significantly with detectable airborne Alternaria and house dust mite concentrations . Notably, Alternaria spore counts were low, with mean levels of 7 and 6 CFU/m3 in the offices and the HVAC supply systems, respectively. Results from another study involving 48 schools with a high incidence of SBS symptoms suggested that Penicillium and Stachybotrys were the main genera associated with these symptoms . In 20 of these schools, Penicillium levels in areas whose occupants reported a high frequency of SBS symptoms significantly exceeded those of areas with a low frequency of complaints as well as Penicillium levels from outdoor air samples. In the other schools, airborne Penicillium concentrations were not elevated, but heavy to very heavy growth of either Penicillium and Cladosporium or Stachybotrys species was found in swab samples from water-damaged areas. Remedial actions taken by many of the schools reportedly resulted in indoor air fungal profiles similar to those found outdoors and were associated with a marked decrease in the frequency of symptom reports. However, a causal relationship could not be established, because significant bias was inherent in the methodology used to evaluate subject complaints and because other possible causes of the complaints were not investigated. Interestingly, in another building with a high frequency of indoor air quality complaints and visible fungal growth in many rooms, the outdoor fungal profile changed considerably during a 6-h observation period, whereas the indoor fungal profile underwent little alteration . Similarly to the study of school buildings, Penicillium was the dominant species in indoor air at all time-points, whereas it was the dominant species in outdoor air in only two of the six samples.
Other studies have confirmed that remedial action can result in a significant decrease in the total airborne viable mold concentration and a decrease in the microbial diversity along with a decrease in most of the symptoms assessed . Notably, the concentration of airborne bacteria also declined after the repair of moisture damage, making it difficult to determine whether bacterial or fungal exposure were mainly responsible for the observed symptoms. Similarly, renovation plus thorough cleaning of buildings containing a public swimming pool resulted in a marked decrease in the number of viable molds, led to a change in the species composition of the molds, and was associated with a decrease in the symptom frequency from 66% before the renovation to 4% after completion of the intervention . However, as emphasized earlier, these data are confounded by discrimination bias and the lack of controls and often include issues of secondary gain. Numerous studies, including several longitudinal studies, have addressed the association between residential dampness and/or mold and wheezing and persistent cough in infants and small children. Although wheezing in infancy does not necessarily develop into asthma later in life, it is an acknowledged risk factor. In a case–control study of 251 pairs of small children, those who were diagnosed with bronchial obstruction were significantly more likely to live in homes with dampness problems in the 2 yr preceding . In a prospective birth cohort study of more than 4000 children from Stockholm, Sweden, home dampness was significantly associated with the occurrence of asthma or recurrent wheeze in children followed for the first 2 yr of their lives . Mold odor reported at baseline, but not water damage or presence of visible molds, predicted asthma incidence in a 6-yr prospective cohort study involving children age 1 to 6 yr at baseline . This association remained significant after adjusting for parental atopy and various other known risk factors for the development of asthma, although there was no adjustment for the presence of specific allergens. In infants at high risk of developing asthma , there was a significant association between frequent wheezing and persistent cough and mothers’ reports of visible signs of molds and mildew . The number of airborne viable mold spores was also significantly associated with wheeze, even after adjusting for several common aero-allergens, environmental exposures, and other known risk factors. The same outcomes were assessed in another study involving 880 infants of mothers who had at least one older child with physician-diagnosed asthma .
In this study, airborne levels of fungi were categorized into undetectable, low , medium , or high levels . Infants exposed to high Penicillium concentrations were at significantly increased risk of developing wheeze and persistent cough during their first year of life. Although the level of Cladosporium spores in indoor air correlated with occupant-reported mold and water leaks, Cladosporium concentrations were not significantly associated with either of these symptoms,4 x 8 grow tray whereas reported mold was associated with persistent cough. A prospective study of a birth cohort involving 499 children of atopic parents demonstrated that those who were exposed to high levels of certain fungal spores had a higher incidence of developing lower respiratory tract illnesses in the first year of life . Specifically, significant associations were detected between lower respiratory tract illness and airborne Penicillium and dust-borne Cladosporium, Zygomycetes, and Alternaria. Notably, these associations were observed after controlling for markers of moisture damage, which independently predicted lower respiratory tract illness. In all three studies that measured fungal concentrations , exposure to mold was assessed on only one occasion early in each infant’s life, few other environmental exposures were accounted for, and only one investigation examined the simultaneous effects of molds and other aero-allergens . Therefore, substantial misclassification of fungal exposure cannot be ruled out, and a causal relationship cannot be definitively established. Results of time series studies have indicated that increased concentrations of outdoor fungal spores are associated with decreases in PEFR in unselected children and in children with asthma and with increases in asthma symptom severity and inhaler use and in the number of emergency hospital visits for asthma in children ; however, this association was not observed in another study . Fungal spore levels have also been reported to be associated with increased mortality from asthma in persons ages 5 to 34 yr .Animal studies also indicate that intratracheal instillation of mycotoxin-producing fungi—particularly Stachybotris chartarum— can induce considerable pulmonary inflammation in rats and mice . Some of these studies have suggested that the inflammatory response is mediated mainly by trichothecenes. However, more recent investigations have provided evidence that other fungal components also contribute to the lung pathology induced by exposure to S. chartarum. Repeated intranasal instillation of S. chartarum spores was found to cause an influx of monocytes, neutrophils, and lymphocytes into BALF and to increase mRNA expression of pro-inflammatory cytokines and several chemokines . These effects were only observed at the higher dose and not at the lower dose . Neither T-helper 1 or T-helper 2 cytokines nor total or specific IgE, IgG1, and IgG2a levels were significantly increased by S. chartarum instillation. Notably, a strain of S. chartarum that produced satratoxin and a strain that did not produce satratoxin were used in the experiments. The inflammatory effects of the two strains were almost identical, indicating that satratoxin was not required for the induction of pulmonary inflammation. Similar results were reported from an investigation of the effects of intratracheal administration of 1 × 105 intact, autoclaved, and ethanol-extracted spores of S. chartarum in 7-dold rats .
During the 72 h following exposure to all three types of fungal spores, there was a significant reduction in alveolar space with simultaneous elevation of TNF-α, IL-1β, and neutrophils in BALF. Intact spores had the greatest effect, followed by autoclaved and ethanol-extracted spores. Differences in the time-course of the response indicated that the trichothecenes were the main contributors to the early inflammation, which peaked 24 h after exposure, although proteins already participated. Peak release of proteins and/or other fungal compounds occurred later in the inflammatory response and appeared to be mainly responsible for prolonging it. In another study, mice received intratrachel instillations of 30, 300, or 3000 spores/g body weight of a trichothecene- or atranone-producing strain of S. chartarum or of Cladosporium cladosporioides . Both of the S. chartarum strains, but not C. cladosporioides, caused marked vascular leakage in the lung, although they had very different time-courses. Significant increases in BALF TNF-α concentrations were noted after treatment with all three fungi but did not show a linear dose–response in the case of the two S. chartarum strains. Conversely, IL-6 levels in BALF rose with increasing spore dose, with only the highest dose of all three fungi producing statistically significant increases. Only the highest dose of the atranone-producing S. chartarum strain significantly raised IL-1β concentrations. However, note that the lowest dose of the other strain induced similar levels, but they were not statistically significantly different from controls. Together, these results clearly suggest that substances other than trichothenes and atranones contributed to lung inflammation and pathology. This confirms the findings of the other studies, which also indicate that mycotoxins play an important role in lung inflammation and pathology but do not support the hypothesis that mycotoxins are solely responsible for these effects. Note that these results cannot be directly translated to humans because they were obtained with very high doses of spores corresponding to between 21 million to more than 1 billion spores for an average 70-kg human. The potential health effects of exposure to Stachybotrys and its associated mycotoxins were examined in 53 occupants of a water-damaged building . There was an association detected between the presence of satratoxin H and spirocyclic lactones and lower respiratory, dermatological, eye, constitutional, and chronic fatigue symptoms. Additionally, occupants of the water-damaged building exhibited a lower proportion of mature T-lymphocytes compared with controls without any contact to the test site. This was not a double blind study, and there was no effort to rule out other causes of the occupants’ symptoms. Therefore, no conclusion can be made from this study regarding a causal effect of trichothecenes on human health.ABPA is an allergic reaction to a fungus that mimics pneumonia; it is characterized clinically by asthma and airway inflammation and serologically by increased titers of Aspergillus-specific IgE in the blood. Increased eosinophils are present in lung tissue.