Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients.Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18mg once daily (n=356) compared with ipratropium 40mg q.i.d. (n=179).Screening forced expiratory volume in one second (FEV1) were 1.25¡0.43 L (41.9¡12.7% of the predicted value) (tiotropium) and 1.18¡0.37 L (39.4¡10.7% pred) (ipratropium). Trough FEV1 at 1 yr improved by 0.12¡0.01 L with tiotropium and declined by 0.03¡0.02 L with ipratropium (pv0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George9s Respiratory Questionnaire total and impact scores were seen with tiotropium (pv0.01). Tiotropium reduced the number of exacerbations (by 24%, pv0.01), and increased time to first exacerbation (pv0.01) and time to first hospitalization for a COPD exacerbation (pv0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments.Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.

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Compared with placebo, 6 µg formoterol b.i.d. was found to be the lowest effective dose in the morning (p=0.008) and evening (p=0.0041) PEF. The mean increases in PEF were 22 and 23 L·min -1 respectively, compared with placebo. After 6 µg formoterol, the mean immediate increase in morning PEF was 42 L·min -1 compared to an increase of only 9 L·min -1 after placebo (p<0.0001). All doses produced a statistically significant decrease in asthma symptoms, day and night, and the need for rescue medication at night. All doses were well-tolerated.In conclusion, the lowest effective dose in this study was formoterol Turbuhaler 6 µg b.i.d.

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A double blind, placebo-controlled study of the ventilatory effects of three new beta 1-selective adrenoceptor blockers was carried out in eight asthmatic patients. Measurements were performed before and 2, 3 and 4 h after ingestion of a single oral dose of placebo, atenolol 100 mg, metoprolol 100 mg or acebutolol 400 mg. At each time ventilatory indices and heart rate were assessed before, during and 15 min after an exercise test. The ventilatory indices were re-assessed after challenge with terbutaline 1.5 mg by inhalation. The three beta-blocking agents caused equal falls in exercise heart rate two hours after ingestion, indicating the equipotency of the cardiac effects. The three agents reduced significantly and to the same extent FEV1 and PEFR both before and after exercise. The respiratory indices clearly improved after stimulation with terbutaline. The response to terbutaline was less marked after acebutolol, which may indicate that it has a lower degree of beta 1-selectivity. The beta-blockers did not show any influence on bronchodilatation during exercise, or on exercise-induced bronchospasm.