|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1998 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
1. Background : The health hazards associated with organic dust exposure have been recognized for several centuries, whereas the pathogenic mechanisms are difficult to define precisely.
2. Objectives : We investigated the effects of organic dust on the lungs and the pathogenic mechanisms, with an object of searching for new methods of diagnosis, therapy and prevention.
3. Methods : We have done (1) a medical examination of farmers in Taiki, Hokkaido, by questionnaire, a chest radiograph, physical examinations and serum antibodies to the organic dust. (2) We examined the dust and clinical samples in vitro by mycological, immunological and polymerase chain reaction (PCR) methods. (3) We developed murine models for experimental therapy.
4. Results : (1) We revealed that 20% of farmers in Taiki show abnormalities of their chest radiographs. We identified 14 cases of hypersensitivity pneumonitis (HP), including a fulminate case. Most of them have serum antibodies to the dust or fungi of their own environment but not to commercially available antigens for the diagnosis of HP.(2) We applied PCR to detect causative agent specific DNAs in host and environment in HP.It may be a new method to investigate the pathogenic mechanisms of fungi in organic dust. We identified four Penicillium species as new antigens of HP.(3) We developed murine models of HP and trichosporonosis using standard strains for Trichosporon antigen, and proved a common pathogenesis of Trichosporon inducing hypersensitivity and infection, depending of the immunological status of the host. The therapeutic dosage of erythromycin significantly suppressed acute neutrophils influx into the lung, intradermal Arthus reaction and the expression of ICAM-1 in the lesions of the experimental HP.
5. Conclusions : We confirmed the pathogenicity of fungi in organic dust and proposed possible new methods for diagnosis and therapy for the pulmonary diseases caused by them.