| All Survey Results of Research on the Health Effects of Exposure to Indoor Mold |
| Ongoing Research as of October 1, 2007 |
| Agency | Project Title |
Project Description |
Agency Contact |
Telephone Number |
|---|---|---|---|---|
| EPA | Isolating and Characterizing IgE Reactive Proteins | To isolate, characterize, and identify allergenic proteins produced by molds. Steve Vesper supplies the starting material from which I purify the allergenic proteins. | Maura Donohue | 513-569-7634 |
| EPA | Mechanistic Indicators of Childhood Asthma (MICA) Study | The Mechanistic Indicators of Childhood Asthma (MICA) study uses air, biologic, and clinical measures as well as novel molecular biology, chemistry, and gene technologies to identify factors that affect individual susceptibility to asthmatic responses. EPA scientists are applying computational methods to analyze, characterize, and possibly quantify combined risk factors that relate to asthma severity in childhood. MICA addresses agency need to study the interplay of environmental and genetic factors to better understand adverse health effects associated with environmental exposures. The purpose of this study is not necessarily directed at mold-related issues, but the secondary data that we collect could address some of the interests that GAO is interested in. The study was not designed to directly address the research questions that a GAO survey intends to inventory. | Jane E. Gallagher | 919-966-0638 |
| EPA | El Paso Children's Health Study and The Detroit Children's Health Study | The El Paso Children's Health Study was conducted in El Paso, Texas, while the Detroit Children's Health study was conducted in Detroit and Dearborn, Michigan. Both studies were primarily focused on the role of residential proximity to roadways in the development of childhood asthma. As part of this data collection activity, we have also collected questionnaire data on indoor exposures, including home dampness and the presence of visible molds. In the future, we plan to examine the relationship between home dampness and the prevalence of asthma symptoms and the levels of pulmonary function and exhaled nitric oxide. | Lucas Neas | 919-966-9961 |
| EPA | Study on Asthma and Environmental Factors, Which Included an Application of the ERMI Index | Historically indoor mold exposures had been assessed with short-term air samples (usually 3 to 5 minutes), which were then evaluated by microscopic counting or culturing, followed by microscopic observations. The results were then compared to short-term outside air samples. In both types of samples, the molds are usually only identified to the genus level, and in some critical cases, unrelated genera are lumped together. Interpreting the meaning of the analytical results was left to the individual receiving them. No scientific method was established to standardize the interpretation. The result has been confusion created by the following specific problems. First, short air samples only provide a "snap-shot" of mold conditions. In reality, the mold in the air changes from hour to hour, day to day, morning to afternoon, and season to season. Second, human identification of molds is highly dependent on the skill and expertise of the analyst. In many cases, the species of molds cannot be determined by microscopic observation of spores. The toxin profiles for each genus is also dramatically different. Third, culture-based results depend on the media used to culture the sample. Some molds grow well on one medium and not another. So you inherently have a mold selection process depending on which medium is used for the culturing. In other cases, a fast growing mold will overwhelm a slow growing mold, and the slow growing mold will be under counted. Fourth, comparison of indoor samples to outdoor samples makes no sense because the species outdoors are different from those indoors. What was needed was an objective method of mold analysis that removed the subjective human element from the process. Ten years ago we set out to develop a DNA-based method of mold analysis. DNA is highly stable and highly specific. But to do this, the relevant DNA of the indoor molds needed to be sequenced. This effort culminated in a new technology called mold-specific quantitative PCR (MSQPCR), which was patented by the U.S. EPA (PTO# 6,387,652). Many commercial laboratories have now been licensed by EPA to perform this analysis (see http://www.epa.gov/nerlcwww/moldtech.htm.), and it is freely available to researchers to use. Next, a standard protocol for sampling the indoor environment and interpreting the MSQPCR results was needed. In conjunction with HUD, we developed a standard sampling and analytical process for dust samples (Vesper et al., Journal of Occupational and Environmental Medicine, 2007; 49:829-833). Dust represents the long-term accumulation of the daily exposures of the person living in the particular environment. By the application of the MSQPCR technology to dust samples in a representative selection of homes across the U.S., we were able to develop the Environmental Relative Moldiness Index, or ERMI, scale for U.S. homes. The ERMI scale can be used to describe the mold burden in any newly sampled home on the basis of its relative position compared to the entire U.S. housing stock. This provides a simple, objective evaluation of the mold burden in a home. We are now using the ERMI scale in epidemiological studies in the U.S. to try to determine if the ERMI values can be used to understand the risk of asthma or related respiratory symptoms. To that end, we have performed and are continuing to perform various studies to try to determine if there is an association. To date we have completed studies in Cleveland, Cincinnati, Chapel Hill, and Detroit, and we are working on studies in Baltimore and New Orleans. In summary, higher ERMI values have been associated with increased risk of asthma or asthma-related symptoms. In the Cleveland study, we were able to show that remediating the water and mold problem in the homes of asthmatic children improved the health of the asthmatic children living in those homes (Kerscmar et al., Environmental Health Perspectives, 2006; 114:1574-1580). However, as with all epidemiological studies, the results demonstrate an association, not cause and effect. | Stephen Vesper | 513-569-7367 |
| EPA | Cross-Reactivity among Mold Extracts | Immunological cross-reactivity among mold extracts complicates the analysis of health effects of any particular mold. The cross-reactivity may result from sequence homology between different mold species proteins, or it may result from glycosylations of the proteins. We are studying both aspects. In vivo studies are looking at the functionality of the cross-reactivity. Do the IgE antibodies raised against one mold extract and binding to another mold extract result in triggering of an allergic or asthmatic event? Western blot analysis is being used to address the question of glycosylation. Does deglycosylation of the proteins change the IgE-reactivity profile when cross-reactivity has been previously observed? | Marsha D. W. Ward | 919-541-1193 |
| EPA | Detection of Mold-Specific Immunoglobulin in Human Sera and Comparison to Immunoglobulin in Mouse Sera | Asthma is a significant public health problem that has been on the increase for the past 30 years in Western societies, especially among children. It has been estimated that up to 90 percent of asthmatics are atopic and have an allergy trigger for their asthmatic episodes. Although indoor mold contamination is known to exacerbate symptoms in asthmatics, its role in the induction of allergic asthma is unclear. Immunoglobulin E (IgE) is an important antibody in Type I allergy and often mediates asthmatic events. Both total and allergen-specific IgE have been used in verifying the allergic status of patients. We have acquired sera from 12 adults (Yeatts et al., 2007) and 22 children (Vesper et al., Journal of Environmental Monitoring, 2007; 9:826-830) with persistent asthma (ranging from mild to severe disease), living within a 30-mile radius of Chapel Hill, North Carolina (NC ACES/PACES), and 100 asthmatic and 100 nonasthmatic children from the Mechanistic Indicators of Childhood Asthma (MICA) study, a nested study under the Detroit Children's Health Study. The purpose of our study is 1) to gain insight into the prevalence of human asthmatic's IgE-reactivity with selected molds and house dust mite (HDM) extracts and 2) to compare the serum IgE-reactive protein profiles of humans and immunized mice. If human and mouse immune systems process the same proteins as allergens, then the animal model provides a valid and strong tool for evaluating human risk from mold exposures. Hypothesis: 1) mold-induced immune responses (the production of mold-specific IgE and IgG) in an animal model can be used to predict human risk regarding exposure to molds and 2) Human and mouse IgE will react with the same mold proteins. Data has been collected and is currently being analyzed. | Marsha D. W. Ward | 919-541-1193 |
| EPA | Early Biomarkers of Allergy Induction | Asthma is a significant public health problem that has been on the increase for the past 30 years in Western societies, especially among children. It has been estimated that up to 90 percent of asthmatics are atopic and have an allergy trigger for their asthmatic episodes. Although indoor mold contamination is known to exacerbate symptoms in asthmatics, its role in the induction of allergic asthma is unclear. The induction of an adaptive immune response, such as an allergy, requires multiple exposures and time. Additionally, due to the complex nature of immune responses evaluating new agents requires in vivo studies. The development of an in vitro method to screen for the allergic potential of molds or other agents would allow a quicker assessment of indoor environments. However, such a method requires distinguishing inflammatory or irritant responses from those leading to allergy. Our study will evaluate the patterns of gene expression in lung tissue following a single acute exposure to mold extracts and a nonallergenic or low allergenic protein (e.g. bovine serum albumin) to distinguish allergic responses from more generalized inflammatory or nonallergic immune responses. The goal is to identify a set of "candidate" biomarker genes from lung tissue mRNA samples by expression microarray analysis and quantitative reverse-transcriptase polymerase chain reaction (quantitative RT-PCR). These biomarker genes may be part of biochemical pathways, or indicators of innate or early adaptive immune responsiveness. A long-term goal of this project is to use the panel or panels of biomarkers identified from these studies to guide the development of an in vitro screening protocol to further refine the system for allergy or asthma hazard identification. Data has been generated and is currently being analyzed. | Marsha D. W. Ward | 919-541-1193 |
| EPA | Identification and Characterization of Mold Allergens | The identification and characterization of mold or fungal allergens will provide insight into the classes of mold proteins that induce allergic responses. Additionally, due to immunological cross-reactivity among mold extracts, it is possible that certain mold proteins may be common mold allergens. Once identified these mold allergens may allow the determination of unhealthy indoor environments. Furthermore, human IgE against these proteins would be indicative of mold exposure potentially allowing thresholds of exposure to be evaluated. In our studies, mouse sera raised against specific mold extracts is used to perform immunoblots to detect IgE reactive proteins in mold extracts followed by mass spectrometric analysis to determine peptide sequence. The sequence data is used to probe protein databases for homologous proteins. When possible a strategy is then developed to confirm the functional identity of the IgE-reactive protein. A manuscript describing the study will soon be submitted to a peer-reviewed journal. Other mold extracts are currently under study. | Marsha D. W. Ward | 919-541-1193 |
| EPA | Relative Potency of Mold Extraction in a Mouse Model | Asthma is a significant public health problem that has been on the increase for the past 30 years in Western societies, especially among children. It has been estimated that up to 90 percent of asthmatics are atopic and have an allergy trigger for their asthmatic episodes. Although indoor mold contamination is known to exacerbate symptoms in asthmatics, its role in the induction of allergic asthma is unclear. It is not only important to identify indoor mold allergens but to assess the potency they have to induce allergic or asthmatic responses in comparison to a well characterized indoor allergen, such as house dust mite. We have compared the capacity of fungal extracts (Stachybotrys chartarum [SCE] and Metarhizium anisopliae [MACA]) and house dust mite extract (HDM) to induce allergic responses in BALB/c mice. Stachybotrys chartarum is found in water damaged homes and Metarhizium anisopliae is licensed for use as an indoor biopesticide. The extracts were administered in doubling doses from 2.5 - 80 µg total protein. A manuscript describing the study will soon be submitted to a peer-reviewed journal. | Marsha D. W. Ward | 919-541-1193 |
| EPA | Study of Putative Asthmagenic Molds | Asthma is a significant public health problem that has been on the increase for the past 30 years in Western societies, especially among children. It has been estimated that up to 90 percent of asthmatics are atopic and have an allergy trigger for their asthmatic episodes. Although indoor mold contamination is known to exacerbate symptoms in asthmatics, its role in the induction of allergic asthma is unclear. Vesper et al. (Vesper et al., Journal Occupational and Environmental Medicine, 2006; 48:852-858) categorized molds statistically more common in water-damaged Cleveland area homes as Group I molds and those found in every home as Group II molds. Remediation of water-damaged homes of asthmatics resulted in a significant reduction in symptoms. However, removal and remediation of water-damage would affect many things in the home besides mold concentrations. Therefore, there is a need to assess the relative allergenic potency of these molds using our mold allergy animal model. Preliminary data suggests that not all Group I molds induce allergic asthma-like responses in the mouse model but some of the nonallergenic molds appear to exacerbate airway responses. | Marsha D. W. Ward | 919-541-1193 |
| EPA | The Effect of Gestational Exposure to Mold on Allergy Induction in a Mouse Model | Asthma is a significant public health problem that has been on the increase for the past 30 years in Western societies, especially among children. It has been estimated that up to 90 percent of asthmatics are atopic and have an allergy trigger for their asthmatic episodes. Although indoor mold contamination is known to exacerbate symptoms in asthmatics, its role in the induction of allergic asthma is unclear. There is little understanding of the effect aeroallergens may have on the developing immune system. Determination of whether these effects increase or decrease susceptibility to allergic asthma induction would lead to strategies to protect children, particularly in the genetically predisposed atopic population. It appears that early in life the immune system is biased to promote allergic or asthmatic responses to certain antigens. Some of these allergens have been studied extensively (e.g. dust mite and cockroach), and specific antigens responsible for sensitization have been characterized. However, few of the mold allergens have been characterized, despite their widespread distribution and potential importance in the induction and exacerbation of asthma. This project focuses on gestational exposures to mold extracts and the effect this exposure has on the development of allergy or asthma in adult life using a mouse model of allergic asthma. In the initial studies, the mouse dams will be exposed to mold extract previously shown to induce allergic asthma responses in a mouse model. Control group dams will be exposed to vehicle. The offspring will be subdivided into three groups for adult exposure to the homologous mold extract, a heterologous allergen (house dust mite), and vehicle to evaluate any changes in allergic responses. Later studies will evaluate other mold extracts or other protein allergens as the homologous allergen to extend and confirm the findings. The impact on the other immune functions and windows of developmental vulnerability will also be assessed. Samples have been collected and the resulting data is currently being analyzed. | Marsha D. W. Ward | 919-541-1193 |
| EPA | U.S. EPA Environmental Technology Verification Program: Environmental and Sustainable Technology Evaluations (ESTE): Verification of Microbial Resistant Building Materials— Gypsum Wallboard | Approximately 90 percent of the interior finished surfaces of buildings are covered with gypsum products. The United States produces an estimated 30 million tons of gypsum board annually. Demand for gypsum products in the United States, Canada, and Mexico will continue to grow, reaching 46.8 million metric tons in 2007. Currently, each year, 3 million to 5 million tons of gypsum board ends up as scrap material and disposed of in landfills, with much of this scrap the result of moisture and mold problems. Mold, being ubiquitous, can be found in any nonsterile environment, while upwards of 40 percent of all homes in North America contain fungal growth with gypsum wallboard being a primary growth material. The goal of this project is the generation of a product evaluation system that will establish the performance of mold resistant building products. This evaluation system can then be used to test building products, the first of which is gypsum wallboard. This verification is intended to be used by building professionals and the consumer public, enabling them to make informed decisions regarding the use of different building products while simultaneously lowering the amount of gypsum scrap material that needs to be landfilled. The objective of this verification project is to evaluate the different types of microbial resistant gypsum products that are currently being marketed. Different manufacturers have come up with separate methods of controlling or eliminating microbial growth on gypsum products including removing microbial growth substrates and adding different antimicrobial compounds to the products. The evaluation of gypsum wallboard would test the following;
• Ability of gypsum products to support fungal (mold) growth • Resistance to moisture uptake • Volatile Organic Compound (VOC) emissions • Sustainability Criteria |
Timothy R. Dean | 919-541-2304 |
| EPA | Relationship of Gypsum Wallboard, Moisture, and Moisture Meters | Uncertainties continue to exist in the relationship of gypsum wallboard, moisture content, and moisture meters. Moisture meters designed to support the wood industry have become a mainstay in the indoor remediation area. Confusion surrounding safe or acceptable levels of moisture in gypsum wallboard is complicated by the varied results obtained by differing detection methods and instrumentation. This research effort is focusing on understanding the response of moisture meters to moisture within gypsum wallboard under varied conditions such as moisture loading, wall construction, temperature and humidity, etc. The initial research focused on a moisture meter routinely used in the field to determine the moisture content in gypsum wallboard. The meter readings are often used qualitatively (higher or lower moisture relative to a reference location) to determine the amount of wallboard to remediate. Because meters vary in their technology and method of detection, it is necessary to establish test procedures to ensure their usefulness and dependability as an aid in wallboard moisture detection and remediation. A method was developed to create a series of gypsum-wallboard-moisture-content-reference standards by exposing wallboard sample sections to static moisture content levels. Gravimetric analysis revealed good accuracy and precision of the reference standards to their theoretical values. The moisture meter was then compared against these reference standards to determine its accuracy and precision. | Dale Greenwell | 919-541-2828 |
| EPA | Laboratory and Field Research on the Efficacy of Chlorine Dioxide for the Remediation of Mold Contaminated Buildings | The goal of this research is to evaluate the efficacy of chlorine dioxide for inactivating a variety of viable mold and mold spores and neutralizing allergens and mycotoxins found in mold-contaminated structures. An underlying objective of the effort is to compare the efficacy of chlorine dioxide fumigation to conventional remediation methods by measuring the presence of viable mold vegetative cells and spores or detectable mycotoxins before and after remediation. The research activity is divided into two phases: Phase 1 is the field research, and Phase 2 is the laboratory research. | Blair Martin | 919-541-7504 |
| EPA | Mold Prevention and Decontamination of Air Conveyance Systems | The presence of moisture on HVAC system cooling coils and drip pans from condensate flow establishes conditions favorable for microbial growth. The established microbial growth can then be responsible for releasing gases (microbial volatile organic compounds, or MVOCs) or particles (BioPM) into the conditioned air stream. In addition, mold, bacteria, and virus containing aerosols in the indoor environment are distributed throughout the building by HVAC operation. Indoor building materials contaminated by mold and bacteria, emit allergenic and pathogenic particles that are distributed throughout the building interior by HVAC system operation. In addition, the presence of a microbial film on the cooling coils results in loss of heat transfer efficiency, overall component operation and the possible cause of condensate blow-by into the supply airduct. This research involves concurrent laboratory and field demonstrations that measure biological contaminants and heat transfer efficiency before and after treatment with UV with and without hydrogen peroxide. Hydrogen peroxide in combination with UV may greatly improve the antimicrobial reaction to quickly eliminate biofilm. Results contribute to the characterization of fungal organisms and their byproducts (MVOC's and BioPM) and will help building owners, building occupants, and building remediators deal with this problem. | Marc Y. Menetrez | 919-541-7981 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| CDC | 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 |
| NIH | Aptamer-Based Microarray for the Detection of Environmental Allergens | Environmental allergenic disease is a major cause of illness and disability in the United States, and there is broad consensus that the prevalence of type I-allergy is increasing worldwide. In spite of the substantial societal and health costs, the methods used to detect and quantify allergens in environmental health studies limit measurement to a few well characterized allergens that represent less than 10 percent of total allergen diversity. Recent advances in biotechnology have yielded potentially useful functional binding biomolecules (aptamers) that can enable low cost, high affinity allergen measurement. Aptamers are selected in vitro from combinatorial oligonucleotide libraries and therefore have several advantages over the traditionally used antibodies for detection of allergens. Among these advantages is higher stability, binding affinities greater than or equal to monoclonal antibodies, a dramatic decrease in production and assay cost, and the ability to target specific IgE binding epitopes of an allergenic protein. The overall goal of this research is to determine the feasibility of using aptamer-based methods for measuring environmental allergens. Two core development issues must be addressed to achieve this goal, and they form the basis for the first two specific aims. First, aptamers that are specific for the whole allergenic protein and aptamers that are specific for an IgE epitope binding peptide within the allergen will be produced via the SELEX method and their binding affinities characterized. Alternaria mold (Alt a 1) and dust mite (Der p 1) allergens will be targeted. Next, the aptamers will be tested in an inhibition type assay to determine cross reactivity, limits of detection, and the ability to mimic IgE epitope binding. Integrating the resulting aptamer-based allergen measurements to enhance quantitation in an ongoing and complementary environmental childhood asthma epidemiological study forms the basis for the third and final aim. Correlations between allergen specific IgE blood levels and environmental level of these allergens measured by antibody-based, aptamer-based, and specific IgE-based methods will be produced. Successful use of aptamers for measuring environmental allergens should lead to a more cost effective, flexible, and health relevant method and thereby provides the potential for a more fundamental understanding of the role of environmental allergens in respiratory health. Allergenic disease is a major cause of illness and disability in the United States. In spite of the substantial health and monetary costs, the methods used to study allergens in the environment are underdeveloped. The purpose of this research is to test the feasibility of a more flexible and low cost allergen measurement method (aptamers). The successful application of this aptamer technique should lead to a more cost effective and health relevant allergen detection method and enable a better understanding of disease caused by and exacerbated by environmental allergens. | David Balshaw | 919-541-2448 |
| NIH | Head-off Environmental Asthma in Louisiana (HEAL) | We are conducting a complex study in post-Katrina New Orleans named the Head-off Environmental Asthma in Louisiana Study (HEAL). The primary goal of HEAL is to implement and test an Asthma Counselor (AC) and environmental intervention program that addresses the multidimensional impact of hurricane Katrina on children with asthma in New Orleans. HEAL is a prospective, cross-sectional observational study. Approximately 200 families with children with moderately severe asthma (4-12 years of age) are enrolled in the HEAL program. All families receive an AC intervention focused on case management, adherence to medications and education on allergen avoidance. The responsibilities of the AC in this study are enhanced relative to previous initiatives such as the National Cooperative Inner City Asthma Study (NCICAS) AC intervention to also provide families with education aimed at reducing mold, allergens, and moisture in their homes, and materials to aid this effort (e.g., cleaning supplies, dust mite proof bed clothes, HEPA air filters and other). Since 90 percent of children with asthma in New Orleans are sensitive to dust allergens, established allergen control measures are incorporated into the AC intervention as well. The AC intervention is administered to families in the HEAL program over a 12-month period during which all children receive an extensive clinical evaluation (at baseline and 12 months), three environmental home evaluations (focused on moisture, mold and other allergens). During the clinical evaluation, allergen skin prick testing will be done to a standardized allergen panel as well as to 10-12 other molds currently found in high concentrations in New Orleans. Blood samples are collected and analyzed for total IgE and specific IgE to individual mold species using an interagency agreement between the National Toxicology Program and the National Institute for Occupational Safety and Health. This comprehensive skin testing of children to such a wide variety of relevant molds is a novel aspect of the study, and will significantly increase the current understanding of the validity of prick skin testing to these fungi since in vitro and in vivo methods of determining specific IgE will be compared. In addition, blood will also be archived for future genetic studies for susceptibility to mold and other environmental triggers of asthma. In addition to the clinical evaluation and monitoring the effectiveness of the AC and environmental intervention (periodic surveys), the study also entails three environmental home evaluations to allow some characterization of the relationships between mold, other allergens, post-Katrina environmental exposures and asthma morbidity. These evaluations are conducted at study baseline (shortly after the child's clinical evaluation), and then at 6 and 12 months afterward. The indoor home evaluation consists of: (1) an in depth visual inspection for mold, moisture, and other indoor allergen problems; (2) a verbal interview with the family; (3) the collection of dust samples from three different rooms (kitchen, living area, and child's bedroom); (4) the collection of indoor and outdoor air samples; and (5) the collection of the HEPA filters from units placed in the child's bedroom. The childrens bedroom dust samples will be analyzed by ELISA for mold, cat, mouse, roach, dust mite, endotoxin, and beta-D-glucans, and by PCR for up to 37 mold species (Steve Vesper at the EPA). The indoor air samples and about one-third of the outdoor air samples will be analyzed for total fungal spores, some genus identifications, pollen, and other air born particles. The HEPA filters will be analyzed for culturable mold and Actinomycetes. The remaining dust and air samples will be archived for future analyses as more funding becomes available. The HEAL project is a collaborative multi-institutional research project conducted by the Tulane University School of Public Health and Tropical Medicine and the New Orleans Department of Health. To support those efforts, Rho, Inc. provides for coordination of data and study activities. An active community advisory group (CAG) has been convened for the s | Patricia C. Chulada | 919-541-7736 |
| NIH | Toxicology Studies of Mold Exposures | The overall goal of this research project is to investigate the potential for molds found in damp or water damaged buildings to cause systemic toxicity. The specific aims of the proposed studies are to: (1) Assess organ system toxicity following inhalation exposure to molds, (2) evaluate the available biomarkers of exposure and effect (both general and specific for the organisms to be studied), and (3) evaluate the contribution of different organisms to overall health effects by studying individual isolates as well as mixtures. NTP will conduct subchronic studies in rodents using inhalation as the route of exposure. Pilot studies will examine feasibility with the duration of follow-up studies to be determined. Two mixtures and 4 isolates of individual organisms will be tested. There will be extensive characterization of the test materials (including an evaluation of relevant mycotoxins, glucans, allergens, particle size, protease activity, colony-forming units, spores, and endotoxin levels) both prior to and during the studies. Proposed test materials include: (1) Mixed culture of molds from a water damaged building from New Orleans, LA (2) Mixed culture of molds from a damp building with reported health effects (sick-building syndrome) (3) Stachybotrys chartarum isolate 1 (macrocyclic tricothecene chemotype) (4) Stachybotrys chartarum isolate 2 (atranone chemotype) (5) Aspergillus versicolor (6) Alternaria alternata Neurotoxicity will be evaluated using a functional observation battery, olfactory sensing, and cognitive tests. Particular attention will be paid to the cardiovascular, respiratory, gastrointestinal, and immune systems during histological evaluation as these organs have been reported to be potential targets following exposure to molds. Significance and expected outcome: These studies will provide important information regarding which fungal organisms may be causative agents for human health effects, target organs for fungal toxicity, the utility of biomarkers other than IgE as measures of exposure and effect, and dose-dependent effects with particular emphasis on respiratory, immune, and neurologic endpoints. | Dori Germolec | 919-541-3230 |
| NIH | Characterization of Floor Level Aerosol (PM) Exposure and Childhood Asthma | A research study is proposed to refine and evaluate a new device to improve the estimation of indoor exposure to inhalable particulate for both children in the first year of life and toddlers. Because they frequently play on the floor, these children may experience significantly higher levels of exposure than older children and adults to PM10 particles and airborne constituents, which are known asthmagens. A total of 200 children ages 6 to 35 months will be enrolled from neighborhood clinics. Parents will be administered a standardized asthma questionnaire (ISAAC) to determine presence and frequency of asthma symtpoms. Exposures will be characterized both qualitatively and quantitatively, to examine if the more precise estimation of PM10 exposure obtained by using a surrogate for personal monitoring. The study will employ a revised iteration of a prototype Pre-Toddler Inhalable Particulate Environmental Robotic (PIPER) Sampler that has been developed and undergone preliminary testing. Sampling will be carried out with both a fixed height stationary sampling station, where inlets of all instruments will be at 110 centimeters height, and the self-propelled computerized PIPER sampler, where inlets of all instruments can be varied between 20 to 110 centimeters above the floor to mirror the varied breathing heights of these children while engaged in play on the floor. Four parameters will be for each household: (1) mass concentration of PM10 particles measured by a real-time monitoring device, (2) real-time particle size and number distribution (0.3-10 urn), (3) air sampling on filters for detailed characterization of the PM10 constituents (pesticides, allergens, and endotoxins), and (4) concentration and composition of airborne fungi (viable and non-viable) collected on glass slides. Measurements will be collected in tandem for each of the 4 types of monitoring. The results of the laboratory analysis for endotoxins, molds and allergens for cockroaches (Bla g Yz), dust mites (Der f 1/p 1), dog (Can f 1), cat (Pel d 1) and mouse (Mus ml) will be evaluated for association with reporting of asthma symptoms. This study seeks to provide an alternative to personal monitoring for a variety of environmental exposures that may be experienced by children too young to be assessed by conventional methods, including those in their first year of life. In addition, it will open up an avenue for more precise estimation of early childhood exposures to asthmagens in the PM10 fraction of aerosols. | Kim Gray | 919-541-0293 |
| NIH | Columbia Center for Children's Environmental Health | The overall theme of the Columbia Center for Children's Environmental Health (CCCEH) is the identification and prevention of risks of neurodevelopmental impairment and childhood asthma from prenatal and postnatal exposure to urban pollutants. Since it was established in 1998, the Center has forged a successful partnership with West Harlem Environmental Action, Inc. (WE ACT), and nine other community organizations to identify and prevent environmental causes of childhood disease in Northern Manhattan and the South Bronx. The Center has enrolled and retained a unique cohort of mothers and children of color who belong to one of the most at-risk urban populations in this country with respect to environmental exposures, social adversity, and childhood health problems. Using molecular epidemiologic approaches, Center investigators have developed a rich body of knowledge about this vulnerable and disadvantaged urban population. They have documented substantial prenatal exposure to indoor and outdoor urban pollutants, including the combustion byproduct polycyclic aromatic hydrocarbons (PAH), environmental tobacco smoke (ETS), pesticides, and pest allergens. The research has demonstrated significant associations between prenatal exposures to those pollutants and adverse birth outcomes and/or neurodevelopmental, immunological, and respiratory health outcomes in children studied through age two. Building on its achievements of the past five years, the Center proposes several important new initiatives. These include follow-up of the mother and child cohort through ages five to seven, as the children enter school, with links to school performance data at age eight. Additional exposure, biomarker, and outcome assessments will allow testing of new etiologic hypotheses in the community based participatory research (CBPR) projects on asthma and growth and development. A new laboratory-based mechanistic research project will elucidate possible mechanisms of in utero sensitization by co-exposure to PAH/diesel exhaust particles and allergens, directly complementing the CBPR asthma project. A CBPR Intervention project on integrated pest management and health-related housing improvements will be conducted in partnership with the New York City Departments of Health and Mental Health and the New York City Housing Authority. A new Community Outreach, Translation, and Application Core (COTAC) will ensure that the Center's findings have local and national public health impact. COTAC initiatives will include: (1) education of medical students, medical residents, and pediatricians about children's environmental health; (2) a new community campaign to improve air and housing quality in New York City, co-led by WE ACT; (3) and risk assessment, cost, and risk prevention analyses on the Center's findings regarding the health effects of environmental exposures and the cost-effectiveness of IPM. In summary, it is important that the Center as an institution be continued as an established and valued resource to the community, scientific researchers, and policymakers. | Kim Gray | 919-541-0293 |
| NIH | Diesel, Allergens and Gene Interaction and Child Atopy | Allergic disorders affect over 40 million children, resulting in two million missed school days and costing society more than 10 billion/year. Atopy, defined as immediate hypersensitivity to specific allergens, is the strongest risk factor for child-onset asthma. The reported increasing incidence of atopic respiratory disorders is exaggerated in urban children living in westernized countries. There is intriguing scientific evidence demonstrating that diesel exhaust particles (DEP), a constituent of truck exhaust, promote expression of Th2 cytokines and production of IgE antibodies. The concern is that these exposures enhance clinical expression of IgE mediated respiratory disorders. Hence, children residing near interstate highways are at potentially high risk for exposures to truck emissions and resultant atopic respiratory disorders. In the Cincinnati metropolitan region, three interstate corridors intersect creating one of the busiest U.S. north/south and east/west commercial truck routes converging on a population of 1.9 million. The proposed investigation will follow two groups of children from birth through early childhood. The first group are children living within 400 meters of interstate highways. This group will be matched by birth date, race and income to a second group living beyond 1 km. There are two study purposes. The first is to measure DEP exposure levels and to determine if children with higher levels of exposure are at an increased risk for atopy and atopic respiratory disorders. The second is to determine if these effects are magnified in a genetically at risk subpopulation. The proposed study is a prospective cohort and nested case control design. The cohort of newborns will be evaluated prospectively for positive skin prick tests (SPT), allergic rhinitis and asthma. Residential exposures to DEP and aeroallergens also will be characterized longitudinally. The children who develop positive SPT will be matched by race and gender to controls having negative but the same number of SPT. The case control study will evaluate potential susceptiblity as measured by cytokine polymorphisms and to determine if exposure to DEP promotes the phenotypic expression of atopy and atopic respiratory disorders. This study design is optimum for determining if young children exposed to DEP have enhanced sensitization to aeroallergens and for dissecting gene-environment interactions. Results of this study may ultimately result in finding a preventable cause of atopic disorders in children. | Kim Gray | 919-541-0293 |
| NIH | HomeBase (Home-Based Asthma Support and Education for Adults) | The overall goal of this proposal is to understand better how to reduce asthma morbidity and health care utilization among low-income, ethnically diverse children ages 3-13. In particular, evidence about the effectiveness of in-home interventions, emphasizing control of environmental triggers relative to clinic-based interventions, is needed. One-half of the participants will receive clinic-based asthma education, self-management support (an asthma action plan and self-monitoring), resources for asthma control (allergy control bedding covers, a peak flow meter, and a medication spacer) and care coordination for one year from an asthma nurse (level 1 intervention). The other half will receive these services plus in-home environmental assessment, an individualized home action plan based on assessment data, education, and social support, encouragement of behavior changes, materials to reduce exposures (bedding covers, vacuums, door mats, cleaning kits, and a HEPA filter), and asthma self-management support for one year from a community health worker (level 2 intervention). A second goal is to learn how to adapt these interventions so they are culturally appropriate for ethnically diverse populations. A third goal is to reduce exposures to other household health risks such as lead, dust, asbestos, pesticides, other toxic household chemicals, and risks for injuries. A fourth goal is to develop better tools for assessing the indoor environment in community-based settings. A final goal is to integrate these activities into the work of the local asthma coalition. The investigators will conduct a randomized controlled trial with 360 subjects using parallel intervention groups and a wait-list control group to compare the effectiveness of the level 1 and 2 interventions with each other and the control group. Primary outcome measures will include asthma-related health status and quality of life, medical care utilization, and exposure to indoor asthma triggers (mites, roaches, mold, tobacco smoke, and pets). Secondary measures include knowledge of asthma, control of environmental triggers, and medical management; self-efficacy; and behaviors related to asthma control. They will assess the costs of the two levels of intervention from the perspective of a health services payer. The investigators hope this research will result in a replicable and sustainable model which can be adopted by health insurers and health care delivery organizations and integrated into a comprehensive, coordinated local asthma control system. The project's organization is based upon partnerships between parents of children with asthma, community-based organizations, public health agencies, and academia, and will follow principles of community-based collaborative research. It is sponsored by the King County Asthma Forum, a local asthma coalition with broad community participation from people with asthma, their families, and 34 agencies, including Public Health-Seattle & King County, the American Lung Association of Washington, the Asthma and Allergy Foundation of American, school districts, community health centers, hospitals, Seattle University, and the University of Washington. | Kim Gray | 919-541-0293 |
| NIH | Indoor and Outdoor NO2 and Asthma Severity in Children | Exposure to aeroallergens and air contaminants is hypothesized to be a major factor in the exacerbation of asthma. Results of our ongoing studies suggest that nitrogen dioxide (NO2) associated indoors with gas appliance use and outdoors with motor vehicle emissions, at levels well below the EPA Air Quality Standard, may be associated with respiratory symptoms in children at risk for developing asthma and with the exacerbation of asthma in asthmatic children. Our data are also suggestive of an interaction between indoor aeroallergens and NO2 concentrations in enhancing respiratory symptoms in infants and asthmatic children. The potential impact is great since 57 percent of homes in the United States use natural or LP gas, traffic volume is increasing and virtually all homes have significant dust allergen levels. We propose a prospective epidemiologic study of 1,533 children with active asthma (5 to 10 years of age), to test the hypothesis that carefully quantified NO2 concentrations associated with indoor sources and vehicle traffic on state and interstate roads are associated with asthma severity. In addition, we will determine if home levels of NO2, in the presence of common indoor dust allergens (Der p 1, Der f 1, Bla g 1, Pel d 1, Can f 1 and fungi), are associated with an increased risk of asthma severity in children sensitized to those allergens. The above hypotheses will be evaluated while adjusting for factors known or suspected to increase risk of more severe asthma, including household and school characteristics. The study population will be drawn from elementary schools in 16 Connecticut towns using a modified version of the ISAAC questionnaire to identify children with active asthma. Initial risk factors will be assessed in a home interview, and asthma severity (symptoms, frequency of ER visits, medication use, lung function) will be assessed prospectively for one year using telephone interviews administered quarterly. At the home visit, dust samples will be collected for allergen and fungi determinations and blood samples collected for antigen specific IgE determinations. Indoor and outdoor NO2 levels will be obtained quarterly for each home. Global Information Systems in combination with road vehicle density data will be used to assess the impact of traffic on asthma severity and outdoor NO2 concentrations at the home. Household gas appliances and traffic-related pollution may represent important environmental exposures for asthmatic children, for which effective interventions can be developed to reduce asthma morbidity. | Kim Gray | 919-541-0293 |
| NIH | Physical and Social Environmental Factors in Adult Asthma Outcomes | The proposed project will prospectively investigate physical and social environmental exposures as determinants of Health-Related Quality of Life (HRQOL) in adult asthma and rhinitis, focusing on the role of severity of disease as a principal mediator between the physical and social environment and HRQOL. The proposed study, a competitive renewal of an R01 near completion, builds upon our current research elucidating multifactorial models of physical and social environmental risks. The specific study aims are: (1) delineate the specific pathways linking physical and social environmental exposures to disease-specific and general HRQOL in adult asthma and rhinitis, including mediation by changing disease status overtime; (2) identify specific risk factors, such as personal socioeconomic status, that modify the impact of these environmental factors on disease severity or the effect of severity on HRQOL in adult asthma and rhinitis. To accomplish these goals, we will assemble a prospective cohort of 636 adults, merging our ongoing asthma-rhinitis cohort (the basis of the current R01) with a second cohort of adults with severe asthma established as part of a methodologically similar study. Subjects will undergo three waves of structured telephone interviews over the study period to ascertain environmental exposures, disease severity, and HRQOL. Two home visits will be conducted in a subset of subjects (n=380) to assess the home environment (including measurements of dust antigen, airborne particulate, and dampness), measure pulmonary function and exhaled fraction of nitric oxide, and collect biological samples to measure secondhand smoke exposure. We will also carry out geocoding for linkage to external data sets for U.S. Census information, traffic density, and levels of ambient air pollutants. We will test predictive models of physical and social environmental factors, including measures of indoor air quality, ambient pollution, and neighborhood and community status, estimating the longitudinal effect of these factors on HRQOL. We will assess the role of disease severity as a mediating factor in the causal pathway leading from environmental exposures to changes in HRQOL; we will also assess selected individual factors that may be effect modifiers of this relationship, especially personal socioeconomic status (SES). Public Health Importance: In order to understand the complex web of factors influencing airway disease outcomes from the perspective of persons with disease, there is a critical need for an analytic approach that can test the effect of multiple combined environmental risk factors on HRQOL, assess the mediating role of disease severity, and take into account individual effect modifiers. The long- term goal of our study is to identify modifiable factors and subgroups at high risk in order to improve HRQOL among adults with asthma. The proposed project builds upon our success in the current R01 by testing more specific pathways in the context of our accumulated experience to date. | Kim Gray | 919-541-0293 |
| NIH | Role of Diesel and Other Vehicular Exhaust in Exacerbation of Childhood Asthma | The burden of childhood asthma disproportionately affects children living in poverty and in urban centers, many of whom are minority ethnic groups. For those living in urban environments with high traffic densities, there is increasing concern about potential adverse respiratory health effects of exposure to diesel and other vehicular exhaust. Epidemiologic studies have shown associations between exposure to high traffic volumes, and especially to high truck traffic—the main source of diesel exhaust in urban settings—and increases in asthma symptoms, asthma hospitalizations, and decreased lung function. Yet, owing to the challenges of separating diesel from spark ignition exhaust, and vehicular exhaust in general from other sources of pollution, quantitative associations between exposure to diesel and other vehicular exhaust and adverse respiratory health outcomes have not been well-characterized. This study will characterize ambient exposures related to vehicular exhaust and other specific air pollutant sources, and evaluate the relationship of these exposures to the exacerbation of asthma among children living in Detroit and Dearborn, Michigan. We will collect ambient and indoor household air quality data which provides both high temporal and spatial resolution of pollution concentrations and utilize state-of-the-art statistical/geospatial models to apportion exposures among pollutant sources including diesel and other vehicular exhaust and to develop individual- specific exposure estimates. We will conduct a two-year longitudinal study involving 210 asthmatic children with 70 each living near high traffic/high truck volume roads, near high traffic/low truck volume roads, and distant from high traffic roads. Daily health measures to be assessed for two consecutive weeks in each of eight seasons will include respiratory symptoms, pulmonary function assessed by hand-held spirometers, medication use, and health services utilization. We hypothesize that: (1) exposures specific to diesel and other vehicular exhaust will be stronger predictors of adverse health status among children with asthma living in a high traffic density urban environment than other pollutant sources, and (2) the presence of cigarette smokers in the household, high levels of common allergens in household dust, or sensitization to such allergens, will yield stronger exposure-response relationships between diesel and other vehicular exhaust and adverse respiratory health outcomes. | Kim Gray | 919-541-0293 |
| NIH | Allosteric DNAzyme Sensors for Practical Detection of Mycotoxins | Mycotoxins are toxic compounds produced by fungi that contaminate crops during growth, transportation, or storage. Contamination of food and feed by mycotoxigenic fungi is an important agricultural and national security concern. For example, several thousand people are sickened annually by mycotoxicoses related to crops contaminated with fungi, and the safety of the food supply is integral to our national health and security. All of these issues demand the development of improved toxin sensor technologies. Current mycotoxin detection methods (e.g., those based on antibodies) have practical shortcomings both in the development of the sensors and in their applications. In this research project, we will develop innovative mycotoxin sensors based on allosteric DNAzymes, which are catalytic DNA molecules that are activated by binding of an analyte such as a mycotoxin. The long-term commercial objective of this project is to develop quantitative mycotoxin sensors for precise assays and also to develop semi-quantitative mycotoxin sensors for rapid field assays. This research will be performed with three specific aims: (1) apply in vitro selection to identify allosteric DNAzymes that have high selectivity and sensitivity to the mycotoxin deoxynivalenol (DON) and other mycotoxins such as fumonisin B1, zearalenone (ZON), and aflatoxin B1; (2) characterize and optimize the allosteric DNAzymes for toxin-sensing properties; and (3) engineer fluorimetric or colorimetric mycotoxin sensors by integrating fluorophore or gold nanoparticle detection systems with the DNAzymes identified in Aims 1-2. In later work, the allosteric DNAzyme sensors will be tested in the field to determine their absolute and relative efficacies as toxin detectors. This includes integration of the DNAzyme sensors with the standard storage and transport aeration system used in grain containment units, which will increase the assay sensitivities by concentrating analytical samples. Relevance to public health: Contamination of food and feed by mycotoxin-producing fungi is one of the most important agricultural and health-related problems in the United States and worldwide. Improved sensors for detecting mycotoxins and thereby revealing the presence of fungi will allow proper remedial actions to be taken. | Jerrold Heindel | 919-541-0781 |
| NIH | Fluorescent Multiplex Array for Indoor Allergens | Development of environmental tests to measure mold allergens using enzyme immunoassay (ELISA) and multiplex array technology (MARIA). This project is focusing on allergenic mold species, Alternaria and Aspergillus, as well as molds that arecommonly found in water damaged homes: Stachybotrys, Aspergillus versicolor, and Penicillium chrysogenum. Specific antibodies will be raised against each mold species and used for immunoassay purposes. The advantage of the MARIA technology is that multiple tests can be done at the same time on a dust or air sample. Both ELISA and MARIA are dependent of the production of well defined monoclonal or polyclonal antibodies to develop sensitive and specific tests. The aim of this project is to develop multiplex tests for a panel of molds that can be used to objectively assess mold exposure in homes, the workplace and public buildings. | Jerrold Heindel | 919-541-0781 |
| NIH | Epidemiology of Asthma: Risk and Prognosis in a Cohort from Birth to Adolescence | Asthma has shown dramatic increase worldwide. The disorder is diagnosed in 7-15 percent of U.S. children and is more prevalent in boys throughout childhood; however, during puberty a gender reversal occurs. We do not know if asthma persists in girls and remits in boys or if there is new onset asthma in girls. In addition, we do not understand factors driving these changes in asthma occurrence, but they seem to be related to gender- specific developments during puberty. We propose to test the following hypotheses: (1) gender reversal of asthma is due to new onset in girls and higher rates of clinical remission in boys; (2) risk factors include early onset of puberty, obesity, pollutants, and early life factors such as parental smoking and lack of breastfeeding; (3) identification of prognostic factors will allow for targeted interventions to prevent persistence and recurrence of asthma in adulthood. In 1989, we recruited a population birth cohort (1,456 children) on the Isle of Wight, an island one mile off the south coast of England with a population of 130,000. This cohort has been extensively phenotyped for asthma and other allergic diseases at 1, 2, 4 and 10 years of age. High follow up proportions (80-95 percent) have been achieved at each age. A wealth of information is available from prior examinations of the cohort. Participants are now adolescents. Therefore, this cohort is uniquely suited to address the above hypotheses. We propose to study these children at the age of 18 years and anticipate that 1,200 will participate. We will assess symptoms, lung function, airway inflammation, and atopic markers using questionnaire, physical examination, spirometry, bronchial provocation, exhaled nitric oxide, sputum induction, skin prick test, and total IgE. Using regression models with clinical markers as outcomes, we will determine the impact of pubertal factors, obesity-related factors (body mass index, serum leptin levels, genotypes for leptin and leptin receptor), and environmental risk factors (including, breastfeeding, tobacco smoke exposure, markers of pollution and agriculture exposure). Using all available information, we will determine a predictive model to identify children who are at high risk of persistent or recurrent asthma in adult life. These results will facilitate prevention of asthma persistence and recurrence. Our work brings together a multidisciplinary research team with a proven record of collaboration and expertise in respiratory medicine, allergy and immunology, epidemiology, genetics, and biostatistics. Note: As secondary objectives, this study correlates repeated measures (at age 6, 10, 18) of exposure (measured by questionaire on dampness in the home) and changes in sensitivity to allergens (obtained by skin test and total IgE) with development and/or progress of asthma. | James P. Kiley | 301-435-0233 |
| NIH | Maternal Vitamin D, Adiposity in Early Life, and Risk of Childhood Asthma | Asthma is the most common chronic disease of childhood in the developed world, and its prevalence in Western industrialized countries is increasing at an alarming rate. Maternal diet during pregnancy represents an important exposure with significant potential to modify immune function in offspring and hence the development of asthma and related atopic disorders in childhood. In addition, fetal growth may be a marker of prenatal processes that have large impact on asthma risk. Fetal growth is now known to be an indicator for risk of other chronic diseases, but the data regarding asthma are remarkably sparse. The goals of this application are to examine the potential impact of maternal dietary factors during pregnancy on the development of asthma and related disorders in early childhood, and to clarify the relationship between size at birth and incident asthma. A longitudinal prospective study is the most appropriate study design to evaluate these goals. This application takes advantage of the resources provided by Project Viva, an ongoing prospective cohort study of pregnant women and their infant offspring among members of Harvard Pilgrim Health Care, a large managed care organization in New England. Data already available from Project Viva include detailed dietary data on mother and infant, along with data on anthropometric, social, environmental, demographic, economic, psychological, and lifestyle variables. By following the Project Viva cohort until the ages of 3-4 years, the current application provides a relatively economical way to obtain updated exposure and outcome data, and to answer scientific questions of major public health importance. This work also brings together a multidisciplinary research team with a proven track record of collaboration and expertise in nutritional, respiratory, and pediatric epidemiology. Note: As a secondary objective, this study correlates exposure to mold/mildew, water in home basement (obtained by questionaire) and sensitization to Alternaria (obtained by blood sample tests for specific IgE) to development of asthma in children. | James P. Kiley | 301-435-0233 |
| NIH | Natural History of Asthma from Birth to Early Adult Life | Many of the factors associated with asthma risk in childhood are linked to lung function alterations in early adult life, which are related, in turn, to later asthma, COPD, and even death. The objective of this project is to assess prospectively the role of early life events and their interaction with genetic variation in determining risk for the development of symptoms and lung function alterations associated with adult asthma and COPD. The project has five specific aims: (1) to determine the relation of early lung function, wheezing LRIs, atopy, and bronchial hyperresponsiveness (BHR) to lung function and respiratory symptoms up to age 28; (2) to determine whether being overweight is associated with persistence of asthma-like symptoms, peak flow variability and airflow limitation to age 28; and whether genetic and developmental factors that control levels of and responses to leptin explain these associations; (3) to establish airway immune biomarker panels that distinguish specific asthma subphenotypes with their distinct pathogenetic mechanisms of development, and to establish the impact of variants in the IL-4 receptor alpha chain, MMP-9 and IL-8 genes on airway biomarkers within subphenotypes; (4) to investigate alterations in airway structure as measured by high- resolution computerized tomography in relation to early wheezing phenotypes, continued symptoms, lung function, BHR, allergen sensitization and biomarkers of airway inflammation; and (5) to assess the roles of (a) circulating levels of ligands of the epidermal growth factor receptor and related MMPs, and (b) variations in the genes encoding for these proteins, as determinants of the risk for asthma, lung function and BHR. We will use a combination of modern imaging approaches, molecular epidemiology, physiological lung function measurements, non-invasive assessment of airway inflammation, targeted genotyping and standard epidemiologic techniques to assess comprehensively the respiratory health of participants in the Tucson Children's Respiratory Study, a nonselected population followed from birth to their mid-20s. As the only respiratory study of adults which exhaustively recorded events occurring in the first 6 years of life, this approach will provide a unique opportunity to assess prospectively the role of early life events in determining risk for adult asthma and COPD. Elucidating these relations will foster the development of new strategies for the prevention and treatment of asthma and, potentially, of airflow limitation in adult life. This long-term study correlates measures of sensitization to specific allergens, including Alternaria (obtained by blood sample IgE and skin prick tests) to the development and progression of asthma and to lung function overtime. The study focuses on sensitization rather than measures of exposure. | James P. Kiley | 301-435-0233 |
| NIH | Stress, Environment, and Genetics in Urban Asthma | The overall goal is to examine the role of psychosocial stressors in a systems biology framework considering multiple biologic pathways by which stress can contribute to asthma causation. We will not only study the independent effect of stress on asthma/wheeze phenotypes in early childhood but also will consider stress as a modifier of physical environmental factors (allergens, cigarette smoking and diesel-related air pollutants) and genetic predisposition on asthma risk. We will determine the independent effect of maternal stress (both prenatal and postnatal) on early childhood asthma phenotypes. We further hypothesize that multi-life stressors prevalent in disadvantaged populations can cumulatively influence immune system development and airway inflammation in early life, thus making the populations more susceptible to other environmental factors and genetic risk factors explaining, in part, observed asthma disparities associated with SES and race/ethnicity. We will take a multi-level approach, measuring both individual-level stress (negative life events, perceived stress, pregnancy anxiety) and community-level stress (neighborhood disadvantage [e.g., percent of subjects living in poverty, percent unemployed], diminished social capital, and high crime/violence rates). We will also assess the influence of stress on the infant hormonal stress response and on T-helper cell differentiation as reflected in cytokine profiles and IgE expression (a topic or pro inflammatory phenotype). Additional physical environmental (indoor allergens, diesel-related air pollutants, tobacco smoke) and genetic factors will be assessed given their influence on the immune response and expression of early childhood asthma/wheeze. This interdisciplinary approach is unique because we are considering the context in which physical exposures and host susceptibility occurs, analyzing their multiplicative joint effects and considering multiple biologic pathways, as such it is consistent with the NIH roadmap objectives. As secondary objectives, sensitization (via blood sample and tests for specific IgE) to altenaria and the correlation of this sensitization to development of asthma in infants and young children. The study does not obtain measures of actual exposure to Alternaria allergen, either by questionnaire or home sample. | James P. Kiley | 301-435-0233 |
| NIH | The Role of Neutrophils in Hypersensitivity Pneumonitis | Hypersensitivity Pneumonitis (HP), or extrinsic allergic alveolitis, is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis and granuloma formation that in some patients progresses to fibrosis. The development of fibrosis in HP is associated with high morbidity rates; unfortunately the lack of information on disease pathogenesis has limited the development of therapies to treat the disease. Additionally, the disease is frequently misdiagnosed due to the variability of disease symptoms, differing diagnostic criteria, and a lack of understanding of the environmental antigens and host/genetic risk factors that lead to disease. The investigator's laboratory has been studying the role of IFN in the development of HP using the Saccharopolyspora rectivirgula (SR) animal model. IFN is a Th1 cytokine that is required for the development of granulomas in the lungs of mice following repeated exposure to SR. The production of IFN is important for the expression of T cell chemokines that recruit T cells into the lung following SR exposure; in the absence of IFN, T cell recruitment and subsequently granuloma formation are reduced. Therefore the cells that produce or regulate IFN production following SR exposure play a pivotal role in disease pathogenesis. The investigator's studies have revealed that neutrophils are a source of IFN during the early stages of HP and depletion of neutrophils prior to SR exposure results in decreased IFN expression. These results suggest that neutrophils play a critical role in the development of HP and understanding the mechanisms that regulate neutrophil recruitment and production of IFN may provide important new insights into disease pathogenesis. The goals of the study are: Specific Aim 1—to understand the role of neutrophils in driving IFN production in the lung following SR exposure. Specific Aim 2—to determine the role of pattern recognition receptors in neutrophil recruitment into the lung. | James P. Kiley | 301-435-0233 |
| NIH | Study on Biomarkers for Exposure to Stachybotrys Chartarum | The lack of proper biomarkers has greatly hampered investigations of the human health effects of the toxigenic fungus, Stachybotrys. Attempts to relate inhalation exposure to pulmonary, immune and neurological toxicities have had only circumstantial evidence supporting the apparent exposure. Epidemiological and pathophysiological studies would be greatly facilitated by the development of biomarkers that can be quantitatively related to the dose and timing of the exposure. We have recently found that purified satratoxin G, a macrocyclic trichothecene from Stachybotrys with two epoxides, forms stable adducts with human serum albumin. This offers the potential for quantitative biomarker 'dosimeters'in the form of protein adducts and related urinary metabolites in parallel to that used for the epoxide derivative of the mycotoxin, aflatoxin B1. Hypothesis: Inhalation exposure of humans to strains of Stachybotrys chartarum producing satratoxin G will result in the formation of covalent adducts of serum albumin and/or hemoglobin in sufficient quantities to be measured using mass spectrometry or radioimmune assay. This project proposes to: (1) complete the identification of the amino acyl satratoxin adducts of recombinant human serum albumin, determine the chemical structure of the adducts, and ascertain the relative reactivity of the amino acyl residues being modified; (2) confirm the presence of these adducts and/or metabolites in samples of biological materials including serum, red blood cells and urine from exposed rats and humans; (3) develop practical quantitative biomarker assays for satratoxin-albumin and hemoglobin adducts using exhaustive proteolysis and immunoaffinity chromatography with analysis by mass spectrometry and by radioimmune assay. Similar mass spectrometry assays will be developed for related urinary metabolites; and (4) develop parallel assays for macrocyclic trichothecenes in environmental dust samples. Relevance: Over the past decade there has been increasing public concern about the health effects of "toxic mold" or "black mold" (i.e. Stachybotrys) in home and work environments. The lack of objective tools to relate the amount of exposure to the observed health problems has hampered attempts to clearly demonstrate such mold-related health effects. This project proposes to develop quantitative assays for such investigations. | Srikanth Nadadur | 919-541-5327 |
| NIH | Study on Spore Dispersal and Germination in Stachybotrys Chartarum | This project is concerned with spore dispersal in the black mold Stachybotrys chartarum, a toxin-producing fungus of growing public health concern as a contaminant of water-damaged buildings. Human exposure to its spores has been associated with a variety of respiratory and neurological illnesses, including a cluster of idiopathic pulmonary hemorrhage (IPH) cases in infants in Ohio. The biological activity of Stachybotrys toxins is a subject of intensive research effort in other laboratories, but little attention has been paid to the mechanisms of spore dispersal that cast these compounds into the air. This project is motivated by the following question: How do the sticky spores of this mold move and contaminate the indoor environment? The first set of experiments will examine the effects of airflow, substrate vibration, and water movement on spore dispersal. The possibility that insects may act as vectors for dispersal of Stachybotrys spores will be the focus of a second aim. Thirdly, spore germination will be assessed using a multi-well plate method in relation to water availability, substrate composition, temperature, conidial age, and density of conidial deposits. These experiments will clarify both the mode of human exposure (an issue of major clinical significance), and the way that the mold spreads through buildings. | Srikanth Nadadur | 919-541-5327 |
| NIH | Chitinases and TGF-ß in Human Asthma (Subproject 3 of a solicited grant entitled "Mechanisms of Initiation and Persistence of Allergic Asthma") | This project seeks to determine the importance of chitins and chitinases in human asthma, with a focus on genetic variants of the chitinases. Chitin is a major structural component of fungi, crustaceans, helminths, and insects. Chitinases are chitin-degrading enzymes, and two occur in mammals, chitrotriosidase (CHIT1) and acidic mammalian chitinase. However their role in allergic airway inflammation and asthma is not well understood. A preliminary study demonstrated that one homozygous variant of CHIT1 protected study participants against sensitization to airborne fungal allergens. This project will examine the relationship of variation in the genes for chitinases to sensitization to four fungi (Alternaria, Aspergillus, Cladosporium and Penicillium), and to asthma. | Marshall Plaut | 301-496-1886 |
| NIH | (1) Initiation of Allergic Immunity by Parasites; (2) Innate and Adaptive Immune Cell Cross-Talk in Lung Allergy (Subproject 2 in the Solicited Grant Entitled "Mechanism of Initiation and Persistence of Allergic Asthma") | One investigator has two related studies. The first is an R01 grant that aims to determine whether chitin, a major structural component of fungi, as well as crustaceans, helminths, and insects, is a key molecule for inducing allergic inflammation, a central feature of allergy and asthma. This is a new area of research, and the role of fungal chitins has not previously been assessed. The studies will determine how chitin stimulates the innate and adaptive immune response and will identify an immune system receptor for chitin. The second study (subproject 2 of a U19) will focus on the potential role of Aspergillus-derived chitin in models of asthma and airway hyper-responsiveness, and will test whether chitin has one or both of two opposing functions: to either stimulate or limit allergic inflammation. | Marshall Plaut | 301-496-1886 |
| NIH | Planning a Multicenter Oral Itraconazole Trial in Chronic Rhinosinusitis Patients | This research project is intended to evaluate the hypothesis that, if the pathology of chronic rhinosinusitis is induced by an abnormal immune response to fungi, an anti-fungal agent will be an effective treatment of the disease. This clinical trial planning grant supports a one year effort to establish a multi-center research team from six medical centers; define patient recruitment strategies; and develop the study protocol, investigator's brochure, manual of operations, and tools for data management and research oversight. The clinical trial, which will require a separate grant application in the future, will investigate the efficacy of oral itraconazole, an anti-fungal agent, in treating patients with chronic rhinosinusitis with nasal polyps. The investigator has preliminary data suggesting that anti-fungal agents are beneficial, but this concept is controversial. This future trial is intended to resolve the controversy. | Marshall Plaut | 301-496-1886 |
| NIH | Relationship between Exposure to Airborne Fungi and Asthma in Inner City Children (a Component of the Inner City Asthma Study Grants) | The Inner City Asthma Study protocol to study the relationship between exposure to airborne fungi and asthma in inner city children includes an environmental intervention to reduce exposure to allergens and tobacco smoke. One component of the environmental research study focused on the role of exposure to fungi, combined with sensitization to these fungi as a determinant of the severity of asthma. This component of the study was completed in 2001 and preliminary analysis of the data indicates that the combination of exposure to fungi and sensitization is an independent risk factor for asthma severity. Fifty percent of children with asthma who enrolled in this study tested positive for Immunoglobulin E (IgE) antibody to at least one fungal extract. IgE is an antibody that participates in allergic reactions. This research also demonstrated that the levels for airborne fungi encountered indoors parallel the levels of fungi encountered outdoors. The levels of fungi encountered indoors were higher in homes with dampness problems, cockroach infestations, and cats. Fungal exposure levels were measured by collecting and culturing air samples and identifying and counting colonies of each fungal species. The study focused primarily on four species of fungi: Alternaria, Aspergillus, Cladosporium and Penicillium. Results for the children who were tested for IgE antibody responses against specific fungi indicated that 36 percent of the children tested positive for antibodies against Alternaria; 28 percent tested positive for antibodies against Aspergillus; 19 percent tested positive for antibodies against Cladosporium; and 13 percent tested positive for antibodies against Penicillium. | Marshall Plaut | 301-496-1886 |
| NIH | The Pathogenesis of Chronic Rhinosinusitis | This project will investigate a new hypothesis concerning the pathogenesis of chronic rhinosinusitis in humans; namely, that the pathology is induced by an abnormal immune response to fungi. Because chronic sinusitis is closely associated with asthma, an allergic-type immune response involving Immunoglobulin E (IgE) antibodies might be expected. However, prior studies by this investigator have demonstrated otherwise. Patients with chronic rhinosinusitis were shown to have exaggerated immune responses to airborne fungi, especially Alternaria, characterized by Immunoglobulin G (IgG) antibodies, particularly IgG4, and lack of IgE antibodies. Allergic reactions are characterized by the production of cytokines by T helper type 2 (Th2) cells. In chronic rhinosinusitis, not only Th2 cytokines, but also T helper type 1 (Th1) cytokines are produced. The grant will extend these findings to compare the immune responses in the blood and sinus tissues of patients with chronic rhinosinusitis to the responses in control participants. The grant will also support studies on the capacity of enzymes derived from Alternaria to activate eosinophils, which are white blood cells most characteristic of allergic inflammation. Eosinophilic inflammation is frequently present in the sinuses of patients with chronic rhinosinusitis. | Marshall Plaut | 301-496-1886 |
| NIH | A Novel Model of Fungal Asthma Using Aeroallergen Sensitization and Challenge | The purpose of this project is to develop a new mouse model to study allergy to the fungus Aspergillus fumigatus in which the fungus is delivered to the animals in the form of airborne spores. The investigators will test whether allergy can be induced in mice using this method and will compare their results to those obtained using the conventional model of allergic sensitization to Aspergillus in which the fungus is delivered in a liquid form. | Alkis Togias | 301-496-1886 |
| NIH | Environmental Proteinases in Human and Experimental Asthma (Subproject 2 of the Asthma and Allergic Diseases Cooperative Research Centers Grant Entitled "Innate Immunity in Allergic Airway Inflammation of Asthma") | The overall objective of this project is to identify early innate immune system signaling pathways that predispose an individual to chronic allergic airway disease. The innate immune system is the component of the human immune system responsible for the initial broad response to infection. The specific hypotheses being tested are that mold enzymes with proteolytic activity, also known as proteinases, that are present in house dust, are more common in the homes of children with asthma compared to children without asthma and are capable of promoting the development of sustained allergy in mice. Proteinases are not unique to mold; however preliminary findings from research supported by this grant indicated that in house dust samples, the only detectable proteinases are of fungal origin. | Alkis Togias | 301-496-1886 |
| NIH | Role of Fungal Microflora in Mucosal Tolerance/Immunity | This project addresses the hypothesis that disruption of the microbial community structure in the gastrointestinal tract by promoting the growth of fungi, such as Candida albicans, may facilitate the development of allergic disease to inhaled allergens. The project utilizes mouse models of asthma and sinusitis. A short course of antibiotics is first administered to the mice and they are then fed Candida albicans to promote colonization of the fungus in their gastrointestinal tract. This approach makes the animals susceptible to developing allergy against other molds. | Alkis Togias | 301-496-1886 |
| NIH | The Asthma Evaluation Study (ACE) (a Component of the Solicited Inner City Asthma Consortium Contract) | The Inner City Asthma Consortium Asthma Control Evaluation (ACE) study was designed to test the hypothesis that asthma control in low income, urban adolescents and young adults can be improved with the addition of exhaled nitric oxide as a marker for treatment guidance to conventional asthma management guidelines. Exhaled nitric oxide is a marker of airway inflammation; therefore, utilization of this marker to guide the management of asthma treatment could have decreased inflammation to a larger extent that conventional asthma management alone. The study was designed as a 12 month clinical trial and involved 546 participants. The study is complete and data analysis is ongoing. A secondary purpose of this study is to examine the role of allergy to molds in influencing the effectiveness of the asthma management plan. In this context, study participants underwent skin testing against a panel of common airborne allergens including the molds Alternaria tenuis, Cladosporium herbarum, a mixture of Aspergillus species, and Penicillium notatum. | Alkis Togias | 301-496-1886 |
| NIH | National Health and Nutrition Examination Survey 2005-2006 / Allergy and Asthma component | The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of adults and children in the United States. In collaboration with NIAID/NIH and CDC/NCHS, we proposed a new allergy/asthma component to NHANES 2005-2006. The main goal of this new study component is to better understand the role that environmental exposures play in allergic sensitization and in the development of allergic diseases including asthma. The following procedures were performed as part of the component: (1) measurement of total and specific immunoglobulin E (IgE) to 19 indoor, outdoor, and food allergens in subjects older than 1 year of age; (2) vacuum dust collection from the bedroom of all subjects, (3) analysis of collected dust for 10 indoor allergens and endotoxin, and (4) administration of allergy and asthma related questionnaires. Two fungal allergens were included in the allergen measurements—Alternaria and Aspergillus. We anticipate that this extensive cross-sectional environmental dataset will generate novel hypothesis regarding the role of environmental exposures in allergy and asthma pathogenesis. In early 2008, this data will be made publicly available to all researchers. | Darryl Zeldin | 919-541-1169 |
| HUD | Determining the National Distribution of Selected Contaminants (Including Mold) in the Residential Environment (i.e., the American Healthy Homes Survey) | Conducted visual assessment, environmental sampling, and collected survey data from households in a nationally representative sample of U.S. housing. Floor dust samples were split with Dr. Steve Vesper of EPA's Office of Research and Development. These were analyzed using mold-specific quantitative PCR (i.e., DNA-based analysis) to identify concentrations of the 36 species of mold that comprise the "environmental relative moldiness index" (ERMI). Results were published: August 2007; JOEM, 9(8): 829. The following data were also collected: ambient humidity, moisture meter readings of selected walls, and whether or not anyone in the household had doctor-diagnosed asthma. Cultured mold was also determined on settled dust samples. Additional analyses are ongoing. | Peter Ashley | 202-402-7595 |
| HUD | Mold Exposure in Homes and the Development of Children's Atopy and Asthma | The main objective of this study is to identify an optimum method that is most predictive for the adverse health effects caused by mold exposure, especially the development of asthma and allergic rhinitis. The study will test two newly developed concepts for the evaluation of moldy buildings: 1) the EPA's Relative Moldiness Index (RMI) based on data analyzed by the Mold Specific Quantitative Polymerase Chain Reaction (MQPCR) assay and 2) the fungal fragment sampling (in combination of two newly developed assay methods). These methods will be tested in a population-based study using the existing birth cohort of the NIEHS-funded Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). The methods will be used to assess the home of children who are at high risk for asthma/atopy at approximately 3 years of age. Note: This award was announced in September, 2007 and had a start date of 11/5/07. | Peter Ashley | 202-402-7595 |
| HUD | New Orleans Healthy Homes Survey | A random sample of homes in New Orleans is being tested for environmental health hazards, including air sampling for mold spores and PCR (DNA-based analysis) for mold in settled dust. Health information for household residents is also being collected via questionnaire. | Peter Ashley | 202-402-7595 |
| HUD | Sampling of Biological Contaminants from Surfaces in Flooded Homes of New Orleans: Development, Evaluation and Implementation of a New Cost-Effective Protocol | University of Cincinnati: Field testing a mold "surface sampler" that was developed in the lab on 30 homes in New Orleans that suffered water damage during Hurricane Katrina. Samples will also be analyzed for Beta-(1--> 3)-D-glucan, a mold surrogate, and dust mite allergen. Results will be used to conduct exposure modeling. | Peter Ashley | 202-402-7595 |
| HUD | Urban Moisture and Mold Program-Continuation Project | The researchers will continue the previous studies performed under the HUD-funded Urban Moisture and Mold Program (UMMP; awarded to Cuyahoga County in 1999). The goal is to obtain longitudinal data on both the participants and on the homes that were remediated for mold and moisture problems as part of the original grant in order to ascertain the sustainability of both the health (asthma improvements) and housing improvements. Asthma control will be assessed for children still living in the dwellings, and dust will be sampled and analyzed for mold using EPA's ERMI as an indicator of the effectiveness of the original interventions. In addition the university proposes to analyze archived serum and house dust samples for selected mycotoxins from the mold Stachybotrys chartarum and analyze these data in the context of the clinical symptom profiles previously gathered on the study participants. Note: This grant award was announced in September 2007 with a start date of 11/1/07. | Peter Ashley | 202-402-7595 |
| HUD | A Critical Review of Current Practices for Managing Moldy Indoor Materials | This research involves the following activities: a review of the scientific literature regarding the remediation of residential mold damage; a review of current guidance on physical interventions of moldy environments (published by professional organizations, etc.), and administration of a Web-based questionnaire to professionals involved in mold assessment and control activities. The purpose is to review the scientific basis for current practices, identify key data gaps in the science, and determine what guidance professionals are following. The findings should help to target research and identify areas where current guidance and practice can be improved. | Peter Ashley | 202-402-7595 |
| HUD | Develop Procedures to Assess Internal Moisture Loads | There is not a complete understanding of the influences certain factors have on a home’s overall moisture content and moisture performance. Which is more harmful to a home, showering without the fan on or having a steel framed house? This project will identify and quantify moisture loads on a home. This information will lead others (ASHRAE, etc.) to develop construction standards and other guidance that will reduce the likelihood of new homes having moisture (and mold) problems. | Mike Blanford | 202-402-5728 |