Pulmonary Rehabilitation for Moderate COPD (GOLD 2) –Does it Have an Effect?

Abstract

Background: Although pulmonary rehabilitation is an integrated part of standard care in patients with severe COPD, it is uncertain whether those with less severe COPD benefit from such treatment. The aim of the present survey was to evaluate the effect of rehabilitation in patients with moderate COPD and to determine their willingness to participate in rehabilitation. Material and methods: In a single-centre, randomized, placebo-controlled, unblinded clinical trial, participants comprised 61 of 133 referred subjects with moderate COPD. Of the 61 participants, 35 were randomized to receive rehabilitation and 26 subjects to receive standard COPD care from their GP. After randomization 19 subjects dropped out. Results: Effects of physical training were seen during the period of intervention. Compared with those receiving standard GP care, those receiving rehabilitation showed improvements in walking distance and leg strength as well as improvements in quality of life; however, the effect was temporary, and at 18 months’ follow-up there was no significant difference between the groups. Only 61 subjects of the referred group of 133 with moderate COPD accepted the offer of rehabilitation. Conclusion: Although an effect was found of pulmonary rehabilitation in subjects with moderate COPD, it disappeared over 18 months. Only a minority of patients with moderate COPD referred for rehabilitation accepted and completed the treatment offer.

Keywords: :

• Moderate COPD
• pulmonary rehabilitation
• elderly
• 6-minute walk
• health-related quality of life

INTRODUCTION

It is estimated that by the year 2020 Chronic Obstructive Pulmonary Disease (COPD) will be among the leading causes of death worldwide. As such, COPD is an increasing burden on society in both developed and developing countries (1), constituting one of the primary causes of morbidity and mortality worldwide. Smoking is the most important factor in the development of COPD (2), creating a toxic provocation of the mucosal epithelium of the airways (3), leading to a progressive reduction in lung function and decrease of elastic recoil.

Despite extensive smoking cessation campaigns, the number of patients with COPD is increasing, and this is estimated to continue at least until the year 2015.

The standard therapy for patients with signs and symptoms of COPD comprises smoking cessation, pharmaceutical treatment and physical activity. The positive effect of pulmonary rehabilitation (PR) has been documented in symptomatic COPD patients with moderate to very severe COPD and an MRC>3 (1). In this group, pulmonary rehabilitation has been shown to increase exercise capacity, reduce breathlessness and improve health-related quality of life (4).

Pulmonary rehabilitation is also extensively used for patients with mild-to-moderate COPD and an MRC < 3; however, its effect in this group is unclear and scientific documentation of any benefit is lacking (5).

Our aim of the present study was to investigate in a randomized clinical setting the short- and long-term effects of a 7-week pulmonary rehabilitation programme on exercise capacity and health-related quality of life in subjects with moderate COPD.

Figure 1  Study schematic of the patient flow.

MATERIALS AND METHODS

Study design

We conducted a single-centre, randomized, placebo-controlled, unblinded clinical trial to evaluate the effect of pulmonary rehabilitation in subjects with moderate COPD. Based on referrals from 56 general practitioners, 133 subjects with moderate COPD were considered for a 7-week pulmonary rehabilitation programme and an 18-month follow-up survey. Subjects were recruited March 2008 –June 2009.

Subjects were randomized 1:1 to pulmonary rehabilitation or control. Randomization was performed using sealed opaque envelopes randomly assigned to the participants. Control was standard community-care undertaken by the subjects’ GPs. The control persons were not to undergo a rehabilitation program during the study (Figure 1). An experienced COPD nurse performed interviews and assessments. All information was recorded on paper charts and subsequently entered into a computerized database.

The study was approved by the regional ethics committee and performed according to the Helsinki Declaration. All participants received written and oral information and signed informed consent agreements. The trial was assigned NCT01320930 at clinicaltrials.gov.

Population

The study was a randomized clinical trial with patients aged 65 years + listed with 56 GPs in Copenhagen. Patients diagnosed with moderate COPD were eligible for pulmonary rehabilitation (6).

• Inclusion criteria: 1) A diagnosis of moderate COPD, FEV1/FVC<0.7 and 50%≤FEV1<80%. 2) Motivation for pulmonary rehabilitation.

• Exclusion criteria: 1) Co-morbidity contraindicating rehabilitation; 2) Participation in pulmonary rehabilitation within the last year; 3) Cognitive disorders limiting the ability to participate in physical training and educational sessions.

Study protocol

The pulmonary rehabilitation programme was in accordance with the standard programme suggested by Lange et al. (7) being an adapted version of the short-term outpatient rehabilitation programme developed by Singh (8). A follow-up and maintenance programme was constructed to preserve the effect of rehabilitation (9, 10).

Pulmonary rehabilitation

The rehabilitation offered by the Health Care Centre consisted of 4 elements: (Figure 1).

1. A preliminary motivational personal interview, V1.

2. An intensive 7-week physical training and educational phase led by a multidisciplinary team starting within 1 month of V1.

3. A final interview following completion of the intensive program, V2 (6 months after V1 for subjects in the control group).

4. Follow-up, V3 at 12 months after V1 and V4 at 18 months after V1.

Preliminary interview, V1

The preliminary interview was a motivational interview to establish the individual goals of the participants (11).

Physical exercise and education

Physical training took place in groups of 10−12 participants with two 90-min sessions a week; the educational sessions were held once a week in groups of 8−10. Training consisted of endurance training, static circuit training, free brisk walking and breathing techniques. The aim was an intensity of 16–17 on a 20 point Borg scale. Compliance with the programme was ensured through follow-up calls after missed sessions. Missed sessions were subsequently replaced. Smoking cessation counselling was given on an individual basis. Dietary intervention consisted of group cookery classes and individual sessions. Smoking cessation and dietary intervention was on an as-needed and voluntary basis.

Final interview, V2

At the final interview the participants’ achievements were compared to their original goals. All participants were encouraged to take up training on a regular basis to maintain the results.

Follow-up/maintenance programme

The maintenance programme lasted for 6 months following the intensive phase of PR. It included a 90-min monthly session focusing on ways of incorporating exercise in daily life. Two sessions focused on exercise activities in the local community; another two sessions on home exercise and the last two sessions on exercise as well as on repetition of relevant topics based on the needs of the participants.

During V1 the subjects completed pulmonary function tests, exercise tests and responded to a Quality-of-Life questionnaire. Randomization took place at the end of V1. Subjects undertaking pulmonary rehabilitation were reassessed at V2, at the end of rehabilitation, and at 12 and 18 months. Subjects in the control group where reassessed at 6, 12 and 18 months. All subjects completed lung function measurements, exercise tests, and a health-related quality of life questionnaire at all follow-up visits.

MEASUREMENTS

Lung function

Spirometric measurements were taken by an experienced technician according to American Thoracic Society (ATS) recommendations using an EasyOne® spirometer (12).

Exercise

Exercise capacity was determined by recording the longest distance walked in one 6MWT (13). Subjects also did the Sit-to-Stand test. The number of repetitions in 30 seconds was recorded (14).

Dyspnoea

The level of dyspnoea was assessed by the MRC scale (15) and by the 10-point BORG scale following the 6-Minute Walk (16).

Health-related quality of life

Health-related quality of life was assessed using the St. George Respiratory Questionnaire (SGRQ) (17).

Statistics

The data were analyzed with the statistical program SPSS version 19.0. Results are expressed as mean ± standard deviations (SD). The effect of pulmonary rehabilitation on exercise capacity was assessed by the 6-Minute Walk and the Sit-to-Stand test. Health-related quality of life was assessed by the St. George Respiratory questionnaire. The short-term effect from V1 to V2 was assessed through a paired t-test and the long-term effect by an ANOVA for repeated measurements for V1, V2, V3 and V4. A two-sample t-test was used to compare the groups at all 4 visits. Values of p < 0.05 were considered significant. A Chi-square test was used to compare the improvements in SGRQ scores.

RESULTS

Baseline

The randomized trial comprised 61 subjects diagnosed with moderate COPD: 35 subjects entered the rehabilitation group with 22 completing the intensive phase of pulmonary rehabilitation; 26 entered the control group with 6 subjects dropping out after randomization (Figure 2). The characteristics of the subjects in the rehabilitation group and the control group are comparable in all areas except FEV₁/FVC (Table 1). We found no significant differences in baseline characteristics between the dropouts and the subjects completing the scheduled programmes (Table 2).

Figure 2  Consort flow chart.

Table 1  Baseline characteristics of the subjects receiving rehabilitation and the control group

	Intervention	Control	p-value
Total treated(n)	22	20
Age(range)	74.1(66–82)	73.2(67–88)	0.6
Female(n)	15	13	0.83
Single(n)	14	11	0.57
BMI	25.56 ± 4.19	26.42 ± 3.89	0.50
FEV1(l)	1.43 ± 0.32	1.57 ± 0.41	0.24
FEV1%	64.27 ± 7.9	67.05 ± 8.8
FEV1/FVC	0.54 ± 0.07	0.6 ± 0.1	0.03
FVC(l)	2.71 ± 0.80	2.68 ± 0.79	0.91
MRC	1.91 ± 0.9	2.0 ± 1.0	0.75
Sit-to-Stand(rep)	13.5 ± 4	12.7 ± 3	0.50
6MW(meters)	392.91 ± 80.77	402.00 ± 80.51	0.72
SGRQ(total)	27.35 ± 17.32	25.75 ± 13.84	0.75
Smokers(n)	11	9
Former smokers(n)	10	10	0.57
Never smokers(n)	1	1
Pack-years	36.95 ± 27.01	44.74 ± 19.90	0.30
BORG	2.7 ± 1.76	3.0 ± 2.26	0.61

Data are presented as mean ± SD. Rep denominates repetitions.

Table 2  Baseline characteristics of the subjects dropping out compared to those participating

	Dropouts	Active	p-value
Total treated(n)	19	42
Age(range)	75.7(66–87)	73.6(66–88)	0.26
Female(n)	10	13	0.39
Single(n)	16	25	0.08
BMI	26.3 ± 4.6	26.0 ± 4.0	0.80
FEV1(l)	1.70 ± 0.5	1.49 ± 0.4	0.14
FEV1%	75 ± 20	65 ± 8
FEV1/FVC	0.62 ± 0.1	0.57 ± 0.1	0.11
FVC(l)	2.79 ± 0.9	2.69 ± 0.8	0.68
MRC	2.16 ± 0.8	1.95 ± 0.9	0.39
Sit-to-Stand(rep)	11.7 ± 3	13.1 ± 3	0.13
6MW(meters)	367.5 ± 88	397.2 ± 80	0.21
SGRQ(total)	25.25 ± 15	26.51 ± 15	0.78
Smokers(n)	6	20
Former smokers(n)	13	20	0.25
Never smokers(n)	0	2
Pack-years	47.8 ± 23	40.7 ± 24	0.28
BORG	2.84 ± 1.6	2.86 ± 2.0	0.98

Data are presented as mean ± SD. Rep denominates repetitions.

Table 3  Exercise capacity assessed by the 6-minute walk, the Sit-to-Stand test and Borg Dyspnea scale

		Short-term				Long-term
		Visit 1	n	Visit 2	n	Visit 3	n	Visit 4	n
6MWT(m,SD)	Intervention	392.91(81)	22	442.29(94)	21	477.63(154)	19	430.69(124)	16
	Control	402.0(80.5)	20	405.8(81)	20	439.4(74)	19	416.06(99)	18
Unpaired t-test		0.72		0.19		0.74		0.71
STS(rep,SD)	Intervention	13.5(4)	22	15.6(5)	21	16.1(5)	18	16.3(6)	16
	Control	12.7(3)	20	13.3(4)	20	13.7(3)	19	14.1(4)	18
Unpaired t-test		0.51		0.13		0.08		0.21
Borg(score,SD)	Intervention	2.7(1.8)	22	3.0(2.4)	19	3.8(2.0)	17	3.2(1.8)	16
	Control	3.0(2.3)	20	2.3(1.4)	20	3.2(1.4)	19	2.8(1.5)	18
Unpaired t-test		0.61		0.26		0.3		0.49

STS denominates Sit-to-Stand test.

Exercise capacity

During the intensive phase of rehabilitation walking distance for the intervention group increased by 46.3 m (p < 0.001) and by 3.8 m (p = 0.7) for the control group (Table 3), being statistically significant (p < 0.01). No statistically significant differences between the intervention and control group were found at V3 and V4. The overall effect of pulmonary rehabilitation in subjects with moderate COPD assessed by the 6-MWT showed a significant short-term improvement in the intervention group but no significant long-term effect when compared with the subjects receiving conventional care.

Additionally, the intervention group showed an increase in mean repetitions of 2.1 in the Sit-to-Stand test (p < 0.01), which was maintained throughout the follow-up. For the control group there was no significant improvement in repetitions (Table 3). No differences in mean ratings of breathlessness (Borg Scale after 6MWT) were found at any time between the two groups (p = 0.8)(Table 3).

Table 4  St. George Respiratory Questionnaire results

		V1	n	V2	n	V3	n	V4	n
	Symptom	34.88(19.4)	20	31.74(20.7)	21	34.70(20.8)	19	38.80(18.5)	16
Intervention	Activity	38.51(24.4)	21	39.80(24.0)	18	41.83(24.8)	19	37.90(28.4)	16
	Impact	15.93(14.1)	20	11.16(12.8)	18	14.39(12.0)	18	15.19(14.3)	15
	Total	27.35(17.3)	18	22.15(14.2)	17	27.03(14.8)	18	26.88(17.8)	15
	Symptom	35.13(22.0)	20	31.50(18.6)	20	28.80(17.9)	20	24.55(19.9)	18
Control	Activity	45.20(21.7)	20	42.98(23.2)	19	38.84(23.0)	20	37.98(22.6)	17
	Impact	11.40(12.3)	20	11.32(8.7)	20	11.87(13.2)	20	8.40(6.4)	17
	Total	25.75(13.8)	20	26.17(11.3)	18	23.06(13.2)	20	19.82(11.0)	17

Quality of Life

The effect of pulmonary rehabilitation on health-related quality of life was assessed using the St. George Respiratory Questionnaire. The two groups were comparable at baseline on the measures of the questionnaire, impact, activity, symptom and total score. For short-term effects, there was no statistically significant change in the intervention group or the control group from V1 to V2 (Table 4). From V1 to V2 we found a change in total score of 6.4(±11.3) for the intervention group, which is more than the generally accepted minimal clinically important difference (MCID) of 4 (18). In the intervention group, 8 subjects improved their total score by more than 4, compared to 9 subjects in the control group (p = 0.73).

In the control group there was no change in SGRQ score at 6 months (p = 0.77). The long-term effect of pulmonary intervention was not significant considering the total score or the component scores of symptoms, activity or impact. However, for the control group the situation was the reverse, as there was a constant improvement in SGRQ score, and the result at 18 months’ follow-up was considerably, but not significantly better, than for the intervention group. The overall effect of pulmonary rehabilitation on health-related quality of life assessed by the St. George Respiratory Questionnaire was not significant (p = 0.14). In those who underwent intervention, 5 maintained an improvement in SGRQ score > 4 compared with 6 in the control group (p = 1.0).

Drop-out

Based on referrals 133 subjects were considered for participation, of whom 72 subjects were not randomized primarily due to lack of motivation and co-morbidities; 61 were randomized: 35 to pulmonary rehabilitation, and 26 to continue the follow-up period with their GP. Between V1 and V2, 13 subjects in the rehabilitation group dropped out with the main reasons being lack of motivation, co-morbidities and others (Figure 2), and at visit 2, 6 patients in the control group declined to attend the healthcare centre for their individual evaluation of level of exercise capacity and quality of life. These findings indicate a dropout rate for rehabilitation in patients with moderate COPD of 39% and 23%, respectively.

DISCUSSION

Within this group of subjects, with newly diagnosed moderate COPD, increased physical capacity during the intensive training phase of pulmonary rehabilitation was demonstrated. Nevertheless, the major finding was that subjects with newly diagnosed moderate COPD are overall unwilling to participate in systematic rehabilitation organised and developed for symptomatic patients with severe disease.

It is generally accepted that pulmonary rehabilitation with exercise training improves exercise capacity and quality of life and reduces dyspnoea during exertion in patients with COPD (19). However, the data supporting this statement are primarily based on patients with severe and very severe COPD. The documentation on the effect of rehabilitation in patients with moderate COPD is limited and contradictory results have been reported (5).

Our results raise two main questions—Does PR benefit exercise capacity and health-related quality of life? And should the relevance of the programme be questioned because of the large number of dropouts both before and during pulmonary rehabilitation? Our results are limited and somewhat contradictory regarding the effect of PR by exercise capacity and health-related quality of life.

The physical tests showed a significant short-term effect of PR on walking distance, estimated by the 6MWT and on leg strength estimated by the Sit-to-Stand test. The improvements were maintained during the 18 months’ follow-up. However, for the control group, an equal improvement was observed in the 6MWT over time, which was also maintained throughout the follow-up. In a large, not randomized, study exploring the effect of rehabilitation for subjects with MRC = 2, Man et al. documents increased walking distance and less dyspnoea at a level similar to subjects with an MRC score of 3 and 4 (20). This contradicts the findings of the Dutch INTERCOM programme in which an intervention group and a comparable control group showed a decrease over time in the 6MWT, however, less so for the intervention group (21).

The improvements in our control group suggest that the increased focus on COPD through interviews and testing has a comparable effect on physical performance. These results are in accordance with previous results on pulmonary rehabilitation for subjects with mild-to-moderate COPD (22, 23).

For health-related quality of life, we found no significant differences between subjects in the PR group and the control group at baseline and at the end of follow-up, estimated through SGRQ. Neither did we find any significant improvement in the group of subjects undergoing rehabilitation regarding health-related quality of life. This supports a previous finding by Ringbaek (24) but is in contrast to the INTERCOM study where the SGRQ score of subjects undergoing intervention remained stable over a two-year period, yet it deteriorated for the subjects receiving usual care. The improvement in exercise capacity is unrelated to improvement in quality of life, and despite an initial improvement in SGRQ, the final outcome is higher than at baseline. The baseline SGRQ scores of the subjects in the intervention and the control group were comparable but seemed to differ from peers not having COPD (25, 26).

Our data thus support the notion that physical training improves walking distance and leg effort at the Sit-to-Stand test in patients with respiratory disease, independent of severity. Nonetheless, the mere focus on the disease through interviews and testing might motivate individuals to increase physical activity in their daily life and thereby improve their overall well-being (27). The improvements seen following pulmonary rehabilitation can be maintained only if physical activity becomes part of the subject's everyday life (28). However, quality of life was unchanged throughout the entire period and the present study indicates that for subjects with limited daily symptoms health-related quality of life is not affected by participating in a pulmonary rehabilitation programme.

The present study had many dropouts (72) before randomization, at randomization and during rehabilitation. Similar results have been reported in a review describing how 75% of patients suitable for PR programmes were omitted due to sampling exclusion and drop-out with the main reasons being 1) disease-related and 2) other reasons including lack of time, motivation or cooperation (29).

These findings correspond with the results of the present study, and there seems to be a mismatch between the pulmonary rehabilitation programme offered and the needs of the subjects. The subjects in question were patients with moderate COPD and limited symptoms in their everyday life, supported by the average MRC scores of 2 and a tendency towards low scores on the SGRQ. It could be that enrolling in a pulmonary rehabilitation programme contributed to directing disproportionate attention on COPD in subjects not feeling unwell beforehand but merely wanting to optimize their health.

Garrod et al. (30) documented the opposite in a study to identify prognostic features of a significant effect of rehabilitation. One such feature is low MRC 1−2, in subjects with moderate COPD and a mean FEV₁ of 65% of predicted and as such comparable to our subjects. The different results may be due to variations within the programmes, with particular emphasis on the educational sessions. Early intervention seems obvious but not at the expense of the participants’ quality of life. Our results indicate that the needs of the individuals are not sufficiently taken into account, despite wishing to do so.

Two kinds of dropouts are identified—more than half of the subjects referred by their GP dropped out before the preliminary interview, indicating a gap between the expectations of the GPs, the subjects and those in care of the rehabilitation program. Roughly a third of the subjects completing the preliminary interview did not complete the intensive phase of pulmonary rehabilitation—the main reasons being lack of motivation, lack of benefits and competing illness.

These findings are in accordance with several other studies—finding discrepancies between the target population of the pulmonary rehabilitation programs and the actual outcome. It has been shown that the approach of the referring GP has a certain impact on the outcome of the patients (31), this has not been explored further in this study but the extensive drop-out before the preliminary interview suggests that this could be a point of interest.

CONCLUSIONS

The effect of pulmonary rehabilitation in patients with moderate COPD is limited to an initial improvement in walking distance at the end of the intensive phase of rehabilitation. However, despite efforts to maintain the improvement through maintenance and follow-up, the results at 12 and 18 months’ follow-up are comparable to the results of a control group receiving community care.

The contradictory results of programmes for this group of patients with less severe dyspnea indicates a need to tailor PR to the groups of patients with varying needs with the main target being incorporation of physical activity in the everyday life of the patients. One way of achieving this could be more specific criteria when including patients in rehabilitation. However, there may be other ways to meet the needs of the patients with COPD.

A certain amount of physical activity is one of the general health recommendations, so is smoking cessation, and medical treatment is the responsibility of the GP for those in need. It seems plausible that the resources are better spent on pulmonary rehabilitation for subjects with severe and very severe COPD, although it may be that the care of subjects with moderate disease should be managed primarily by the GPs.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.