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Eighteen patients, who had previously taken part in a 2 wk cross-over comparison between formoterol and salbutamol, now took part in a one year double-blind study comparing salbutamol 200 micrograms b.i.d. with formoterol 12 micrograms b.i.d. Additional doses were taken when needed and were recorded. Ten patients were started on formoterol and eight on salbutamol. After one month, the patients were allowed to shift to the alternative drug. Two patients withdrew from the study. At the end of the study, 13 of 16 patients were on formoterol, thus showing a long-lasting preference for this drug. Forced expiratory volume in one second (FEV1) dose-response curves for inhaled salbutamol were repeatedly recorded during the study, and no tachyphylaxis was found. One patient stopped taking inhaled steroids but continued taking formoterol and theophylline. He deteriorated with a decreased response to salbutamol. After re-introduction of inhaled steroids his condition improved. This case indicates that effective bronchodilator therapy may mask the deterioration of asthma.

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.

The influence of the mucosa on the contractile responses to cholinergic nerve stimulation in an in vitro nerve muscle preparation of ferret trachea was studied. Repeated contractions were induced by alternating direct vagal nerve stimulation (DNS) and electrical field stimulation (EFS). With intact mucosa there was a marked successive decrease of the contractile responses. During 60 minutes the responses decreased to 46 +/- 8% of baseline (Mean +/- SEM, n = 6), compared to 86 +/- 2% in preparations, in which the mucosa was initially removed. The mucosa dependent inhibition could be partly blocked by indomethacin (10 microM). The inhibitory effect could be transferred via the bath fluid from a donor preparation with intact mucosa to a recipient preparation with removed mucosa. Fluid transferred from a donor preparation with removed mucosa or from indomethacin treated preparations did not affect the contractile responses in the recipient preparation. We conclude that ferret tracheal mucosa can release a factor which inhibits the contractile responses to cholinergic nerve stimulation. The release of this factor can be blocked to a major part by indomethacin and the factor can be transferred from a donor to a recipient preparation.

To study the cardioselectivity of xamoterol, eight asthmatic patients took part in a randomised, double-blind, cross-over study, in which xamoterol or saline were infused, followed by four increasing doses of terbutaline i.v. Circulatory studies showed a significant increase of systolic blood pressure after xamoterol 0.1 mg/kg compared to saline (P less than 0.05), and heart rate tended to increase. Diastolic blood pressure did not show any significant changes after the different treatments. Skeletal muscle tremor measurements with terbutaline stimulation did not show any differences after pre-treatment with either xamoterol or saline. Mean values of FEV1 did not reveal any significant difference before or after terbutaline stimulation between xamoterol and saline pre-treatments. However, in one patient, FEV decreased 60% after xamoterol, an effect which was reversed by terbutaline. Xamoterol did not have any effect on beta-adrenoceptor mediated skeletal muscle tremor and no significant effect on beta-adrenoceptor mediated bronchodilation in doses which gave a significant increase of systolic blood pressure. Thus, xamoterol was shown to be a selective beta 1-adrenoceptor agonist in man.

The aim of this study was to evaluate if treatment with inhaled formoterol is appreciated by asthmatics and whether it causes tachyphylaxis. Twenty stable asthmatics were included in a randomized, double-blind, crossover study. They were treated for two weeks either with formoterol or salbutamol, with one week washout inbetween. They were given 12 micrograms formoterol or 200 micrograms salbutamol twice daily and instructed to use additional spray doses on demand. On a diary card they recorded the number of doses, asthma symptoms and peak expiratory flow rate (PEFR) before every dose. Forced expiratory volume in one second (FEV1) dose-response curves for salbutamol (total dose 1.3 mg) were performed before and after each treatment period to evaluate development of tachyphylaxis. There was a significant difference in favour of formoterol concerning symptoms, PEFR recordings, spray consumption, and preference. Fifteen patients preferred formoterol and two salbutamol. The dose-response curves before formoterol and before, as well as after salbutamol were almost identical. After formoterol the curve had changed; both basal and maximum values were higher than before. Thus, no evidence of tachyphylaxis was found, compared to the ordinary beta-stimulant treatment.