Research to Elucidate the Underlying Mechanisms of Airway Hyperreactivity.

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To elucidate the underlying mechanisms of bronchial hyperreactivity we have employed several sorts of animal models originally developed by us as well as normal subjects and patients with asthma and COPD. A summary of the results and conclusions which the research has attained to the present is as follows;1) ype C influenza virus infection induced airway hyperresponsiveness in Beagle dogs, especially 1 to 3 weeks after the infection, when an increase in the number of ast cells and concentrations of histamine, TXB2 and PGF2alpha in BALF were observed. Histological study also revealed damage and desquamation of the epithelial cells of the airways, which may suggest dysfunction of the EDRF.2) Ascaris suum antigen inhalation produced a higher incidence rate of LAR (late asthmatic response) in sensitized guinea pigs with silica as an adjuvant. At the LAR a distinct eosinophilic infiltration was observed in the mucosal tissue. The LAR can be blocked by administration of the selective and com … More petitive leukotriene blocker, ONO-1078. Airway hyperresponsiveness was also observed after the LAR, and was sustained for three to four day, which is possibly attributable to eosinophil infiltration.3) Superoxide inhalation produced airway contraction and subsequent airway hyperresponsiveness in cats, which was blocked by the administration of SOD, a scavenger of superoxide. In another study SOD also attenuated the increase in airway responsiveness after ozone inhalation. The results indicate that superoxide is an important factor in the production of hyperresponsiveness in the airway.4) After blocking sympathetic and parasympathetic nerves, inhalation of capsaicin or citric acid produced a dilatation of constricted airways in cats and human subjects, which was blocked by hexamethonium (C6), a ganglion blocker, The results indicate bronchial C-fiber receptors as well irritant receptors are also the receptors for the NAIS, which composes the reflex pathways. In addition, the stimulation of the NAIS also inhibited the immediate allergic reaction, revealing a protection against increase in lung resistance as well as histamine concentration.5) Through the study of single submucosal glands taken from cat trachea the effects of the autonomic nerves, substance-P, and VIP on contraction and secretion were determined. We also found that a substance is produced by epithelial cells which inhibits the mucous secretion. Less