[show abstract][hide abstract] ABSTRACT: Subject matter experts systematically reviewed evidence on the effectiveness of housing interventions that affect health outcomes, primarily asthma, associated with exposure to moisture, mold, and allergens. Three of the 11 interventions reviewed had sufficient evidence for implementation: multifaceted, in-home, tailored interventions for reducing asthma morbidity; integrated pest management to reduce cockroach allergen; and combined elimination of moisture intrusion and leaks and removal of moldy items to reduce mold and respiratory symptoms. Four interventions needed more field evaluation, 1 needed formative research, and 3 either had no evidence of effectiveness or were ineffective. The 3 interventions with sufficient evidence all applied multiple, integrated strategies. This evidence review shows that selected interventions that improve housing conditions will reduce morbidity from asthma and respiratory allergies.
Journal of public health management and practice: JPHMP 08/2010; 16(5 Suppl):S11-20. · 0.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Housing conditions can contribute to allergen exposures that are linked to asthma, but little is known about which of those conditions are most likely to predict high levels of allergens in settled house dust.
We pooled allergen, housing condition, occupant behavior, demographic, and other data from nine asthma studies (n=950 homes in 6 US cities). Dust mite (Der f 1 or Der p 1), cockroach (Bla g 1 or Bla g 2), mouse (Mus m 1), cat (Fel d 1) and dog (Can f 1) allergens were measured in settled dust from kitchens or bedrooms, and concentrations were categorized according to previously published asthma symptom thresholds. We calculated odds ratios (OR) using logistic regression to identify those housing conditions and occupant behaviors that were associated with clinically significant allergen levels, after adjusting for numerous confounding variables.
The adjusted results show that high cockroach allergen was associated with cracks or holes in walls (OR=2.1), high dust mite allergen was associated with mold odor (OR=2.5), housing built before 1951 (OR=2.1), and single-family home with slab on grade (OR=1.9); and mouse allergen was associated with rodent control or signs of rodents (OR=3.62) and inversely associated with presence of a cat (OR=0.20). Water leaks and below average housekeeping had unadjusted high odds ratios for high cockroach allergen.
We have identified a number of housing conditions that are consistently associated with increased allergen dust concentrations. This study indicates that screening for housing-based asthma triggers should include presence of cats, dogs, cockroaches, or rodents; water leaks; mold or mold odor; holes or cracks in walls; and below average housekeeping. Single family houses that have basements or crawl spaces or are built before 1951 are also important predictors for increased allergens in housing.
Environmental Research 11/2009; 110(2):189-98. · 3.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Damp building-related illnesses (DBRI) include a myriad of respiratory, immunologic, and neurologic symptoms that are sometimes etiologically linked to aberrant indoor growth of the toxic black mold, Stachybotrys chartarum. Although supportive evidence for such linkages is limited, there are exciting new findings about this enigmatic organism relative to its environmental dissemination, novel bioactive components, unique cellular targets, and molecular mechanisms of action which provide insight into the S. chartarum's potential to evoke allergic sensitization, inflammation, and cytotoxicity in the upper and lower respiratory tracts. Macrocyclic trichothecene mycotoxins, produced by one chemotype of this fungus, are potent translational inhibitors and stress kinase activators that appear to be a critical underlying cause for a number of adverse effects. Notably, these toxins form covalent protein adducts in vitro and in vivo and, furthermore, cause neurotoxicity and inflammation in the nose and brain of the mouse. A second S. chartarum chemotype has recently been shown to produce atranones-mycotoxins that can induce pulmonary inflammation. Other biologically active products of this fungus that might contribute to pathophysiologic effects include proteinases, hemolysins, beta-glucan, and spirocyclic drimanes. Solving the enigma of whether Stachybotrys inhalation indeed contributes to DBRI will require studies of the pathophysiologic effects of low dose chronic exposure to well-characterized, standardized preparations of S. chartarum spores and mycelial fragments, and, coexposures with other environmental cofactors. Such studies must be linked to improved assessments of human exposure to this fungus and its bioactive constituents in indoor air using both state-of-the-art sampling/analytical methods and relevant biomarkers.
[show abstract][hide abstract] ABSTRACT: The adverse health effects of Stachybotrys chartarum have often been linked to exposure to the trichothecene mycotoxins. Recent studies have shown that in addition to mycotoxins this fungus is capable of producing and secreting in vivo proteins such as hemolysins and proteinases. Spore extracts obtained from a high trichothecene producing isolate JS 58-17 exhibited a significantly lower proteolytic activity compared to the low trichothecene producer, JS 58-06. Growing isolates on rice or potato dextrose agar results in higher proteolytic activity of the spores compared to those grown on drywall. Proteinases in the spore extracts can hydrolyze gelatin and collagen I and IV. Analysis of zymograms shows the presence of several proteins with proteolytic activity in the spores of S. chartarum. Human tracheal epithelial cells exposed to spore extracts produced significantly higher levels of IL-6, IL-8, and TNF-alpha than control cells. This stimulation of cytokine production was completely abolished by Pefabloc, a serine protease inhibitor. Neutrophil numbers and proinflammatory cytokine (IL1-beta and TNF-alpha) concentrations were highly elevated in the lungs of 7 day old rat pups exposed intratracheally to 4 x 10(4) spores/gm body weight compared to control. No significant differences in those inflammatory indices in vivo were noted between the treatments with the high trichothecene producer, isolate JS 58-17 and JS 58-06, which does not produce macrocyclic trichothecenes. Immunohistochemistry revealed reduced collagen IV labeling in spore-induced lung granulomas in rat pups exposed to both isolates. These results suggest that proteinases from S. chartarum spores significantly contribute to lung inflammation and injury.
[show abstract][hide abstract] ABSTRACT: Acute pulmonary hemorrhage developed during isoflurane anesthesia in 2 Himalayan cats undergoing routine dental cleaning and prophylaxis.
The cats were siblings and lived together. In both cats, results of pre-operative physical examinations and laboratory testing were unremarkable. Blood pressure and oxygen saturation were within reference ranges throughout the dental procedure. Approximately 15 to 20 minutes after administration of isoflurane was begun, frothy blood was noticed within the endotracheal tube. Blood was suctioned from the endotracheal tube, and the cats were allowed to recover from anesthesia.
1 cat initially responded to supportive care but developed a second episode of spontaneous pulmonary hemorrhage approximately 30 hours later and died. The other cat responded to supportive care and was discharged after 4 days, but its condition deteriorated, and the cat died 10 days later. Subsequently, it was discovered that the home was severely contaminated with mold as a result of storm damage that had occurred approximately 7 months previously. Retrospective analysis of banked serum from the cats revealed satratoxin G, a biomarker for Stachybotrys chartarum, commonly referred to as "toxic black mold."
Findings highlight the potential risk of acute pulmonary hemorrhage in animals living in an environment contaminated with mold following flood damage.
Journal of the American Veterinary Medical Association 10/2007; 231(5):731-5. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: After Hurricane Katrina, many New Orleans homes remained flooded for weeks, promoting heavy microbial growth.
A small demonstration project was conducted November 2005-January 2006 aiming to recommend safe remediation techniques and safe levels of worker protection, and to characterize airborne mold and endotoxin throughout cleanup.
Three houses with floodwater lines between 0.3 and 2 m underwent intervention, including disposal of damaged furnishings and drywall, cleaning surfaces, drying remaining structure, and treatment with a biostatic agent. We measured indoor and outdoor bioaerosols before, during, and after intervention. Samples were analyzed for fungi [culture, spore analysis, polymerase chain reaction (PCR)] and endotoxin. In one house, realtime particle counts were also assessed, and respirator-efficiency testing was performed to establish workplace protection factors (WPF).
At baseline, culturable mold ranged from 22,000 to 515,000 colony-forming units/m3, spore counts ranged from 82,000 to 630,000 spores/m3, and endotoxin ranged from 17 to 139 endotoxin units/m3. Culture, spore analysis, and PCR indicated that Penicillium, Aspergillus, and Paecilomyces predominated. After intervention, levels of mold and endotoxin were generally lower (sometimes, orders of magnitude). The average WPF against fungal spores for elastomeric respirators was higher than for the N95 respirators.
During baseline and intervention, mold and endotoxin levels were similar to those found in agricultural environments. We strongly recommend that those entering, cleaning, and repairing flood-damaged homes wear respirators at least as protective as elastomeric respirators. Recommendations based on this demonstration will benefit those involved in the current cleanup activities and will inform efforts to respond to future disasters.
Environmental Health Perspectives 01/2007; 114(12):1883-9. · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources.
In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2-17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children's total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year.
Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11).
Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.
Environmental Health Perspectives 11/2006; 114(10):1574-80. · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite the growing body of evidence showing adverse health effects from inhalation exposure to the trichothecene-producing mold Stachybotrys chartarum, controversy remains. Currently, there are no reliable assays suitable for clinical diagnosis of exposure. We hypothesized that satratoxin G (SG) -albumin adducts may serve as biomarkers of exposure to this fungus.
We studied the formation of adducts of SG with serum albumin in vitro using Western blots and mass spectrometry (MS) and searched for similar adducts formed in vivo using human and animal serum.
Samples of purified human serum albumin that had been incubated with increasing concentrations of SG showed concentration-dependent albumin bands in Western blots developed with anti-SG antibodies. MS analysis found that as many as 10 toxin molecules can be bound in vitro to one albumin molecule. The sequencing of albumin-adduct tryptic peptides and the analysis of pronase/aminopeptidase digests demonstrated that lysyl, cysteinyl, and histidyl residues are involved in the formation of these adducts. Serum samples from three patients with documented exposure to S. chartarum similarly revealed lysine-, cysteine-, and histidine-SG adducts after exhaustive digestion, affinity column enrichment, and MS analysis. These adducts were also found in the sera from rats exposed to the spores of S. chartarum in contrast to control human subjects and control animals.
These data document the occurrence of SG-albumin adducts in both in vitro experiments and in vivo human and animal exposures to S. chartarum. Relevance to clinical practice: SG-amino acid adducts may serve as reliable dosimeter biomarkers for detection of exposure to S. chartarum.
Environmental Health Perspectives 09/2006; 114(8):1221-6. · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: We sought to determine if specific molds were found in significantly higher concentrations in the water-damaged homes of asthmatic children compared with homes with no visible water damage.
The mold concentrations in the dust in asthmatic children's bedrooms in water-damaged homes (N = 60) and control homes (N = 22) were measured by mold-specific quantitative polymerase chain reaction.
Two molds, Scopulariopsis brevicaulis and Trichoderma viride, had significantly (P < 0.05) higher concentrations in asthmatics' homes compared with control homes and three other molds (Penicillium crustosum group, Stachybotrys chartarum, and Wallemia sebi) had P values <0.1.
A relative moldiness index was developed to predict the likely development of asthma in water-damaged homes in Cleveland.
Journal of Occupational and Environmental Medicine 09/2006; 48(8):852-8. · 1.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Stachybotrys chartarum has been linked to building-related respiratory problems including pulmonary hemorrhage in infants. The macrocyclic trichothecenes produced by S. chartarum have been the primary focus of many investigations. However, in addition to trichothecenes this fungus is capable of producing other secondary metabolites and a number of protein factors. This study examines the effects of intact, autoclaved, and ethanol-extracted spores on the lungs of infant rats as an approach to differentiate between secondary metabolites and protein factors. Seven-day-old infant rats were exposed intratracheally to 1 x 10(5) spores/g body weight (toxic strain JS58-17) and sacrificed at various times up to 72 h. The inflammatory response was measured by morphometric analysis of the lungs and determination of inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid. Alveolar space was greatly reduced in animals exposed to fungal spores compared to phosphate buffered saline (PBS)-treated controls. The largest effects were observed in pups treated with intact spores where alveolar space 24 h after treatment was 42.1% compared to 56.8% for autoclaved spores, 51.1% for ethanol-extracted spores, and 60.6% for PBS-treated controls. The effects of different spore preparations on inflammatory cells, cytokine, and protein concentrations in the BAL fluid can be ranked as intact > autoclaved > extracted. Tumor necrosis factor alfa (TNF-alpha), interleukin 1-beta (IL-1beta), and neutrophils were the most sensitive indicators of inflammation. The difference between autoclaved (100% trichothecene toxicity, denatured/enzymatically inactive proteins) and intact (100% trichothecene activity, unaltered/released proteins) spores indicates the involvement of fungal proteins in the inflammatory response to S. chartarum and sheds new light on the clinical importance of "nontoxic" strains.
[show abstract][hide abstract] ABSTRACT: Fungal concentrations were measured in the dust of 6 homes in Cleveland, Ohio, where an infant developed pulmonary hemorrhage (pulmonary hemorrhage homes [PHH]) and 26 reference homes (RH) with no known fungal contamination. Quantitative polymerase chain reaction assays for 82 species (or assay groups) were used to identify and quantify fungal concentrations. The ratios of the geometric means of PHH to RH were >1 for 26 species (group I). However, the same ratios were <1 for 10 species (group II). Probit analysis of the sum of the logs of the concentrations of these 2 groups resulted in a 95% probability range for separating PHH from RH homes. The same 82 fungal species were also tested for hemolysin production on sheep's blood agar (incubated at 37 degree C). Hemolysins were more commonly produced by group I species (42%) compared with group II species (10%).
Journal of Occupational and Environmental Medicine 06/2004; 46(6):596-601. · 1.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Satratoxin-G (SG) is the major macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum (atra) and has been implicated as a cause of a number of animal and human health problems including pulmonary hemorrhage in infants. However, there is little understanding where this toxin is localized in the spores and mycelial fragments of this species or in the lung impacted by SG-sequestered spores. The purpose of this study was to evaluate the distribution of SG in S. chartarum spores and mycelium in culture, and spore-impacted mouse lung in vivo, using immunocytochemistry. SG was localized predominately in S. chartarum spores with moderate labelling of the phialide-apex walls. Labelling was primarily along the outer plasmalemma surface and in the inner wall layer. Only modest labelling was observed in hyphae. Toxin localization at these sites supports the position that spores contain the highest satratoxin concentrations and that the toxin is constitutively produced. In impacted mouse lung, highest SG labelling was detected in lysosomes, along the inside of the nuclear membrane in nuclear heterochromatin and RER within alveolar macrophages. Alveolar type II cells also showed modest labelling of the nuclear heterochromatin and RER. There was no evidence that the toxin accumulated in the neutrophils, fibroblasts, or other cells associated with the granulomas surrounding spores or mycelial fragments. These observations indicate that SG displays a high degree of cellular specificity with respect to its uptake in mouse lung. They further indicate that the alveolar macrophages play an important role in the sequestration and immobilization of low concentrations of the toxin.
[show abstract][hide abstract] ABSTRACT: Stachylysin is a proteinaceous hemolytic agent that is produced by Stachybotrys chartarum. Stachylysin was found, using immunohistochemical and immunocytochemical methods, to be localized in S. chartarum spores/mycelia primarily in the inner wall suggesting that it is constitutively produced. Spores instilled in mouse or rat lung tissues resulted in granuloma formation, which showed the highest stachylysin concentration in the inner wall of the spore and near the spore, with less at distance indicating that it had diffused out from the spore. The in vitro high stachylysin producing strain (58-06) was also highest in vivo, based on immunohistochemistical staining. More stachylysin was observed in the mouse lung tissue at 72 h than at 24 h indicating that production/release is a relatively slow process. The localization of stachylysin in macrophage phagolysosomes suggests that these cells may be involved with hemolysin inactivation. This would be consistent with what is known about asp-hemolysin produced by Aspergillus fumigatus.
[show abstract][hide abstract] ABSTRACT: Observing that the conidia of Stachybotrys chartarum can germinate in the lung of infant rats, it became important to ascertain whether an infection can ensue. Viable conidia of S. chartarum were instilled into the lungs of 4 and 14 day-old rat pups. Germination was observed frequently in the lungs of 4 day-old but rarely in the 14 day-old pups. In the 4 day-old pups, pulmonary inflammation with hemorrhagic exudates was observed and resulted in about 15% mortality rate compared to 0% for the controls instilled with phosphate buffered saline. Acute neutrophilic inflammation and intense interstitial pneumonia with poorly formed granulomas observed three days following exposure were associated with fungal hyphae and conidia. The surviving experimental pups showed significantly slower weight gain for seven days. Dilution plating and quantitative PCR analysis were used to follow total fungal load in the rat pups lung homogenates. In the 4 day-old rat pups viable fungi decreased rapidly and were less than 1% by day seven. Similarly, fungal DNA decreased exponentially and was only 0.03% by fourteen days after exposure. However, 14 day-old rat pups showed neither the lethal effects of exposures to viable conidia of S. chartarum nor the slower weight gain, and the fungal load decreased even more rapidly. We conclude that S. chartarum conidia can initially germinate and form hyphae but even in the immature rat pups do not establish an effective infection, although a very limited persistence cannot be excluded.
[show abstract][hide abstract] ABSTRACT: Between 1993 and 2000, 30 infants were hospitalized with acute pulmonary hemorrhage at Rainbow Babies and Children's Hospital in Cleveland. Most infants presented with severe pulmonary symptoms requiring intensive support, but a few infants had less severe hemorrhage. Three quarters of the patients required ventilator support and blood transfusions. Eleven patients had transitory hemoglobinuria. Five patients died, but infants who survived did well. There are currently no specific treatment modalities, although we have advised moving to a different home and avoiding environmental tobacco smoke. Subsequently, rebleeding from the lower respiratory tract has decreased from 5 of 7 infants to 1 in 21. On the basis of decreased subsequent fatal hemorrhage, high dose glucocorticoids seem to be of some value. Several patients revealed continued low-grade alveolar hemorrhage for months after their initial bleed, even after removal from their original home environments.
[show abstract][hide abstract] ABSTRACT: In recent years cases of often fatal pulmonary hemorrhage in infants have been associated with water damaged homes and the toxigenic fungus Stachybotrys chartarum. The fungal spores contain mycotoxins which could be injurious to the rapidly developing lung. In order to understand the developmental pathophysiology of this disease we developed an infant rat model of stachybotrytoxicosis describing the effects of fungal spores on survival, growth, histopathology of the lung and respiration. Conidia of S. chartarum were instilled intratracheally (1.0-8.0 x 10(5)/gm wt.) in 4-d old Sprague-Dawley rat pups. Two control groups received either sterile PBS or a suspension of spores extensively extracted with ethanol to remove toxins. Lethal dose response was determined (LD50 = 2.7 x 10(5) spores/gm wt.). All dead pups had extensively hemorrhagic lungs. Growth of surviving animals was impaired in a dose-dependent manner. Changes of pulmonary function parameters in rats treated with 1.1 x 10(5) spores/g were consistent with an increased respiratory resistance. Histology of lungs revealed fresh hemorrhage, sparse hemosiderin-laden macrophages, and evidence of inflammation including thickened alveolar septa infiltrated by lymphocytes and mononuclear cells and intra-alveolar macrophages. Significant increases (p = 0.001) in numbers of macrophages (2-fold), lymphocytes (5-fold) and neutrophils (7-fold) were found in BAL fluid. Hemoglobin was elevated 2-fold (p = 0.004). Proinflammatory mediator IL-1beta increased more than 6-fold and TNF-alpha 30-fold (p = 0.001). Extracted spores had a minimal effect on all examined parameters in BAL fluid indicating that mycotoxins are primarily responsible for the hemorrhagic and inflammatory response.
[show abstract][hide abstract] ABSTRACT: Stachybotrys chartarum is a toxigenic fungus that has been associated with human health concerns, including pulmonary hemorrhage and hemosiderosis. This fungus produces a hemolysin, stachylysin, which in its apparent monomeric form has a molecular mass of 11,920 Da as determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. However, it appears to form polydispersed aggregates, which confounds understanding of the actual hemolytically active form. Exhaustive dialysis or heat treatment at 60 degrees C for 30 min inactivated stachylysin. Stachylysin is composed of about 40% nonpolar amino acids and contains two cysteine residues. Purified stachylysin required more than 6 h to begin lysing sheep erythrocytes, but by 48 h, lysis was complete. Stachylysin also formed pores in sheep erythrocyte membranes.
Infection and Immunity 03/2001; 69(2):912-6. · 4.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: A strain of Stachybotrys chartarum was recently isolated from the lung of a pulmonary hemorrhage and hemosiderosis (PH) patient in Texas (designated the Houston strain). This is the first time that S. chartarum has been isolated from the lung of a PH patient. In this study, the Houston strain and 10 strains of S. chartarum isolated from case (n = 5) or control (n = 5) homes in Cleveland were analyzed for hemolytic activity, siderophore production, and relatedness as measured by random amplified polymorphic DNA analysis.
Applied and Environmental Microbiology 07/2000; 66(6):2678-81. · 3.68 Impact Factor