title: [Etiology, pathogenesis and management of senile inflammatory pulmonary diseases].
abstract: We studied the etiology, pathogenesis and management of therapy-resistant inflammatory pulmonary diseases. First, to understand the pathogenesis of rhinovirus (RV) infection-induced exacerbation of bronchial asthma, we infected cultured human tracheal epithelial cells with RV. The epithelial cells produced a variety of proinflammatory cytokines, intercellular adhesion molecules (ICAM-1) and low-density lipoprotein receptor, and increased the permeability across the epithelial cells. These findings suggest that these factors and the increased permeability may cause airway inflammation, resulting in the exacerbation of asthma. Glucocorticoid and bafilomycin inhibited RV infection in the epithelial cells by reducing ICAM-1 expression and RV RNA entry from the acidic endosomes to the cytoplasm. Second, we revealed the mechanisms of aspiration pneumonia induced by silent aspiration in patients with cerebral infarction. We also developed a pharmacologic treatment for preventing aspiration pneumonia with amantadine, which stimulates the dopaminergic neurons; the angiotensin-converting enzyme inhibitors, which decrease substance P catabolism; and cilostazol, which inhibits platelet aggregation and induces cerebral vasodilation. Third, we demonstrated that exhaled carbon monoxide concentrations caused by heme oxygenase-1 upregulation, may be a useful noninvasive means of monitoring airway inflammation and of controlling elderly patients with bronchial asthma. Finally, we demonstrated that microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema caused by cigarette smoke in Japanese patients with chronic pulmonary emphysema.
authors.affiliation: Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Hidetada
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000375:Aging; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D006801:Humans; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D011015:Pneumonia, Aspiration / Q000517:prevention & control; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000517:prevention & control; D011656:Pulmonary Emphysema / Q000209:etiology / Q000517:prevention & control
chemical_list: D006419:Heme Oxygenase (Decyclizing)