Interval versus Continuous High-Intensity Exercise in Chronic Obstructive Pulmonary Disease

Context Exercise training improves quality of life in patients with chronic obstructive pulmonary disease, but many of these patients cannot tolerate continuous exercise. The effects of intermittent exercise are not known. Contribution The authors randomly assigned 100 inpatients with chronic obstructive pulmonary disease in a 3-week respiratory rehabilitation program to receive either high-intensity continuous exercise or high-intensity exercise alternating with low-intensity exercise (interval exercise). After 5 weeks, the 2 groups had similar respiratory symptoms in daily activities and 6-minute walking distance, but the interval exercise group adhered better to the exercise protocol. Cautions The study focused on initiation of exercise and not on outpatient or home-based maintenance of exercise. Implications For pulmonary rehabilitation, interval exercise is as effective as continuous high-intensity exercise and is better tolerated. The Editors Low exercise capacity is an important systemic manifestation of advanced chronic obstructive pulmonary disease (COPD) associated with poor health-related quality of life, exacerbations, and death (14). Physical exercise, therefore, represents an important element of COPD management (5, 6). If performed under supervision during respiratory rehabilitation, exercise training improves health-related quality of life and may improve prognosis (79). Dyspnea and leg fatigue limit the ability of patients with COPD to exercise, and patient response to exercise is highly variable (10). It is challenging to find endurable exercise programs that are still effective. Current guidelines recommend endurance exercise at constant and high intensity (70% of maximum exercise capacity) (11, 12). For example, if a patient achieves 100 watts in an incremental exercise test, workload would be set at 70 watts for the entire exercise session of at least 20 minute's duration. Strong evidence from randomized trials shows that patients achieve clinically important improvements of health-related quality of life and exercise capacity with a continuous exercise protocol (1316). However, patients with severe COPD are often unable to tolerate continuous exercise (17), which can be frustrating for them and can limit their long-term adherence to exercise programs. Effective alternatives to continuous exercise are required to offer this important intervention to more patients with COPD. The American Thoracic Society and the European Respiratory Society state, on the basis of 2 randomized trials (18, 19), that interval exercise may be an alternative. The benefits of interval exercise may be similar to those of continuous training, but this method is associated with less dyspnea (11, 12). Although studies indicated that interval exercise is well tolerated (1821), evidence about its effectiveness relative to continuous exercise is inconclusive; previous trials had methodological limitations and were small (22). Because of perceived better tolerability of interval exercise, randomized trials should be explicitly designed to show that interval exercise is no less effective (clinical noninferiority) (22). Thus, the aim of our trial was to assess whether interval exercise is no less effective than high-intensity continuous exercise in patients with severe COPD and whether patient tolerance of the interval exercise protocol is superior to that of continuous exercise. Methods Design Overview We conducted a randomized, controlled noninferiority trial to compare the effects of interval exercise with those of high-intensity continuous exercise in patients with severe COPD. We previously described the detailed study protocol (23) and report this trial following the recommendations of the extended Consolidated Standards of Reporting Trials (CONSORT) statement for noninferiority and equivalence trials (24). Setting The trial took place in a public rehabilitation clinic, Klinik Barmelweid, in Aargau, Switzerland. The ethics committee of the Kantonsspital Aarau, Aargau, Switzerland, approved the study protocol, and all study participants provided written informed consent. Participants We screened patients admitted to the respiratory medicine unit and included consecutive patients following inclusion criteria similar to those of previous respiratory rehabilitation trials (7): COPD as defined by FEV1FVC ratio less than 70% of predicted, FEV1 less than 50% of predicted after bronchodilation corresponding to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III to IV (5), and German as first or daily language. Exclusion criteria included cardiovascular, musculoskeletal, or neurologic disorders that inhibited physical exercise or the performance of exercise tests (6). We also excluded patients who had received a diagnosis of cancer (excluding skin cancer) within the past 2 years and were undergoing treatment. Randomization and Interventions A third party not involved in the execution of the trial (DatInf GmbH, Tuebingen, Germany) provided online central randomization using a computerized minimization procedure, thereby ensuring concealment of randomization (25). Stratification variables were exercise capacity (6-minute walking distance < 300 or 300 meters), the presence of affective disorders (Hospital Anxiety Depression Scale scores < or 8), stability of pulmonary condition (stable or exacerbation within the last 8 weeks), and the need for oxygen at rest (Pao 2< 55 mm Hg or 55 mm Hg). Patients followed an inpatient respiratory rehabilitation of approximately 3 week's duration that included 12 to 15 exercise sessions. On weekdays, patients usually participated in 1 exercise session. Twelve physical therapists worked with an approximately equal number of patients from both treatment groups. Apart from exercise, the rehabilitation program was identical for both groups and included breathing therapy, relaxation therapy, guided walking tours, and patient education (23). At discharge, physiotherapists prescribed home-based exercise for each patient. Patients with cycle ergometers at home were instructed to exercise for at least 20 minutes per day. If no cycle ergometers were available, daily walking, swimming, or stair climbing was prescribed. High-Intensity Continuous Exercise Patients randomly assigned to this intervention exercised on electromagnetically braked cycle ergometers (Ergometrics 900S, Ergoline, Bitz, Germany) with a target workload of 70% or more of maximum exercise capacity (Figure 1). This exercise protocol has been used in earlier respiratory rehabilitation trials (7). To determine maximum exercise capacity, patients pedaled unloaded for 3 minutes at 20 watts to warm up. Then, we used increments of 7.5 watts per minute until patients had to stop because of symptoms or cardiovascular stopping criteria. In each exercise session, patients completed a warm-up period of 2 minutes at 20% of maximum exercise capacity, high-intensity exercise for 20 minutes, and a run-out phase of 2 minutes (gradual decrease from 70% to 0%). If patients could not sustain the workload because of perceived dyspnea (modified Borg [26] ratings> 5 on a scale from 0 to 10) or because heart rate exceeded safety limits, physical therapists let patients rest for 1 minute before continuing in the assigned phase. If patients had to rest more than twice per session, physical therapists lowered the workload by steps of 10% of baseline maximum exercise capacity for the following exercise sessions. If workload was too low (modified Borg ratings< 3 or patients or physical therapists considered the workload to be too low), physical therapists increased the workload by steps of 10% of baseline maximum exercise capacity. Figure 1. Exercise protocols. Interval Exercise The target workload for this group was 50% (high-intensity intervals) and 10% (low-intensity intervals) of short-term maximum exercise capacity as determined by a steep ramp test (27, 28). The steep ramp test is an incremental cycle ergometer test in which patients pedal cycle ergometers unloaded for 2 minutes and then at increments of 25 watts every 10 seconds until they cannot maintain a pedaling frequency above 50 pedals per minute or their heart rate exceeds the limit set by the normal incremental exercise test. We used the steep ramp test because workload for interval exercise can be underestimated if it is based on normal incremental exercise tests (28). Fifty percent of short-term maximum exercise capacity corresponds, on average, to 90% to 100% of normal maximum exercise capacity (27). We chose a workrecovery ratio of 1:2 that prevents high lactate accumulation and is well tolerated by patients (28). In each session, patients had a warm-up period of 2 minutes at 10% of the short-term maximum exercise capacity and then exercised for 20 minutes alternating between high-intensity intervals for 20 seconds and low-intensity intervals for 40 seconds (Figure 1). Patients also had a slowdown period of 2 minutes before completing the training session. We adjusted the exercise load for each patient individually if workload was too high or too low as described earlier; physiotherapists lowered or increased the workload by steps of 10% of short-term maximum exercise capacity, but the length of intervals remained constant (23). Outcomes and Measurements Our primary outcome for effectiveness was the difference from baseline in Chronic Respiratory Questionnaire (CRQ) scores 5 weeks after randomization as measured by the self-administered German-language version (29, 30) with standardized dyspnea questions (31). The CRQ is a widely used instrument in respiratory rehabilitation and measures dyspnea, fatigue, emotional functioning, and ability to cope with COPD (7, 32). Domain and total (average of domains) scores are presented on a Likert-type scale from 1 (most severe impairment) to 7 (no impairment). We selected assessment at 5 weeks after randomization as the primary outcome fo