Exercise Rehabilitation and Chronic Obstructive Pulmonary Disease Stage

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1 Exercise Rehabilitation and Chronic Obstructive Pulmonary Disease Stage MICHAEL J. BERRY, W. JACK REJESKI, NORMAN E. ADAIR, and DANIEL ZACCARO Department of Health and Exercise Science, Department of Public Health Science, and Department of Medicine, Wake Forest University, Winston-Salem, North Carolina To determine the extent to which patients with Stage I COPD experience improvements in physical performance and quality of life as a result of exercise training, and to compare these improvements with those seen in Stage I and II patients, 151 patients with COPD underwent a 12-wk exercise program. Outcomes were measured at baseline and follow-up. Physical performance was evaluated by means of a 6-min walk, treadmill time, an overhead task, and a stair climb. General health-related quality of life was assessed in terms of the domains of Social Function, Health Perceptions, and Life Satisfaction. Disease-specific health-related quality of life was assessed with the Chronic Respiratory Disease Questionnaire (CRQ). Six-minute walk distance increased significantly in Stage I (200.5 ft [95% CI: 165.4, 235.7]), Stage II (238.3 ft [143.3, 333.3]), and Stage III (112.1 ft [34.6, 189.6]) participants. Treadmill time increased significantly in Stage I (0.42 min [0.20, 0.64]) and Stage II (0.64 min [0.14, 1.4]) participants. Time to complete the overhead task decreased significantly in Stage I (0.91 s [1.72, 0.11]) and Stage II (1.39 s [2.66, 0.13]) participants. None of the measures of general health-related quality of life improved in any of the three groups. Participants in Stages I, II, and III all experienced improvements in the CRQ domains of dyspnea (0.72 [0.53, 0.91], 0.47 [0.02, 0.91], and 0.46 [0.05, 0.87], respectively) and fatigue (0.49 [0.33, 0.66], 0.54 [0.20, 0.87], and 0.55 [0.05, 1.05], respectively). These results suggest that all patients with COPD will benefit from exercise rehabilitation. Berry MJ, Rejeski WJ, Adair NE, Zaccaro D. Exercise rehabilitation and chronic obstructive pulmonary disease stage. AM J RESPIR CRIT CARE MED 1999;160: Staging or grading the severity of chronic obstructive pulmonary disease (COPD) has been proposed as a means for categorizing this heterogeneous disorder (1). The defining physiologic abnormality in COPD is airflow limitation, commonly assessed by the 1-s forced expiratory volume (FEV 1 ). The FEV 1 has been shown to correlate with disability and death in COPD and is considered an important staging criterion. Patients with Stage I or mild COPD are believed to comprise the largest number of patients with COPD, and their disease has been thought to have minimal impact on health-related quality of life (1). Ferrer and coworkers reported that patients with mild COPD have a substantially compromised health-related quality of life (2). In addition, Carter and associates have shown that patients with mild COPD have a reduced physical work capacity (3, 4). One key component in the management of patients with COPD is pulmonary rehabilitation, the cornerstone of which is exercise. Improvements in physical function and quality of life are purported benefits of exercise training (5, 6). Unfortunately, pulmonary rehabilitation is generally not prescribed (Received in original form January 8, 1999 and in revised form April 20, 1999) Supported by Grant HL from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by Grant AG10484 from the National Institute of Aging of the National Institutes of Health. Correspondence and requests for reprints should be addressed to Dr. Michael J. Berry, Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC berry@wfu.edu Am J Respir Crit Care Med Vol 160. pp , 1999 Internet address: until there are significant symptoms with an advanced stage of the disorder (7 9). Previous studies examining the efficacy of exercise training with pulmonary patients show that most of the patients in these studies would be classified as Stage II or III or as having moderate or severe disease. Despite the fact that patients with Stage I or mild disease have a reduced quality of life and physical work capacity, we are aware of no studies that have specifically examined the effects of exercise training in these patients. Therefore, the primary aim of this investigation was to determine if patients with Stage I COPD experience improvements in physical performance and health-related quality of life as a result of exercise training. A secondary aim was to compare the effects of exercise training on these outcomes in this group of patients with those of patients with Stage II or III COPD. METHODS Participants Participants in this study were part of the Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial (REACT). REACT is a clinical trial examining the effects of short-term exercise (3 mo) versus long-term exercise (18 mo) on physical function and healthrelated quality of life in patients with COPD. Participants for the present investigation consisted of 151 ambulatory, community-dwelling persons ranging in age from 55 to 80 yr. Primary inclusion criteria included (1) expiratory airflow limitation that was not reversible by bronchodilator inhalation, such that the FEV 1 /FVC was less than 70% and the FEV 1 was greater than 20% of predicted, and (2) reported difficulty in performing at least one of the following activities as a result of dyspnea: walking a city block, grocery shopping, doing house-

2 Berry, Rejeski, Adair, et al.: COPD Stage and Exercise 1249 hold chores, lifting objects chest height or higher, walking up stairs, and getting up out of a chair. Reversibility was defined as an increase in FEV 1 greater than 12% and or 200 ml after inhalation of 200 g of albuterol. Other elements for inclusion into the study included (1) the ability to walk continuously for 6 min, (2) a willingness to participate in all aspects of the study, (3) no active participation in a regular exercise or pulmonary rehabilitation program for the preceding 6 mo, and (4) absence of a comorbid disease that would make it unlikely that the person could participate in an exercise program. Disease severity was staged on the basis of American Thoracic Society recommendations (1). Participants with an FEV 1 greater than 49% of predicted were classified as having Stage I or mild disease; those with an FEV 1 between 35 and 49% were classified as having Stage II or moderate disease; and those with an FEV 1 less than 35% of predicted were classified as having Stage III or severe disease. Predicted FEV 1 values were from Knudson and coworkers (10). Descriptive data on the participants are shown in Table 1. Procedures Participants initially underwent 3 d of screening and testing. During the first visit, participants signed an informed consent, performed spirometry and lung volume testing, and completed questionnaires to assess health-related quality of life. During the second visit, the participants performed a graded exercise test on a treadmill. During the third visit, participants completed additional questionnaires and three different physical function tests. These physical function tests consisted of a 6-min walk, an overhead task, and a stair climb. After completion of testing and screening, participants began a facility-based 12-wk program of exercise training. After the 12 wk of training, the participants completed 3 d of follow-up testing, using the same schedule of testing described for baseline testing. TABLE 1 DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF THE PARTICIPANTS AT BASELINE* Mild (n 99) Stage Moderate (n 36) Severe (n 16) Sex, male/female (n/n) 54/45 22/14 10/6 Age, yr Height, cm Weight, kg Smoking status Current, n Past, n Never, n Pack-years Comorbid illnesses (n with) Arthritis Hypertension Circulatory problems Coronary heart disease Diabetes Cancer Comorbid illnesses (n with) or more Education (n with) 12 yr yr yr Income (n making) $10,000/yr $10,000 $24,999/yr $25,000 $49,999/yr $49,999/yr * Values for age, height, weight, and pack-years are means SEM. Exercise Intervention The exercise training program consisted of walking, upper body strength training, and stretching exercises. Classes met thrice weekly for 1 h. Before beginning exercise, oxygen saturation, heart rate, and blood pressure were measured. Each patient then walked for 30 min on an indoor track. Participants were instructed to walk at a rating of perceived dyspnea (RPD) of 3 4 (moderate somewhat hard) based on the Borg categorical scale (11). At 20 min into exercise, participant heart rate, oxygen saturation, and RPD were recorded. After 30 min of walking, participants then performed upper extremity strength training exercises. Two sets of eight repetitions of biceps curls, triceps extension, shoulder flexion, shoulder abduction, and shoulder elevations were performed. Primary Outcome Measures Physical function. Physical function was assessed by four physical performance tests: time on treadmill from the graded exercise test (see below), a 6-min walk, an overhead task, and a timed stair climb up two flights of stairs. The 6-min walk test was administered in a gymnasium. Participants were asked to walk as far as possible in 6 min. No encouragement or feedback was given. Participants were allowed to determine their own pace and were allowed to stop and rest if necessary. Participants then performed an overhead task that required them to raise their arms such that the upper arm was parallel to the floor and move three 2.5-lb weights across a row of four pegs as quickly as possible. Participants were instructed to move the weights, one at a time, from peg to peg, going from left to right. Participants were scored on the time it took to move the weights from the first peg to the fourth peg. The stair climb task consisted of a timed ascent up two flights of steps, with 10 steps in each flight. Once the subject began the stair climb, no verbal encouragement or feedback was given. Health-related quality of life. The domains of Social Functioning, Health Perceptions, and Life Satisfaction were assessed as measures of general health-related quality of life. Social functioning and perceived health were assessed using questions from the SF-36 (12). A global index of life satisfaction was assessed using the Ladder of Life analog scale (13). Disease-specific health-related quality of life was assessed by means of the Chronic Respiratory Disease Questionnaire (CRQ) (14). The CRQ consists of 20 items and is divided into 4 dimensions: Dyspnea, Fatigue, Emotions, and Mastery. Secondary Outcome Measures Pulmonary function tests. Pulmonary function tests were performed using a Medical Graphics Corporation (St. Paul, MN) 1085D plethysmograph. Spirometry and lung volume measurements were performed according to guidelines of the American Thoracic Society (15, 16). Participants were asked to refrain from using bronchodilators for 3 4 h before being tested. Graded exercise test. Graded exercise tests were performed in the morning before the use of any bronchodilators. Each participant performed a modified Naughton protocol on a treadmill (Quinton Q-4000) in which the grade and or belt speed was increased by a specified amount at 2-min stages (17). Oxygen consumption ( V O 2 ) was measured continuously with a Medical Graphics Corporation CPX-D metabolic cart. The pneumotachograph and gas analyzers were calibrated before each test according to manufacturer specifications. Statistical Analyses To determine if there were improvements after exercise training within the mild, moderate, and severe groups, dependent t tests were used to test for differences between the baseline and follow-up measures. Single-factor between-groups analysis of variance (ANOVA) was then used to compare the difference scores among the three groups. Significance was set at the 0.05 level for all analyses. RESULTS There were 151 participants in this study, of which 99, 36, and 16 were staged as having mild, moderate, and severe disease, respectively. Demographic and clinical characteristics of the

3 1250 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL participants at baseline are shown in Table 1. Pulmonary function test measures at baseline and follow-up and the absolute change (with 95% confidence intervals) from baseline to follow-up are summarized in Table 2. Significant differences were found when comparing the changes from baseline to follow-up in the FEV 1 (liters) and the FEV 1 FVC ratio for the mild group. There were no other significant differences when comparing the changes from baseline to follow-up in pulmonary function measures within any of the three groups. In addition, no significant differences were found in any of the pulmonary function measures when comparing the changes among the three groups. Compliance, defined as the number of exercise sessions attended divided by the total possible number of sessions that could have been attended and expressed as a percentage, was % for the entire patient data set. Compliance for the mild, moderate, and severe groups was , , and %, respectively. There was no significant difference in compliance rates among the three groups. Physical Function Measures of physical function from the physical performance tests are presented in Table 3. All three groups increased 6-min walk distance from baseline to follow-up. In addition, there was a trend (p 0.08) for the mild and moderate groups to have greater increases in their 6-min walk distance than the severe group. The mild and moderate groups significantly decreased the amount of time required to perform the overhead task, whereas the severe disease group did not. When comparing differences from baseline to follow-up among the three groups, there was no significant difference in the amount of time required to complete the overhead task. Time to complete the stair climb was significantly faster in the group with mild disease after exercise training. There was no significant difference in the time required to complete the stair climb between baseline and follow-up in either the moderate or severe groups. No significant differences were found when comparing changes in stair climb time from baseline to follow-up among the three groups. Treadmill time increased in all three groups by a similar amount; however, only the increases in the mild and moderate groups were significant. There was no significant difference in increase in treadmill time among the three groups. Peak oxygen consumption increased significantly (p 0.01) from to ml kg 1 min 1 after exercise training in the group with mild disease (95% CI: 0.38, 1.50). Peak oxygen consumption increased nonsignificantly (p 0.63 and 0.67) from to ml kg 1 min 1 (95% CI: 0.62, 1.01) and from to ml kg 1 min 1 (95% CI: 1.20, 1.81) after exercise training in the groups with moderate and severe disease, respectively. There were no significant differences in the increases among the three groups (p 0.30). Health-related Quality of Life General health-related quality of life measures are shown in Table 4. There were no significant changes from baseline to follow-up among any of the groups for any of the domains of general health-related quality of life (i.e., Social Function, Health Perception, or Life Satisfaction). Disease-specific quality of life measures are presented in Table 5. All three groups showed significant improvements in their Dyspnea and Fatigue scores from baseline to follow-up and there was no significant difference in those increases among the three groups. Emotional Function improved significantly only in the group with mild disease. There was, however, no significant difference in the Emotional Function changes from baseline to follow-up among the three groups. Both the mild and moderate groups improved their Mastery scores significantly from baseline to follow-up. The severe disease group had a slight decrease in their Mastery score after exercise training. In addition, there was a trend for the changes in Mastery scores from baseline to follow-up to differ significantly among the three groups (p 0.06). DISCUSSION In general, the results show similar gains in physical performance and health-related quality of life among participants with mild, moderate, and severe disease after exercise train- TABLE 2 PULMONARY FUNCTION DATA AT BASELINE AND FOLLOW-UP IN THE THREE GROUPS OF PARTICIPANTS* Measure Time Mild Moderate Severe p Value FEV 1, L Baseline Follow-up Difference (0.084, 0.002) (0.114, 0.009) (0.056, 0.069) 0.58 p Value FEV 1, % predicted Baseline Follow-up Difference 1.50 (3.07, 0.16) 1.11 (3.07, 0.85) 0.06 (2.48, 2.36) 0.77 p Value FEV 1 /FVC, % Baseline Follow-up Difference 1.63 (2.41, 0.84) 1.03 (2.59, 0.53) 1.00 (2.87, 0.87) 0.68 p Value RV/TLC, % Baseline Follow-up Difference 0.20 (1.90, 1.50) 1.20 (0.90, 3.30) 1.00 (5.10, 7.10) 0.74 p Value The p value in row 4 of each measure indicates whether the difference from baseline to follow-up is significant. The p value in column 6 indicates whether the differences among the three groups are significant. FEV 1 is the forced expiratory volume in 1 s. FEV 1 /FVC is the ratio of the forced expiratory volume in 1 s to forced vital capacity. RV/TLC is the ratio of the residual volume to total lung capacity.

4 Berry, Rejeski, Adair, et al.: COPD Stage and Exercise 1251 TABLE 3 PHYSICAL PERFORMANCE TEST MEASURES AT BASELINE AND FOLLOW-UP IN THE THREE GROUPS OF PARTICIPANTS* Measure Time Mild Moderate Severe p Value Six-minute walk, ft Baseline 1, , , Follow-up 1, , , Difference (165.4, 235.7) (143.3, 333.3) (34.6, 189.6) 0.08 p Value Overhead task, s Baseline Follow-up Difference 0.91 (1.72, 0.11) 1.39 (2.66, 0.13) 1.06 (3.16, 1.05) 0.78 p Value Stair climb, s Baseline Follow-up Difference 0.57 (0.96, 0.18) 0.23 (0.57, 1.02) 1.14 (2.60, 0.32) 0.14 p Value Treadmill time, min Baseline Follow-up Difference 0.42 (0.20, 0.64) 0.64 (0.14, 1.14) 0.41 ( 0.30, 1.11) 0.63 p Value The p value in row 4 of each measure indicates whether the difference from baseline to follow-up is significant. The p values in column 6 indicate whether the differences among the three groups are significant. Increases in 6-min walk distance and treadmill time are indicative of improvement. Decreases in overhead task and stair climb time are indicative improvement. ing. These results are unique in that previous studies have shown pulmonary rehabilitation, which includes exercise training, to result in improvements in physical performance and health-related quality of life primarily in patients with moderate or severe disease but not mild disease. While the findings of improvements in exercise capacity and health-related quality of life in the mild patients are new and novel, they are not unexpected. Previous research with healthy older adults has demonstrated that exercise training will result in improvements in exercise capacity (18, 19) and health-related quality of life (20). Maltais and colleagues (21) have shown that patients with moderate and severe COPD can achieve similar gains in maximal oxygen uptake and maximal work capacity after exercise training. Our investigation extends these findings to include patients with mild disease. In addition, we have shown that the similar improvements in maximal work capacity and maximal oxygen uptake in patients at each stage of COPD is accompanied by improvements in physical function and quality of life. Despite the proven benefits of exercise training in patients with COPD, its use has been challenged by Albert (22) on the basis that it is not cost effective and that previous studies supporting its use for patients with COPD are flawed. Even the most comprehensive study to date of the efficacy of pulmonary rehabilitation was criticized (23). Albert argued that patients with mild disease were included in the study of Ries and colleagues and that this biased the results of the trial, because patients with mild disease would have been expected to make greater gains after exercise training than those with severe disease. The study by Ries and coworkers (23) is further criticized because it evaluated the effects of a comprehensive rehabilitation program, not just an exercise program. Albert argues that because exercise training is the most expensive component of a comprehensive rehabilitation program, the ef- TABLE 4 MEASURES OF GENERAL HEALTH RELATED QUALITY OF LIFE AT BASELINE AND FOLLOW-UP IN THE THREE GROUPS OF PARTICIPANTS* Domain Time Mild Moderate Severe p Value Social Function Baseline Follow-up Difference 2.04 (4.95, 0.87) 0.00 (4.93, 4.93) 2.67 (10.90, 5.57) 0.49 p Value Health Perception Baseline Follow-up Difference 1.71 ( 0.77, 4.21) 3.33 ( 0.65, 7.32) 0.63 (4.74, 3.49) 0.52 p Value Life Satisfaction Baseline Follow-up Difference 0.10 ( 0.36, 0.56) 0.06 ( 0.87, 0.98) 0.56 ( 0.62, 1.75) 0.76 p Value The p value in row 4 of each measure indicates whether the difference from baseline to follow-up is significant. The p values in column 6 indicate whether the differences among the three groups are significant. Increases in Social Function, Health Perception, and Ladder of Life scores are indicative of improvements.

5 1252 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL TABLE 5 DISEASE-SPECIFIC MEASURES OF QUALITY OF LIFE AT BASELINE AND FOLLOW-UP IN THE THREE GROUPS OF PARTICIPANTS* CRQ domain Time Mild Moderate Severe p Value Dyspnea Baseline Follow-up Difference 0.72 (0.53, 0.91) 0.47 (0.02, 0.91) 0.46 (0.05, 0.87) 0.29 p Value Fatigue Baseline Follow-up Difference 0.49 (0.33, 0.66) 0.54 (0.20, 0.87) 0.55 (0.05, 1.05) 0.90 p Value Emotional function Baseline Follow-up Difference 0.16 (0.05, 0.27) 0.11 ( 0.16, 0.38) 0.21 ( 0.19, 0.62) 0.72 p Value Mastery Baseline Follow-up Difference 0.17 (0.07, 0.27) 0.39 (0.05, 0.74) 0.05 ( 0.32, 0.22) 0.06 p Value The p value in row 4 of each measure indicates whether the difference from baseline to follow-up is significant. The p values in column 6 indicate whether the differences among the three groups are significant. Increases in scores are indicative of improvement. fects of exercise training should be studied independent of other rehabilitation components, such as educational and psychological services. This investigation addresses these two criticisms. We have shown that patients with severe, moderate, and mild disease make similar gains in physical function and health-related quality of life, and that exercise training alone is effective in achieving these improvements. One limitation of this study was the effect that the unequal group sizes had on the analyses. Because the group with mild disease included such a large number of patients (99) as compared with the moderate (36) and severe (16) groups, there were a number of differences between the baseline and followup measures that were of equal magnitude among the three groups but achieved significance only within the mild group. For example, emotional function in the CRQ increased by 0.2, 0.4, and 0.3 units in the mild, moderate, and severe groups, respectively; however, only the change of 0.2 units in the mild group was significant. The effect of unequal group sizes on the power of the statistical analyses should be considered when interpreting the results of this investigation. The results of this study reinforce the findings of a metaanalysis on randomized clinical trials with patients with COPD, which reported a significant positive effect size for pulmonary rehabilitation on functional exercise capacity and disease-specific health-related quality of life (6). In the current study, all three groups made significant gains in the 6-min walk distance after exercise rehabilitation. The smallest gains were made in the group with severe disease, with the moderate group making more than twice the gains of the severe group. Despite the magnitude of the difference between the two groups, the severe group improvements were clinically important and similar to those found in other investigations with severely diseased patients (5). Participants with both moderate and severe disease experienced improvements in dyspnea and fatigue; however, only those with moderate disease had significant changes in mastery. There were no improvements seen in emotional function for participants with either moderate or severe disease. More notable is the fact that the present data extend previous research by demonstrating that the favorable effects of exercise training generalize to patients with mild disease. In fact, this group of patients experienced increases on all subscales of the Chronic Respiratory Disease Questionnaire, albeit the changes in Emotional Function and Mastery were not clinically meaningful (24). The meta-analysis that was conducted on the CRQ reported significant effect sizes for all four subscales and noted that minimal clinically important differences were limited to the Dyspnea and Mastery subscales (6). We cannot be certain why we failed to see clinically meaningful changes in mastery for patients in any of the three disease categories. However, a likely explanation is that most of the previous studies were multiinterventional (5, 25, 26). Perhaps mastery is more affected by behavioral components of rehabilitation as opposed to exercise. This would suggest that a multidisciplinary program of pulmonary rehabilitation is needed if gains in all domains of disease-specific quality of life are to be realized. This idea is supported by the work of Reardon and coworkers, who found that improvements in quality of life made as a result of participating in a comprehensive outpatient pulmonary rehabilitation program are not related to improvements in exercise endurance (27). Future research efforts should be directed toward identifying whether exercise, educational, or psychological interventions are the most important in promoting improvements after pulmonary rehabilitation (28, 29). Results from this investigation failed to show differences in any of the components of general health-related quality of life that were measured. Other investigations using measures of general health-related quality of life have also failed to find significant changes in the general health-related quality of life of patients with COPD who are undergoing pulmonary rehabilitation (23, 30, 31). The results of the present study suggest that exercise therapy with COPD patients has no effect on general components of health-related quality of life. In summary, the results of this investigation show that all patients with COPD, despite the severity of the disease, will benefit from participation in an exercise training program. In addition, the gains made among the different stages will not differ significantly. On the basis of these findings, we would recommend that all patients with COPD, regardless of their disease severity, by referred for exercise rehabilitation or be encouraged to begin exercise training on their own. These patients should be referred to such programs at any point and

6 Berry, Rejeski, Adair, et al.: COPD Stage and Exercise 1253 not just after they have experienced an exacerbation of their disease. References 1. American Thoracic Society Standards for diagnosis and care of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 152:S77 S Ferrer, M., J. Alonso, J. Morera, R. M. Marrades, A. Khalaf, M. C. Aguar, V. Plaza, L. Prieto, and J. M. Anto Chronic obstructive pulmonary disease stage and health-related quality of life: The Quality of Life of Chronic Obstructive Pulmonary Disease Study Group. Ann. Intern. Med. 127: Carter, R., B. Nicotra, W. Blevins, and D. Holiday Altered exercise gas exchange and cardiac function in patients with mild chronic obstructive pulmonary disease. Chest 103: Carter, R., B. Nicotra, and G. Huber Differing effects of airway obstruction on physical work capacity and ventilation in men and women with COPD. Chest 106: Goldstein, R. S., E. H. Gort, D. Stubbing, and G. H. Guyatt Randomised controlled trial of respiratory rehabilitation. Lancet 344: Lacasse, Y., E. Wong, G. H. Guyatt, D. King, D. J. Cook, and R. S. Goldstein Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. Lancet 348: Casaburi, R Exercise training in chronic obstructive lung disease. In R. Casaburi and T. L. Petty, editors. Principles and Practices of Pulmonary Rehabilitation. W. B. Saunders, Philadelphia Petty, T. L., and G. G. Weinmann Building a national strategy for the prevention and management of and research in chronic obstructive pulmonary disease. National Heart, Lung, and Blood Institute Workshop Summary. Bethesda, Maryland, August 29 31, J. Am. Med. Assoc. 277: Petty, T. L Pulmonary rehabilitation of early COPD: COPD as a systemic disease. Chest 105: Knudson, R. J., R. C. Slatin, M. D. Lebowitz, and B. Burrows The maximal expiratory flow volume curve: normal standards, variability, and effects of age. Am. Rev. Respir. Dis. 113: Borg, G. A Psychophysical bases of perceived exertion. Med. Sci. Sports Exerc. 14: Ware, J. E. J., and C. D. Sherbourne The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med. Care 30: Andrews, F. M., and Withey, S. B Social Indications of Well- Being: America s Perceptions of Life Quality. Plenum, New York. 14. Guyatt, G. H., L. B. Berman, M. Townsend, S. O. Pugsley, and L. W. Chambers A measure of quality of life for clinical trials in chronic lung disease. Thorax 42: American Thoracic Society Snowbird workshop on standardization of spirometry. Am. Rev. Respir. Dis. 119: American Thoracic Society Standardization of spirometry 1987 update. Am. Rev. Respir. Dis. 136: Berry, M. J., P. H. Brubaker, M. L. O Toole, W. J. Rejeski, J. Soberman, P. M. Ribisl, H. S. Miller, R. F. Afable, W. Applegate, and W. H. Ettinger Estimation of V. O 2 in older individuals with osteoarthritis of the knee and cardiovascular disease. Med. Sci. Sports Exerc. 28: Seals, D. R., J. M. Hagberg, B. F. Hurley, A. A. Ehsani, and J. O. Holloszy Endurance training in older men and women. I. Cardiovascular responses to exercise. J. Appl. Physiol. 57: Coggan, A. R., R. J. Spina, D. S. King, M. A. Rogers, M. Brown, P. M. Nemeth, and J. O. Holloszy Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. J. Appl. Physiol. 72: King, A. C., C. B. Taylor, and W. L. Haskell Effects of differing intensities and formats of 12 months of exercise training on psychological outcomes in older adults. Health Psychol. 12: Maltais, F., P. LeBlanc, J. Jobin, C. Berube, J. Bruneau, L. Carrier, M. J. Breton, G. Falardeau, and R. Belleau Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 155: Albert, R. K Is pulmonary rehabilitation an effective treatment for chronic obstructive pulmonary disease? No. Am. J. Respir. Crit. Care Med. 155: Ries, A. L., R. M. Kaplan, T. M. Limberg, and L. M. Prewitt Effects of pulmonary rehabilitation on physiologic and psychosocial outcomes in patients with chronic obstructive pulmonary disease. Ann. Intern. Med. 122: Jaeschke, R., J. Singer, and G. H. Guyatt Measurement of health status: ascertaining the minimal clinically important difference. Controlled Clin. Trials 10: Busch, A. J., and J. D. McClements Effects of a supervised home exercise program on patients with severe chronic obstructive pulmonary disease. Phys. Ther. 68: Wijkstra, P. J., R. V. Altena, J. Kraan, D. S. Postma, and G. H. Koeter Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home. Eur. Respir. J. 7: Reardon, J., K. Patel, and R. L. ZuWallack Improvement in quality of life is unrelated to improvement in exercise endurance after outpatient pulmonary rehabilitation. J. Cardiopulm. Rehab. 13: Fishman, A. P Pulmonary rehabilitation research. Am. J. Respir. Crit. Care Med. 149: Berry, M. J., and S. A. Walschlager Exercise training and chronic obstructive pulmonary disease: past and future research directions. J. Cardiopulm. Rehab. 18: Ojanen, M., A. Lahdensuo, J. Laitinen, and J. Karvonen Psychosocial changes in patients participating in a chronic obstructive pulmonary disease rehabilitation program. Respiration 60: Toshima, M. T., R. M. Kaplan, and A. L. Ries Experimental evaluation of rehabilitation in chronic obstructive pulmonary disease: short term effects on exercise endurance and health status. Health Psychol. 9:

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