Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Assessing the Impact of Tiotropium on Lung Function and Physical Activity in GOLD Stage II COPD Patients who are Naïve to Maintenance Respiratory Therapy: A Study Protocol.
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 18 microg once daily (n=356) compared with ipratropium 40 microg 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 (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) 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. Physical activity status is increasingly recognized as a reliable predictor of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). The reduction in physical activity occurs earlier in the clinical course of COPD than previously appreciated, possibly arising from breathlessness, reduced exercise tolerance, and adoption of a more sedentary lifestyle. To date, no clinical trial has evaluated the impact of pharmacotherapy on both lung function and physical activity. We recently designed a study that evaluates the impact of tiotropium (a once-daily inhaled anticholinergic) on lung function and physical activity in a maintenance/treatment-naïve Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II COPD cohort. Previous studies have demonstrated that tiotropium improves lung function and exercise tolerance; whether these benefits translate into improvements in physical activity is the focus of the current work. Here we describe the rationale and challenges in developing and implementing this study and review its unique features and novel design, including: utility of direct activity monitoring in multicenter clinical trials; importance of behavioral-modification techniques (including motivational interviewing to improve patient self-efficacy and adherence for a healthy, more active lifestyle); utility of individualized activity plans that provide an integrated approach with pharmacotherapy and behavioral modification to help patients achieve a more active lifestyle.
To date there is uncertainty regarding the long-term benefits and risks of treatment with tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy on mortality, hospitalisation, exacerbations of COPD and pneumonia. The addition of combination treatment to tiotropium has shown improvements in average health-related quality of life and lung function.