Inhaled beta-stimulants - A study of high-dose v. conventional-dose treatment in asthmatic outpatients

A randomised double-blind controlled trial was conducted in order to compare pulmonary function and protective effects of salbutamol 200 μg v. 1000 μg by inhalation. Twenty-three known asthmatics took part in the study for a period of 12 weeks. Pulmonary function tests were performed at home (peak expiratory flow-rate (PEFR)) and in the laboratory (vital capacity (VC), forced expiratory volume in 1 second (FEV₁) and PEFR) before and after treatment. Bronchial responsiveness was measured as the provocative dose of histamine that caused a decrease of 30% of the area under the flow-volume curve (AFVE₃₀) 90 minutes after pre-treatment with the study medication. The 20 patients (10 per treatment group) who completed the study were comparable at base-line in respect of physiological and pulmonary function measurements. Median PEFR, FVC and FVC₁ did not differ between the treatment groups for the duration of study. Histamine challenge testing demonstrated a significant decrease in protection that was only seen after 8 weeks of treatment in the high-dose group (P < 0,05). Changes in pulse rate, blood pressure as well as side-effects were similar in the two groups. Thus treatment with higher doses of β-stimulants in outpatients had no demonstrable advantage. A significant impairment of the ability to protect against histamine-induced bronchoconstriction was shown; this may relate to β-receptor down-regulation and hence the development of tachyphylaxis.