DEVELOPMENT OF DIAGNOSIS AND TREATMENT BASED ON PATHOPHYSIOLOGY OF CHRONIC COUGH

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I. Basic research1. guinea pig models for atopic cough and cough variant asthma have been developed.1) Using the atopic cough model, it has been disclosure d that increased level of substance P resulted from antigen-induced inactivation of neutral endopeptidase is important in the antigen-induced increase in cough sensitivity, and that there may bean interaction between histamine and substance P.2) Using the cough variant asthma model, It is clarified that cough is elicited via antigen-induced bronchoconstridion, and that leukotrienes, but not tachykinins, are involved in the cough.2. We developed a apparatus to give quantitative mechanical pressure stress to guinea pig airway. The Mechanical pressure stress to airway induced cough reflex hypersensitivity associated with airway neutrophilic inflammation., suggesting self-perpetuating cycle between cough and cough hypersensitivity.II. Clinical research1. In addition to the difference of pathophysiologic feature between atopic cough and cough variant astluna, we elucidated the long-term outcome is also different between these two condition.: Nearly 30% patients with cough variant asthma develops typical asthma within several years but no patient with atopic cough does.2. Bronchial hyperresponsiveness and no use of long-tern inhaled corticosteroids were risk factors of typical asthma onset from cough variant asthma.3. Our prospective study confirmed that cough variant asthma, atopic cough and sinobronchial syndrome are common causes of chronic cough in Japan.