Whereas the previous proposal determined that several components contribute to adverse pulmonary effects produced by inhaled machining fluid aerosols, this research proposal will test the hypothesis that mycobacteria contamination of machining fluids produces hypersensitivity pneumonitis in exposed workers. Two case reports in the literature have documented that occupational exposure to machining fluid aerosols is associated with hypersensitivity pneumonitis. Recently, eight additional outbreaks (i.e., eight different machining plants) of hypersensitivity pneumonitis have been identified. In 7 of these 8 outbreaks, Mycobacterium chelonae was identified as a major contaminant of each machining fluid. Also, antibodies to M. chelonae were more common in workers exposed to machining fluid aerosols, and serum from each of 6 patients diagnosed with hypersensitivity pneumonitis was positive in an ELISA for antibodies to M. chelonae. In addition, pilot work in the laboratory has recently demonstrated that repeated tracheal instillation of M. chelonae can produce hypersensitivity pneumonitis-like histological changes in the mouse lung. Taken together, these results are suggestive but not proof of a link between hypersensitivity pneumonitis and exposure to M. chelonae-contaminated machining fluid aerosols. Thus, a new occupational problem has surfaced in which a targeted microbe, M. chelonae, has not been routinely assayed in machining fluids or previously considered in the pathogenesis of hypersensitivity pneumonitis. Since epidemiologic studies can typically provide only relational information, the applicant proposes to use an animal model of hypersensitivity pneumonitis to determine whether M. chelonae is responsible for the induction of hypersensitivity pneumonitis in machining fluid workers. Although indirect evidence suggests that M. chelonae is involved in the recent outbreaks of hypersensitivity pneumonitis, the findings from these proposed controlled laboratory studies are needed in proving causality prior to instituting control strategies such as the appropriate biocide for eradicating the critical microbial contaminant of machining fluids.

National Institute of Health (NIH)
National Institute for Occupational Safety and Health (NIOSH)
Research Project (R01)
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Safety and Occupational Health Study Section (SOH)
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New York University
Public Health & Prev Medicine
Schools of Medicine
New York
United States
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Gordon, Terry; Nadziejko, Christine; Galdanes, Karen et al. (2006) Mycobacterium immunogenum causes hypersensitivity pneumonitis-like pathology in mice. Inhal Toxicol 18:449-56
Gordon, T; Galdanes, K (1999) Factors contributing to the acute and subchronic adverse respiratory effects of machining fluid aerosols in guinea pigs. Toxicol Sci 49:86-92
Gordon, T; Harkema, J R (1995) Mucous cell metaplasia in the airways of rats exposed to machining fluids. Fundam Appl Toxicol 28:274-82