Cite this article as: BMJ, doi:10.1136/bmj.38258.662720.3A (published 25 October 2004) Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study William D-C Man, Michael I Polkey, Nora Donaldson, Barry J Gray, John Moxham Abstract
NHS) but also to real improvements in quality of life andfunctional ability in breathless and vulnerable patients with
Objective To evaluate the effects of an early community based
pulmonary rehabilitation programme after hospitalisation for
Pulmonary rehabilitation is a multidisciplinary programme
acute exacerbations of chronic obstructive pulmonary disease
of care for patients with chronic respiratory impairment that is
individually tailored and designed to optimise each patient’s
Design A single centre, randomised controlled trial.
physical and social performance and autonomy. Pulmonary
Setting An inner city, secondary and tertiary care hospital in
rehabilitation leads to statistically significant and clinically mean-
ingful improvements in health related quality of life, functional
Participants 42 patients admitted with an acute exacerbation of
exercise capacity, and maximum exercise capacity in patients
with stable COPD.3 4 Consequently, the recent guidelines on the
Intervention An eight week, pulmonary rehabilitation
management of COPD published by the National Institute for
programme for outpatients, started within 10 days of hospital
Clinical Excellence (NICE) and the British Thoracic Society rec-
ommend that pulmonary rehabilitation should be made
Main outcome measures Incremental shuttle walk distance,
available to all appropriate patients.5 However, the effects of early
disease specific health status (St George’s respiratory
pulmonary rehabilitation of outpatients in the acute recovery
questionnaire, SGRQ; chronic respiratory questionnaire, CRQ)
phase after hospital admission for acute exacerbations of COPD
and generic health status (medical outcomes short form 36
have not previously been studied. Patients are particularly
questionnaire, SF-36) at three months after hospital discharge.
vulnerable after a hospital admission, and we assumed that early
Results Early pulmonary rehabilitation, compared with usual
pulmonary rehabilitation of outpatients would lead to notable
care, led to significant improvements in median incremental
improvements in exercise capacity and health status, as it does in
shuttle walk distance (60 metres, 95% confidence interval 26.6
metres to 93.4 metres, P = 0.0002), mean SGRQ total score
We assessed the feasibility and safety of an early pulmonary
( − 12.7, − 5.0 to − 20.3, P = 0.002), all four domains of the CRQ
rehabilitation programme for outpatients and determined the
(dyspnoea 5.5, 2.0 to 9.0, P = 0.003; fatigue 5.3, 1.9 to 8.8,
effects on exercise capacity and quality of life, compared with
P = 0.004; emotion 8.7, 2.4 to 15.0, P = 0.008; and mastery 7.5,
usual care, at three months after a hospital admission for acute
4.2 to 10.7, P < 0.001) and the mental component score of the
SF-36 (20.1, 3.3 to 36.8, P = 0.02). Improvements in the physicalcomponent score of the SF-36 did not reach significance (10.6,
Conclusion Early pulmonary rehabilitation after admission to Patients
hospital for acute exacerbations of COPD is safe and leads to
We recruited 42 patients admitted to King’s College Hospital in
statistically and clinically significant improvements in exercise
London with a primary diagnosis of acute exacerbation of
capacity and health status at three months.
COPD. All were deemed sufficiently unwell by the duty medicalregistrar to warrant admission to hospital. Exclusion criteriaincluded comorbidity that could limit exercise training. In addi-
Introduction
tion, to allow for a suitable washout period, we also excluded
Admissions to hospital for acute exacerbations of chronic
patients who had attended a pulmonary rehabilitation
obstructive pulmonary disease (COPD) are a massive burden to
programme in the preceding year. All patients gave written
the NHS. Over the past decade, such admissions have increased
by 50%, and annual hospital costs for COPD in the United King-dom amount to more than £587m ($1.05bn;€850m).1 Exacerba-
Protocol
tions are also associated with impaired quality of life, reduced
All admitted patients received standard treatment, including
exercise capacity, and increased risk of readmission.2 Interven-
nebulised bronchodilators, oxygen, oral or intravenous antibiot-
tions designed to hasten recovery and improve symptoms afteradmission to hospital may lead not only to reduced use of health
The CONSORT checklist of items to include when reporting a randomised
care in the future (and subsequent economic benefits to the
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on self management of the disease, nutrition, and lifestyle issues). Table 1 Patients’ characteristics on day of hospital discharge. Values are
Respiratory physiotherapists and nurses supervised the exercise
means with standard deviations unless otherwise indicated
component, as did health centre based fitness instructors. Physi-
Usual care group (n=21) Rehabilitation group (n=21)
otherapists, respiratory nurses, an occupational therapist, a dieti-
cian, a respiratory doctor, a smoking cessation adviser, a social
worker, a pharmacist, and a lay member of a patients’ group
supervised education activities on a rolling rota. Patients also
received individualised home exercise programmes, which
encouraged at least 20 minutes of exercise per day. Assessment of outcome
We reassessed primary outcome measures (exercise capacity and
Unpaired t tests were used for comparisons between groups.
disease specific and generic health status) at three months afterhospital discharge. In addition, we recorded secondary outcome
ics, non-invasive ventilation (if required), and a one to two week
measures of use of hospital resources, including number of
course of oral prednisolone (30-40 mg daily). On discharge from
readmissions, hospital days, and visits to the accident and emer-
hospital, patients were allocated to either an early pulmonary
gency department not requiring admission. We gathered this
rehabilitation programme (within 10 days of hospital discharge)
information principally from hospital records, corroborated by
or usual care. Both groups of patients were discharged having
optimal medical treatment, with a summary of their admission,to the care of their general practitioner and received standard
Blinding
follow up outpatient appointments with a pulmonary specialist.
Owing to the nature of the intervention and financial and logis-
All patients received home diaries, which included a disease spe-
tical considerations, it was not possible to blind the patients or
the assessors. The assessors were either the investigator respon-sible for assignment or members of the pulmonary rehabilitation
Baseline assessment
team who were directly or indirectly involved in the delivery of
We made baseline assessments in the 24 hours before patients
were discharged from hospital and assigned to the intervention. We measured exercise capacity by the incremental shuttle walk
Sample size calculation
test,6 a standardised, externally paced, corridor walking test,
The primary outcome measure for the study was the incremen-
which is reproducible after a single practice walk. Patients are
tal shuttle walk distance. On the basis of previous audit data, a
instructed to walk along a 10 metre course in time with
sample size calculation estimated that at least 30 patients (15 in
prerecorded signals; initial walking speed is set at 0.50 metres per
each group) would be required to show a 50 metre difference in
second, and increased each minute by 0.17 metres/second. The
shuttle walk distance (standardised difference 1.2) with 90%
distance walked correlates well with maximum consumption of
oxygen. The incremental shuttle walk is commonly used in pul-
Data analysis and statistical methods
monary rehabilitation programmes in the United Kingdom as a
We analysed data on an intention to treat basis. We made no
functional outcome measure of maximum exercise capacity. We
attempt to impute “missing” data from those participants who
used the St George’s respiratory questionnaire (SGRQ) and the
were lost to follow up. We calculated means (standard deviations)
chronic respiratory disease questionnaire (CRQ), both well vali-
or medians (ranges or interquartile ranges) as appropriate. We
dated in patients with COPD7 8 and often used outcome
used unpaired t tests to compare mean differences between
measures in pulmonary rehabilitation studies, to measure
groups for SGRQ, CRQ, and SF-36 scores. Because of the highly
disease specific health status. We measured generic health status
skewed distribution we used Mann-Whitney and univariate
with the short form, 36 item questionnaire for medical outcomes
median regressions to compare median shuttle walks between
groups. We used the Mann-Whitney test to test differences
Assignment
between groups in hospital bed days. We used incident rate ratios
A random number generator was our tool to assign an interven-
and the Poisson regression for rates of hospital readmission and
tion to the first patient entering the study. We used the minimisa-
accident and emergency visits. We used SPSS, version 12, and
tion method to assign patients further to the intervention group,
Stata, version 8, for the computations.
taking into account five factors: age ( < 70 years or ≥ 70 years),sex, length of hospital admission ( < 7 days or ≥ 7 days),
incremental shuttle walk distance at discharge ( < 100 metres or
≥ 100 metres), and predicted forced expiratory volume in one
Flow and follow up of participants
second (FEV ; < 30% or ≥ 30%). Table 1 shows baseline charac-
Figure 1 shows the progress of participants through the study.
We initially assessed 69 patients for eligibility over a six monthperiod. Seventeen patients were not enrolled for medical reasons
Pulmonary rehabilitation
or met exclusion criteria: coexisting unstable ischaemic heart
A multidisciplinary team ran the pulmonary rehabilitation
disease (n = 7), pulmonary rehabilitation in preceding year
programme, which consisted of two classes per week for eight
(n = 4), coexisting probable or definite diagnosis of lung cancer
weeks. Patients were given a choice of three locations around the
(n = 3), chronic alcohol abuse (n = 2), and wheelchair bound
London boroughs of Lambeth and Southwark, but the classes
owing to rheumatoid arthritis (n = 1). Ten patients refused
were run by the same team with the same equipment. Each class
consent: “felt too ill” (n = 4), “clash with other social activities”
lasted two hours, consisting of one hour of exercise (aerobic
(n = 3), “no likely benefit to me” (n = 3). Of the 42 patients
walking and cycling, strength training for the upper and lower
recruited, three month exercise capacity and health status data
limb) and one hour of educational activities (with an emphasis
were not available for eight patients because they died (n = 3),
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exceeded the recognised minimal clinically important differ-
ences for these measures. In addition, the rehabilitation groupmade far fewer visits to accident and emergency departments,
and we saw a trend towards reduced hospital readmission rate
Discussion
Attendance at a community based pulmonary rehabilitation
programme shortly after a hospital admission for an acute exac-
erbation of COPD leads to clinically important improvements inexercise capacity and health status at three months. Further-
more, the number of attendances at the accident and emergency
department was lower and hospital admission was required in
Comparison with other studies Excellent evidence supports the benefits of pulmonary rehabili-
tation in stable patients with COPD.3 4 This study examines theeffects of this outpatient intervention in patients during the early
recovery period after a hospital admission for an acute exacerba-tion. Despite optimal medical treatment during hospital
were lost to follow up because they had moved abroad or out of
admission, patients at discharge take considerable time to
area (n = 2), developed serious comorbidity unrelated to COPD
recover to baseline levels of physical functioning and health sta-
(n = 2), and withdrew because of allocation to usual care (n = 1).
tus. Previous studies have shown that up to 25% of patients after
The mean attendance rate at the pulmonary rehabilitation class
an acute exacerbation do not fully recover to baseline peak flow
was 73%, with 6 of the 18 patients attending less than 50% of the
at three months10 and that the recovery period in health status is
classes. No adverse events were reported in the early
long even in patients who do not have further exacerbations.11
rehabilitation group. Table 2 shows baseline and three month
Our data indicate that patients can safely participate in a
data in the usual care and early pulmonary rehabilitation groups.
community based pulmonary rehabilitation programme for out-
Exercise capacity, the SGRQ impacts and total score, all four
patients shortly after an exacerbation and that such a
domains of the CRQ, and the mental component score of the
programme speeds up recovery from the debilitating effects of a
SF-36 in favour of early pulmonary rehabilitation improved sig-
hospital admission. Furthermore, the magnitude of the effects of
nificantly. The magnitude of these mean improvements greatly
early pulmonary rehabilitation on exercise capacity and health
Table 2 Baseline and three month data. Data are mean scores (SD) and differences between groups were compared by using unpaired t tests unless otherwise indicated Usual care (n=16) Early rehabilitation (n=18) Mean difference between Outcome measure At discharge At three months At discharge At three months groups (95% CI)
St George’s respiratory questionnaire (range 100-0)‡:
Chronic respiratory disease questionnaire§:
* Median difference. †Mann-Whitney test. ‡Decreased score denotes improvement. Minimal clinically important difference is 4 points on the total score. §Increased score denotes improvement. Minimal clinically important difference is 2.5 (dyspnoea domain), 2 (fatigue domain), 3.5 (emotion domain) and 2 (mastery domain). ¶Increased score denotes improvement. **Incident rate ratio. ††Poisson regression. BMJ Online First bmj.com
status are considerably greater than, and in addition to, the
What is already known on this topic
effects of bronchodilator or corticosteroid therapy.12
Hospital admission for acute exacerbations of chronic
Limitations of the study
obstructive pulmonary disease (COPD) is an enormous
The study did not explore the mechanisms by which early
pulmonary rehabilitation achieves its effects. Possible explana-tions include physiological improvements in skeletal muscle
Pulmonary rehabilitation is an effective,
function, desensitisation to dyspnoea, and psychosocial lifestyle
non-pharmacological intervention in the management of
changes. Dysfunction of the skeletal muscles is well recognised in
stable patients with COPD, and the recent guidelines from
patients with COPD13 and is particularly marked during a hospi-
the National Institute for Clinical Excellence recommend
tal admission14 owing to a variety of factors, including atrophy
that it should be made available to all patients who would
resulting from disuse, systemic inflammatory mediators, and use
of corticosteroids. A limitation of this study is that, for obviousreasons, it was not possible to blind patients to the intervention. What this study adds
Hence a placebo effect cannot be excluded as the principal
Early pulmonary rehabilitation, in the recovery period after
mechanism for the improvements observed. However, it should
hospital discharge after an admission for an acute
be noted that early pulmonary rehabilitation led to considerable
exacerbation of COPD, leads to significant improvements in
improvements in the distances covered in the incremental shut-
functional capacity and quality of life at three months
tle walk. The maximum distance walked during this test
correlates well with peak oxygen consumption,6 hence it is likelythat a true physiological training effect contributed to theimprovements. The psychological effects, effects of self education
trend towards fewer hospital inpatient days. The results therefore
about the disease, or placebo effects of pulmonary rehabilitation
imply that early pulmonary rehabilitation may reduce usage of
in an often socially isolated group of patients should not be
healthcare resources and bring improvements in exercise capac-
minimised. A recent, multicentre, randomised controlled trial
showed that an education programme for patients (consisting of
Larger randomised studies are required to determine
weekly visits by a health professional for a two month period,
whether the benefits of early pulmonary rehabilitation translate
with monthly telephone follow up) led to reduced use of health-
into improved health economics. Other unanswered questions
care resources in patients with severe COPD.15 Another
include the long term effects of early pulmonary rehabilitation,
limitation of the study is that the assessors were not fully blinded
and the optimal structure, location, and duration of pulmonary
to treatment allocation as they may have been directly or
indirectly involved in the delivery of the intervention. This intro-
Despite medical optimisation during hospital admission for
duces an element of bias to the results, but it is important to note
acute exacerbations of COPD, early pulmonary rehabilitation
that the SGRQ and the SF-36 questionnaires are completed by
after discharge from hospital leads to additional notable
the patients themselves, without direct input from investigators,
improvements in exercise capacity and health status at three
and the incremental shuttle walk and the CRQ are highly stand-
ardised outcome measures that do not place subjective require-
We thank the Southwark and Lambeth pulmonary rehabilitation team for
running and supervising the rehabilitation programme described in thiswork. Viability of the programme
Contributors: WD-CM conceived the idea of the study, obtained grant
Exercise training after an acute exacerbation of COPD is not a
funding, designed the protocol, recruited subjects, collected and analysed
novel concept. Behnke et al looked at the effects of an initial, 10
data and wrote the first and final drafts of the manuscript. MIP helped
day, inpatient training programme, followed by six months of
design the protocol of the study, interpreted data, and helped write the first
supervised home training, compared with usual care, in patients
and final drafts of the manuscript. ND helped design the study, performedstatistical analysis of the data and helped write the first and final drafts of
admitted for an acute exacerbation of COPD.16 They showed
the manuscript. BJG helped design the study, recruited patients, interpreted
improvements in six minute walking distance and sum scores on
data and helped write the first and final drafts of the manuscript. JM was the
the questionnaire on chronic respiratory disease at three months
senior investigator, and will act as guarantor. He helped conceive the idea
and six months after training compared with control. However,
and design of the study, obtained grant funding, interpreted data, andhelped write the first and final drafts of the manuscript. Christine Jones and
such a programme would not be viable in terms of manpower or
Caroline Mooney helped in the recruitment of subjects. Renata Morello,
finance, given that inpatient stay contributes 54% of all direct
Sheena Radford, Julie Backley, Lynda Haggis, Claire Bradley, Lauren
healthcare costs associated with COPD in the United Kingdom.17
Moore, and Debbie James were involved in data collection and were mem-
In contrast, a community based pulmonary rehabilitation
bers of the multidisciplinary team that provided the active intervention.
programme for outpatients is a more realistic option. Previous
Funding: This study was supported by a British Lung Foundation Trevor
data support the cost effectiveness of pulmonary rehabilitation
Clay Memorial Grant. WD-CM is a clinical research training fellow of theMedical Research Council (UK). The Southwark and Lambeth pulmonary
programmes on an outpatient basis and the likelihood of finan-
rehabilitation team is in part funded by “Pursuing Perfection,” coordinated
by the NHS Modernisation AgencyCompeting interests: None declared. Possible health economic impact and outlook
Ethical approval: The local research ethics committee approved the study.
The a priori primary outcome measures were exercise capacity,as measured by the incremental shuttle walk, and health status.
British Lung Foundation. Lung report III—casting a shadow over the nation’s health.
However, secondary outcome measures included use of hospital
London: British Lung Foundation, 2003.
resources, and fewer visits were made to the accident and emer-
Garcia-Aymerich J, Farrero E, Felez MA, Izquierdo J, Marrades RM, Anto JM. Risk fac-tors of readmission to hospital for a COPD exacerbation: a prospective study. Thorax
gency department in the group undergoing early pulmonary
rehabilitation. Patients in the treated group were readmitted 30%
Griffiths TL, Burr ML, Campbell IA, Lewis-Jenkins V, Mullins J, Shiels K, et al. Resultsat 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised con-
less often than patients in the control group, and there was a
trolled trial. Lancet 2000;355:362-8. BMJ Online First bmj.com
Lacasse Y, Brosseau L, Milne S, Martin S, Wong E, Guyatt GH, et al. Pulmonary reha-
15 Bourbeau J, Julien M, Maltais F, Rouleau M, Beaupre A, Begin R, et al. Reduction of
bilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev
hospital utilization in patients with chronic obstructive pulmonary disease: a
disease-specific self-management intervention. Arch Intern Med 2003;163:585-91.
National Institute for Clinical Excellence (NICE). Chronic obstructive pulmonary dis-
16 Behnke M, Taube C, Kirsten D, Lehnigk B, Jorres RA, Magnussen H. Home-based exer-
ease: national clinical guideline for management of chronic obstructive pulmonary dis-
cise is capable of preserving hospital-based improvements in severe chronic
ease in adults in primary and secondary care. Thorax 2004;59(suppl 1).
obstructive pulmonary disease. Respir Med 2000;94:1184-91.
Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walk-
17 Britton M. The burden of COPD in the U.K.: results from the confronting COPD sur-
ing test of disability in patients with chronic airways obstruction. Thorax 1992;47:1019-
vey. Respir Med 2003;97(suppl C):S71-9.
18 Griffiths TL, Phillips CJ, Davies S, Burr ML, Campbell IA. Cost effectiveness of an out-
Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of healthstatus for chronic airflow limitation. The St. George’s respiratory questionnaire. Am Rev
patient multidisciplinary pulmonary rehabilitation programme. Thorax 2001;56:779-
Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of qual-ity of life for clinical trials in chronic lung disease. Thorax 1987;42:773-8.
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I.
Conceptual framework and item selection. Med Care 1992;30:473-83.
10 Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and
recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am JRespir Crit Care Med 2000;161:1608-13.
Respiratory Muscle Laboratory, Guy’s, King’s, and St Thomas’ School of Medicine,
11 Spencer S, Jones PW. Time course of recovery of health status following an infective
King’s College Hospital, London SE5 9PJ
exacerbation of chronic bronchitis. Thorax 2003;58:589-93.
William D-C Man MRC clinical research fellow
12 Aaron SD, Vandemheen KL, Hebert P, Dales R, Stiell IG, Ahuja J, et al. Outpatient oral
John Moxham professor of respiratory medicine
prednisone after emergency treatment of chronic obstructive pulmonary disease. NEngl J Med 2003;348:2618-25.
King’s College Hospital, London SE5 9RS
13 Man WD, Soliman MG, Nikoletou D, Harris ML, Rafferty GF, Mustfa N, et al.
Nora Donaldson senior lecturer in statistics
Non-volitional assessment of skeletal muscle strength in patients with chronic obstruc-
Barry J Gray consultant physician in respiratory medicine
tive pulmonary disease. Thorax 2003;58:665-9.
14 Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, et al.
Muscle force during an acute exacerbation in hospitalised patients with COPD and its
Michael I Polkey consultant physician in respiratory medicine
relationship with CXCL8 and IGF-I. Thorax 2003;58:752-6.
Correspondence to: W D-C Man [email protected]BMJ Online First bmj.com
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