CHRONIC OBSTRUCTIVE pulmonary disease is a growing

364 ORIGINAL ARTICLE Effectiveness of Pulmonary Rehabilitation in Reducing Health Resources Use in Chronic Obstructive Pulmonary Disease Mateu Rubí, MD, Feliu Renom, MD, Ferran Ramis, MD, Magdalena Medinas, PhD, María J. Centeno, RN, Maite Górriz, RN, Eulàlia Crespí, PT, Belén Martín, BSc, Joan B. Soriano, MD ABSTRACT. Rubí M, Renom F, Ramis F, Medinas M, Centeno MJ, Górriz M, Crespí E, Martín B, Soriano JB. Effectiveness of pulmonary rehabilitation in reducing health resources use in chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2010;91:364-8. Objective: To determine the effectiveness of a multidisciplinary, outpatient pulmonary rehabilitation (PR) program in patients with severe and very severe chronic obstructive pulmonary disease (COPD). PR is recommended in advanced COPD, but there is limited evidence on the effectiveness of PR in reducing health care resources when applied in outpatients. Design: Before and after intervention, a prospective research trial of patients enrolled in a PR program. Setting: Outpatient respiratory department in a specialized hospital. Participants: We considered prospectively 82 consecutive patients with advanced COPD and finally studied 72 patients who completed the PR intensive phase. Intervention: PR program. Main Outcome Measures: The effectiveness of this PR program was assessed by comparing health resources use from the year before and the year after PR. Clinical variables including dyspnea; the body mass index, obstruction, dyspnea, exercise capacity (BODE) index; and the Chronic Respiratory Questionnaire and health resources use including the number of exacerbations, the number of hospitalizations, and days of hospitalization. Results: Patients had a forced expiratory volume in the first second percentage predicted (mean SD) of 33.0 9.8 and a BODE index of 5.0 2.0. Significant improvements after PR were found in dyspnea, exercise capacity, and quality of life and on the BODE index (P.05). Compared with the 12 months before PR, there were also significant reductions during the year after PR on exacerbations (3.4 3.5 vs 1.9 2.0, P.002), hospitalizations (2.4 2.0 vs 0.9 1.2, P.001), and days of hospitalization (36.1 32.7 vs 16.1 31.3, P.001) (ie, a reduction of 44%, 63%, and 55%, respectively; all P.05). Conclusions: We conclude that a multidisciplinary, outpatient PR program substantially reduces health resources use in patients with severe and very severe COPD. Key Words: Chronic obstructive pulmonary disease; Composite; Disease exacerbation; Health services; Hospitalization; Rehabilitation. 2010 by the American Congress of Rehabilitation Medicine CHRONIC OBSTRUCTIVE pulmonary disease is a growing public health problem, both in developed and developing countries. 1 It is currently the fourth leading cause of death in the world, 2 and it is the only 1 of the top 10 chronic diseases still with a rising mortality. 3 Patients with COPD are frequent consumers of health care resources. 4,5 Individually, outpatient exacerbations and hospitalizations are associated with lung function decline 6 and increased mortality. 7 Furthermore, there is a subgroup of patients with advanced COPD (10% 12%) with frequent exacerbations estimated to account for 60% to 70% of the total costs attributed to COPD. 8 Currently, there is irrefutable evidence 9,10 on the benefits of PR on multiple clinical outcomes such as exercise capacity, dyspnea, and quality of life in patients with COPD; major professional medical societies recommend it. 1,11,12 Accordingly, PR should be considered for all patients with chronic respiratory disease who have persistent symptoms, have limited activity, or are unable to adjust to illness despite optimal medical management. 11 A further goal of PR is the reduction of associated costs, 10 but there is limited evidence of the usefulness of PR to diminish health care resources use. 13 The implementation of PR remains a challenge, and one potential reason is the limited availability of studies concluding an improvement in health care resources. Therefore, the aim of our study was to determine the effectiveness of an outpatient PR program in patients with severe and very severe COPD and to assess its impact on health care resources quantified by improvements in the number of exacerbations and the number and length of hospitalizations. METHODS Participants We recruited all consecutive patients with severe and very severe COPD (forced expiratory volume in the first second, 50% after bronchodilation) as per Global Initiative for Obstructive Lung Disease criteria 1 in a stable clinical phase (no worsening during the previous month before study inclusion) who were referred to enter our multidisciplinary PR program. Exclusion criteria for PR were severe cardiovascular disease or any other serious comorbidity preventing from leisure exercise. From the Respiratory Unit, Hospital Joan March, Bunyola (Rubí, Renom, Ramis, Medinas, Centeno, Górriz, Crespí); Department of Research Methodology, Psychology School, Universitat de les Illes Balears, Esporles (Martín); Program of Epidemiology and Clinical Research, Fundación Caubet-CIMERA Illes Balears, Bunyola (Soriano); and Centro de Investigación Biomédica en Red (CIBER) de enfermedades respiratorias, Spain (Soriano). Correspondence to Joan B. Soriano, MD, Program of Epidemiology & Clinical Research, CIMERA, Recinte Hospital Joan March, Carretera Soller Km 12, 07110, Bunyola, Spain, e-mail: jbsoriano@caubet-cimera.es. Reprints are not available from the author. 0003-9993/10/9103-00624$36.00/0 doi:10.1016/j.apmr.2009.09.025 BODE COPD CRQ mmrc PR 6MWT List of Abbreviations body mass index, obstruction, dyspnea, exercise chronic obstructive pulmonary disease Chronic Respiratory Questionnaire modified Medical Research Council pulmonary rehabilitation six-minute walk test

REHABILITATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Rubí 365 Current smoking was not an exclusion criterion if patients accepted to enroll in a smoking-cessation program. Pulmonary Rehabilitation Program PR was conducted by a multidisciplinary team that included pneumologists, psychologists, physiotherapists, and an occupational therapist all coordinated by a liaison nurse/case manager. The PR program was divided into 2 phases: intensive and maintenance (fig 1). The intensive phase included education, exercise training, respiratory physiotherapy, and occupational therapy for 8 weeks. COPD education strategies included selfmanagement exercises in treatment devices and the recognition of exacerbations. The training exercises were always supervised by a physiotherapist who conducted 24 sessions (ie, 3 sessions a week of a 1.5-h duration for 8 weeks. Sessions were conducted in groups of 4 to 6 participants and included peripheral muscle training in lower limbs by means of aerobic exercise of low-intensity resistance by means of walking, stairs and cycle ergometer, combined strength/resistance training of upper limbs through a series of 10 repetitions against progressive resistance, respiratory and physical education, and specific training of respiratory muscles and breathing technique exercises of thoracic and abdominal muscles. Exercises were increasing in intensity or duration based on individual progress within each session. Resting periods were determined according to the dyspnea level or oxygen saturation. Patients also received an individualized exercise program to perform at home that was monitored in successive visits. Occupational therapy was also conducted during the final 2 weeks, emphasizing energy-saving techniques for activities of daily living. In a maintenance phase lasting from week 9 to week 52, all patients were encouraged to continue doing their exercises at home according to the pattern established during the program. Patients were evaluated every 2 to 3 months by their chest physician and nurse, and psychosocial support was provided if needed. At any time, a telephone contact was available to resolve any doubts, and, should an exacerbation be envisaged, patients were assessed by their chest physician in charge. Design and Assessments Ours was a prospective research study of patients. The study design was a before and after intervention trial of patients enrolled in a PR program. The protocol was accepted by our hospital ethics committee, and informed consent was obtained from all participants. Patients underwent assessments before and after the intensive phase. All questionnaires were administered by an experienced psychologist (MM) on paper, and then results were uploaded into a computerized database. Pulmonary function tests were determined by forced spirometry, and a bronchodilator test was performed according to American Thoracic Society/European Respiratory Society guidelines 14 with a Collins spirometer. a Exercise capacity was determined by recording the longest distance walked for up to two 6MWTs assessed in a 60-m, flat-surface corridor. There were 12 (16.6%) patients who performed one 6MWT and 60 performed 2. Quality of life was assessed by the CRQ. The limitation of functional status by dyspnea was determined by the the Borg index, 15 the mmrc scale, and the dyspnea scale of the CRQ questionnaire. Dyspnea by the Borg scale was assessed at the end of the 6MWT. The BODE index, a simple multidimensional grading system that combines the body mass index, airflow obstruction, dyspnea, and exercise capacity in COPD patients, was calculated according to Celli et al 16 ; BODE has a 10-point scale in which higher scores indicate a higher risk of death. To quantify the use of health care resources (exacerbations and number and length of hospitalizations), hospital records were compared between the year before and the year after PR. Exacerbations were defined as any sustained increase of baseline symptoms that required a modification of management or treatment. Only hospitalizations related to COPD exacerbations were included and analyzed. Statistical Analysis Qualitative variables are expressed in percentages, and quantitative variables are summarized as mean SD if normality can be assumed. The outcome variables 6MWT, CRQ, number of exacerbations, and hospital admissions were not normally distributed. Therefore, for the comparison of data before and after PR, the Wilcoxon test for repeated variables was used for quantitative variables. Results were considered statistically significant at P less than.05. The statistical software used was SPSS 12.0. b RESULTS We considered 82 patients with severe and very severe COPD in a stable clinical phase. Of them, 39 patients were users of home oxygen therapy. Of these 82 patients initially considered, 10 (12%) were withdrawn. Two left during the intensive phase because of a lack of motivation, and 8 were excluded because of exacerbations preventing them from performing the training exercise (see fig 1). The characteristics of the 72 patients who completed the intensive phase of the PR Fig 1. A flowchart of the pulmonary rehabilitation program.

366 REHABILITATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Rubí Table 1: Demographic and Clinical Characteristics of the Participants Sex (male), n (%) 72 (100) Age (y) 67.0 8.5 Smoking status, n (%) Current smokers 14 (19.4) Former smokers 57 (79.2) Never smokers 1 (1.4) Pack years 71.4 32.3 BMI 27.0 5.9 Charlson index 1.9 1.1 FEV 1 (L) 0.9 0.3 FEV 1 percent predicted 33.0 9.8 FVC (L) 2.2 0.6 FVC predicted (%) 62.9 14.8 6MWT 319.8 122.6 BODE index 5.0 2.0 NOTE. Values are mean SD unless otherwise stated. The Charlson comorbidity index (not corrected by age) ranges from 0 to 33. The BODE index ranges from 0 to 10. Abbreviations: BMI, body mass index; FEV 1, forced expiratory volume in the first second; FVC, forced vital capacity. program are shown in table 1. They were all men, with a significant smoking history, and 19.4% were still current smokers at enrollment. They had severe COPD according to forced spirometry and a BODE index of 5.0 2.0. In the 12 months before entering the PR program, the mean yearly rate of all COPD exacerbations was 3.4, with an average 2.4 hospitalizations and 36.1 days in the hospital. There were no statistically significant differences in any baseline variable assessed when compared with the 10 individuals who withdrew (data not shown). After the intensive period of 2 months, no significant changes were observed in lung function. However, as expected, there were significant improvements in the 6MWT (P.001) and the BODE index (P.002) (table 2). Regarding symptoms, significant reductions were observed in dyspnea as measured by the Borg scale (P.004) and the CRQ dyspnea questionnaire (P.001); this was not appreciated with the mmrc (P.251) (table 3). In all other dyspnea assessments and quality of life as per the CRQ questionnaire total and individual domains, there was a statistically and clinically relevant improvement (see table 3). Finally, compared with the previous 12 months, during the year after PR, patients experienced a 44% decline in number of exacerbations, a 63% decline in hospitalizations, and a 55% decline in days of hospitalization (fig 2). The number of patients requiring hospitalizations went from 50 (74.6%) in the previous year to 27 (40.2%) 1 year after PR, which accounts for a 46% reduction. DISCUSSION Our study reports a significant reduction in the use of health care resources and confirms a benefit on clinical outcomes after Table 3: Changes After PR on Borg Scale Index, mmrc, and CRQ (Total Score and Domains) Variable Pre-PR Post-PR P MCID 29 Borg scale index 4.5 1.7 3.9 1.5.004 1.0 mmrc 2.4 0.7 2.3 0.8.251 NA CRQ total score 85.1 15.6 100.4 13.7.001 10.0 CRQ emotional 31.5 7.5 36.0 7.4.001 3.5 CRQ disease control 21.3 5.6 24.3 4.6.001 2.0 CRQ fatigue 16.7 4.5 20.9 4.2.001 2.0 CRQ dyspnea 15.3 3.1 19.2 3.7.001 2.5 NOTE. Values are mean SD unless otherwise stated. Borg scale as per reference 15 was assessed at the end of the 6MWT. Abbreviations: MCID, minimal clinically important difference; NA, not available. a multidisciplinary PR program in patients with severe and very severe COPD. Although the evidence on the benefits of PR in COPD on exercise capacity, dyspnea, and quality of life is indisputable, the level of evidence about reduction in use of health care resources is lower. 9 Griffiths et al 13 showed a decrease in the number of home medical visits and the number and days of hospitalization with a program of 18 sessions and 6 weeks of PR. A subsequent report showed that this program was cost-effective. 17 Foglio et al 18 showed a reduction in exacerbations and hospitalizations during the 2 years after a PR program. Others showed reductions in hospitalization rates and length of stay with self-management programs including exercises at home and some components of conventional rehabilitation. 19 Similar to our study design, other uncontrolled studies show the positive effects of PR on some outcomes associated with health care resources by comparing the year before and after PR. 20-24 In our setting, only 1 study concluded a beneficial effect on health-related costs with a significant decrease in the number of exacerbations but without assessing hospitalizations and only after a 6-month PR program. 25 Therefore, our work confirms a decrease in the number of exacerbations, hospitalization number, and length of stay of a PR program. Moreover, although it was not a primary objective of our study, we confirm the beneficial effects of a PR program on dyspnea, exercise capacity, and quality of life in patients with advanced COPD. An improvement in PR in these 3 outcomes has the highest level of evidence (evidence A), 9,11 and all 3 outcomes Table 2: Changes After PR on FEV 1, 6MWT, and BODE Index Variable Pre-PR Post-PR P FEV 1 33.0 9.8 33.6 11.1.895 6MWT 319.8 122.6 370.7 93.9.001 BODE index 5.0 2.0 4.4 1.7.002 NOTE. Values are mean SD. The BODE index ranges from 0 to 10. Abbreviation: FEV 1, forced expiratory volume in the first second. Fig 2. The changes after PR on the number of hospitalizations because of COPD, the number of COPD exacerbations, and the number of days in the hospital during the last 12 months (mean and standard error bars)., pre-pr; e, post-pr.

REHABILITATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Rubí 367 have proved to be strong predictors of future exacerbations, increased use of health care resources, 26-28 and even mortality. 11 The improvements in dyspnea were both statistically and clinically significant in the CRQ dyspnea questionnaire (on the assumption that there are significant clinical differences if 2.5). 29 However, no significant differences were observed in the mmrc questionnaire. Others have suggested that the latter, by using a rougher scale, is not sensitive enough to detect changes in patients with very advanced COPD and high functional disability. 30 Very recently, Evans et al 31 concluded that all COPD patients, irrespective of their baseline mmrc grade, the benefit from PR, and even the ones with the mildest dyspnea, achieve significant improvements in exercise performance. In all other assessments, improvements both statistically and clinically significant were observed except in exercise capacity (the suggested clinically significant improvement of 54m or more [for walking distance in the 6MWT] was not attained). 32 Again, this high threshold has been challenged in patients with moderate to severe COPD, 33 where it was recommended to use preferably a gain of 10 percentage points or 35m in absolute value as a threshold to consider a clinically significant improvement. Accordingly, our patients experienced an increase of 14.6% and 47m in absolute value. Despite the overwhelming scientific evidence, PR programs are not widely implemented. Reasons include the high variability and lack of uniformity of PR programs and its components as well as a disregard of their cost-effectiveness by administrators. 34 Another reason suggested is the alleged high cost of setting up a multidisciplinary team, usually far away from the patient s home, sometimes requiring ambulance transport. To enhance the implementation of PR in routine clinical practice, it is important to reproduce the effects obtained in other clinical studies and settings 10 and to more clearly define the benefits of PR for any funding agency. 34,35 Study Limitations Some limitations of our study deserve discussion; a beforeafter intervention design is intrinsically lacking a control group. It was considered unethical to refuse offering this intervention to patients. Our design was considered superior to other study designs such as a historic or an unrelated clinical series. Five (6%) participants died in the maintenance phase. Mortality in our study is similar to that observed in similar studies showing 6% mortality in the United Kingdom, 13 8.4% in the United States, 36 10% in Spain, 37 and 4.4% in Uruguay. 38 We offered low-intensity exercise although the newest American Thoracic Society/European Respiratory Society consensus recommended a higher-intensity exercise; however, it is also noted that lower-intensity exercise might also have a beneficial effect by encouraging greater compliance in the long-term. 11 All our participants were men, so our results cannot be extrapolated to women with COPD. A final limitation to consider is the potential for regression to the mean, which is inherent to all before-after PR interventions. Indeed, all of these patients were referred to us because they had just recently had a hospitalization or other seriously negative event that was captured in the 1-year baseline period. 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