LIMITED BRONCHOCONSTRICTION TO METHACHOLINE USING PARTIAL FLOW-VOLUME CURVES IN NONASTHMATIC SUBJECTS

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Abstract
Whether the plateau of the dose-response to nonsensitizing stimuli, such as methacholine, could be explained by the airway dilation that follows lung inflation in nonasthmatics was investigated. Maximal expiratory partial flow-volume curves were used to measure the response of the airways to doubling doses of inhaled methacholine up to 256 mg/ml (a noncumulative dose of 340 .mu.mol delivered to the mouth during tidal breathing) in 12 nonasthmatics on 2 days. Maximal expiratory complete flow-volume curves and FEV1 [forced expiratory volume] were also obtained along with the partial curves. Flows were measured at 40% of control vital capacity using the complete (.ovrhdot.V40c) and the partial (.ovrhdot.V40p) curves. A maximal response plateau of 2 or more doubling concentrations was demonstrated in all subjects based on .ovrhdot.V40p and in 10 subjects based on FEV1. The level of the plateau was the highest for the .ovrhdot.V40p (mean .+-. SD = 65 .+-. 19% of baseline), intermediate for .ovrhdot.V40c (45 .+-. 22%), and the lowest for FEV1 (16 .+-. 11%). There was more than a 100-fold range in responsiveness expressed as the provocative concentration to cause a 40% fall of baseline in .ovrhdot.V40p (PC40); the lower the PC40, the higher the level of the plateau. All the results were reproducible between the 2 days. Whether the plateau may have been due to a tachyphylaxic effect of cumulative doses of methacholine was investigated. The maximal response after increasing concentrations of methacholine up to 256 mg/ml was not different from the response obtained after single dose of 256 mg/ml. The limited bronchoconstriction observed in nonasthmatics is not due to the airway dilation that follows lung inflation, nor to tachyphylaxis to methacholine.