LIMITED MAXIMAL AIRWAY NARROWING IN NONASTHMATIC SUBJECTS - ROLE OF NEURAL CONTROL AND PROSTAGLANDIN RELEASE

Publisher Website
Google Scholar
Abstract
In nonasthmatic subjects with normal airway responsiveness to methacholine, maximal airway narrowing is limited to a mild or moderate degree. We investigated whether the maximal response plateau or the position of the dose-response curve is due to functional inhibition by neurogenic mechanisms or to prostaglandin release. Four nonasthmatics inhaled doubling concentrations of methacholine up to 256 mg/ml (67 mg delivered duirng tidal breathing), following by 4-fold-increasing doses of salbutamol up to 80 mg/ml (24 mg during tidal breathing) on 5 separate days. On each day 30 min before the test, the subjects inhaled (using a dosimeter) saline, propranolol (11 mg), or hexamethonium (910 mg), or, 2 h before the test, ingested indomethacin (75 mg) or placebo. The response to methacholine was measured from volume history standardized partial and complete maximal expiratory flow-volume curves, as FEV1, and the flows at 40% of the control FVC (.ovrhdot.V40P and SSSD+V40C). Compared with saline, on average, baseline .ovrhdot.V40P was 18% lower after propranolol and 18% higher after hexamethonium. Indomethacin did not affect baseline values. There was no systematic difference between the 5 days in the dose of methacholine to cause a 10% fall in FEV1 or a 40% fall in .ovrhdot.V40P, or in the maximal response with FEV1, .ovrhdot.V40P, and .ovrhdot.V40C, or in .ovrhdot.V40P/.ovrhdot.V40C at 256 mg/ml methacholine. We conclude that limited maximal airway narrowing to methacholine in nonasthmatics is not due to a change in adrenergic, cholinergic, or ganglion-transmitted-nonadrenergic inhibitory activity nor to the release of prostaglandins. Furthermore, the bronchodilatory effect of a deep inspiration is not caused by a neurogenic reflex mechanism or the release of prostaglandins.