Effects of pretreatment with inhaled methoxamine on bronchial responses to histamine in asthmatic subjects

Abstract

The underlying mechanisms of bronchial obstruction in asthma are complex. Both bronchospasm and bronchial oedema are thought to play pivotal roles in asthma, but their respective importance in a given asthmatic individual is unknown. To address this question, we assessed the effects of pretreatment with inhaled methoxamine, a potent alpha 1-adrenoceptor agonist, on bronchial response to inhaled histamine in 10 asthmatic subjects. The study was conducted according to a double-blind, cross-over, randomized and placebo-controlled design. In each subject, dose-response curves for the effects on forced expiratory volume in one second (FEV1) of serially doubling doses of inhaled histamine were obtained on three different days, 15 min after pretreatment with either methoxamine (10 mg) or duplicated placebo. Histamine, first dose 100 micrograms (543 nmol), was delivered by a breath-activated dosimeter every 5 min. FEV1 was measured in triplicate after each dose and the largest value was retained. There was no difference in baseline and prechallenge FEV1 after placebo and methoxamine. Mean coefficient of variation of decrease in FEV1 induced by histamine on the two placebo days was 6.7 +/- 2%. On average, the bronchial responses to histamine were not modified by pretreatment with methoxamine as compared to placebo (delta FEV1 = 0.83 +/- 0.14 l on methoxamine versus 0.85 +/- 0.11 l and 0.86 +/- 0.13 l on the two placebo days).(ABSTRACT TRUNCATED AT 250 WORDS)