Tiotropium/olodaterol, with or without ExT, improved EET in patients with COPD taking part in an SMBM program. Combination bronchodilation, with or without ExT, did not provide additional increases in objective PA compared with SMBM alone but did reduce PA-related dyspnea and difficulty. Clinical trial registered with www.clinicaltrials.gov (NCT02085161).

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler. Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).295 and 291 patients were treated in MORACTO 1 and 2, respectively. Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001). Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies. Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.

IntroductionChronic obstructive pulmonary disease (COPD) is associated with exercise limitation and physical inactivity, which are believed to have significant long-term negative health consequences for patients. While a number of COPD treatments and exercise training programmes increase exercise capacity, there is limited evidence for their effects on physical activity levels, with no clear association between exercise capacity and physical activity in clinical trials. Physical activity depends on a number of behaviour, environmental and physiological factors. We describe the design of the PHYSACTO trial, which is investigating the effects of bronchodilators, either alone or with exercise training, in combination with a standardised behaviour-change self-management programme, on exercise capacity and physical activity in patients with COPD. It is hypothesised that bronchodilators in conjunction with a behaviour-change self-management programme will improve physical activity and that this effect will be amplified by the addition of exercise training.Methods and analysisPatients are being recruited from 34 sites in Australia, New Zealand, the USA, Canada and Europe. Patients receiving a multicomponent intervention designed to support behaviour change related to physical activity are randomised to four treatment arms: placebo, tiotropium, tiotropium+olodaterol, and tiotropium+olodaterol+exercise training. The primary outcome is improvement in exercise capacity after 8 weeks, measured by endurance time during a shuttle walk test. The secondary outcome is improvement in physical activity, including objective accelerometer assessment and patient-reported functioning using the Functional Performance Inventory—Short Form and the novel hybrid PROactive instrument. Additionally, the influence of moderating variables (ie, factors influencing a patient's choice to be physically active) on increases in physical activity is also explored.Ethics and disseminationThe study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.Trial registration numberNCT02085161.

IntroductionChronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study.Methods and analysisPHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies.Ethics and disseminationThe study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations.Trial registration numberNCT02085161.

This study explored the impact of a self-management behaviour modification (SMBM) programme with/without bronchodilators and with/without exercise training (ExT) to improve daily physical activity on psychological and cognitive outcomes in COPD patients as a secondary analysis of the PHYSACTO trial.A 12-week, four-group, randomised, partially double-blind, placebo-controlled, parallel-group trial of SMBM in addition to tiotropium 5 µg, tiotropium/olodaterol 5/5 µg, tiotropium/olodaterol 5/5 µg plus ExT, or placebo was conducted in 304 patients. Outcomes included anxiety (Hospital Anxiety and Depression Scale (HADS)-A), depression (HADS-D and Patient-Health Questionnaire (PHQ)-9) and cognitive function (Montreal Cognitive Assessment (MoCA)).All outcomes showed statistically and clinically significant improvements after 12 weeks independent of treatment group. However, greater improvements in HADS-A and MoCA were seen in patients who exhibited greater increases in physical activity and exercise capacity, respectively, whereas greater improvements in HADS-D and PHQ-9 were seen in patients who exhibited increases in either physical activity or exercise capacity.The results indicate that SMBM with/without bronchodilators or ExT was associated with improved psychological and cognitive functioning. Anxiety reduced with increased physical activity, cognitive function improved with increased exercise capacity, and depression reduced with increases in either physical activity or exercise capacity. Interventions that increase daily physical activity or exercise capacity may improve psychological and cognitive outcomes in COPD.