Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial

Transcription

1 22 Gutensohn N, Cole P. Childhood social environment and Hodgkin s disease. N Engl J Med 1981; 304: Isager H, Andersen E, Hyllested K. Risk of multiple sclerosis inversely associated with birth order position. Acta Neurol Scand 1980; 61: Blaser MJ, Chyou PH, Nomura A. Age at establishment of H00elicobacter pylori infection and gastric carcinoma, gastric ulcer, and duodenal ulcer risk. Cancer Res 1995; 55: Teh BH, Lin JT, Pan WH, et al. Seroprevalence and associated risk factors of Helicobacter pylori infection in Taiwan. Anticancer Res 1994; 14: Rothenbacher D, Bode G, Berg G, et al. Prevalence and determinants of Helicobacter pylori infection in preschool children: a population-based study from Germany. Int J Epidemiol 1998; 27: Rothenbacher D, Bode G, Winz T, Berg G, Alder G, Brenner H. Helicobacter pylori in out-patients of a general practitioner: prevalence and determinants of current infection. Epidemiol Infect 1997; 119: Fall CH, Goggin PM, Hawtin P, Fine D, Duggleby S. Growth in infancy, infant feeding, childhood living conditions, and Helicobacter pylori infection at age 70. Arch Dis Child 1997; 77: Tsugane S, Yuko T, Takahashi T, Watanabe S, Sugano K. Salty food intake and risk of Helicobacter pylori infection. Jpn J Cancer Res 1994; 845: Blaser MH. Helicobacters are indigenous to the human stomach: duodenal ulceration is due to changes in gastric microecology in the modern era. Gut 1998; 43: Wang JT, Sheu JC, Lin JT, Wang TH, Wu MS. Direct DNA amplification and restriction pattern analysis of Helicobacter pylori in patients with duodenal ulcer and their families. J Infect Dis 1993; 168: Blecker U, Lanciers S, Keppen E, Vandenplas Y. Evolution of Helicobacter pylori positivity in infants born from positive mothers. J Pediatr Gastroenterol Nutr 1994; 19: Ashorn M, Miettinen A, Ruuska T, Laippala P, Maki M. Seroepidemiologial study of Helicobacter pylori infection in infancy. Arch Dis Child Fetal Neonatal Ed 1996; 72: F Gold B, Khanna B, Huang LM, Lee CY, Banatvala N. Helicobacter pylori acquisition in infancy after decline of maternal passive immunity. Pediatr Res 1997; 41: Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial T L Griffiths, M L Burr, I A Campbell, V Lewis-Jenkins, J Mullins, K Shiels, P J Turner-Lawlor, N Payne, R G Newcombe, A A Lonescu, J Thomas, J Tunbridge Summary Background Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease. We undertook a randomised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients wellbeing over 1 year. Methods 200 patients with disabling chronic lung disease (the majority with chronic obstructive pulmonary disease) were randomly assigned a 6-week multidisciplinary rehabilitation programme (18 visits) or standard medical management. Use of health services was assessed from hospital and general-practice records. Analysis was by intention to treat. Findings There was no difference between the rehabilitation (n=99) and control (n=101) groups in the number of patients admitted to hospital (40 vs 41) but the number of days these patients spent in hospital differed significantly (mean 10 4 [SD 9 7] vs 21 0 [20 7], p=0 022). The rehabilitation group had more primary-care consultations at the generalpractitioner s premises than did the control group (8 6 [6 8] vs 7 3 [8 3], p=0 033) but fewer primary-care home visits (1 5 [2 8] vs 2 8 [4 6], p=0 037). Compared with control, the rehabilitation group also showed greater improvements in Section of Respiratory Medicine, Department of Medicine, University of Wales College of Medicine, Llandough Hospital, Penarth CF64 2XX (T L Griffiths MRCP, A A Lonescu MD, J Tunbridge); Department of Public Health Medicine (M L Burr MD) and Department of Medical Computing and Statistics (N Payne BSc, R G Newcombe PhD), University of Wales College of Medicine, Cardiff; and University Hospital of Wales and Llandough Hospital NHS Trust, Penarth (I A Campbell FRCP, V Lewis-Jenkins BSc, J Mullins MCSP, K Shiels SRD, J Thomas MRCP, P J Turner-Lawlor SROT), UK Correspondence to: Dr T L Griffiths ( griffithstl@cf.ac.uk) walking ability and in general and disease-specific health status. Interpretation For patients chronically disabled by obstructive pulmonary disease, an intensive, multidisciplinary, outpatient programme of rehabilitation is an effective intervention, in the short term and the long term, that decreases use of health services. Lancet 2000; 355: Introduction Chronic obstructive pulmonary disease and other chronic pulmonary disorders cause disability and handicap to patients, whose care becomes an increasing burden to the health services as well as the patients families. Although medication may provide limited subjective benefit, many patients remain symptomatic with impaired quality of life. The role of rehabilitation programmes for improving health in these patients has been recognised, 1 3 and guidelines for rehabilitation 4,5 have been published. A meta-analysis of exercise-based respiratory rehabilitation in patients with chronic obstructive pulmonary disease 6 reviewed 14 randomised controlled trials of rehabilitation versus care without rehabilitation, and confirmed statistically and clinically significant short-term benefits for rehabilitation. The studies reviewed in the metaanalysis were done in various settings in the hospital and the community, and lasted 4 weeks to 6 months. Another large randomised controlled trial 7 has shown a long-term benefit for an 8-week outpatient programme in terms of walking ability and a sense of self efficacy for walking and breathlessness. However, there was no effect on general health status or use of health services. Subsequently, two randomised controlled trials have shown benefit for a 3-month community programme 8 and a 3-month outpatient programme, 9 in terms of exercise tolerance, disease-specific (but not general) health status, and activity of daily living scores. 362 THE LANCET Vol 355 January 29, 2000

2 338 patients referred 138 did not fit entry criteria or refused to participate 200 randomised 99 assigned to rehabilitation group 101 assigned to control group 1 died before 6 weeks 3 died before 6 weeks 5 with missing data at 6 weeks 7 with missing data at 6 weeks 93 completed 6-week assessment 91 completed 6-week assessment 1 had missing data at 1 year 1 had missing data at 1 year 5 died between 6 weeks and 1 year 92 completed 1-year assessment 88 completed 1-year assessment 9 died between 6 weeks and 1 year Trial profile Based on completion of health-status questionnaires A pulmonary rehabilitation programme was set up at our hospital, which functions both as a teaching hospital and district general hospital. We designed the introduction of this programme as a randomised controlled trial and compared standard care with outpatient, multidisciplinary, pulmonary rehabilitation. We investigated the short-term and long-term effects of the intervention. We present data on the outcomes of health service use, walking tolerance, and health status. A health economic analysis will be reported elsewhere. Methods Patients Consultants in local hospitals and local general practitioners were invited to refer patients to the pulmonary rehabilitaton unit for assessment and entry into the study (figure). They were asked to refer patients who, in their judgment, had chronic obstructive bronchitis, emphysema, or chronic poorly reversible asthma or bronchiectasis. Patients were accepted into the study if their forced expiratory volume in 1 s (FEV 1 ), measured at a time of clinical stability, was less than 60% of predicted with less than 20% reversibility in response to inhaled -agonist. A patient was defined as having stable disease if he or she had had no change in symptoms or medication for 2 months before entry. Patients with additional, non-obstructive but disabling pulmonary disease, who matched the spirometric criteria, were not specifically excluded; however, they formed a very small proportion of the patients referred. Predicted values used for reporting pulmonary function were those referred to by Cotes. 10 Patients were excluded if they could not walk, or if they had severe sensory or cognitive impairment or symptomatic ischaemic heart disease. The study was approved by the Bro Taf Medical Research Ethics Committee, and all patients gave written informed consent. Design and procedures All patients were reviewed (TLG, AAI, or JT). Medical treatment was reviewed and changed if clinically appropriate. If necessary, referrals were made for smoking-cessation counselling and to the dietetic, occupational therapy, or physiotherapy services currently available at our hospital. If any changes were made to management, entry to the study was deferred for 2 months after the last change. Baseline measurements were made, then individuals were randomly assigned to treatment and control groups, with stratificaton by sex and by primarily obstructive versus non-obstructive lung disease. Randomisation with random number sequences was generated in the Department of Public Health Medicine, University of Wales College of Medicine, as a numbered sequence of sealed envelopes. Treatment was allocated in the rehabilitation unit by sequential opening of these envelopes as each patient entered the study. This was an open study for patients and therapists but the technicians doing the walking and questionnaire testing were not involved in the delivery of the rehabilitation programme and were not aware of the randomisation. The rehabilitation programme was multidisciplinary, with dedicated occupational therapy, physiotherapy, and dietetic staff. Contributions were also made by a specialist respiratory nurse and a smoking-cessation counsellor. Patients attended the rehabilitation unit on 3 half days per week for 6 weeks. Each session was about 2 h long. The first third of the time was spent in educational activities aimed at giving patients an understanding of THE LANCET Vol 355 January 29,

3 pulmonary pathophysiology, and the mechanisms of breathlessness, identification of and how to deal with breathlessness, the importance of exercise, methods of clearance of pulmonary secretions, the importance of good nutritional status, pulmonary medicines and their uses, and how to apply the lessons of rehabilitation in daily life. An exercise session followed with individually prescribed training programmes that aimed to achieve 30 min of exercise for the legs and arms. Treadmill training was done by patients and started at 80% of the maximum walking speed achieved in the 10 m shuttle-walk test. 11 Patients were encouraged to walk for as long as possible at this rate, and when limited, were asked to score their breathlessness on a modified Borg scale. 12 This score was then used as a target degree of breathlessness to be achieved in static cycling exercise of similar duration. Once 10 min was achieved, the walking and cycling rates were increased to maintain exercise duration and end-ofexercise Borg score. Patients also exercised on a stepping maching or a fixed step. Circuit training on various pieces of apparatus for a set period of time was done to exercise the arms; arms were unsupported with or without weights or elastic resistance. As many repetitions as possible in 2 min were done on each piece of apparatus. Patients already using ambulatory oxygen supplementation at home were offered oxygen for exercise training if their haemoglobin oxygen saturation (measured by pulse oximetry [SpO 2 ]) decreased by more than 4% or to below a value of 90%. Patients who did not use ambulatory oxygen at home were not offered supplemental oxygen unless SpO 2 decreased below 80% or desaturation was accompanied by unacceptable degrees of dyspnoea or fatigue, which were reversible by delivering oxygen to achieve 90% SpO 2. Patients were encouraged to follow a home-exercise routine, concentrating on activities useful to the individual. After a refreshment break, the final third of the session looked at psychological issues relating to chronic disability. This session included teaching techniques for practical stress management and relaxation, to promote skills in the patients mastery and control over their illness. The rehabilitation sessions incorporated the flexibility to allow work with individuals eg, to set goals, attend to special needs in terms of activities of daily living, or to give specific physiotherapy advice. Individual dietary advice was also given. Patients with a bodymass of less than 20 kg/m 2 were given specific advice with or without formal supplementation, and those with body-mass index greater than 25 kg/m 2 were given advice on how to lose weight. Dietetic support was offered where appropriate. At the end of the rehabilitation programme, patients were encouraged to continue at home the various strategies they had been taught. They were also invited to join a patient-run group that met weekly at the local leisure centre for social activities and a programme of exercise, supervised by the leisure centre s fitness instructors. The patients in the control group continued with their usual outpatient or primary-care follow-up for 1 year and were then offered pulmonary rehabilitation. The databases of our hospital and the six surrounding district general hospitals were searched for dates of patients admissions to hospital and the days spent in hospital. These were divided into respiratory and non-respiratory categories by means of the International Classification of Diseases, ninth revision, codes assigned at discharge. At the end of the 1-year follow-up period, proformas were circulated to the patients general practitioners. These were completed from the primary-care record of the number of consultations at the surgery, the number of home visits, and the number of contacts with other primary-care staff. Contacts were subdivided for respiratory and non-respiratory causes according to the opinion of the general practitioner. In a few instances this information was obtained by a visit to the practice concerned, and for patients who had died the centrally archived primary-care records were examined. Before randomisation and at the end of the 1-year follow-up, a record was made of patients self-reported, current use of respiratory medicine. Measures of walking capacity and health-status were made before randomisation, after 6 weeks, and after 1 year. The Control group Rehabilitation (n=101) group (n=99) Sex Male Female Age (years)* 68 3 (8 1) 68 2 (8 2) Smoking (pack-years) 45 7 (21 9) 43 5 (31 1) Number taking maintenance oral prednisolone Body-mass index (kg/m 2 )* 25 3 (5 0) 25 2 (4 6) Lung function* FEV 1 (L) 0 89 (0 42) 0 91 (0 38) FEV (16 4) 39 7 (16 2) FVC 56 6 (17 1) 55 9 (15 1) FEV 1 /FVC 0 49 (0 13) 0 49 (0 13) TLC (20 1) (17 0) VC 68 1 (17 1) 66 7 (16 1) RV (48 8) (43 4) T L CO 48 0 (20 9) 51 3 (20 0) KCO 80 4 (35 4) 82 1 (28 6) Diagnosis COPD Poorly reversible asthma Bronchiectasis with airflow obstruction 2 4 Other 2 2 *Mean (SD). Number of packs (20 cigarettes) smoked per day multiplied by years of smoking. % predicted. Control: 1 calcified empyema, 1 pulmonary fibrosis and bronchiectasis secondary to sarcoidosis; rehabilitation: 1 mixed silicosis and emphysema, 1 mixed pulmonary fibrosis and emphysema. FVC=forced vital capacity, VC=vital capacity, TLC=total lung capacity (by helium dilution), RV=residual volume (by helium dilution), T L CO=single-breath transfer-factor for carbon monoxide, KCO=T L CO divided by alveolar volume. Table 1: Baseline characteristics of patients walking test and questionnaires were administered to patients on the same visit and the completeness of the questionnaires was ensured by the technical staff. Walking capacity was measured by the 10 m shuttle-walk test. 11 This is a standard, externally paced, incremental, maximal, corridor-walking test, which is reproducible after a single practice. Patients did two tests at least 30 min apart, with the distance walked noted on the second attempt. Patients scored their breathlessness on the modified Borg scale at the end of exercise. 12 Generic health status was measured with the medical outcomes survey short form 36 item questionnaire. 13 This self-completed questionnaire has been validated for use in patients with chronic obstructive pulmonary disease. 14,15 The questionnaire has eight domains that cover a range of physical and psychosocial functioning. The scores can be transformed to give an overall physical and a mental component score. 16 There is also a question that relates to perceived change in health (health transition). Disease-specific health-status was measured with the St George s respiratory questionnaire, a standard, self-completed questionnaire validated for use in patients with chronic respiratory disease. 15,17 It has domains of symptoms, activities, and impacts and yields a total summary score. The chronic respiratory disease questionnaire 18 was also completed. This questionnaire is individualised for dyspnoea and standardised for domains of fatigue, emotional function, and mastery. Because of the openness of the study, patients were not shown their previous scores. The hospital anxiety and depression score 19 was used to quantify these traits on a scale of 0 (no anxiety/depression) to 21 (maximum anxiety/depression). It is a self-completed questionnaire with scores greater than 8 indicating clinically relevant anxiety or depression. Analyses About 50% of outpatents with chronic obstructive pulmonary disease at our hospial before the study were admitted at least once in each year. Previous retrospective studies have shown a 38 55% decrease in days in hospital after rehabilitation Realistically, we expected a 25% decrease in admission rate, which would have an important effect on health service resources. If 95 patients were recruited to each group the expected 2 value would be 364 THE LANCET Vol 355 January 29, 2000

4 12 67 with a power of 0 95 to detect a difference of this magnitude. Allowing for a 5% deficiency in data collection we therefore planned to recruit 200 patients. All the analyses presented were based on intention to treat. Thus, all available study patients were included in the analyses (with allowance for death and defaulting) whether or not they had completed their assigned intervention. ANCOVA was used to compare postrehabilitation and 1-year results between the two groups, with the corresponding baseline value as a covariate. Non-parametric variables with a single observation, such as the number of admissions, were analysed with the U test. Results The diagnoses of the participants are given in table 1. Because the subset of patients with non-obstructive pulmonary disease was so small and their inclusion in the analysis did not affect the outcome of the study, we present data with all patients included in the analysis. At some time points information was not available for health status or walk testing, and these patients were excluded from analyses at those time points. Returns from primary care were complete for 199 of the 200 patients and secondary-care data are complete, irrespective of completeness of the walking and health-questionnaire data. Ten of the patients assigned to the rehabilitation group did not complete at least 12 of the 18 programmed sessions. Of those who had rehabilitation, only 26 attended at least ten of the weekly patient-run exercise and social meetings during their year of follow-up. Death was not a primary endpoint of the study but we noted that six of 99 patients in the rehabilitation group died during the study. The certified cause of death in three of these patients was a complication of chronic lung disease. 12 of 101 patients in the control group died during the study, eight due to complications of chronic lung disease. Deaths not caused by chronic lung disease were due to malignant disease, myocardial infarction, and subarachnoid haemorrhage. There were no significant differences between the two groups in demography or lung-function values (table 1). Eight patients in the control group and 14 in the rehabilitation group had a body-mass index of less than 20 kg/m 2. Mean FEV 1 (litres) for men and women were 0 99 (SD 0 46) and 0 76 (0 32) in the control group and 1 01 (0 35) and 0 76 (0 38) in the rehabilitation group. There were no significant differences between groups for any of these variables. There was no difference between the control and rehabilitation groups in the numbers of patients admitted at least once during the follow-up period (41 vs 40). However, for patients who were admitted, there were significant differences in the numbers of admissions and days spent in hospital (table 2). We then excluded admitted patients who died during the study from the analysis, to see whether the differences arose because the greater number of patients who died in the control group than in the rehabilitation group (eight vs three) used a disproportionate amount of hospital care; large differences remained (although not significant with the smaller number of patients). There were substantial differences between the groups in the pattern of primary-care use (table 3). Although the overall number of general-practitioner contacts was similar in the two groups, there was a higher frequency of attendance at the general-practitioner s surgery and a lower rate of home visits by a general practitioner in the rehabilitation group than in the control group. Exclusion Control Rehabilitation p* group group All patients admitted Total Hospital admissions Respiratory illness 1 9 (1 4) 1 4 (1 3) All causes 2 2 (1 5) 1 7 (1 1) Days spent in hospital Respiratory illness 18 1 (19 3) 9 4 (10 2) All causes 21 0 (20 7) 10 4 (9 7) Per admission 9 0 (7 6) 6 0 (3 4) Patients admitted and still alive at 1 year Total Hospital admissions Respiratory illness 1 9 (1 4) 1 5 (1 3) 0 14 All causes 2 1 (1 4) 1 7 (1 2) 0 15 Days spent in hospital Respiratory illness 17 4 (20 6) 9 6 (10 5) All causes 20 0 (21 5) 10 6 (10 0) Per admission 9 0 (8 3) 6 0 (3 4) 0 26 Data are mean (SD), except for totals. *U test. 3 -test. Table 2: Use of secondary care in participants admitted at least once during study period of patients who died from the analysis did not change the pattern of results. Although there were lower rates of use of all bronchodilator medications in the rehabilitation group than in the control group, these differences reached significance only for the use of anticholinergic drugs taken by inhaler (p=0 004) and oral theophylline (p=0 045). Values for shuttle-walk distance, Borg breathlessness scores, and health-status questionnaires at baseline were generally more favourable in the rehabilitation group than in the control group (table 4). The differences between the groups created by the randomisation did not reach the minimum clinically important difference for any of the domains for which this difference has been determined. Generally, there was a small decline in walking ability and health status in the control group throughout the study. The large differences in outcomes between the groups were, therefore, due mainly to changes in the rehabilitation group. Differences between the groups at follow-up time (adjusted for baseline) are shown in table 5. Although there was a significant effect of treatment on walking ability, the breathlessness score at the end of exercise did not differ between groups. There were significant differences between the groups immediately after rehabilitation in all dimensions of health status, Control Rehabilitation p* group group All patients Total Consultations at primary-care premises Respiratory illness 4 5 (6 0) 4 7 (4 5) 0 21 All causes 7 3 (8 3) 8 6 (6 8) Primary-care home visits Respiratory illness 1 8 (3 2) 1 3 (2 4) 0 34 All causes 2 8 (4 6) 1 5 (2 8) Contacts with practice nurse 2 0 (5 8) 1 8 (3 5) 0 87 Patients alive at 1 year Total Consultations at primary-care premises Respiratory illness 4 9 (6 3) 5 0 (4 6) 0 34 All causes 7 9 (8 6) 8 9 (6 8) Primary-care home visits Respiratory illness 1 8 (3 2) 1 3 (2 4) 0 34 All causes 2 6 (4 4) 1 5 (2 8) 0 11 Contacts with practice nurse 1 7 (4 5) 2 0 (3 6) 0 99 Data are mean (SD). *U test. Table 3: Use of primary-care facilities during the year from entry to the study THE LANCET Vol 355 January 29,

5 Outcome measure Control group Rehabilitation group Baseline 6 weeks 1 year Baseline 6 weeks 1 year Shuttle-walk test Walk distance (metres) 125 (97) 123 (99) 113 (83) 140 (94) 211 (118) 148 (103) Exercising Borg score (range 0 10) 4 4 (1 8) 4 7 (1 7) 4 3 (1 6) 3 9 (1 5) 4 1 (1 8) 4 1 (1 7) SGRQ scores (range 100 0) Symptoms 76 7 (16 3) 75 8 (18 8) 73 2 (19 8) 74 0 (19 7) 68 5 (22 3) 71 3 (21 6) Activities 82 5 (14 3) 83 0 (12 7) 84 2 (13 4) 82 7 (12 9) 76 5 (15 8) 78 5 (17 8) Effects 57 6 (17 2) 60 0 (15 2) 59 0 (16 7) 52 0 (16 1) 43 8 (17 8) 48 8 (21 6) Total 68 3 (12 7) 69 6 (11 7) 69 0 (13 3) 64 9 (12 8) 57 8 (15 5) 61 5 (17 5) CRDQ scores Dyspnoea (range 5 35) 13 6 (4 1) 12 8 (5 0) 13 9 (5 1) 13 9 (3 8) 19 0 (6 4) 15 9 (6 0) Fatigue (range 4 28) 12 2 (4 1) 11 7 (4 4) 11 8 (4 0) 13 2 (5 0) 17 3 (5 6) 13 9 (5 3) Emotion (range 7 49) 30 2 (8 5) 28 8 (8 4) 28 7 (9 2) 29 5 (8 4) 36 2 (7 7) 30 5 (9 3) Mastery (range 4 28) 16 0 (4 8) 15 6 (5 0) 15 7 (6 0) 16 3 (5 2) 20 1 (5 2) 17 5 (5 7) Short form 36 (range 0 100) Physical functioning 18 2 (18 7) 16 0 (16 9) 18 8 (18 4) 21 5 (18 6) 32 6 (23 8) 28 0 (23 9) Role limitation (physical) 14 9 (30 0) 6 0 (14 1) 8 3 (18 4) 12 1 (27 3) 35 5 (39 9) 20 7 (32 7) Bodily pain 60 2 (28 5) 57 9 (30 9) 54 9 (30 0) 65 1 (29 9) 68 4 (27 9) 65 3 (31 3) General health perception 28 8 (17 9) 27 1 (15 2) 28 1 (16 2) 33 4 (19 2) 35 6 (19 3) 35 2 (19 8) Vitality32 1 (17 5) 32 1 (16 9) 34 8 (20 3) 37 3 (18 6) 50 1 (20 3) 43 4 (21 3) Social functioning 42 5 (26 6) 37 9 (23 8) 42 6 (24 8) 50 3 (28 0) 65 5 (27 5) 53 4 (27 8) Role limitation (emotional) 29 0 (38 5) 23 4 (37 4) 27 7 (40 2) 34 3 (39 1) 60 2 (41 5) 38 4 (41 6) Mental health 63 5 (20 9) 62 8 (20 5) 62 1 (22 2) 64 7 (19 6) 74 4 (16 5) 67 8 (19 9) Health transition 37 9 (25 2) 37 0 (25 3) 39 8 (24 5) 37 4 (26 3) 61 9 (26 9) 51 1 (30 1) Physical component score 27 5 (6 9) 26 2 (6 7) 26 6 (7 6) 28 7 (8 3) 31 3 (9 8) 30 5 (9 2) Mental component score 41 9 (10 2) 41 1 (9 4) 42 1 (11 6) 44 0 (10 6) 51 1 (10 3) 45 5 (10 9) HAD (range 0 21) Anxiety8 9 (4 3) 8 9 (4 6) 9 0 (4 3) 8 6 (4 7) 7 3 (3 9) 8 1 (4 5) Depression 7 5 (4 3) 7 9 (2 3) 7 6 (3 4) 7 3 (3 2) 5 6 (3 4) 6 2 (3 9) All data are mean (SD). SGRQ=St George s respiratory questionnaire. CRDQ=chronic respiratory disease questionnaire. HAD=hospital anxiety and depression score. Table 4: Results at baseline, 6 weeks, and 12 months after entering the study except for pain in the short form 36 item questionnaire. The initial treatment effect measured with the St George s respiratory questionnaire and Chronic Respiratory Disease questionnaire had a 95% CI that was greater than the minimum clinically important difference for these two assessment methods. The differences between the groups for walking and many of the health-status measures, although smaller, remained significant after 1 year. As well as being statistically significant, the mean difference in total St George s respiratory questionnaire score was still greater than the minimum clinically important difference at 1 year. Discussion The rehabilitation programme we studied had many components designed to have an effect on physical impairments, disability, and handicap in a broad way. The benefits in use of health services and functional and health status cannot, therefore, be ascribed to any of the individual components in isolation. However, one intention of the programme was to change patient s behaviour and attitude to their disability and handicap. Our primary intention was to look at the patients use of health care without any preconception of the areas that might change after rehabilitation. Our initial stratifications did not take account of coexisting illness but the randomisation produced groups similar in age, sex, lung function, and health status. We reported use of primary and secondary health-care services for all causes of contact and for those contacts primarily for respiratory disorders. The days spent in hospital were substantially lower in the rehabilitation group than in the controls. This difference was mainly due to differences in admissions for respiratory disorders. Previous uncontrolled and retrospective studies have found a 38 55% average decrease in days patients spent in hospital after rehabilitation programmes but no such differences in admission were seen in a randomised controlled trial reported by Ries and colleagues. 7 Our study, with more comprehensive healthstatus improvements, confirms that in those patients who are admitted, the number of days spent in hospital by the rehabilitation group is half the number of the control group. The decrease in average bed occupancy, equivalent to 4 days per patient rehabilitated, was derived from reductions in the frequency and duration of admissions, even though rehabilitation did not decrease the number of patients who needed to be admitted. Use of primary care was more efficient after rehabilitation in that patients had more consultations on their general practitioners premises and less at home compared with the controls. This change was as much brought about by differences in consultation for non-respiratory matters as for primarily respiratory problems, and may be the result of overall improved fitness or changes in behaviour or attitudes to illness. This information could have important implications for resource management within the National Health Service and a full health-economic analysis for this intervention is underway. The differences in the health-status responses between control and rehabilitation groups immediately after rehabilitation were greater than those in most previously reported randomised 8,9,23 25 and non-randomised studies with similar outcome measures. The results for the chronic respiratory disease questionnaire show a standardised treatment effect (difference in response between control and rehabilitation groups divided by the pooled SD) at the top of the 95% CI determined for the response of the dyspnoea domain in the meta-analysis of Lacasse and colleagues. 6 The treatment effects in the domains of fatigue, emotional function, and mastery are above the 95% CI for these domains in the meta-analysis. 6 In our study, not only disease-specific assessments but also the generic short form 36 item questionnaire detected significant differences between the groups, in contrast to previous studies that have not shown general health-status improvement. 7,9 The programme used was both intensive 366 THE LANCET Vol 355 January 29, 2000

6 Outcome measure After 6 weeks p* After 1 year p* Shuttle-walk distance (m) 75 9 (61 0 to 90 8) (10 9 to 45 3) Exercising Borg scores 0 1 ( 0 6 to 0 4) ( 0 3 to 0 6) SGRQ Symptoms 5 7 ( 9 9 to 1 4) ( 4 4 to 4 5) Activities 6 7 ( 10 0 to 3 3) ( 9 8 to 2 2) Effects 12 4 ( 16 2 to 8 7) ( 10 9 to 1 4) Total (MCID=4) 9 4 ( 12 3 to 6 5) ( 8 4 to 1 2) CRDQ Dyspnoea (MCID=2 5) 6 1 (4 6 to 75) (0 3 to 3 5) Fatigue (MCID=2) 4 9 (3 6 to 6 1) (0 2 to 2 9) Emotion (MCID=3 5) 7 8 (6 0 to 9 7) ( 0 1 to 4 5) Mastery (MCID=2) 4 3 (3 1 to 5 5) (0 1 to 3 2) Short form 36 Physical functioning 14 9 (9 6 to 20 2) (2 1 to 13 3) Role limitation (physical) 29 9 (21 2 to 38 6) (5 9 to 20 9) Bodily pain 6 4 ( 0 6 to 13 4) (0 68 to 15 5) General health perception 6 3 (2 1 to 10 4) ( 2 8 to 8 1) Energy/vitality 15 3 (10 3 to 20 3) ( 2 7 to 9 9) Social functioning 19 1 (11 2 to 27 1) ( 4 1 to 12 6) Role limitation (emotional) 34 9 (23 9 to 45 9) ( 1 8 to 21 4) Mental health 10 5 (6 6 to 14 4) (0 7 to 9 9) Health transition 25 0 (18 0 to 32 0) (3 8 to 19 6) Physical component score 4 5 (2 4 to 6 6) (1 2 to 5 4) Mental component score 8 8 (6 4 to 11 3) ( 0 3 to 5 3) HAD Anxiety 1 5 (2 4 to 0 6) ( 2 0 to 0 1) Depression 2 1 (2 8 to 1 3) ( 2 2 to 0 4) See footnote for table 4. All data are mean (95% CI). *ANCOVA. Increase denotes improvement. Decrease denotes improvement. MCID=minimum clinically important difference. Table 5: Difference between control and rehabilitation groups adjusted for baseline and interdisciplinary. The effort expended on teaching knowledge, coping strategies, and life skills, coupled with a rigorous exercise-training programme, seems to have been highly effective. A major finding of our study is that statistically and clinically significant differences were still detetable between the groups 1 year after entry. However, the diference between the control and rehabilitation groups became smaller with time, as in previous studies, 26,30 32 suggesting a progressive loss of effect in the rehabilitation group. Home-care pulmonary rehabilitation may provide more sustained benefit over 18 months. 32 In a domiciliary setting, the strategies of rehabilitation may more easily become part of the daily routine. An observational study including 26 patients with chronic obstructive pulmonary disease (average FEV 1 43% predicted) undergoing 8 10 weeks of outpatient rehabilitation showed maintenance of health-status improvement but not walking ability after 1 year. 29 However, this study group was smaller and less severely impaired than the patients in our study, with no deaths occurring during follow-up. The decrease in the effects of rehabilitation seen in our study could be the result of several causes: the progressive nature of the disease, inability of patients to continue regular exercise, or intercurrent acute exacerbations leading to physical deconditioning that patients find hard to reverse. Our data cannot distinguish between the possibilities. A study that collected data at more time points and included inquiry into intercurrent exacerbations and home-exercise patterns might help to find out the important factors influencing long-term outcome. A notable feature of our findings is that the St George s respiratory questionnaire seems to be more sensitive to long-term change after rehabilitation than the chronic respiratory disease questionnaire, since the mean difference between the groups still exceeded the minimum clinically important difference. We speculate that this could be related to differences in the type of questionnaires. Responses to the chronic respiratory disease questionnaire were registered on a seven-point Likert scale that allowed a graded response. The St George s respiratory questionnaire, however, has many questions with dichotomous answers. The fall-off in functioning during 1 year after a large response to rehabilitaton may have led to a disproportionate decrease in the preceived degree of wellbeing irrespective of the absolute presence or absence of different health-status attributes. The short form 36 item questionnaire, although validated for use in patients with chronic obstructive pulmonary disease, 13,15 has not been widely used in studies of pulmonary rehabilitation. However, because patients with chronic lung disease commonly have coexisting illnesses, and the effects of rehabilitation are seen in many parts of life, we included this generic questionnaire as an outcome measure. Disease-specific questionnaires may not reflect the broader effects on patient s wellbeing. An important feature of our results is the lack of benefit at 1 year in the general health perception, social functioning, vitality, and role limitation by emotional problems and, consequently, the overall mental component score of the short form 36. The anxiety component of the hospital questionnaire anxiety and depression scale and the emotion component of the chronic respiratory disease questionnaire showed a similar pattern although the impact score of the St George s respiratory questionnaire did show benefit at 1 year. This pattern suggests that the more emotionally-based benefits of rehabillitation are less robust than the physical ones. The intensive attention of rehabilitation therapists during the rehabilitation period, which is subsequently withdrawn, may have a bearing on this. Alternatively, although our programme had many behavioural elements, a clinical psychologist was not part of the multidisciplinary team so there might have been limited effectiveness in this area. Although only 25% of patients in the rehabilitation THE LANCET Vol 355 January 29,

7 group attended the patient-led support sessions after the 6-week programme, long-term benefits were seen in this group. Thus, the long-term effectiveness of pulmonary rehabilitation may be largely determined by the initial programme rather than by follow-up sessions. A randomised controlled trial comparing a communitybased programme that incorporated formal weekly or monthly follow-up found no differential effect of follow-up intensity. 31 Our study therefore provides convincing evidence that an intensive, broadly based rehabilitation programme can have long-term benefits in terms of walking ability and health status. Multidisciplinary pulmonary rehabilitation should therefore be adopted as an integral part of the long-term management of patients with chronic respiratory disability. Contributors Tim Griffiths led the investigating team, directed the rehabilitation unit, coordinated the study, and prepared the first draft of the paper. Michael Burr and Ian Campbell initiated the study, secured funding, and facilitated the project. Jane Mullins, Patricia Turner-Lawlor, Vanessa Lewis-Jenkins, and Kathleen Shiels designed and delivered the rehabilitation programme and contributed to the organisation of the study. Nicola Payne and Robert Newcombe did the statistical analysis. Alina Ionescu and Jose Thomas medically assessed patients and assisted with demographic data collection. Judi Tunbridge was responsible for logistical support, collection of primary and secondary health-care data, and data entry. All investigators contributed to the writing of the paper. Acknowledgments This study was funded by a project grant from the Wales Office of Research and Development for Health and Social Care. We thank Sian Jones and Sonja Edwards for their contributions to the rehabilitation programme; Angela Korsman and Hazel Brown for doing the exercise and questionnaire testing; and our hospital and generalpractice colleagues for referring patients to the programme and providing information on use of health services. References 1 American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152 (suppl): S European Respiratory Society. Consensus statement: optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995; 8: British Thoracic Society. Guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997; 52 (suppl 5): S American Association of Cardiovascular and Pulmonary Rehabilitation/American College of Chest Physicians. Pulmonary rehabilitation. Joint American Association of Cardiovascular and Pulmonary Rehabilitation/American College of Chest Physicians evidence-based guidelines. Chest 1997; 112: American Thoracic Society. Pulmonary rehabilitation Am J Respir Crit Care Med 1999; 159: Lacasse Y, Wong E, Guyatt GH, King D, Cook DJ, Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. Lancet 1996; 348: Ries AL, Kaplan RM, Limberg TM, Prewitt L. Effects of pulmonary rehabilitation on physiologic and psychosocial outcomes in patients with chronic obstructive pulmonary disease. Ann Intern Med 1995; 122: Cambach W, Chadwick-Straver RVM, Wagenaar RC, van Keimpema ARJ, Kemper HCG. The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial. Eur Respir J 1997; 10: Bendstrup KE, Ingemann Jensen J, Holm S, Bengtsson B. Out-patient rehabilitation improves activities of daily living, quality of life and exercise tolerance in chronic obstructive pulmonary disease. Eur Respir J 1997; 10: Cotes JE. Lung function, 3rd edn. Oxford: Blackwell Scientific Publications, Singh SJ, Morgan MDL, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax 1992; 47: Borg GAV. Psychophysical basis of perceived exertion. Med Sci Sports Exerc 1982; 14: Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): conceptual framework and item selection. Med Care 1992; 30: Mahler DA, Mackowiak JI. Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with COPD. Chest 1995; 107: Harper R, Brazier JE, Waterhouse JC, Walters SJ, Jones NMB, Howard P. Comparison of outcome measures for patients with chronic obstructive pulmonary disease (COPD) in an outpatient setting. Thorax 1997; 52: Ware JE, Kosinski M, Keller SD. Physical and mental health summary scales: a users manual. Boston: Health Assessment Laboratory, Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-completed measure for chronic airflow limitation the St George s Respiratory Questionnaire. Am Rev Respir Dis 1992; 145: Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987; 42: Zigmund AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: Petty TL, Nett LM, Finigan MM, et al. A comprehensive care program for chronic airway obstruction: methods and preliminary evaluation of symptomatic and functional improvement. Ann Intern Med 1969; 70: Hudson LD, Tyler ML, Petty TL. Hospitalization needs during an outpatient rehabilitation program for severe chronic airway obstruction. Chest 1976; 70: Johnson HR, Tanzi F, Balchum OJ, et al. Inpatient comprehensive pulmonary rehabilitation in severe COPD. Respir Ther 1980; 3: Goldstein RS, Gort EH, Stubbing D, Avendano MA, Guyatt GH. Randomised controlled trial of respiratory rehabilitation. Lancet 1994; 344: Wijkstra PJ, Van Altena R, Kraan J, Otten DS, Postma DS, Koeter GH. Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home. Eur Respir J 1994; 7: Wedzicha JA, Bestall JC, Garrod R, Garnham R, Paul EA, Jones PW. Randomized controlled trial of pulmonary rehabilitation in severe chronic obstructive pulmonary disease patients, stratified with the MRC dyspnoea scale. Eur Respir J 1998; 12: Ketelaars CAJ, Abu-Saad HH, Schlosser MAG, Mostert R, Wouters EFM. Long-term outcome of pulmonary rehabilitation in patients with COPD. Chest 1997; 112: White RJ, Rudkin ST, Ashley J, et al. Outpatient pulmonary rehabilitation in severe chronic obstructive pulmonary disease. J R Coll Phys 1997; 31: Singh SJ, Smith DL, Hyland ME, Morgan MDL. A short outpatient pulmonary rehabilitation programme: immediate and longer term effects on exercise performance and quality of life. Respir Med 1998; 92: Foglio K, Bianchi L, Bruletti G, Battista L, Pagani M, Ambrosino N. Long-term effectiveness of pulmonary rehabilitation in patients with chronic airway obstruction. Eur Respir J 1999; 13: Vale F, Reardon JZ, ZuWallack RL. The long-term benefits of outpatient pulmonary rehabilitation on exercise endurance and quality of life. Chest 1993; 103: Wijkstra PJ, Ten Vergert EM, van Altena R, et al. Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease. Thorax 1995; 50: Strijbos JH, Postma DA, van Altena R, Gimeno F, Koeter GH. A comparison between an outpatient hospital-based pulmonary rehabilitation program and a home-care pulmonary rehabilitation program in patients with COPD. Chest 1996; 109: THE LANCET Vol 355 January 29, 2000