Co-Investigator(Kenkyū-buntansha) |
KUBO Keishi SHINSHU UNIV. SCH. OF MED. PROFESSOR, 医学部, 教授 (80143965)
HONDA Takayuki SHINSHU UNIV. SCH. OF MED. ASSOCIATED PROFESSOR, 医学部, 助教授 (80238815)
FUJIMOTO Keisaku SHINSHU UNIV. SCH. OF MED. ASSISTANT PROFESSOR, 医学部, 助手 (70242691)
蜂谷 勤 信州大学, 医学部, 助手 (20303464)
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Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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Research Abstract |
The inhalation of Ascaris suum twice a week for 8 weeks induced a marked accumulation in the airway of inflammatory cells, especially eosinophils, and goblet cell hyperplasia of epithelial cell in allergic sheep naturally sensitized by Ascaris. The eosinophil infiltration into the subepithelial mucosa and goblet cell hyperplasia were distributed from central airway to the small airway, and the changes were marked in the small airways. These changes are consistent with the changes observed in the patient with asthma developed to the airway remodeling. However, the apparent thickening of basement membrane, airway smooth muscle hyperplasia, and increase in submucosal glands observed in asthmatic airway remodeling were not observed in this animal model. To establish animal model of asthmatic airway remodeling, further examination may be needed. In clinical study, we measured the inflammatory cells, ECP, tryptase, and TGF-beta in induced sputum and exhaled nitric oxide (ENO) in patients wit
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h asthma, and examined the relationship with airway remodeling. The presence of airway remodeling was assessed by fixed airflow limitation and bronchial wall thickness (rt. B1) evaluated by using a chest HRCT. In asthmatics, the eosinophil numbers and the levels of ECP, TGF-beta were significantly higher than those in healthy subjects. Some asthmatics showed a higher tryptase level in sputum. However, there was no significant difference in these inflammatory cells and mediators between the asthmatics with and without airway remodeling, however, the level of TGF-beta in sputum had a tendency to increase in asthmatics with remodeling. The concentration and production of ENO dependent on the increase in airway pressure were significantly higher in asthmatics than those in healthy subjects. The ENO in asthmatics was significantly correlated positively with eosinophilia in sputum and negatively with FEVィイD21ィエD2. The concentration and production of ENO in asthmatics with airway remodeling were significantly lower than those in asthmatics without airway remodeling, whereas there was no significant difference in sputum eosinophilia between the two groups. It has been suggested that a sustaining eosinophilic airway inflammation may be associated with the development of airway remodeling. The eosinophilic inflammation evaluated induced sputum and the level of tryptase and TGF-beta in sputum may not be able to predict the presence of airway remodeling, however, the discrepancy of sputum eosinophilia and ENO production may be predicted the presence of airway remodeling. Less
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