CHEST Recent Advances in Chest Medicine

Transcription

1 CHEST Recent Advances in Chest Medicine Pulmonary Rehabilitation A Review of the Recent Literature Roger S. Goldstein, MBChB, FCCP ; Kylie Hill, PhD ; Dina Brooks, PhD ; and Thomas E. Dolmage, MSc Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, comprehensive intervention that can be integrated into the management of individuals with chronic lung disease. It aims to reduce symptoms, optimize function, increase participation in daily life, and reduce healthcare resource utilization. In this review, we summarize the new developments in PR over the past 5 years. Issues related to patient assessment include a comparison of cycle- and walking-based measures of exercise capacity, the emergence of multidimensional indices, the refinement of the minimal clinically important difference, and the importance of assessing physical activity. Issues related to exercise training focus on strategies to optimize the training load. We also comment on the acquisition of self-management skills, balance training, optimizing access, and maintaining gains following completion of PR. CHEST 2012; 142(3): Abbreviations: 6MWD 5 6-min walk distance; AECOPD 5 acute exacerbation of COPD; BODE 5 BMI, airflow obstruction, dyspnea, and exercise capacity; HH 5 helium-hyperoxia; HO 5 heliox; HRQL 5 health-related quality of life; MCID 5 minimal clinically important difference; NIPPV 5 noninvasive positive pressure ventilation; PR 5 pulmonary rehabilitation; RCT 5 randomized controlled trial; TCEMS 5 transcutaneous electrical muscle stimulation; VF 5 ventilationfeedback In 1952, Barach et al 1 reported on the importance of exercise for patients with emphysema, and in 1969, Petty et al 2 described a comprehensive care program for patients with COPD that included exercise training. However, because early studies of pulmonary rehabilitation (PR) were unable to demonstrate convincing evidence of a physiologic training adaptation, 3 opinions on its benefits remained equivocal. In 1991, Casaburi et al 4 reported an increase in lactate threshold after high-intensity cycle training in COPD, an Manuscript received February 3, 2012; revision accepted May 6, Affiliations: From the Department of Respiratory Medicine (Drs Goldstein and Brooks and Mr Dolmage) and Respiratory Diagnostic and Evaluation Services (Mr Dolmage), West Park Healthcare Centre, Toronto, ON, Canada; Department of Physical Therapy (Drs Goldstein and Brooks) and Department of Medicine (Dr Goldstein), University of Toronto, Toronto, ON, Canada; School of Physiotherapy and Curtin Health Innovation Research Institute (Dr Hill), Curtin University, Bentley, WA, Australia; and Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research (Dr Hill), University of Western Australia, Crawley, WA, Australia. Funding/Support: Dr Goldstein is supported by the University of Toronto-NSA Chair in Respiratory Rehabilitation Research. Dr Brooks is supported by a Canada Research Chair. observation later shown to reflect improved quadriceps oxidative capacity. 5 The subsequent accumulation of high-quality data to support the effectiveness of PR 6,7 means that its application for those with chronic lung disease is endorsed by professional societies. 8,9 PR is an evidence-based, multidisciplinary, comprehensive intervention that reduces symptoms, optimizes function, increases participation, and reduces health-care resource utilization. Its main components are supervised exercise training, self-management education, and psychosocial support. In this review, we summarize recent developments in PR, focusing on patient assessment, exercise training, and program delivery mainly for patients with COPD. The emerging evidence for PR in diseases other than COPD is briefly summarized. Correspondence to: Roger S. Goldstein, MBChB, FCCP, Department of Respiratory Medicine, West Park Healthcare Centre, 82 Buttonwood Ave, Toronto, ON, M6M 2J5, Canada; roger.goldstein@westpark.org 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: /chest Recent Advances in Chest Medicine

2 Patient Assessment Common components of patient assessment comprise measures of lung function, exercise capacity, and health-related quality of life (HRQL). Over the past 5 years, key developments pertain to the (1) choice of assessments to evaluate exercise capacity, (2) introduction of multidimensional indices, (3) refinement of the minimal clinically important difference (MCID), and (4) use of physical activity as an outcome measure. Assessing Exercise Capacity Compared with cycling-based assessments, it is now clear that walking can induce greater arterial oxygen desaturation,10,11 which at least in part reflects a greater ventilatory response during cycling. 12 Moreover, constant power tests are more responsive than incremental tests, and these protocols are recommended to demonstrate changes in exercise tolerance in response to an intervention. 16 Walking assessments are more responsive than cycling assessments when evaluating the effects of bronchodilation on exercise tolerance.17 These findings will assist health-care professionals to match the assessment protocol more closely to the exercise outcomes of interest. Multidimensional Indices Multidimensional indices combine several constructs to formulate an aggregate score. The most well-known is the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, which was developed in The BODE index combines measures of BMI, airflow obstruction, dyspnea, and exercise capacity, thereby encompassing the pulmonary and systemic effects of COPD. The capacity of the BODE index to predict mortality varies among studies. 18,19 Alternative multidimensional measures that do not include exercise capacity are the age, dyspnea, and airflow obstruction (ADO) index 19 ; the dyspnea, airflow obstruction, smoking status, and exacerbation fre quency (DOSE) index, 20 and the self-reported general health, self-reported physical activity, dyspnea, and airflow obstruction (HADO) index. 21 Although each of these indices has been associated with clinical events such as hospitalization or mortality, many of them may have a similar capacity to predict mortality as one of the common component measures: the Medical Research Council dyspnea scale. 22 Another aggregate measure is the COPD Assessment Test. 23 This eightitem, valid, reliable tool can be used for evaluative or discriminatory assessments. 15,23 Minimal Clinically Important Difference The MCID is the smallest difference in score that can be detected or noticed within a homogenous patient group 24 and is intended to help drive clinical decisions related to program development, such as initiating or discontinuing a particular treatment strategy. Both anchor and distribution-based methods have been used to establish an MCID, although estimates using different methodologies often are disparate. The MCID appears to depend on the intervention. For example, the MCID for the change in endurance shuttle walk test following use of a bronchodilator was 65 s, but it was closer to 186 s following a PR program. 25 As they are developed from group data, the MCIDs should not be used to interpret changes in individual patients. 26 Physical Activity Robust data demonstrate that patients with COPD are inactive compared with healthy age- and sexmatched control subjects 27 ( Fig 1 ) and that this sedentary lifestyle is a predictor of clinical outcomes, including hospitalization and mortality. 28,29 Although optimizing physical activity is increasingly seen as an important goal of PR, the best way to measure this outcome remains a challenge. Self-report questionnaires lack precision because of recall and social desirability bias. 30 Pedometers lack sensitivity to detect the slow walking speeds characteristic of severe disease. 31 Accelerometers and portable metabolic monitors, although accurate, 32,33 are expensive and require technical expertise. Work done during the 6-min walk and incremental shuttle walk tests is strongly associated with average daily energy expenditure 34 (Fig 2 ), suggesting that field-based walking tests are markers of physical activity. We still require a simple, accurate, and inexpensive measure of physical activity to evaluate the impact of PR. Exercise Training Aerobic exercise training increases exercise tolerance, reduces dyspnea and fatigue, improves HRQL, 6 and reduces health-care resource utilization. 35 Training loads. 60% of maximum exercise capacity are associated with physiologic adaptation. 4,8 However, not all patients can tolerate high-intensity training, 36 and some experience little improvement in exercise capacity. 37 These so-called nonresponders are characterized by a profound ventilatory limitation to exercise 37 such that the training intensity is constrained by intolerable symptoms. 36 Even for those who can tolerate training intensities at a high percentage of their peak aerobic capacity, the training load in absolute terms is modest. 38 Recent training initiatives that have focused on reducing the extent to which the ventilatory limitation during exercise curtails the training stimulus include (1) interval training, (2) changing journal.publications.chestnet.org CHEST / 142 / 3 / SEPTEMBER

3 Figure 1. Percentages of time spent in each of the activities or body positions in healthy subjects and patients with COPD during the day. Others refers to cycling or undetermined activity (2% in healthy elderly subjects and 3% in patients with COPD). Reprinted with permission of the American Thoracic Society. Copyright 2012 American Thoracic Society. Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171: Official Journal of the American Thoracic Society. the gas inspired during exercise, (3) ventilatory strategies such as noninvasive ventilation, (4) transcutaneous electrical muscle stimulation (TCEMS), and (5) partitioning the exercising muscles. Because evidence for these strategies has been derived from studies of patients with COPD, their effectiveness in patients with other respiratory conditions is unknown. Moreover, initiatives such as noninvasive positive pressure ventilation (NIPPV), which increases the training stimulus borne by the peripheral muscles by reducing the ventilatory load, may be of less value if coexisting heart failure is the main mechanism of exercise limitation. Strategies to Optimize Training Interval Training: Using fixed intervals of highintensity exercise interspersed with low-intensity exercise or rest has been shown to elicit physiologic training effects consistent with skeletal muscle conditioning in healthy adults 39 and those with advanced COPD. 40 The high-intensity exercise maximizes training stimulants, and the low-intensity or rest intervals allow for relief of dyspnea or leg fatigue. A recent meta-analysis of eight trials (388 patients) that compared interval to continuous exercise noted no differences between groups in the magnitude of effect between the training approaches, 41 a fi nding supported by a recent Cochrane review. 42 However, the interval train ing protocols varied considerably between stud ies, and, therefore, the most efficacious approach remains a topic of interest. In clinical practice, an interval-based training program can be implemented in the absence of sophisticated equipment. However, until the patient learns to alternate work and rest periods and manipulate work rates independently, interval training will require a higher staffto-patient ratio than continuous training. Manipulating the Inspired Gas: Supplemental Oxygen In COPD, increasing the F io 2 during exercise reduces ventilation, hyperinflation, and dyspnea 43 in a dose-dependent manner (maximum gains at an F io 2 of 50%). 44 Short-term benefits have been shown, even among those who do not desaturate to 88% on exertion. 44,45 However, supplemental oxygen during exercise training in those who are not hypoxemic at rest remains controversial. A meta-analysis of five randomized controlled trials (RCTs) 46 in which patients trained while breathing either supplemental oxygen or ambient air noted an increase in cycle exercise endurance (weighted mean difference, 2.7 min; 95% CI, min) and reduced dyspnea on test completion (Borg scale weighted mean difference, 2 1.2; 95% CI, to 2 0.1) but no differences in maximum power, peak rate of oxygen uptake, performance during field-based walking tests, or HRQL. Figure 2. A, B, Correlation (solid line) and 95% prediction intervals (dashed lines) for the relationship between average daily energy expenditure and (A) body weight-walking distance product for the 6MWT ( r , P,.001) and (B) body weight-walking distance product for the ISWT ( r , P,.001). 6MWT 5 6-min walk test; ISWT 5 incremental shuttle walk test. (Reprinted with permission from Hill et al.34 ) 740 Recent Advances in Chest Medicine

4 Studies have reported no benefit on physical activity or HRQL when supplemental oxygen was prescribed for domiciliary use in these patients Heliox and Helium-Hyperoxia Replacing nitrogen with helium decreases airway resistance in the medium and large airways. In the laboratory setting, 79% helium and 21% oxygen (heliox [HO]) increases inspiratory capacity, reduces dynamic hyperinflation, reduces dyspnea, and increases cycle endurance [mean SD, to min; P,.001]. 50 At submaximal exercise intensities, HO also increases muscle blood flow, 51 which enhances oxygen delivery to the quadriceps and improves exercise endurance. 52 Changing the inspired gas from HO to 60% helium and 40% oxy gen (helium-hyperoxia [HH]) confers additional benefits in cycle 53 and walking54 endurance in COPD, especially in those with more severe airflow obstruction. A training study of HH demonstrated greater gains in cycle exercise endurance in the HH group compared with the ambient air control group ( min vs min, P,.05). 55 Despite higher exercise intensity and training duration in the HH group ( P,.05) ( Fig 3 ), on completion of training, there were no differences between groups in the peak rate of oxygen uptake. 55 In another study, 2 months of exercise training with HH did not confer additional gains in peak exercise capacity or exercise endurance compared with supplemental oxygen or ambient air. 56 In clinical practice, barriers to the widespread use of supplemental oxygen, HO, and HH during PR include cost and awkwardness of administration. Moreover, it is unclear whether using these gases will confer a sustainable benefit. Supplemental oxygen at home is infrequently used, 57,58 and neither HO nor HH are likely to be offered outside of the hospital setting. Ventilatory Strategies: Noninvasive Positive Pressure Ventilation NIPPV reduces the inspiratory work of breathing, enhances oxygenation of the quadriceps, decreases dyspnea, and increases exercise capacity A literature review 62 reported that greater gains in exercise capacity in a group that trained with NIPPV compared with no ventilatory assistance was an inconsistent finding. The application of nocturnal NIPPV during PR in patients with mild hypercapnic respiratory failure was associated with small improvements in daytime arterial blood gases and gains in some components of HRQL. 63 Ongoing implementation of NIPPV together with community PR served to sustain these gains 2 years following randomization and to confer greater gains in 6-min walk distance (6MWD). 64 In clinical practice, the cost and technical support requirements for NIPPV will preclude its use in the community as an adjunct to exercise training. Ventilation-Feedback A novel ventilatory strategy used a computerized ventilation-feedback (VF) system to set a slow respiratory rate and prolong expiratory time. Collins et al 65 undertook an RCT in which patients with COPD received either exercise training plus VF, exercise alone, or VF alone. The use of VF during exercise reduced hyperinflation more than exercise training alone, and adding VF to exercise training tended to confer greater gains in exercise endurance than exercise training alone ( P 5.051). Further study is needed to confirm these findings. Uptake in clinical practice may be limited by the need for sophisticated equipment and the time needed to teach the technique to patients. Transcutaneous Electrical Muscle Stimulation: Muscles may be conditioned without voluntary contraction using TCEMS. The stimulation protocol should target specific aspects of muscle function. The electrical training protocol is defined by the pulse frequency Figure 3. Mean exercise training variables across the 6-week rehabilitation program in the air ( ) or helium-hyperoxia ( ) groups. A, Training intensity. B, Duration of exercise. The dashed lines indicate the duration of exercise prescribed, whereas the symbols depict the duration of exercise completed. Values are presented as mean SD. * P,.05 in the helium-hyperoxia group vs air group. (Reprinted with permission from Eves et al. 55 ) journal.publications.chestnet.org CHEST / 142 / 3 / SEPTEMBER

5 (5-100 Hz), the duration of stimulation and rest periods (ie, on and off times), and the number of repetitions. A protocol designed to increase strength must induce forceful contractions using the highest tolerated current intensity without inducing fatigue and can do so at high frequencies ( Hz), with long on times and much longer off times over a few total repetitions (, 15). 66,67 An endurance protocol aims to elicit fatigue using a low pulse frequency (eg, 8 Hz); brief (2-4 s), but similar on and off times; and repetitions for a longer duration (30-60 min). In healthy subjects, such protocols improve muscle endurance, capillary density, and oxidative enzyme activity. 68 In 2002, the application of TCEMS for patients with COPD was encouraged by the publication of positive trials showing that electrical stimulation for 6 weeks conferred greater gains in muscle function and exercise capacity compared with control subjects. 69,70 Bourjeily-Habr et al 69 stimulated the quadriceps, hamstring, and calf muscles and reported gains in strength and the distance achieved during the incremental shuttle walk test. Neder et al 70 stimulated the quadriceps and demonstrated an increase in muscle strength, peak rate of oxygen uptake, and cycle exercise endurance. A study of home TCEMS (50 Hz) reported that improvement in quadriceps force, endurance, and cross-sectional area was associated with a more favorable muscle anabolic-to-catabolic ratio. 71 Changes in muscle cross-sectional area and force-generating capac ity were related to the stimulation intensity achieved. Because patients who could not tolerate large increases in stimulation intensity had only minimal increase in walking endurance, TCEMS may be of limited benefit to them. 71 Although the stated goal of TCEMS is to improve strength, most studies also aim to improve endurance, so patients were stimulated with high frequencies (50 Hz) and a low ratio of on to off time. In contrast to these hybrid strength and endurance protocols, Nuhr et al 72 stimulated the quadriceps and hamstring muscles in patients with chronic heart failure daily for 10 weeks using low frequency (15 Hz) and a high ratio of on to off time (impulse trains for 2 s, interrupted by 4 s for 2 h bid). This protocol targeted endurance by closely simulating brief rhythmic ambulatory muscle contraction, resulting in improved oxidative enzymes, anaerobic threshold, and 6MWD. Work investigated the cardiorespiratory responses to TCEMS. During a single application, both lowand high-frequency TCEMS elicited similar rates of oxygen uptake, minute ventilation, heart rate, and symptoms of dyspnea that were just above those expected at rest but well below that expected of conventional whole-body (ie, walking) training. 73 This finding suggests that both forms of stimulation would be acceptable therapeutic options in the rehabilitation environment. In 2011, Abdellaoui et al 74 reported that TCEMS (35 Hz) increased quadriceps force, type 1 muscle fibers, and 6MWD in patients hospitalized with an acute exacerbation of COPD (AECOPD). This study extends previous work by Zanotti et al, 75 who noted that for patients with COPD who were invasively ventilated following an AECOPD, TCEMS plus active limb exercise improved muscle strength and decreased the time to transfer from bed to chair; these gains were greater than any seen in a group who performed active limb exercise without TCEMS. Given the very low cardiopulmonary stress associated with TCEMS, establishing the optimal stimulation protocol for its use will continue to be of interest in the area of PR. Partitioning the Exercising Muscle Mass: In 2006, Dolmage and Goldstein 76 reported that during incremental cycle exercise, patients with COPD achieved the same peak rate of oxygen uptake while cycling with one leg as they did with two legs. Compared with cycling with two legs, cycling with one leg during prolonged endurance time by 17 min, meaning that by limiting the total exercising muscle volume, a highintensity train ing stimulus could be provided with less ventilatory load. In an RCT of one- vs two-leg cycle train ing for 30 min three times per week for 7 weeks, the between-group difference in the peak rate of oxygen uptake was 0.19 L/min (95% CI, L/min). 77 In 2009, Bjørgen et al 78 compared one- vs two-leg cycling using an interval training approach and noted a significant between-group difference in change in the peak rate of oxygen uptake (single leg, 0.20 L/min; two legs, 0.09 L/min) ( Fig 4 ). No additional benefit was conferred by increasing the F io 2 during one-leg training. 83 Although the implementation of one-leg cycle training in clinical practice requires only a simple adaptation of a cycle ergometer, the impact of this training approach on outcomes such as HRQL remains to be determined. Other Advances Increasing Peripheral Muscle Strength Quadriceps cross-sectional area is a predictor of mortality independent of lung function. 84 Reductions in muscle volume lead to impairments in force-generating capacity, which in turn, decreases exercise capacity, 85 reduces balance, 86 and increases fall risk. 87 Because aerobic exercise training confers little increase in muscle strength, 88 resistance training, nutritional support, testosterone, and dietary creatine supplementation have been explored as strategies to increase muscle mass. Although resistance training increases force-generating 742 Recent Advances in Chest Medicine

6 Figure 4. Forest plot demonstrating overall effect for difference in peak rate of oxygen uptake achieved with one- vs two-legged cycling. This figure has been published previously as follows: (i) Pulmonary Rehabilitation. Evans RA, Goldstein RS. In: Physical Medicine and Rehabilitation: Principles and Applications, Book Series of Comprehensive Biomedical Physics; Copyright Elsevier; Figure 7 (in press) 79 ; (ii) Evans RA, Goldstein RS. Role of Pulmonary Rehabilitation in COPD. Focus on COPD. 2010;1(4): ; (iii) Evans RA, Goldstein RS. Pulmonary rehabilitation. In: SK Jindal, eds. Handbook of Pulmonary and Critical Care Medicine. New Delhi, India: Jaypee Brothers Medical Publishers Ltd; 2010; Figure ; and (iv) Evans RA, Goldstein RS. Pulmonary rehabilitation: an overview including new and innovative strategies-reprinted by permission of Edizioni Minerva Medica from: Minerva Pneumologica. 2011; 50(1): capacity, 89 and these gains may be enhanced with the use of testosterone, 90 it is unclear whether this confers additional improvements in performance above aerobic exercise training alone. 89 The impact of nutritional interventions 91 and creatine supplementation 92 remains inconclusive, creating a need for additional investigation in this area. Arm Training Systematic reviews 93,94 of RCTs examining the effect of arm training in COPD noted improvements in arm exercise performance, and RCTs of arm train ing completed after these systematic reviews have confirmed improvements in arm muscle strength, arm exercise performance, arm function, and ease of performing activities of daily living. 95,96 Costi et al 95 reported that 15 sessions over 3 weeks of arm training during PR that comprised five unsupported arm exercises performed at 50% of the patient s maximum force improved arm function and activities of daily living at the end of the study and at 6-month follow-up. In 2011, Janaudis-Ferreira et al 96 reported that 6 weeks of arm training performed three times a week during PR at loads equal to the 10- to 12-repetition maximum using free weights and a multistation gym conferred between-group differences in arm function, arm exercise capacity, and muscle strength. These data support the inclusion of an arm training program in PR. Fall Risk Individuals with COPD have reductions in all subcomponents of postural control, including biomechanical constraints, stability limits/verticality, anticipatory postural adjustments for postural transitions, reactive postural response strategies, weighting of sensory information for orientation, and postural stability during gait.86 In response to balance perturbations, they have an increased center of pressure displacement and a delayed reaction time for balance recovery. 86,97 Almost one-half of the individuals in a PR program reported at least one fall in the preceding year, 98 and almost one-third of those under the care of a pulmonologist reported a fall over a 6-month period. 99 Clinical balance tests, number of medications, and comorbid conditions discriminate between self-reported fallers and nonfallers, 98,99 with balance confidence and the use of supplemental oxygen being independent predictors of falls. 98 PR without specific balance training does not affect balance in a meaningful way. 100 The role of a balance training program to reduce falls in those at greatest risk remains to be reported. journal.publications.chestnet.org CHEST / 142 / 3 / SEPTEMBER

7 Rollator Prescription The use of a rollator (ie, wheeled walker) has been shown to confer gains in 6MWD and reduce dyspnea on exertion. 101 Such changes appear to be the consequence of the forward lean position and fixation of the arms, serving to optimize ventilatory capacity as well as improved mechanical efficiency. 102,103 Although those who need to rest during a 6-min walk test are most likely to benefit from the use of a rollator, 101 whether these devices enhance exercise training among those with the greatest functional limitations is unknown. Self-Management Self-management teaches the skills for patients to comply with disease-specific treatment; guides health behavior changes; and assists patients to optimize their coping skills, mastery, and self-efficacy related to their chronic condition. 104 It often includes diseasespecific education, action plans, and goal setting. A Cochrane review of self-management revealed reductions in hospitalizations and a small improvement in HRQL. 104 Because studies noting reduced hospitalizations or faster recovery from AECOPD have combined aspects of self-management education with access to a case manager, 105,106 it is important to clarify which support intervention was the major influence on the observed improvements. Psychologic Support Anxiety and depression are common in COPD 107 and have been associated with poor exercise capacity, worse HRQL, greater dyspnea, and increased healthcare resource utilization. 108,109 Data from a metaanalysis of six RCTs demonstrate that comprehensive PR reduces anxiety and depression, 110 the main responsible component being exercise training. 111 Although studies on cognitive behavioral therapy in COPD suggest a reduction in psychologic distress, 112,113 it is unclear whether these gains are over and above those seen following a comprehensive PR program or which patients are most likely to benefit. Acute Exacerbations Further Challenges Acute exacerbations have deleterious effects on physical activity, 114 muscle function, 115 exercise capacity, and HRQL. 116 Studies have demonstrated that PR is safe and effective during or immediately following an AECOPD. Man et al 117 reported that PR within 10 days of discharge from the hospital improved the distance walked during an incremental shuttle walk test (between-group difference, 60 m; 95% CI, m), and Seymour et al 118 extended these observations to include a reduction in readmission to the hospital for repeat exacerbations (usual care vs PR, 33% vs 7%; OR, 0.15; 95% CI, ). Work demonstrated that resistance exercise performed during hospitalization for AECOPD optimized muscle force without increasing systemic inflammation. 119 It is possible that for patients hospitalized with an AECOPD, resistance exercise added to standard early mobilization followed by ongoing participation in PR after discharge will emerge as a pattern of best practice. Improving Access PR is mostly offered at hospital outpatient settings, and long journey time and parking costs limit attendance or program completion. 120 A multicenter Canadian study demonstrated similar outcomes between PR provided in an outpatient department and PR at home.121 Those who trained at home received a visit from an exercise specialist to establish the training program, were assigned a cycle ergometer for use in their home, and were encouraged through weekly telephone calls. 121 Therefore, home-based PR, if appropriately resourced, offers an alternate approach to accessing this service for patients with COPD. Another barrier to providing PR, particularly in remote settings, is the perception that an effective exercise program is contingent on the availability of expensive equipment, such as treadmills and cycle ergometers. However, a study demonstrated that high-intensity ground walking performed in isolation from other forms of exercise training was effective at increasing functional exercise capacity, 14 suggesting that the exercise component of PR can be effectively delivered in the absence of sophisticated exercise equipment. Access to PR in remote settings might be facilitated by the use of telemedicine. In 2011, a study that provided access to an established PR program through videoconferencing plus some local clinic resources reported gains in HRQL and exercise capacity of similar magnitude to those achieved following outpatient PR. 122 Other technology applications with a potential to enhance PR include the use of cell phones and motion sensors to encourage physical activity during daily life 123,124 and interactive Internet-based interfaces to provide education and guidance regarding self-management of dyspnea and exercise. 125 Maintaining Benefits Regular physical activity after formal PR slows the decline in HRQL 126 and may decrease hospital admissions and mortality. 29 Completion of annual repeat PR programs confers short-term gains without longterm benefits after 2 years. 127 Monthly supervised exercise training plus regular telephone contact after 744 Recent Advances in Chest Medicine

8 PR does not maintain gains 128,129 nor does monthly visits to a physiotherapist offered in conjunction with abbreviated PR following an AECOPD. 130 In contrast, weekly classes at a hospital or community setting appears to preserve improvements following PR. 131,132 The issue of long-term adherence to PR will require a more integrated approach between health facilities and community facilities. Respiratory Conditions Other Than COPD Over the past few years, RCT data have emerged to support the effectiveness of exercise training in persons with interstitial lung disease, 133 life-long asthma, 134 bronchiectasis, 135 and pulmonary hypertension. 136 Over the next few years, data from current RCTs will be available to support the effectiveness of PR in chronic lung diseases other than COPD Future Directions PR has a positive impact on exercise capacity, HRQL, dyspnea, and fatigue 6 and reduces healthcare resource utilization. 35 Recent interest in the systemic nature of COPD has resulted in the use of multidimensional indices. There are exciting novel approaches to optimize training in patients with marked ventilatory limitation to exercise, and evidence is increasing to support PR in respiratory conditions other than COPD. Issues that continue to challenge us include (1) optimizing access to PR, (2) translating gains in exercise capacity into increased physical activity, (3) strategies to maintain the gains made during PR, (4) minimizing the deleterious effects of AECOPD, and (5) establishing whether PR confers a survival benefit. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript. References 1. Barach AL, Bickerman HA, Beck G. Advances in the treatment of non-tuberculous pulmonary disease. Bull N Y Acad Med ;28(6): Petty TL, Nett LM, Finigan MM, Brink GA, Corsello PR. A comprehensive care program for chronic airway obstruction. Methods and preliminary evaluation of symptomatic and functional improvement. Ann Intern Med ;70(6): Belman MJ, Kendregan BA. Exercise training fails to increase skeletal muscle enzymes in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis ;123(3): Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis ;143 (1 ): Maltais F, LeBlanc P, Simard C, et al. Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;154 (2 pt 1 ): Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev ;(4 ):CD Puhan MA, Gimeno-Santos E, Scharplatz M, Troosters T, Walters EH, Steurer J. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev ;(10 ):CD Nici L, Donner C, Wouters E, et al ; ATS/ERS Pulmonary Rehabilitation Writing Committee. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med ; 173 (12 ): Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical practice guidelines. Chest ;131 (suppl 5 ):4S-42S. 10. Turner SE, Eastwood PR, Cecins NM, Hillman DR, Jenkins SC. Physiologic responses to incremental and selfpaced exercise in COPD: a comparison of three tests. Chest ;126 (3 ): Hill K, Dolmage TE, Woon L, Coutts D, Goldstein R, Brooks D. Comparing peak and submaximal cardiorespiratory responses during field walking tests with incremental cycle ergometry in COPD. Respirology ;17 (2 ): Hsia D, Casaburi R, Pradhan A, Torres E, Porszasz J. Physiological responses to linear treadmill and cycle ergometer exercise in COPD. Eur Respir J ;34 (3 ): Eaton T, Young P, Nicol K, Kolbe J. The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients. Chron Respir Dis ;3 (1 ): Leung RW, Alison JA, McKeough ZJ, Peters MJ. Ground walk training improves functional exercise capacity more than cycle training in people with chronic obstructive pulmonary disease (COPD): a randomised trial. J Physiother ;56 (2 ): Dodd JW, Hogg L, Nolan J, et al. The COPD Assessment Test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study. Thorax ;66 (5 ): Palange P, Ward SA, Carlsen KH, et al ; ERS Task Force. Recommendations on the use of exercise testing in clinical practice. Eur Respir J ;29 (1 ): Pepin V, Saey D, Whittom F, LeBlanc P, Maltais F. Walking versus cycling: sensitivity to bronchodilation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;172 (12 ): Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med ;350 (10 ): Puhan MA, Garcia-Aymerich J, Frey M, et al. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index. Lancet ;374 (9691 ): Jones RC, Donaldson GC, Chavannes NH, et al. Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: the DOSE index. Am J Respir Crit Care Med ;180 (12 ): Esteban C, Quintana JM, Aburto M, Moraza J, Capelastegui A. A simple score for assessing stable chronic obstructive pulmonary disease. QJM ;99 (11 ): journal.publications.chestnet.org CHEST / 142 / 3 / SEPTEMBER

9 22. Nishimura K, Izumi T, Tsukino M, Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest ;121 (5 ): Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J ;34 (3 ): Wright JG. The minimal important difference: who s to say what is important? J Clin Epidemiol ;49 (11 ): Pepin V, Laviolette L, Brouillard C, et al. Significance of changes in endurance shuttle walking performance. Thorax ;66 (2 ): Dolmage TE, Hill K, Evans RA, Goldstein RS. Has my patient responded? Interpreting clinical measurements such as the 6-minute-walk test. Am J Respir Crit Care Med ;184 (6 ): Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;171 (9 ): Garcia-Aymerich J, Farrero E, Félez MA, Izquierdo J, Marrades RM, Antó JM ; Estudi del Factors de Risc d Agudització de la MPOC Investigators. Risk factors of readmission to hospital for a COPD exacerbation: a prospective study. Thorax ;58 (2 ): Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Antó JM. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax ;61 (9 ): Garfield BE, Canavan JL, Smith CJ, et al. Stanford sevenday physical activity recall questionnaire in chronic obstructive pulmonary disease [published online ahead of print December 19, 2011]. Eur Respir J. doi: / Jehn M, Schmidt-Trucksäss A, Schuster T, Hanssen H, Halle M, Köhler F. Pedometer accuracy in patients with chronic heart failure. Int J Sports Med ;31 (3 ): Pitta F, Troosters T, Spruit MA, Decramer M, Gosselink R. Activity monitoring for assessment of physical activities in daily life in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil ;86 (10 ): Hill K, Dolmage TE, Woon L, Goldstein R, Brooks D. Measurement properties of the SenseWear armband in adults with chronic obstructive pulmonary disease. Thorax ;65 (6 ): Hill K, Dolmage TE, Woon L, Coutts D, Goldstein R, Brooks D. Defining the relationship between average daily energy expenditure and field-based walking tests and aerobic reserve in COPD. Chest ;141 (2 ): Griffiths TL, Burr ML, Campbell IA, et al. Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial [published corrections appears in Lancet. 2000;355(9211):1280]. Lancet ; 355 ( 9201 ): Maltais F, LeBlanc P, Jobin J, et al. Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med ; 155 (2 ): Troosters T, Gosselink R, Decramer M. Exercise training in COPD: how to distinguish responders from nonresponders. J Cardiopulm Rehabil ;21 (1 ): Punzal PA, Ries AL, Kaplan RM, Prewitt LM. Maximum intensity exercise training in patients with chronic obstructive pulmonary disease. Chest ;100 (3 ): Burgomaster KA, Hughes SC, Heigenhauser GJ, Bradwell SN, Gibala MJ. Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. J Appl Physiol ;98 (6 ): Vogiatzis I, Terzis G, Nanas S, et al. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest ;128 (6 ): Beauchamp MK, Nonoyama M, Goldstein RS, et al. Interval versus continuous training in individuals with chronic obstructive pulmonary disease a systematic review. Thorax ;65 (2 ): Zainuldin R, Mackey MG, Alison JA. Optimal intensity and type of leg exercise training for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev ; (11 ):CD O Donnell DE, D Arsigny C, Webb KA. Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;163 (4 ): Somfay A, Porszasz J, Lee SM, Casaburi R. Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic COPD patients. Eur Respir J ; 18 ( 1 ): Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R. Benefits of supplemental oxygen in exercise training in nonhypoxemic chronic obstructive pulmonary disease patients. Am J Respir Crit Care Med ;168 (9 ): Nonoyama ML, Brooks D, Lacasse Y, Guyatt GH, Goldstein RS. Oxygen therapy during exercise training in chronic obstructive pulmonary disease. Cochrane Database Syst Rev ;(2 ):CD Sandland CJ, Morgan MD, Singh SJ. Patterns of domestic activity and ambulatory oxygen usage in COPD. Chest ;134 (4 ): Nonoyama ML, Brooks D, Guyatt GH, Goldstein RS. Effect of oxygen on health quality of life in patients with chronic obstructive pulmonary disease with transient exertional hypoxemia. Am J Respir Crit Care Med ;176 (4 ): Moore RP, Berlowitz DJ, Denehy L, et al. A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia. Thorax ;66 (1 ): Palange P, Valli G, Onorati P, et al. Effect of heliox on lung dynamic hyperinflation, dyspnea, and exercise endurance capacity in COPD patients. J Appl Physiol ;97 (5 ): Vogiatzis I, Habazettl H, Aliverti A, et al. Effect of helium breathing on intercostal and quadriceps muscle blood flow during exercise in COPD patients. Am J Physiol Regul Integr Comp Physiol ;300 (6 ):R1549-R Chiappa GR, Queiroga F Jr, Meda E, et al. Heliox improves oxygen delivery and utilization during dynamic exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;179 (11 ): Eves ND, Petersen SR, Haykowsky MJ, Wong EY, Jones RL. Helium-hyperoxia, exercise, and respiratory mechanics in chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;174 (7 ): Laude EA, Duffy NC, Baveystock C, et al. The effect of helium and oxygen on exercise performance in chronic obstructive pulmonary disease: a randomized crossover trial. Am J Respir Crit Care Med ;173 (8 ): Eves ND, Sandmeyer LC, Wong EY, et al. Helium-hyperoxia: a novel intervention to improve the benefits of pulmonary reha bilitation for patients with COPD. Chest ; 135 ( 3 ): Scorsone D, Bartolini S, Saporiti R, et al. Does a low-density gas mixture or oxygen supplementation improve exercise training in COPD? Chest ;138 (5 ): Lacasse Y, Lecours R, Pelletier C, Bégin R, Maltais F. Randomised trial of ambulatory oxygen in oxygen-dependent COPD. Eur Respir J ;25 (6 ): Recent Advances in Chest Medicine

10 58. Nonoyama ML, Brooks D, Guyatt GH, Goldstein RS. Ambulatory gas usage in patients with chronic obstructive pulmonary disease and exertional hypoxemia. J Cardiopulm Rehabil Prev ;28 (5 ): O Donnell DE, Sanii R, Giesbrecht G, Younes M. Effect of continuous positive airway pressure on respiratory sensation in patients with chronic obstructive pulmonary disease during submaximal exercise. Am Rev Respir Dis ; 138 (5 ): van t Hul A, Kwakkel G, Gosselink R. The acute effects of noninvasive ventilatory support during exercise on exercise endurance and dyspnea in patients with chronic obstructive pulmonary disease: a systematic review. J Cardiopulm Rehabil ;22 (4 ): Borghi-Silva A, Oliveira CC, Carrascosa C, et al. Respiratory muscle unloading improves leg muscle oxygenation during exercise in patients with COPD. Thorax ; 63 ( 10 ): Corner E, Garrod R. Does the addition of non-invasive ventilation during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease augment patient outcome in exercise tolerance? A literature review. Physiother Res Int ;15 (1 ): Duiverman ML, Wempe JB, Bladder G, et al. Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic patients with COPD. Thorax ;63 (12 ): Duiverman ML, Wempe JB, Bladder G, et al. Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: a randomized controlled trial. Respir Res ;12 : Collins EG, Langbein WE, Fehr L, et al. Can ventilationfeedback training augment exercise tolerance in patients with chronic obstructive pulmonary disease? Am J Respir Crit Care Med ;177 (8 ): Vanderthommen M, Duchateau J. Electrical stimulation as a modality to improve performance of the neuromuscular system. Exerc Sport Sci Rev ;35 (4 ): Filipovic A, Kleinöder H, Dörmann U, Mester J. Electromyostimulation a systematic review of the influence of training regimens and stimulation parameters on effectiveness in electromyostimulation training of selected strength parameters. J Strength Cond Res ; 25 ( 11 ): Thériault R, Boulay MR, Thériault G, Simoneau JA. Electrical stimulation-induced changes in performance and fiber type proportion of human knee extensor muscles. Eur J Appl Physiol Occup Physiol ;74 (4 ): Bourjeily-Habr G, Rochester CL, Palermo F, Snyder P, Mohsenin V. Randomised controlled trial of transcutaneous electrical muscle stimulation of the lower extremities in patients with chronic obstructive pulmonary disease. Thorax ;57 (12 ): Neder JA, Sword D, Ward SA, Mackay E, Cochrane LM, Clark CJ. Home based neuromuscular electrical stimulation as a new rehabilitative strategy for severely disabled patients with chronic obstructive pulmonary disease (COPD). Thorax ;57 (4 ): Vivodtzev I, Debigaré R, Gagnon P, et al. Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial. Chest ;141 (3 ): Nuhr MJ, Pette D, Berger R, et al. Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure. Eur Heart J ;25 (2 ): Sillen MJ, Wouters EF, Franssen FM, Meijer K, Stakenborg KH, Spruit MA. Oxygen uptake, ventilation, and symptoms during low-frequency versus high-frequency NMES in COPD: a pilot study. Lung ;189 (1 ): Abdellaoui A, Préfaut C, Gouzi F, et al. Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study. Eur Respir J ;38 (4 ): Zanotti E, Felicetti G, Maini M, Fracchia C. Peripheral muscle strength training in bed-bound patients with COPD receiving mechanical ventilation: effect of electrical stimulation. Chest ;124 (1 ): Dolmage TE, Goldstein RS. Response to one-legged cycling in patients with COPD. Chest ;129 (2 ): Dolmage TE, Goldstein RS. Effects of one-legged exercise training of patients with COPD. Chest ; 133 ( 2 ): Bjørgen S, Hoff J, Husby VS, et al. Aerobic high intensity one and two legs interval cycling in chronic obstructive pulmonary disease: the sum of the parts is greater than the whole. Eur J Appl Physiol ;106 (4 ): Evans RA, Goldstein RS. Physical Medicine and Rehabilitation: Principles and Applications. Book Series of Comprehensive Biomedical Physics. Philadelphia, PA: Elsevier. In press. 80. Evans RA, Goldstein RS. Role of pulmonary rehabilitation in COPD. Focus on COPD. 2010;1(4): Evans RA, Goldstein RS. Pulmonary rehabilitation. In: Jindal SK, Shankar PS, Raoof S, Gupta D, Aggarwal AN, eds. Handbook of Pulmonary and Critical Medicine. New Delhi, India: Jaypee Brothers Medical Publishers; 2010: Evans RA, Goldstein RS. Pulmonary rehabilitation: an over view including new and innovative strategies. Minerva Pneumol. 2011;50(1): Bjørgen S, Helgerud J, Husby V, Steinshamn S, Richadson RR, Hoff J. Aerobic high intensity one-legged interval cycling improves peak oxygen uptake in chronic obstructive pulmonary disease patients; no additional effect from hyperoxia. Int J Sports Med ;30 (12 ): Marquis K, Debigaré R, Lacasse Y, et al. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;166 (6 ): Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med ;153 (3 ): Beauchamp MK, Sibley KM, Lakhani B, et al. Impairments in systems underlying control of balance in COPD. Chest ;141 (6 ): Moreland JD, Richardson JA, Goldsmith CH, Clase CM. Muscle weakness and falls in older adults: a systematic review and meta-analysis. J Am Geriatr Soc ;52 (7 ): Bernard S, Whittom F, Leblanc P, et al. Aerobic and strength training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med ;159 (3 ): O Shea SD, Taylor NF, Paratz JD. Progressive resistance exercise improves muscle strength and may improve elements of performance of daily activities for people with COPD: a systematic review. Chest ;136 (5 ): Casaburi R, Bhasin S, Cosentino L, et al. Effects of testosterone and resistance training in men with chronic obstruc tive pulmonary disease. Am J Respir Crit Care Med ;170 (8 ): Ferreira IM, Brooks D, Lacasse Y, Goldstein RS, White J. Nutritional supplementation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev ;(2 ): CD Al-Ghimlas F, Todd DC. Creatine supplementation for patients with COPD receiving pulmonary rehabilitation: a systematic review and meta-analysis. Respirology ; 15 (5 ): journal.publications.chestnet.org CHEST / 142 / 3 / SEPTEMBER