Optimal duration of pulmonary rehabilitation for individuals with chronic obstructive pulmonary disease a systematic review

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1 Original Paper Optimal duration of pulmonary rehabilitation for individuals with chronic obstructive pulmonary disease a systematic review Chronic Respiratory Disease 8(2) ª The Author(s) 2011 Reprints and permission: sagepub.co.uk/journalspermissions.nav DOI: / crd.sagepub.com Marla K Beauchamp 1,2, Tania Janaudis-Ferreira 2, Roger S Goldstein 2,3,4, and Dina Brooks 1,2,3 Abstract The purpose of this review was to determine the impact of duration of pulmonary rehabilitation on measures of health-related quality of life and exercise tolerance in individuals with chronic obstructive pulmonary disease (COPD). Randomized controlled trials (RCTs) comparing different lengths of pulmonary rehabilitation in patients with COPD were identified after searches of six electronic databases (MEDLINE, PubMed, CINAHL, EMBASE, Physiotherapy Evidence Database [PEDro] and the Cochrane Library of clinical trials) and reference lists of pertinent articles. Two reviewers performed the searches and assessed trial quality using PEDro and Jadad scales. Five RCTs met inclusion criteria. The mean PEDro score was 6 (range 3-8) and mean Jadad was 2 (range 1-3). Three trials reported a difference in health-related quality of life in favour of the longer duration program; two trials reported a benefit in exercise capacity in favour of longer programs. A meta-analysis of results was not possible due to considerable heterogeneity in program duration and outcomes. er duration pulmonary rehabilitation programs appear to have a more favourable effect on health-related quality of life in individuals with COPD; results for exercise capacity are less clear. The limited literature prevents a more definitive conclusion on optimal duration of rehabilitation. Keywords chronic obstructive pulmonary disease, rehabilitation, exercise training Introduction Pulmonary rehabilitation (PR) is an accepted non-pharmacological intervention for individuals with chronic obstructive pulmonary disease (COPD). 1 The rehabilitation program provided by a multidisciplinary team typically consists of exercise, disease-specific education, psychological, and social support. There is strong evidence that PR increases exercise tolerance, reduces symptoms, and improves health-related quality of life in patients with COPD. 1,2 However, despite these initial improvements, benefits tend to diminish following completion of the rehabilitation program. 3 5 Lack of adherence to the rehabilitation exercise program is thought to be the main contributor to the diminution of outcomes for patients with COPD. 6,7 This raises questions regarding the most favourable duration of PR to both optimize and maintain benefits in exercise capacity and health-related quality of life. In the literature, PR programs vary from as short as a few weeks 8 to as long as 3 years. 9 Clinical practice 1 Graduate Department of Rehabilitation Science, University of Toronto, Toronto, Ontario, Canada 2 Department of Respiratory Medicine, West Park Healthcare Centre, Toronto, Ontario, Canada 3 Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada 4 Department of Medicine, University of Toronto, Toronto, Ontario, Canada Corresponding author: Dina Brooks, Department of Physical Therapy, University Avenue, Toronto, Ontario M5G 1V7, Canada dina.brooks@utoronto.ca

2 130 Chronic Respiratory Disease 8(2) guidelines from the American College of Chest Physicians (ACCP) state that there is no consensus regarding the optimal duration of pulmonary rehabilitation for patients with COPD. 1 However, the ACCP guidelines recommend programs of longer than 12 weeks in duration to better promote maintenance of benefits over time. Several trials have been conducted to determine if shorter programs are comparable to longer duration programs The purpose of the current article is to systematically summarize the literature comparing different lengths of PR in order to provide recommendations for clinical practice and to inform further research. Methods Search strategy Study identification began with electronic searching of computerized databases (MEDLINE, PubMed, EMBASE, CINAHL, PEDro, and Cochrane) from inception until June, Key terms for the search included: COPD, duration, rehabilitation, length, short, long and exercise. Secondary searches included hand searching reference lists of all identified studies, key author searches and use of the PubMed related articles function. Inclusion criteria Two members of the research team performed the search and assessed the studies (MB and TJ). Initially, titles and abstracts were assessed and then the full texts of relevant studies were retrieved. Only randomized trials comparing different lengths of pulmonary rehabilitation (exercise training with or without education) were considered for inclusion. More than 90% of study participants must have been diagnosed with COPD defined as: (1) a clinical diagnosis of COPD; (2) one of the following, (a) best recorded FEV 1 /FVC ratio < 0.70, (b) best recorded FEV 1 of <80% predicted. The search identified studies of all languages. Specific exclusion criteria comprised: (1) studies evaluating maintenance interventions after pulmonary rehabilitation; and (2) only abstract available with no further information. Quality assessment Two members of the review team (MB and DB) independently assessed the internal validity of the studies and interpretability of the data. The quality assessment was rated according to a 0 to 5 scale suggested by Jadad 15 including items related to randomization, blinding and withdrawals. Each trial was also given a score on the Physiotherapy Evidence Base Database (PEDro) scale. 16 The PEDro scale scores 10 items: random allocation, concealed allocation, similarity at baseline, subject blinding, therapist blinding, assessor blinding, completeness of followup, intention-to-treat analysis, between-group statistical comparisons and point and variability estimates. Items are scored as either present (1) or absent (0) and a score out of 10 is obtained by summation. The scale has been shown to be a valid measure of the methodological quality of clinical trials. 17 Data extraction and analysis Data extraction was performed by one of the investigators (MB) using a standardized form. The results of the studies were summarized according to the effect of length of the rehabilitation program on three main outcomes: measures of exercise capacity, healthrelated quality of life and adherence. A clinically important change was defined as defined as 54 m for the 6-minute walk test, units for the Chronic Respiratory Questionnaire 19 and 47.5 m for the incremental shuttle walking test. 20 Results Search results The study selection process is outlined in Figure 1. The initial search yielded 628 trials; 519 were not related to the study objectives or were duplicate articles. Five studies met inclusion criteria for this review. As the methodology used in these studies was heterogeneous with respect to type of exercise training, program length and outcome measures, a metaanalysis of results was not possible. Quality assessment There was consistent agreement between reviewers for the quality assessment. Study quality ratings based on Jadad and PEDro scales are provided in Table 1. The studies achieved a mean Jadad score of 2 (range 1 to 3) and mean PEDro score of 6 (range 3 to 8). Three trials 10,12,13 reported allocation concealment and blinding of outcome assessors for at least one key outcome, and only one trial 10 provided details about randomization.

3 Beauchamp et al. 131 Results identified by electronic and hand search (n = 628) Title or abstract not related to the research question or repetitive articles (n = 519) Potential articles related to the research question obtained for full-text analysis (n = 10) 5 studies identified for inclusion in systematic review Articles excluded as not meeting the inclusion criteria (n = 5) Reasons for exclusion: 2 inappropriate study type 1 a sub-analysis of a larger trial already included 1 a protocol in Spanish 1 a comparison of different volumes of training with same duration Figure 1. Flow diagram illustrating study selection. Table 1. Quality assessment results Study Description of randomization Allocation concealment Description of withdrawals Blinding of outcome assessors Jadad score PEDro score Green 12 þ/ þ þ þ/ 2/5 8/10 Swerts 14 þ/ þ 1/5 3/10 Sewell 13 þ/ þ þ þ 2/5 7/10 Berry 10 þ þ þ þ 3/5 7/10 Foy 11 þ/ þ 2/5 5/10 þ: requirement fulfilled, : requirement not fulfilled or not reported, þ/ : requirement partially fulfilled. Rehabilitation programs A total of 451 older adults (mean age 69 years) with moderately severe COPD (mean FEV 1 <80% predicted and 30% predicted; FEV 1 /FVC <70%) were randomized to either a short or long duration PR program. Participants were predominately male (range 56% to 88% male). The characteristics of the rehabilitation programs are provided in Table 2. Two studies by the same group 12,13 compared program durations of 4 weeks with 7 weeks, two studies from another group 10,11 compared programs of 3 months with 18 months, and one study 14 compared 8 weeks of PR with 20 weeks. Two studies involved exercise training alone 10,11 and the other three included education sessions Training frequency varied from 2 to 3 times a week. All programs included an aerobic exercise component (walking and/or cycling), and four programs also included strength training. Exercise capacity A measure of exercise capacity (functional walk test, treadmill endurance time, timed stair climb and overhead task) was considered in four 10,12 14 out of the five studies (Table 3). Two trials reported a difference in exercise tolerance favouring the longer duration program. 10,14 Berry et al. 10 found a difference of 30.5 m in 6-minute walk distance (6MWD) and

4 Table 2. Description of Rehabilitation Programs Study Program Duration Frequency of Program Program Component Time Initial Load Home Program Green 12 Short 4 weeks 7 weeks Swerts 14 Short 8 weeks 20 weeks Sewell 13 Short 4 weeks 7 weeks Berry 10 Short 3 months 18 months Foy 11 Short 3 months 18 months 2x/week Education (discussions and practical demos) Short 3x/week for 8weeks 2x/week for 2weeks, 1x/week for 2weeks, and then every other week for the next 8weeks Exercise (walking, mobility and strength) er for Short Group N/A N/A Walking 30 min Self-selected velocity Physiotherapy (breathing techniques, respiratory muscle training, mobilization for spine and shoulder girdle) 30 min N/A N/A N/A Relaxation Therapy 30 min N/A Cycling 15 min Steady state- HR at 50-70% age predicted maximum 2x/week Exercise (alternating aerobic and resistance) Aerobic- walking or cycling Strength- bicep curl, sit to stand, pull ups and steps ups Education (relaxation, disease education, diet, benefits, energy conservation, medications, chest clearance, and breathing control techniques) 1 hr Aerobic- 85% of capacity estimated from ISWT Short group given written instructions to continue the program at home for the remaining 12 weeks Daily walks at home and home strength training twice per week 1 hr N/A Short group given written information on the education sessions 3x/week Aerobic (walking) 30 min RPE 3-4/10 Short group encouraged to exercise at home and told Strength (bicep curls, triceps extension, and shoulder flexion, abduction and elevation) 3x/week Warm-up (slow walking, arm circles, trunk rotations, and shoulder, chest and side stretches) Aerobic min RPE min N/A Strength (bicep curls, triceps extension, and shoulder flexion, abduction and elevation Cool-down 5 min N/A 30 min N/A about YMCA and other nearby centres 5 min N/A Short group encouraged to exercise at home 132

5 Table 3. Outcomes and key findings of primary studies Study Population Comparison Outcomes Significant within subject findings Significant between group findings Green 12 Total 4 wks vs. 7 wks CRQ Not reported. Improvements in CRQ favoured long group (mean difference (95% CI)): n¼44 Short group tested at wks 0 and 4 BPQ -Total CRQ 0.61* (-0.15 to -1.08) Short -Dyspnea 0.80* (-0.13 to -1.48) -Emotion 0.89* (-0.33 to -1.45) n¼23, 67% M group tested at wks 0 and yrs ISWT -Mastery 0.84* (-0.10 to -1.58) FEV L TET n¼21, 61% M 68+9yrs FEV L Swerts 14 Total 8 wks vs. 20 wks 12MWT At 8 wks both groups improved 12MWT: Difference of 60 m in 12MWT in favour of long group y at 26 wks n¼27, 89% M 81m for long group FEV1 33% pred. All participants tested at wks 0, 8, 26, and 52 Dyspnea on VAS 107 m for short group Increase of 92m in 12MWT at 52 wks in long group vs. a 47m decline in short group y Short At wks 26 and 52 the short group showed a decrease (84m and 132m respectively) in 12MWT from wk 8 n¼14 n¼11 (continued) 133

6 Table 3 (continued) Study Population Comparison Outcomes Significant within subject findings Significant between group findings Sewell 13 Total 4 wks vs. 7 wks Primary In short group: Short group had higher ESWT at 7 wks (mean difference 124.6sec (95% CI ) n¼100, 56% M ISWT -56.9m* increase in ISWT from 0 to 4wks and 34.2m increase from 0 to 6 months 70+8yrs Short group tested at wks 0, 4 and 7 and 6 months FEV L group tested at wks 0 and 7 and 6 months sec increase in ESWT from 0 to 4wks; 115 sec increase from 4 to 7wks; sec increase from 0 to 7wks ESWT - Increase of >0.5* in CRQ for dyspnea, emotion and fatigue at wk 4 -Increase of 0.6* from wk 4 to 7 for CRQ mastery Short Secondary -Increase in BPQ at wks 4 and 7 n¼50, CRQ 68+8yrs In long group: FEV L BPQ -52.4m* increase in ISWT from wks 0 to 7 and 28.8m increase from wk 0 to 6-months sec increase in ESWT from wks 0 to 7 and 121 sec increase from wk 0 to 6-months -Increase >0.5* in all domains of CRQ from wks 0 to 7 n¼50, -Increase in BPQ from wks 0 to yrs FEV L No differences btw groups at 7 wks or 6 months in other outcomes (continued) 134

7 Table 3 (continued) Study Population Comparison Outcomes Significant within subject findings Significant between group findings Berry 10 Total 3 months vs. 18 months Primary In short group: Improvements in long compared to short group: n¼140, 56% M 6MWT -6MWT increased 62.4m* from 0 to 3 months and 43.2m from 0 to 9 months All participants tested at months 0, 3, 9, 15 and 18 -walked 30.5m farther on 6MWT [553 (533 to 572) vs. 521 (499 to 543) m] Short Timed stair-climb In long group: -climbed stairs 1.3 sec faster n¼70-6mwt increased 68m* from 0 to 3 months, 71.7m* at 9 months, 65.6m* at 15 months and 67m* at 18 months 67yrs Overhead task FEV 1 59 % pred. Within subject findings not available for other measures. FAST functional performance inventory n¼70 Secondary 68yrs V02 peak from GXT FEV1 58 % pred. PASE [11.6 (11 to 12.2) vs (12.3 to 13.5) sec] -12% less disability [1.53 (1.43 to 1.63) vs (1.61 to 1.81)]. Compliance (continued) 135

8 Table 3 (continued) Study Population Comparison Outcomes Significant within subject findings Significant between group findings Foy 11 Total 3 months vs. 18 months CRQ At 3 months all participants improved CRQ scores from baseline: Improvements in long compared to short group at 18 months: n¼140, 56%M -Dyspnea 0.65* -CRQ dyspnea 0.47 Attendance -Fatigue 0.55* -CRQ fatigue 0.53* All participants tested at months 0, 3, and 18 Short -Emotion CRQ emotion Mastery CRQ mastery 0.26 n ¼ 70 Percentage of peak HR from GXT 67+6yrs FEV 1 59 % pred. Moderated by gender: men in long vs. short group showed better scores in all domains of CRQ at 18 months but no difference for women in any subscale n¼ yr FEV1 58% pred. 136

9 Beauchamp et al seconds on a stair climb test in favour of the 18- month group versus the 3-month group. Similarly, Swerts et al. 14 reported a difference of 60 m in the 12MWD in favour of a 20-week versus an 8-week program. In this study at 1-year follow-up, the authors noted a persistent increase in12mwd (92 m) in the 20-week group compared to a deterioration of 47 m in the 8-week group. In the two trials of shorter duration programs (< 12 weeks), one trial 13 reported a higher endurance shuttle walk test performance (124.6 sec) in patients randomized to a 4-week program versus 7 weeks at 7 weeks follow-up, but at 6 months there was no difference between groups. Finally, one study 12 reported no difference in exercise tolerance (incremental shuttle walk test) in a 4-week versus a 7-week program. Health-related quality of life A measure of health status or disability was considered in four studies (Table 3) Three studies used the Chronic Respiratory Questionnaire (CRQ), two studies 12,13 used the Breathing Problems Questionnaire (BPQ) and one study 10 used the Fitness Arthritis and Seniors Trial functional performance inventory. Three trials reported a difference in health-related quality of life in favour of the longer duration program. Green et al. 12 found a significant and clinically important difference in all domains of the CRQ in favour of the 7-week group compared to the 4-week group; Berry et al. 10 noted 12% less disability in the 18-month group versus the 3-month group and Foy et al. 11 found significantly better scores for all domains of the CRQ in the 18-month group compared to the 3-month group. In the latter study, it was found that men in the longer duration group showed significantly better scores for the CRQ in all domains compared to the shorter duration group, whereas no differences between groups were found among women. One study 13 showed no difference in health status between patients randomized to 4 versus 7 weeks of rehabilitation with both groups showing a significant decline in health-related quality of life at 6 months. Adherence to exercise Only two studies 10,11 reported attendance rates with no difference noted between groups. Swerts and colleagues 14 reported adherence to a home exercise program in all patients in the long duration group, compared to only three patients in the short program. Physical activity in daily life was only measured in one study 10 using a questionnaire. The authors noted no differences in physical activity in the 3 month versus the 18 month group. No study reported any difference in withdrawals between groups or adverse events. Discussion The results of this review suggest that longer duration PR programs have a more favourable effect on health-related quality of life in individuals with COPD; however, the impact of duration of PR on exercise capacity remains unclear. Findings also indicate that (1) the duration of rehabilitation may not impact all outcomes equally and (2) patient-related factors such as gender may modify the effect of duration on outcomes following rehabilitation. In three of four studies that considered healthrelated quality of life, results favoured longer duration programs. Consistent with these findings, a recent investigation of the duration of PR required to achieve a plateau in quality of life in patients with COPD found that at least 8 weeks (24 sessions) were required before scores on the CRQ stabilized. 21 Of interest, in the study by Foy and colleagues, 11 long-term (18-month) PR conferred significant additional benefits in quality of life scores in men, but only modest effects in women compared to the 3-month program. In this study, women tended to have dramatic increases in quality of life in the first 3 months, whereas men required the full 18 months to achieve similar clinically significant gains. These results add to the growing body of evidence on gender differences in the presentation and course of COPD Of the four studies that evaluated exercise capacity, only two trials 10,14 found that exercise tolerance was improved in the longer duration program. Of note, the two studies 12,13 with equivocal results were comparisons of short duration programs (<8 weeks) and included a small number of sessions. The long duration training group performed only 14 sessions of exercise training which is considerably less than the 28 session threshold suggested to induce greater training effects in patients with COPD. 26 Importantly, while Sewell et al. 13 reported clinically important improvements in exercise tolerance after just 4 weeks of exercise, at 6 months the change from baseline did not approach the minimal clinically important difference for either group. In contrast, maintenance of gains in exercise tolerance was noted at 1-year

10 138 Chronic Respiratory Disease 8(2) follow-up for the 20-week training group (34 sessions) in the study of 20 versus 8 weeks by Swerts and colleagues. 14 Other reports evaluating long-term (>6 month) PR programs have demonstrated persistent and clinically relevant changes in exercise tolerance at 1 year 27 and 18 months 28 post training. Therefore, while it is possible to produce training effects from short programs, longer duration PR programs are likely necessary to promote long-term maintenance of exercise capacity. The American College of Sports Medicine guidelines for exercise in older adults recommend 16 weeks of supervised aerobic exercise training to induce training adaptations (grade A evidence). 29 It has also been suggested that 15 to 20 weeks is the minimum length for studies evaluating the efficacy of various intensities, frequencies and duration of exercise on fitness parameters. 30 In contrast, current guidelines for COPD recommend 12 weeks or more of PR, although there is little evidence (grade 2C) to support this recommendation. 1 Further randomized controlled trials are needed to elucidate the optimal duration and frequency of PR. A primary goal of PR should be to increase physical activity and adherence to exercise in daily life 26 ; however, this outcome was only assessed in two trials 10,14 using indirect methods. Swerts and colleagues 14 noted greater self-reported adherence to a home exercise program in the long group, while Berry et al. 10 reported no between-group differences in physical activity assessed by a questionnaire. Although, in this latter study, patients in the long duration group were instructed not to include the supervised PR sessions in their questionnaires. 10 Of note, a recent study showed that while exercise performance and health-related quality of life improved after 3 months of PR, the changes in physical activities in daily life as measured by an activity monitor were limited to an improvement in movement intensity during walking. 31 Improvement in the time spent walking was only obtained after 6 months of structured rehabilitation. This study underscores the importance of longer programs to effectively increase physical activity levels in patients with COPD. Given that effective PR requires complex behavioural changes, a patient s self-efficacy and compliance may be facilitated by longer exposure to rehabilitation interventions. The main limitations of this review are the small number of studies that met our inclusion criteria and the methodological shortcomings of these studies. An important step in conducting a systematic review is to assess the likelihood of the included trials to generate unbiased results that are sufficiently precise to allow for application to clinical practice. 32 The PEDro and Jadad scales help the reader determine whether a study is internally valid and whether the statistical information provided is adequate for the results to be interpretable. 16,33 In this review, the overall study quality was fair to moderate, highlighting the need for further well-designed trials in this area. In addition, there was considerable clinical heterogeneity with respect to the durations of PR and outcome measures in the primary studies. Conclusions based on comparisons of studies with different durations, performed in different centres with considerable differences in program content and intensity of training must be interpreted with caution. Finally, burden to the patient and cost-effectiveness are also important considerations for future work weighing the benefits versus costs of longer programs. In summary, the findings of this review suggest that longer duration PR programs have more favourable effects on health-related quality of life in individuals with COPD; results for exercise capacity are less clear. The small number of trials limits more definitive conclusions regarding optimal duration of PR for maintaining outcomes and promoting long-term exercise adherence. Issues of setting, training volume and gender warrant further investigation for their potential to influence the impact of duration on outcomes after PR. Funding Dina Brooks is supported by a Canada Research Chair; Marla Beauchamp by the Canadian Institutes of Health Research; and Roger Goldstein by the University of Toronto National Sanitarium Association Chair in Respiratory Rehabilitation Research. References 1. Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary rehabilitation: Joint accp/aacvpr evidence-based clinical practice guidelines. Chest 2007; 131: 4S 42S. 2. Lacasse Y, Martin S, Lasserson TJ, and Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A cochrane systematic review. Eura Medicophys 2007; 43: Foglio K, Bianchi L, Bruletti G, Battista L, Pagani M, and Ambrosino N. -term effectiveness of pulmonary rehabilitation in patients with chronic airway obstruction. Eur Respir J 1999; 13:

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