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.

The efficacy and safety of salmeterol alone was compared with the combination of salmeterol plus ipratropium and with placebo during long-term treatment in patients with stable chronic obstructive pulmonary disease. In addition, the single-dose effect in response to the first dose of treatment was studied over 12 h.The patients (n=144; age 64 7 yrs, forced expiratory volume in one second (FEV1) 44 11% pred) participated in a three-centre double-blind double-placebo parallel group study and were randomized after a run-in period of 2 weeks to receive either salmeterol 50 mg b.i.d., salmeterol 5 mg b.i.d. plus ipratropium 40 mg q.i.d. or placebo for a period of 12 weeks.The single-dose study demonstrated that salmeterol produced a significant increase in FEV1 (peak of 7% pred) and specific airway conductance (sGaw) (maximum of 60% baseline) for $12 h. The combination of salmeterol plus ipratropium elicited a greater bronchodilator response (11% and 94% increases respectively) than salmeterol alone during the first 6 h after inhalation. During treatment there were significant improvements in daytime symptom scores and morning peak expiratory flow in both the salmeterol and the salmeterol plus ipratropium groups (p<0.001), with an associated decrease in the use of rescue salbutamol. Improvements in FEV1 and sGaw were greater in the salmeterol plus ipratropium group than in the patients receiving only salmeterol. Thirty-five patients had an exacerbation; 11 (23%) in the salmeterol group (versus placebo NS), six (13%) in the salmeterol plus ipratropium group (versus placebo p<0.01) and 18 (36%) in the placebo group.In conclusion, in patients with severe stable chronic obstructive pulmonary disease, long-term treatment with either salmeterol alone or salmeterol plus ipratropium is safe and effective. There was added benefit from the combination therapy in terms of improvement in airways obstruction, but not for improvement in symptom control or need for rescue salbutamol. Eur Respir J 2000; 15: 878±885. Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by the presence of airflow obstruction, due to chronic bronchitis or emphysema, and is generally progressive but may be partially reversible [1]. The goals of pharmacotherapy in this disorder are to induce bronchodilation and facilitate expectoration in order to improve symptoms, prevent recurrent exacerbations and so enhance the quality of life [2]. In patients with stable COPD, the spirometric response to bronchodilators such as b 2 -agonists, anticholinergic drugs and methylxanthines is at best very modest. However, even in the absence of significant bronchodilation, an improvement in symptoms and exercise tolerance can be demonstrated [3].Salmeterol xinofoate, a long-acting b 2 -agonist, has been shown in single-dose studies to induce a spirometric improvement over a 12-h period in patients with COPD [4± 6]. In addition, three studies in patients with COPD over periods of 1±3 months have found that treatment with salmet...