Grantee Research Project Results
Final Report: Interstitial Lung Disease: Moisture, Molds, and Mycotoxins
EPA Grant Number: R825251Title: Interstitial Lung Disease: Moisture, Molds, and Mycotoxins
Investigators: Storey, Eileen , Hodgson, Michael J , Jarvis, Bruce , Yang, Chin , Turner, William
Institution: University of Connecticut , University of Maryland - College Park
EPA Project Officer: Chung, Serena
Project Period: December 2, 1996 through December 1, 1999 (Extended to October 1, 2001)
Project Amount: $572,710
RFA: Air Quality (1996) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Air
Objective:
The objective of this research project was to examine the association between moisture and Interstitial Lung Disease (ILD). The original project evolved from the examination of the relationship between ILD and moisture in homes and work sites to include five related projects. These projects included a case-control study of ILD, a case-control study of sarcoidosis, exposure assessment of sources among metal workers, a study of lung disease among schoolteachers with an assessment of schools for the presence of moisture and bioaerosols, and a mortality study.Summary/Accomplishments (Outputs/Outcomes):
Case-Control Study of ILD
A pathology registry was used to identify all biopsy-confirmed ILD cases from 1992 to 1998. A final review of a pathology registry in April 1999 brought the total number of lung disease cases diagnosed between 1992 and 1998 to 1,668. Of these, 1,262 were excluded because they represented cancer or a disease other than ILD. Of the 406 remaining ILD biopsies, only 141 had a pulmonologist listed. The names of 28 additional cases were acquired from a few of the pulmonologists who were originally asked to participate in the study. A total of 169 biopsy-proven ILD cases were eligible for participation. The physicians of 131 eligible cases responded to the enrollment letter. Thirty-eight cases were excluded for various reasons (e.g., death, moved out of state, mail problems, etc.). Fourteen additional cases were excluded because some participating physicians were selective about which of their patients they allowed the researchers to contact. Of the 79 remaining cases, 53 returned questionnaires.
One control was matched to each case based on sex, age (+5 years with the exception of one pair that was +7 years apart), and ethnicity (White and non-White). All study subjects were asked to complete a self-administered questionnaire. Cases biopsied on or after January 1, 1997, were asked to participate in the home site visit portion of the study after their questionnaire was returned. The questionnaire addresses moisture and aerosolization in buildings, including the home and work environment. During the home site visit, physical and bioaerosol measurements were taken by trained field personnel to assess moisture risk factors within the home. An engineer from Turner Building Science, LLC, blinded to case/control status, evaluated sketches of each home, which included geography. These sketches are a part of each home's exposure assessment. Three separate analyses have resulted from this work.
Study One: This methodological analysis explored the relationship between the data from the self-administered questionnaires and the home site visit checklist. Responses from the questionnaire were compared to those from the home site visit (e.g., Is there a history of leaks or flooding in the home? Is there an external exhaust fan in the bathroom?) and differences were found in the way inhabitants and trained personnel viewed the dwellings. The ability of physical and bioaerosol measurements to predict moisture also was examined. Sixty-four study subjects were included in this analysis.
Study Two: This part of the study included the 29 matched case-control pairs for which home site visits were performed. The differences in the homes of ILD case and control subjects, using the descriptions of moisture risk factors, physical measurements, and bioaerosol measurements, were examined. Although 30 cases agreed to participate in the study, only 29 controls were matched to them. The data for this study is being analyzed.
Study Three: This study was based on the questionnaires from 50 matched case-control pairs. It explored occupational, home, family, and personal medical history factors in the development of ILD.
Case-Control Study of Sarcoidosis
A case-control study of sarcoidosis was conducted to explore a potential association with occupational and environmental exposure. All 59 patients seen between 1992 and 1997 in a pulmonary division and unmatched controls from orthopedic surgeons received two copies of a self-administered questionnaire inquiring about occupational and environmental histories. Approximately 52.2 percent of the patients and 32.4 percent of the controls responded. Patients were significantly more likely to have been exposed to inorganic dusts (odds ratio [OR] 3.48; 95 percent confidence interval [CI]: 1.02 - 11.80), molds (OR 9.8; 95 percent CI: 0.98 - 98.40), and solvents or oils in the work place (OR 9.8; 95 percent CI: 1.60 - 48.0) than controls. They described exposure at home through moldy basements (OR 2.37; 95 percent CI: 0.97 - 5.8) or mold on bathroom walls (OR 5.69; 95 percent CI: 1.3 - 25.6) more frequently than controls. Sarcoidosis may represent a disease at least partly attributable to occupational and environmental exposures. These results led to sampling in the homes of some of the study subjects. Thirty-six of the 51 identified subjects participated. Only one subject still worked for the same employer. This employer refused to participate. Occupational exposures for one patient with sarcoidosis were identified. This patient worked for the metalworking facility described in the next section.
Exposure Assessment in a Metal Working Facility
The Division of Occupational and Environmental Medicine (Division) conducted research on the causes of an outbreak of hypersensitivity pneumonitis (HP) first recognized at a metalworking plant in the autumn of 1997. The magnitude of the outbreak was substantial. Sixty-one workers (of 125 workers at the plant, of which 106 worked in production) visited the Division clinic, and 35 of the 61 evaluated were diagnosed with ILD. Although a specific etiological agent was not identified, the investigators recommended a number of changes at the plant to control exposure from bioaerosols generated in the plant. With plant improvements implemented, 51 percent of the 35 workers with diagnosed ILD were able to return to the work environment within 2 years of recognition of the outbreak.
Epidemiological Study
Questionnaire: The Division initially surveyed the manufacturing staff in 1997, and then repeated the questionnaire with the complete plant employee group 1 year later in September 1998. The questionnaire asked workers questions designed to: (1) identify personal risk factors for respiratory disease (e.g., home and lifestyle characteristics, respiratory disease history); (2) determine each person's current experience with respiratory and systemic complaints such as shortness of breath, cough, wheeze, fever, chills, fatigue, and aches; (3) determine periodicity/work-relatedness of symptoms; and (4) characterize work exposure by establishing the individual's current job title, work location in the plant, and time spent machining and/or polishing. The first questionnaire was offered to production personnel, and 1 year later the followup was offered to the complete plant employee group, front office, and production. To identify areas in the plant and the specific job activities that may be associated with the disease outbreak, a review of the work zones and job titles of individuals with HP was completed. Relative to the plant population, polishers, inspectors, broach operators, and machine operators were strongly represented in the diagnosed patient group. Fewer engineers, toolmakers, and supervisors developed ILD at this plant.
Collaboration with the National Institute for Occupational Safety and Health (NIOSH): A cross-sectional medical survey, industrial hygiene sampling program, and immunological study were conducted in collaboration with the Division of Respiratory Disease Studies at NIOSH. Because there were many more cases of HP diagnosed at the Division clinic than expected, the Division recognized that there may be some characteristics and/or exposures at the plant that would help explain the cause(s) of the disease. This, together with a concern that other workers at the plant were at considerable risk for having this respiratory disease, led the Division to request collaboration from NIOSH. The local and state health departments and the employer joined the Division in this request. Research activities in collaboration with NIOSH included a cross-sectional epidemiological study, an industrial hygiene-sampling program, and immunological research.
Identifying sources of exposure is difficult. Throughout the time of the outbreak, the Division's industrial hygienist collected longitudinal data to track plant changes that may have changed worker exposures. Sampling focused on emissions from water-based point sources. An industrial hygiene team from NIOSH collected additional environmental samples in November 1998.
Ninety-three percent of those who took part in the cross-sectional study provided NIOSH with blood samples to test for immunological reactivity with environmental samples taken from the plant extracts, specifically the wet dust collector (assumed to have effectively collected and then redispersed biological material generated in the production process), and with selected microbes (<em>Mycobacteria</em>, <em>Fusarium</em>, <em>Aspergillus</em>, and <em>Thermophylic Actinomycete</em>). Medical results, questionnaire responses, and environmental data were analyzed to identify the relationship between health status and occupational/environmental exposures, and to characterize risk factors in the occupational setting. Investigators from NIOSH and the Division are preparing a manuscript to detail the results.
Schools
As the prevalence and seriousness of childhood asthma and teacher/school staff respiratory health complaints have increased, the indoor environment in schools and the health consequences to the occupants have become a larger concern to society. Research at the University of Connecticut has focused on three major areas: (1) development of an epidemiological and engineering approach to understanding school building indoor air quality and occupant health consequences; (2) chart review of teachers treated at the Division clinic to improve understanding of school related illnesses; and (3) improvements for tracking illnesses with environmental components in school populations.
School Epidemiology and Engineering Approach: Research programs in the Division have utilized epidemiological surveys and physiological testing techniques for evaluating work-relatedness. The researchers have revised these to address general environmental investigations of schools. The protocol includes risk factor and health questionnaire surveys of students and teachers, and pulmonary function testing cross week (Monday morning before school, Monday afternoon, and Friday afternoon). The results from the Division's research on occupational and environmental health and exposures at schools have indicated a relationship among school building occupancy, moisture, and respiratory health. The results from two pilot research programs, one comparing teachers' health at schools with and without moisture problems and the second following a small group of asthmatic children over 3 years of middle school, imply a relationship between school building occupancy and respiratory health.
Questionnaire and Checklist Development: The researchers have used questionnaires with school staff, parents of students in schools, and students to better understand the relationship between the environment in the building and health symptoms that occupants experience. The questions on the survey are designed to:
1. Describe the participants and their health status.
2. Determine symptoms, how often they occur, and assess how severely the occupants experience health symptoms.
3. Explore factors in their homes that affect these types of health symptoms.
4. Establish occupants' exposure to the building's environment.
5. Explore work-relatedness of the health complaints.
6. Provide guidance on intervention (correcting building indoor environment problems).
7. Identify individuals at risk.
The researchers have used validated questions from the International Union Against Tuberculosis and from Arnow and Fink to identify symptoms indicative of asthma and HP and have adapted them for use in the school environment by introducing school-related qualifiers and measures of exposure in the school building. Additionally, the school research team, with interest in symptom frequency and severity, developed a symptom grid inquiring about respiratory and other symptoms. The researchers, in collaboration with Turner Building Science, LLC, developed a field approach for linking environmental and epidemiological data. This semi-quantitative checklist method collected field variables as a surrogate for determining the presence and level of bioaerosols.
Teacher Clinical Review: For the last several years, the clinic has treated an increasing number of teachers with asthma and other illnesses, and has recommended removal from the school unless the presumed causes of the illness could be remediated. On an individual basis, the frequency and, at times, the severity of teachers' respiratory symptoms were largest during school sessions and diminished during class breaks. Teachers who develop building-related disease are faced with a difficult situation. Removal from the environment can be costly to the individual patient in that the teacher's ability to work in his or her selected profession may be diminished, and to society in that experienced teachers, who have become a premium in many communities, may leave teaching prematurely.
The investigators developed a protocol to retrospectively review the charts of outpatients treated at the Occupational and Environmental Medicine clinic from 1990 to the present, and characterize the illnesses of teachers and school staff seen at the clinic. An application for human subject review was completed and approved. Ultimately, this review will contribute information to indicate intervention strategies and guide future research.
Tracking Environmental Illness in Schools: Because school nurses have responsibilities to provide nursing care to school populations, they represent an opportunity to improve the understanding of the scope of respiratory illness in the population. With some additional guidance, the school health office could become a source of data on these illnesses and provide additional information related to the role that the building may be playing in symptom frequency and severity. Through involvement with schools experiencing indoor air quality problems, the researchers have been gathering information that will be helpful in understanding the strengths and limitations of school-based health information and in developing improved tracking systems.
Mortality Study
To further explore lung disease among teachers and metalworkers, the researchers collected mortality data from 1985 to 1996 using the Multiple Cause of Death File compiled by the National Center for Health Statistics (NCHS). The NCHS data file includes all causes of death listed on the death certificate. The reserachers used specific codes from the ninth revision of the International Classification of Diseases (ICD-9), Standard Occupation Codes (SOC), and Census occupation codes to capture deaths by specific diseases and occupations and industries. A proportional mortality study was implemented. Expected counts were adjusted for age, race, sex, and year of death, and the reference population for each occupation consisted of other occupations of the same socioeconomic status. A one-tailed test was performed to identify proportional mortality ratios (PMR) greater than 1.0. The disease data were examined in three ways: for all diseases combined, for each disease individually, and by disease groupings based on disease type (e.g., pulmonary diseases and connective tissue diseases).
Journal Articles on this Report : 6 Displayed | Download in RIS Format
Other project views: | All 13 publications | 8 publications in selected types | All 6 journal articles |
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Bracker A, Storey E, Yang C, Hodgson MJ. An outbreak of hypersensitivity pneumonitis at a metalworking plant: a longitudinal assessment of intervention effectiveness. Applied Occupational and Environmental Hygiene 2003;18(2):96-108. |
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Dangman KH, Cole SR, Hodgson MJ, Kuhn C, Metersky ML, Schenck P, Storey E. The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers. American Journal of Industrial Medicine 2002;42(2):150-162. |
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Dangman KH, Storey E, Schenck P, Hodgson MJ. Effects of cigarette smoking on diagnostic tests for work-related hypersensitivity pneumonitis: data from an outbreak of lung disease in metalworkers. American Journal of Industrial Medicine 2004; 45(5):455-467. |
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Hodgson MJ, Bracker A, Yang C, Storey E, Jarvis BJ, Milton D, Lummus Z, Bernstein D, Cole S. Hypersensitivity pneumonitis in a metal-working environment. American Journal of Industrial Medicine 2001;39(6):616-628. |
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Mahooti-Brooks N, Storey E, Yang C, Simcox NJ, Turner W, Hodgson M. Characterization of mold and moisture indicators in the home. Journal of Occupational and Environmental Hygiene 2004;1(12):826-839. |
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Vesper S, Dearborn DG, Yike I, Allan T, Sobolewski J, Hinkley SF, Jarvis BB, Haugland RA. Evaluation of Stachybotrys chartarum in the house of an infant with pulmonary hemorrhage: quantitative assessment before, during, and after remediation. Journal of Urban Health 2000;77(1):68-85. |
R825251 (Final) |
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Supplemental Keywords:
indoor air, health effects, risk, exposure, children, bacteria, fungus, engineering, epidemiology, measurement methods, occupation, school teachers, metalworkers, Health, Scientific Discipline, Air, Geographic Area, air toxics, State, Epidemiology, Disease & Cumulative Effects, Biochemistry, indoor air, Biology, health effects, risk assessment, interstitial lung disease, exposure and effects, effects assessment, population based study, airway disease, pulmonary disease, mold exposure, lung dysfunction, public health, bioaerosols, ambient particulates, harmful environmental agents, Connecticut (CT), indoor air quality, mycotoxinsProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.