Bronchial reactivity in normal subjects and patients with asthma

Thomson, Neil Campbell (1979) Bronchial reactivity in normal subjects and patients with asthma. MD thesis, University of Glasgow.

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In experimental animals and man it has been postulated that antigen-induced bronchospasm is due to the liberation of chemical mediators from mast cells, and that these mediators may act either directly on bronchial smooth muscle or via reflex vagal pathways. In exercise-induced asthma similar mechanisms may operate, possibly following non-immunological release of chemical mediators. The pathogenic mechanism underlying the increased airway reactivity to non-specific stimuli characteristic of asthma, and the transient bronchial hyper-reactivity found in some normal subjects is unknown, although it has been suggested that these responses may be due to stimulation of vagal irritant receptors in the bronchial epithelium. The purpose of this study was, therefore, to determine the relative importance of the direct and reflex vagal effects of various stimuli upon bronchial smooth muscle. This was investigated by examining the effects of chemical mediators, non-specific stimuli and exercise upon the airways of normal subjects and patients with asthma. Histamine is thought to be an important primary chemical mediator released from human mast cells, while, in some species dopamine has been implicated in type I hypersensitivity. The possible sites of action of these chemical mediators upon bronchial smooth muscle were, therefore, examined. Firstly, the effects on airflow resistance of an inhaled receptor antagonist clemastine, and an inhaled receptor antagonist cimetidine were studied in normal subjects and asthmatic patients. No significant changes in specific conductance (sGaw) were seen in normal subjects. In asthmatic patients, however, a significant increase in forced expiratory volume in 1-sec (FEV1) occurred at 60, 90 and 120 minutes following the inhalation of clemastine, whereas inhaled cimetidine had no bronchodilator effect. Clemastine and cimetidine were then tested on histamine-induced bronchoconstriction in normal subjects and asthmatic patients. Clemastine significantly reduced the fall in sGaw in normal subjects, and FEV1 in asthmatic patients, whereas cimetidine had no protective effect. Clemastine and the anticholinergic drug ipratropium bromide were tested on methacholine-induced bronchoconstriction in normal subjects. Ipratropium bromide, but not clemastine significantly reduced the fall in sGaw after methacholine. These results suggest that if histamine is shown to be an important mediator of immediate type hypersensitivity in human asthma, then the predominate site of action of histamine upon the airways is probably directly on bronchial smooth muscle receptors.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Immunology
Date of Award: 1979
Depositing User: Enlighten Team
Unique ID: glathesis:1979-76515
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 14:14
Last Modified: 19 Nov 2019 14:14

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