A method for measuring the effects of anticholinergics on histamine-induced bronchoconstriction in normal subjects. Oxitropium bromide provides dose-dependent protection.
To study whether it would be possible to assess anticholinergic drugs in normal subjects with histamine-(HIST) induced bronchoconstriction, three doses of oxitropium bromide (100, 200 and 400 micrograms) was inhaled in random order by twelve normal volunteers in a single-blind, placebo-controlled study. Dose response slope [DRS = maximal percentual fall in pulmonary function/maximal noncumulative histamine dose (mumol)] was used as an index of bronchial reactivity, and was calculated for FEV1 (DRSFEV1) and area under the flow-volume curve (DRSAEFV). The bronchial reactivity and its reproducibility was first tested with a standard provocation method. An abbreviated, single-dose, method was used in the measurement of the effects of oxitropium. The reproducibility of HIST-provocations were good with intraclass correlations of 0.97 and 0.99 for logDRSFEV1 and logDRSAEFV, respectively. However, DRSAEFV seemed to be better in this respect as DRSFEV1. Also, the single-dose method gave results that were comparable to the standard one. The largest dose of oxitropium diminished the median DRS from 2.6 to 0.01 and from 5.2 to -0.2 for FEV1 and AEFV, respectively. All oxitropium doses differed significantly from placebo (P < 0.01) and from each other (P < 0.05) with DRSAEFV-values, but when DRSFEV1 was used, a significant difference was detected only between placebo and active treatment (P < 0.01). In conclusion, since the vagal mechanisms seem to be the predominant system mediating HIST-induced bronchoconstriction in normal subjects, it is possible with DRSAEFV to evaluate the efficacy of anticholinergics against HIST-induced bronchoconstriction in these subjects.
Department of Clinical Pharmacology, University of Turku, Finland.
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Seppälä
D000328:Adult; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine; D006801:Humans; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D011897:Random Allocation; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D016037:Single-Blind Method
D010276:Parasympatholytics; D012602:Scopolamine Derivatives; D006632:Histamine; C017590:oxitropium