1998 Fiscal Year Final Research Report Summary
Studies on the inflammatory changes in the airway mucosa of patients in the early stage of asthma and the necessity for inhaled glucocorticoids therapy for these patients.
| Project/Area Number |
08457185
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | DOKKYO UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
FUKUDA Takeshi Dokkyo University School of Medicine, Professor, 医学部, 教授 (90088873)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Yasutsugu Dokkyo University School of Medicine Lecturer, 医学部, 講師 (00254996)
NUMAO Toshio Dokkyo University School of Medicine Lecturer, 医学部, 講師 (60172748)
TODA Masao Dokkyo University School of Medicine Lecturer, 医学部, 講師 (50175478)
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| Project Period (FY) |
1996 – 1998
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| Keywords | bronchial asthma / early stage of asthma / airway inflammation / inhaled glucocorticoids / airway hyperresponsiveness / basement membrane thickening / eosinophil infiltration / airway wall remodeling |
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| Research Abstract |
Necessity for starting inhaled glucocorticoids therapy from the early stage of asthma was suggested from the results of the following clinical studies and animal experiment.
1. Inflammatory changes in the bronchial mucosa of asthma patients whose asthma onset had been within one year : Like patients with chronic asthma, eosinophil infiltration was observed both in the submucosa and epithelium. Most of eosinophils were activated. Although the mean value of basement membrane thickness was significantly less than that of patients whose asthma history was more than 2 years, there were patients with markedly thickened basement membrane.
2. The effects of inhaled glucocorticoids started soon after the onset of asthma on the short-term prognosis : In most of asthmatics in whom inhaled glucocorticoids therapy was started within one year after the asthma onset, asthma symptoms completely disappeared within one month and bronchial responsiveness to acetylcholine was normalized. In such cases, the
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patients often discontinue to attend hospital, which made it difficult to perform follow up studies. In contrast, in asthmatics who were treated with sustained-release theophylline and inhaled beta2-agonist, asthma control was not perfect and most of them visited to our out clinic on exacerbations.
3. Effects of high-dose inhaled glucocorticoids therapy on thickening of basement membrane in chronic asthma : Bronchial biopsies were done after receiving high-dose inhaled glucocorticoids therapy for at least 3 years in five patients with chronic asthma in whom bronchial biopsies had been performed before this therapy and the thickness of basement membrane in both specimens was compared. The intensity of eosinophil infiltration decreased after high-dose inhaled glucocorticoids therapy, but the thickness of basement membrane unchanged, suggesting that inhaled glucocorticoids therapy is not effective for established airway remodeling.
4. Protective effect of leukotriene receptor antagonist on airway wall thickening in a guinea pig model of chronic asthma : Guinea pigs sensitized with ovalbumin (OA) and subsequently challenged with aerosolized OA once a week over 24 weeks showed marked airway wall thickening, in particular the smooth muscle layer. When animals were treated with leukotriene receptor antagonist, the airway wall thickening was blocked, suggesting the inhibitory effect of this drug on airway remodeling. Less
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