Sterk P J, Timmers M C, Dijkman J H
Am Rev Respir Dis. 1986 Oct;134(4):714-8. doi: 10.1164/arrd.1986.134.4.714.
Maximal airway narrowing to inhaled nonsensitizing stimuli is limited to a mild degree in nonasthmatic and mildly asthmatic subjects. We investigated whether this limitation is due to a nonspecific inhibitory mechanism (with regard to the agonist) by comparing the maximal response plateaus of histamine and methacholine dose-response curves. Twenty subjects (15 nonasthmatics, 5 asthmatics) were selected in order to cover a wide distribution of airway responsiveness from the normal into the mildly asthmatic range. The subjects inhaled doubling doses of either histamine (up to 54 mumol) or methacholine (up to 340 mumol), delivered to the mouth during tidal breathing, on 2 separate days. The response was measured from volume-history-standardized, partial expiratory flow-volume curves as the flow at 40% of the control vital capacity (V40p), and expressed as the percentage fall from baseline value. Sixteen subjects demonstrated a plateau for both histamine and methacholine. The maximal response on the plateau was not significantly different between the 2 agonists, nor was there a difference in the provocative dose causing a 40% fall in V40p (PD40). The slope of the dose-response curve was significantly steeper for histamine than for methacholine (p less than 0.001), whereby the histamine plateau was reached at relatively lower doses (p less than 0.01). The maximal response was inversely related to logPD40, and this relationship did not differ between histamine and methacholine. We conclude that maximal airway narrowing in vivo is limited by an inhibitory mechanism that is not dependent on the pharmacodynamic properties of the agonist. The results suggest that the extent of inhibition and the degree of airway responsiveness are determined by related mechanisms.
在非哮喘和轻度哮喘受试者中，吸入非致敏刺激时气道最大程度狭窄仅限于轻度。我们通过比较组胺和乙酰甲胆碱剂量反应曲线的最大反应平台，研究了这种限制是否归因于一种（针对激动剂的）非特异性抑制机制。选择了20名受试者（15名非哮喘患者，5名哮喘患者），以涵盖从正常到轻度哮喘范围内广泛分布的气道反应性。受试者在2个不同的日子里，于潮气呼吸时经口吸入双倍剂量的组胺（最高54 μmol）或乙酰甲胆碱（最高340 μmol）。反应通过体积历史标准化的部分呼气流量-容积曲线进行测量，以对照肺活量（V40p）40%时的流量表示，并以相对于基线值的下降百分比来表示。16名受试者的组胺和乙酰甲胆碱反应均出现平台期。两种激动剂在平台期的最大反应无显著差异，导致V40p下降40%的激发剂量（PD40）也无差异。组胺剂量反应曲线的斜率显著陡于乙酰甲胆碱（p<0.001），由此组胺在相对较低剂量时即达到平台期（p<0.01）。最大反应与logPD40呈负相关，且组胺和乙酰甲胆碱之间这种关系无差异。我们得出结论，体内气道最大程度狭窄受一种不依赖于激动剂药效学特性的抑制机制限制。结果表明，抑制程度和气道反应性程度由相关机制决定。
