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 micrograms v. 1,000 micrograms 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 less than 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 beta-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 beta-receptor down-regulation and hence the development of tachyphylaxis.