Measuring the bronchial effect of bronchodilating drugs in healthy subjects after methacholine provocation. Salbutamol as a model drug

Abstract

To study whether it would be possible to assess bronchodilating drugs in healthy subjects with methacholine - induced bronchoconstriction, salbutamol 100, 200 and 300 micrograms was inhaled in random order by 12 healthy volunteers in a double-blind, placebo-controlled study. Dose response "slope" (DRS = maximum percentage fall in pulmonary function/maximal noncumulative methacholine dose (mumols] was used as an index of bronchial reactivity, and was calculated for forced expiratory flow volume in 1 s (DRSFEV1) and area under the flow-volume curve (DRSAEFV). Bronchial reactivity and its reproducibility were first tested by a standard methacholine provocation method. An abbreviated, single-dose method was used to measure the effect of salbutamol. The reproducibility of methacholine provocation was good, and the single-dose and standard methods gave comparable results. The DRS-values of all the doses of salbutamol differed significantly from placebo and from each other. AEFV did not show any advantage over the FEV1 in this context. A significant negative association between the dose of salbutamol (microgram/kg) and airway reactivity was observed. In conclusion, use of the DRS showed it possible to evaluate the protective efficacy of beta 2-adrenergic agonists against induced bronchoconstriction in healthy subjects.