Survey Results of HHS and HHS-Sponsored Research on the Health Effects of Exposure to Indoor Mold
Centers for Disease Control and Prevention (CDC) Survey Results
Ongoing Research as of October 1, 2007

Project
Title		 Project
Description		 Agency
Contact		 Telephone
Number
Development of New Immunodiagnostic and Detection Techniques for Indoor Fungi Airborne fungi are ubiquitous in the environment and are among the most common bioaerosols that humans inhale. Interest in measuring exposure to fungi has increased dramatically in recent years due to the known associations between exposure and adverse health effects, such as asthma, but also potential links to sick building syndrome and a range of other undefined disorders. Occupational exposure to fungi is a growing concern in a number of work environments, such as in offices, schools, and jobs involving the handling of fungal contaminated farm or biowaste products. Many strategies have been employed to sample, identify and interpret exposure to fungi; however, no strategy serves all purposes, as exposure is a complex and dynamic process. To date, the interpretation of personal exposure and sensitization to fungal allergens has been restricted to a few select species; however, the importance of many other species remains unrecognized and exposure guidelines have not been proposed. A recent skin prick test study we conducted examined the prevalence of sensitization to fungi that are commonly isolated from water-damaged, atypical homes but are not routinely included in skin prick testing panels. The results of that study implicated a number of other fungi as important aeroallergen sources, in particular Paecilomyces variotii. P. variotii is a cosmopolitan filamentous fungus that has gained notoriety in the scientific literature as a thermophylic pathogen in both immunocompromised and immunocompetent patients. Previous studies have shown that exposure to P.variotii can be extremely high in certain environments and is considered an occupational hazard for building remediation workers and a potential cause of respiratory diseases including allergy, asthma, and hypersensitivity pneumonitis. To date, the association between P. variotii and respiratory disease remains unexplored due to a lack of available diagnostic reagents. To gain a better understanding of its role in occupational and building-related complaints, it is necessary to develop methods to measure the extent of exposure. To that end, it is essential to have sensitive tests but also tests that are species-specific for various fungal species. Antibody-based tests are particularly suited for such a task, but cross-reactivity between fungal species can be problematic. Species-specific monoclonal antibodies (mAb) could be developed to specifically detect P. variotii in the environment, but the development of quantitative methods will require purification of the specific antigens. The objectives of this proposal are to identify allergens that are expressed on the surface of P. variotii spore and hyphal walls and develop species-specific Abs to these antigens. The overall goals will be to develop more accurate environmental and clinical tests for this fungus. Specifically, we will (1) identify, isolate and characterize the surface expressed spore and hyphal wall allergens; (2) generate P. variotii cDNA, clone, and express recombinant forms of these allergens; (3) develop species-specific mAbs to the recombinant allergens and (4) design accurate and precise immunoassays for the detection and quantification of P. variotii in environmental and clinical samples. This project will ultimately help solve a number of the problems associated with measuring personal exposure to P. variotii as well as help to protect America's workforce and the public in general from harmful fungal exposure. Donald Beezhold 304-285-5963
Utilizing Mass Spectrometry to Analyze Samples From Mice Exposed to Fungal Aerosols The fungal community consists of several thousand diverse species that are able to colonize in a variety of environments, especially damp dwellings. Spores, which are produced by the fungi in response to a nutrient deprived environment, can become airborne and inhaled by the host. In many cases, these spores would simply be degraded by the lung's resident macrophages and neutrophils; however, prolonged exposure over time can allow the fungi to establish disease in the host. To date, no animal models have been made utilizing a dry aerosol exposure of the fungal spores and instead involve harvesting the spores in a liquid and then, if desired, creating aerosols. Thus, specific aim 1 of this project consists of developing such a model on the grounds that the common liquid spore suspension removes and dilutes most surface antigen present on the spore, and a dry aerosol exposure would theoretically result in differences in immune response characteristics. Using this model, we will expose mice to different fungi and characterize the difference in immune responses compared to liquid instillation. In addition, recent evidence suggests that fungi secrete proteases into the lung that will create specific peptide fragments. Therefore, specific aim 2 is to subject lung lavages to mass spectrometry analysis in order to obtain a unique fingerprint spectrum that can be used diagnostically to identify fungal exposure. Furthermore, fungi also secrete mycotoxins that can be severely detrimental to the host when entering the blood stream. These toxins can form adducts with abundant serum proteins. Thus, a third specific aim is to use mass spectrometry to identify and characterize serum protein adducts associated with different parent fungi. The data resulting from this project will be very useful to the mycology field, as well as the medical community due to the potential of better diagnostics. Donald Beezhold 304-285-5963
Study on Identification and Typing (Fingerprinting) Medically Important Fungal Organisms Using DNA To develop and validate DNA-based methods for identification and fingerprinting medically important fungi. Fungal species identification and strain discrimination is critical to determine disease etiology, to detect novel agents of disease, to identify organisms that are intrinsically resistant to antifungal drugs, and to detect clusters of nosocomial infection among hospitalized patients. This knowledge is central to the development of strategies to manage and prevent invasive fungal infections in high-risk patient populations. Current identification methods are laborious, lack reproducibility, and are not amenable to Web-based data sharing. The absence of a robust species/strain identification scheme has hampered the rapid identification of novel species and the associated burden of disease. Additionally, DNA-based methods will ensure objectivity of identification and portability of data. Mary E. Brandt 404-639-0281
Building-Related Asthma Research in Maine Public Schools This research study compares health and environmental indices longitudinally in three schools, chosen with respect to dampness history and remediation status, in order to study remediation effectiveness. Specifically, cross-sectional surveys will be done annually for three years in a dry school, a damp school preremediation with remediation scheduled in the study period, and a remediated damp school. This design allows characterization of exposure-response relations for building-related respiratory disease within schools and temporal comparisons between schools. The project has the long term objective of building capacity on a state and regional level for stakeholders and policy makers to improve poor indoor environmental quality in schools, thereby reducing any associated adverse effects on staff and student health, productivity, and well-being. To achieve this objective, we will gather and disseminate information on the effectiveness of renovations of damp schools in improving respiratory health and indoor environmental quality and demonstrate that maintenance personnel and school nurses can use simple environmental and health survey tools to monitor indoor environmental quality and to guide early remediation of problems. Jean Cox-Ganser 304-285-5818
Hazard Evaluation and Technical Assistance #2001-0255-2868 This project investigated health outcomes in employees in relation to exposure indices and measurements in a water-damaged hospital and a comparison hospital. Jean Cox-Ganser 304-285-5818
Health Effects of Exposure to Water-Damaged New Orleans Homes Six Months After Hurricanes Katrina and Rita In the aftermath of Hurricanes Katrina and Rita, visible mold growth occurred in approximately 24 percent of New Orleans, Louisiana homes. Exposure to indoor dampness and mold has been associated with nasal and throat symptoms, cough, wheeze, asthma exacerbations in sensitized asthmatics, and hypersensitivity pneumonitis. We aimed to better understand the relationship between respiratory symptoms and exposure to water-damaged homes in posthurricane New Orleans. Given the recommendation about respirator use and the observation that respirator use was common among the public following the hurricanes, a second objective was to determine the effect of respirator use on symptoms. We conducted a population-based investigation to address these issues. Kristin Cummings 304-285-6102
Evaluation and Validation of a Novel Bioaerosol Personal Sampler The purpose of this project is to develop a series of aerosol samplers, which are devices that collect airborne particles such as fungal spores and fungal spore fragments. These samplers are small and lightweight enough that they can be worn by individuals, which allows assessment of personal exposure to aerosol particles. The samplers are size-selective; that is, they are designed to separate intact spores from smaller fragments, which allows separate measurements of each. This is useful because some reports suggest that spore fragments may stimulate a stronger allergic response than do intact spores. The samplers collect the larger airborne particles in one or more disposable plastic centrifuge tubes, which are commonly used in laboratories. Since the samples are collected in these tubes, the tubes can then be unscrewed, and the samples can be processed directly in the tubes. This makes processing easier and reduces sample loss. Smaller particles that are not deposited in the tubes are collected on a filter, which can be removed for sample extraction and processing. William G. Lindsley 304-285-6336
Hazard Evaluation and Technical Assistance # 2007-0097: Bennington, Vermont State Office Building This project concerns a water-damaged building with a cluster of sarcoidosis and excess asthma incidence, for which we have provided pulmonary function characterization and exposure characterization in support of Vermont Health Department epidemiologic characterization. JuHyeong Park 304-285-5967
Remediation Impact on Respiratory Health of Office Workers in a Water-Damaged Building This project involves cross-sectional health and environmental characterization of a water-damaged building before, during, and after remediation to test hypotheses related to the identification and prevention of work-related asthma in office buildings. Surveys have been conducted in 2001 to 2002, 2004, 2005, and 2007. We have examined incidence density of asthma pre- and postoccupancy of the building, exposure-reponse relations, objective measures of respiratory disease, and natural history of building-related symptoms and disease over time, and remediation efforts. JuHyeong Park 304-285-5967
Organic Vapors from Molds Growing on Building Materials Moldy or musty odors in damp buildings have been attributed to volatile organic compounds produced by molds (MVOCs), some of which have been implicated in upper respiratory tract irritation of building occupants. This laboratory project grows mold on damp construction material substrates and uses evacuated canisters to collect the volatile organic compounds (VOCs) produced. Gas chromatography/mass spectrometry is used to directly quantitate the VOCs from the evacuated canisters. All VOCs produced in the test systems will be reported with MVOCs being only those compounds released by mold-inoculated substrates. Concentration results will be input into prepackaged computer models for simulating concentrations of total VOCs and MVOCs that might be present in damp buildings. The ultimate goal of the project is development and validation of methods that can be used to measure and characterize VOCs in response to complaints about mold odor or dampness in buildings. Terri Pearce 304-285-6211
The Development of Monoclonal Antibody-Based Immunodiagnostics for Fungal Hemolysins as Potential Biomarkers of Fungal Exposure. Although the infectious and allergic adverse health effects of fungi are well documented, the effects of mycotoxins and other fungal products on human health are much more controversial. Furthermore, the current lack of sampling techniques that provide representative samples combined with the absence of standardized sample analysis techniques have so far prevented the establishment of environmental exposure guidelines for fungi. A comprehensive literature review on "Damp Indoor Spaces and Health" by the National Academy of Sciences' Institute of Medicine (2004) emphasized some of the current methodological challenges associated with fungal monitoring techniques and identified the development of valid and standardized quantitative exposure-assessment methods as a high research priority. The overall goal of this project is to develop monoclonal antibody (mAb)-based immunodiagnostics for the design of accurate and precise mold monitoring and surveillance techniques. mAb-based immunoassays have been demonstrated to provide highly specific and reproducible analytical techniques with proven potential for standardization, automation, and the development of on-site point-of-need assay formats. Fungal hemolysins have been suggested as possible biomarkers of fungal exposure, and we propose to use them as model antigens to demonstrate the analytical potential of immunoassays in exposure assessments. We will produce mAbs against four different fungal hemolysins and develop serological and environmental immunoassays for their measurement in patients' sera and environmental samples, respectively. The specific aims of this research proposal are: (1) The production of mAbs against chrysolysin, nigerlysin, Asp-hemolysin and terrelysin that are produced by P. chrysogenum, A. niger, A. fumigatus and A. terreus, respectively. (2) Investigation of hemolysin expression and design of environmental immunoassays for their detection. (3) Investigation of hemolysin stability in serum and design of serological immunoassays for their detection. We hypothesize that this approach will lead to objective measures of fungal exposure and promote the rational management of the causes and consequences of fungal contamination in indoor environments. The standardized methods resulting from this project will allow reproducible and comparable analyses in longitudinal and multicenter studies and, in turn, facilitate large-scale epidemiological studies. Such studies will provide critical insight in and fundamental understanding of the underlying patterns and dynamics of fungal contamination in indoor environments. This type of research will give NIOSH the opportunity to provide much needed scientific leadership in the field of bioaerosol assessment and eventually support the development of objective exposure guidelines based on actual exposure-disease and dose-response relationships. Ultimately, industrial hygienists and building managers as well as clinical and research allergists will be able to implement better building management and patient care and thus help to better protect America's workforce and the public in general from harmful fungal exposures. Detlef Schmechel 304-285-6024
Health Hazard Evaluation: HETA-2004-0387, Gro-west, Utica, New York We performed environmental sampling before and after decontamination using chlorine dioxide to determine its effectiveness in mold remediation. Allison Tepper 513-841-4386
Health Hazard Evaluation: HETA-2005-0135, Alcee Fortier Senior High School, New Orleans, Louisiana We compared visual contrast sensitivity measurement among employees of a very moldy school in New Orleans to that of employees of a non-moldy school to determine if there was an effect of mold exposure on the visual components of the central nervous system Allison Tepper 513-841-4386
Development of an Animal Model to Evaluate the Contribution of the Fungal Product, ß-glucan, on the Pulmonary Inflammatory Potential of Indoor Dust Samples. The Indoor Air Quality Initiative in DRDS/NIOSH is evaluating the effect of dampness/water damage on fungal growth, mold content of indoor dust samples, and occupant illness and respiratory symptoms. PPRB/NIOSH is providing scientific assistance to this effort by developing animal models (rat and mouse) to evaluate the pulmonary inflammatory response to the fungal product, ß-glucan, and dusts containing this fungal product. The time course and dose response relationships for ß-glucan-induced responses were obtained. Indoor dust samples were collected from buildings associated with respiratory symptoms and from buildings with no health complaints. Dust samples were evaluated for spore content, mold content, and ß-glucan activity. These dust samples are being evaluated in the animal models for inflammatory potency using exposure by intratracheal instillation. Biological potency of various indoor dust samples will be related to ß-glucan content, endotoxin content, spore count, and occupant symptoms. Such information will assist DRDS Scientists in determining the relative importance of indoor mold as an etiologic agent in adverse pulmonary symptoms of occupants of damp or water-damaged buildings. Shih-Houng Young 304-285-5710