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Pulmonary rehabilitation for dyspnea in the palliative-care setting

Sachs, Sharona; Weinberg, Richard L

Current Opinion in Supportive and Palliative Care: June 2009 - Volume 3 - Issue 2 - p 112–119
doi: 10.1097/SPC.0b013e32832b7248
Respiratory problems: Edited by David C. Currow and Amy P. Abernethy
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Purpose of review Although pulmonary rehabilitation has reproducibly improved dyspnea and quality of life indices in patients with chronic obstructive pulmonary disease (COPD), its suitability to the palliative-care setting is not well established. Evolutions in exercise design, self-monitored home-based programs, and understanding of the patient populations that may benefit are rendering pulmonary rehabilitation more feasible for patients with significant impairment. In this review, we focus on the recent developments that translate most successfully into the palliative-care setting.

Recent findings Several lower intensity protocols – including interval training and single-leg ergometry – compare positively with the gold standard of high-intensity aerobic exercise in improving dyspnea and functional capacity. Passive strategies such as neuromuscular electrical stimulation have been demonstrated to improve muscle strength and mass and reduce exertional dyspnea. Home-based, self-monitored programs compare favorably with outpatient hospital-based programs. There is increasing evidence that pulmonary rehabilitation is well tolerated and effective for patients with severe COPD, and that other diseases associated with disabling dyspnea may improve symptomatically with pulmonary rehabilitation.

Summary Recent innovations in pulmonary rehabilitation interventions and setting allow the flexibility to facilitate its incorporation into an individualized palliative plan of care. Appropriately tailored, pulmonary rehabilitation may provide additional opportunities to optimize functional capacity and reduce symptom burden.

Capital Hospice and Palliative Care Consultants, 6565 Arlington Blvd, Suite 500, Falls Church, Virginia, USA

Correspondence to Sharona Sachs, MD, 6565 Arlington Blvd, Suite 500, Falls Church, VA 22042, USA Tel: +1 703 396 6197; fax: +1 703 779 1372; e-mail: ssachs@capitalhospice.org

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Introduction

Pulmonary rehabilitation has developed an expanded role in the care of people with advanced respiratory disease. Within the past 2 years, the American College of Chest Physicians (ACCP) and the American Thoracic Society (ATS)/European Respiratory Society (ERS) have both issued position papers reinforcing the role of pulmonary rehabilitation in the care of patients with chronic obstructive pulmonary disease (COPD), and less specifically, those with severe respiratory symptoms. The most consistently cited improvements are in degree of dyspnea and health-related quality of life (HRQOL) [1,2]. The ATS/ERS statement articulates that pulmonary rehabilitation ‘should no longer be viewed as a last ditch effort for patients with severe respiratory impairment’, reflecting the hitherto uncomfortable positioning of pulmonary rehabilitation at the outer edge of traditional therapeutic intervention. The ATS/ERS defines pulmonary rehabilitation as ‘an evidence based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. Integrated into the individualized treatment of the patient, pulmonary rehabilitation is designed to reduce symptoms, optimize functional status, increase participation, and reduce health-care costs through stabilizing or reversing systemic manifestations of the disease’ [2].

At its core, pulmonary rehabilitation is predicated on the model of medical-care delivery as a partnership between patient and healthcare providers in which education, self-efficacy and self-care are stressed. This philosophy, implemented through a multidisciplinary approach directed at enhanced symptom control rather than specific disease modification, is precisely aligned with the goals of palliative care. However, many palliative-care specialists see pulmonary rehabilitation as an intervention reserved for patients more functionally preserved than a traditionally defined palliative-care population, just as many pulmonologists and internists still view pulmonary rehabilitation as a ‘last ditch effort’ with inconsistent impact on ‘hard’ endpoints of disease outcome such as forced expiratory volume at one second (FEV1) and mortality. The perceived place of pulmonary rehabilitation on the fringe of both curative intent and palliative intent therapy reflects the positioning of its target population at the optimal transitional meeting point between these therapeutic philosophies. The incorporation of pulmonary rehabilitation into palliative practice (and of palliative specialists into pulmonary rehabilitation) offers a powerful model for dynamic collaboration in managing patients with chronic progressive disease.

Disease trajectory in chronic respiratory illness is difficult to define. Unlike the general pattern seen in cancer-related progressive disease, in which there is a fairly precipitous decline from relatively preserved function to death, cardiopulmonary disease is associated with a gradual decline from moderate function to death with multiple symptomatic dips along the way [3]. As the primary symptom is dyspnea and the functionally preserved preterminal phase is long, there is a profound need for symptomatic intervention above and beyond that offered by optimization of disease-specific therapy. In these diseases, perhaps more than any others, the opportunities for upstream palliative-care involvement are huge, and the signposts signaling transition from curative to palliative intent therapy are often not well recognized by either patients or clinicians. Incorporation of pulmonary rehabilitation into a palliative strategy represents a unique opportunity to foster seamless transition from curative to palliative intent therapy. This process requires a flexible understanding of the heterogeneous population likely to derive benefit and ongoing reassessment of whether and how the interventions that decrease dyspnea, improve HRQOL, maintain function and self-esteem, and lessen depression and social isolation earlier in disease can be preserved at later stages, when ability to participate in active exercise is more limited.

There are several areas of active investigation in pulmonary rehabilitation that has specific implications for palliative care. These include unresolved questions about what interventions – type, site, and duration – are most effective and which patient populations and disease states are likely to derive benefit. In this review, we focus on the current literature that addresses these areas in order to define the elements of pulmonary rehabilitation that translate most successfully into the palliative-care setting. We have specifically limited our focus to those developments in pulmonary rehabilitation that broaden its application to higher levels of disease severity, streamline resource utilization, and demonstrate impact on subjective indices such as dyspnea and HRQOL.

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Pulmonary rehabilitation: the role of exercise

Although efforts are being made to adapt pulmonary rehabilitation to other cardiopulmonary disease states in which disabling dyspnea is a prominent complaint, the primary pooled data assessing the optimal structure and efficacy of pulmonary rehabilitation programs are from the COPD population. Unless otherwise specified, this will be the population referenced herein. The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) has issued guidelines for the elements that should be included in a pulmonary rehabilitation program, but as yet there is no uniformly agreed upon program composition [4]. The single mandatory component of a pulmonary rehabilitation program is aerobic-exercise training. A comprehensive program includes the addition of disease-management education, chest physiotherapy instruction, and/or psychosocial support [1]. In the graded evidence-based guidelines of the ACCP/AACVPR, there is a high grade of evidence that such a comprehensive pulmonary rehabilitation program improves dyspnea and HRQOL, and that the exercise strategy should include focus on the muscles of ambulation. Lacasse et al.[5] have analyzed 31 randomized controlled trials in a Cochrane review from 2006. Looking at studies in which a minimum of 4 weeks of exercise with or without education or psychosocial support were compared with conventional care, they found that pulmonary rehabilitation was associated with clinically significant improvements in dyspnea, fatigue, sense of control over disease, and emotions. There were trends toward improvement in indices of exercise capacity slightly below the set threshold for clinical significance.

Some form of exercise reproducibly plays a key role in the short-term benefit derived from pulmonary rehabilitation. Carrieri-Kohlman and colleagues [6,7] have studied the ‘dose–response’ curve for exercise. They prospectively randomized 103 patients to one of three programs: dyspnea self-management, in which individualized education sessions about dyspnea, disease exacerbation recognition, and self-care strategies were coupled with a home walking prescription, daily log, and telephone monitoring; this program plus approximately bimonthly supervised treadmill exercise sessions for 2 months; or the identical education program plus 24 supervised treadmill exercise sessions over the same interval. The group receiving education and the full complement of exercise sessions had the greatest improvement in exercise performance and reduction in exercise-associated dyspnea at 6 and 12 months. At 2 months, there was a dose-dependent improvement in HRQOL in the exercise groups. Interestingly, over time (4, 8, and 12 months), all three groups demonstrated comparable improvements in dyspnea and HRQOL scores.

The investigators also evaluated the impact of all three regimens on depression in those judged by the Center for Epidemiological Studies Depression scale to be at high risk. All three interventions resulted in equal and significant reductions in depressed mood. Patients at high risk of depression who underwent the most intensive exercise intervention had the greatest improvement in dyspnea, compared with those receiving lesser or no exercise [8]. Other investigators confirm improvements in dyspnea and self-esteem related to comprehensive pulmonary rehabilitation [9] and cite significant reductions in depression and anxiety in addition to and independent of improvements in dyspnea and HRQOL [10].

In an effort to isolate those components of a comprehensive program responsible for improvements in functional status, exercise tolerance and HRQOL, Norweg et al.[11] randomized 43 outpatients to either exercise alone (predominantly treadmill based); exercise plus a structured behavioral intervention emphasizing dyspnea-management techniques (so-called activity training); and exercise plus didactic lectures in healthy lifestyle (including pathophysiology and medications), stress management, and relaxation. Although limited by study size, there was a suggestion that activity training in addition to exercise conferred the highest short-term benefit to older patients, and that the addition of the lecture series did not translate into discernible benefit with regard to HRQOL. There was no demonstrable difference in exercise tolerance among the treatment groups. Further studies are required to better isolate the minimal elements necessary to optimize improvements in HRQOL and dyspnea. The disease-management educational strategies and psychosocial interventions that translate easily into the palliative-care setting clearly add value, but have not consistently demonstrated independent influence on dyspnea perception and HRQOL.

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Active exercise strategies: continuous versus interval training

High intensity endurance training directed at the muscles of ambulation (cycling or treadmill) is the cornerstone of traditional pulmonary rehabilitation. However, patients that have significant functional impairment may not be able to undergo such a program. Several investigators have examined lower intensity exercise alternatives with promising results [12,13]. Puhan et al.[13] assessed the impact of exercise intensity on both ability to comply with the exercise prescription and impact on HRQOL. They randomized 98 patients with severe COPD to either continuous high-intensity exercise at a target workload of 70% of maximal exercise capacity; or so-called interval exercise, which consisted of periods of lesser intensity exercise to 50% target workload interspersed with even lower intensity (10%) intervals. Patients in both exercise groups derived significant and comparable benefit with regard to HRQOL after 5 weeks. Patients in the continuous high intensity group had a significantly higher incidence of unintended breaks. In a recently published subgroup analysis [14], the authors examined the outcome differences in patients who required more than one major break (lasting more than 1 min) versus those that did not. The subgroup compositions were relatively equivalent with respect to degree of impairment. Patients able to complete the prescription with one or fewer breaks had significantly greater increments in exercise capacity, with a nonstatistically significant improvement in HRQOL. Although limited by the constraints of a-posteriori subgroup analysis, the data support the need to tailor exercise prescription to capacity.

Another such strategy that has been recently investigated is the effect of one-legged exercise training in the setting of severe COPD. Hypothesizing that cycling with a single leg (lesser muscle mass) would impose less of a ventilatory stress and potentially allow a higher muscle-specific intensity/training effect than conventional bipedal cycling, Dolmage and Goldstein [15••] randomized 18 patients (mean FEV1 38% ± 17% predicted) to either 7 weeks of three times per week (TIW) 30-min sessions of continuous two-legged cycling to maximum tolerated intensity; or the same schedule of exercise with cyclists using one leg for 15 min, then switching to the other leg for the remaining 15 min. Both groups increased their training intensity and total work, but the one-legged cyclists had greater improvements in aerobic capacity. Further studies defining the ideal population for such a protocol and impact on HRQOL are planned.

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Active exercise strategies: respiratory muscle training, noninvasive support

Other variations on active exercise under investigation include using computer-assisted feedback to alter respiratory pattern with exercise [16•] and specifically targeting the muscles of respiration for training. Many investigators have explored whether specific inspiratory muscle training can positively influence exercise tolerance or dyspnea. Results have been mixed, with some studies citing improvements in inspiratory muscle strength/endurance and dyspnea, and others showing no benefit [17–19]. Given the available evidence, the burdens of added complexity and exercise stress do not seem to be balanced by sufficient benefit in the palliative-care setting.

Other evolving strategies to assist patients with significant impairment in participating in graduated exercise programs include a variety of adjunctive noninvasive ventilatory options. There are increasingly sophisticated strategies tailored to disease pathophysiology that have been shown to reduce dyspnea and enhance exercise tolerance. Given our goal of providing the broadest application to a palliative-care population, detailed discussion of these are beyond the scope of this chapter; however, the reader is referred to recent reviews by Ambrosino et al.[20,21•].

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Passive exercise strategies: neuromuscular electrical stimulation

Transcutaneous NMES has been investigated as an alternative to whole body exercise in patients with severe cardiopulmonary compromise, most notably, those with severe COPD and congestive heart failure (CHF). First employed in preventing deconditioning in healthy athletes recovering from injury and in paraplegics, NMES has been shown to improve muscle strength, muscle mass, and exercise performance [22]. Although study sizes are small, several investigators [22–24] have shown that this intervention is well tolerated and either alone [22] or in combination with exercise [23] leads to improvements in strength, muscle mass, exercise capacity, and sense of dyspnea during activities of daily living. These benefits were demonstrable in the patient population likeliest to be seen in the palliative-care setting – patients with severe COPD and low-body weight who were often too dyspneic to participate to maximum training effect in standard exercise programs [23]. In an even more severely impaired population – bed-bound ventilator-dependent COPD patients with marked peripheral muscle atrophy – Zanotti et al.[24] combined NMES with active limb mobilization and showed significant improvements in muscle strength and patient function, measured as reduction in the number of days needed to transfer from bed to chair. Neder et al.[25] investigated the adaptability of this intervention to the home setting, and demonstrated that in patients with disabling dyspnea, a 6-week home-based NMES program was well tolerated and improved some but not all indices of peripheral muscle strength and endurance. Most importantly, there were substantial and statistically significant improvements in whole body exercise endurance and in the dyspnea domain of the HRQOL questionnaire. Vivodtzev et al.[26•] have recently comprehensively reviewed the feasibility and efficacy studies of NMES in COPD to date.

In patients with moderate to severe CHF, NMES has shown analogous benefit with regard to improved muscle mass and exercise endurance [27], and has been shown to yield equivalent results compared with conventional-exercise training [28]. In a severely compromised population awaiting heart transplantation, NMES showed positive impact on muscle mass and endurance, and conferred the additional benefit of significant improvements in HRQOL [29]. In both the COPD and CHF populations, the authors warn of a possible confounding effect on HRQOL from the additional attention conferred on the NMES study groups. Even with this caveat, NMES is an exciting intervention ripe for adaptation to the palliative-care setting given its potential for home-based treatment, tolerability, and consistent demonstration of objective benefit.

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Pulmonary rehabilitation logistics: intervention duration

The optimal duration of pulmonary rehabilitation has not been definitively established, but there are clear trends. In a randomized controlled trial comparing 4 versus 7 weeks of twice per week (BIW) outpatient rehabilitation, patients completing the longer program had improved Chronic Respiratory Questionnaire scores (the primary endpoint), and statistically significant increments in dyspnea reduction, emotional well being, and mastery [30]. When compared with 10 sessions, 20 sessions of comprehensive outpatient pulmonary rehabilitation produced statistically significant improvements in exercise capacity, global HRQOL, and specific activity and symptom indices [31]. Twice weekly sessions have been demonstrated to be inferior TIW sessions [32]. These results have led to the ATS/ERS guideline suggesting a minimum of 20 sessions implemented on a TIW schedule, of which at least one per week may be home based [2].

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Pulmonary rehabilitation logistics: intervention site

Potential barriers to participation in pulmonary rehabilitation by patients receiving care treatment in the palliative-care setting include the imposed burden of travel to an out-of-home setting and the complexity of services entailed in a comprehensive pulmonary rehabilitation program, which might limit access because of cost. Several recent studies have investigated variations on the traditional pulmonary rehabilitation model that address these burdens.

Over the last decade, significant attention has been focused on integrating standard pulmonary rehabilitation interventions into the home environment, with the primary objective of offsetting the diminution of benefit frequently seen over time following formal program participation. Initially, the home setting was investigated as a follow-up to formal outpatient pulmonary rehabilitation in an attempt to follow the intensive supervised exercise ‘induction’ phase with a home-based ‘maintenance phase’. Such home-based follow-up programs have been shown to confer either short-term or durable enhancement in exercise tolerance [33,34•,35,36].

In an important variation on this theme, Wewel et al.[37•] looked at a home-based intervention without preexposure to formal pulmonary rehabilitation. These investigators evaluated whether a short-term telephone intervention could alter activity, exercise tolerance, and HRQOL in a population of patients with severe COPD (mean FEV1 32.3 ± 9.4%predicted) who had not undergone preceding pulmonary rehabilitation. They first assessed baseline activity and home environment over 2 weeks in 21 participants. They then intervened with every-other-day phone calls to encourage three daily sessions of 15-min exercise to a predetermined individualized target. Patients were assessed with pre6-min-walk distances and post6-min-walk distances (6-MWD), Borg scale dyspnea measurement, activity monitors, and two quality of life scales. Total activity, 6-MWD, and vitality, social activity, and psychological indices of one of the two HRQOL instruments were significantly improved by the intervention.

The feasibility and efficacy of providing a fuller complement of rehabilitation services in the home setting have also been evaluated. Studying a 12-week program of home rehabilitation involving supervising physician, physiotherapist and nurse compared with no intervention, Wijkstra et al.[38] demonstrated improvements in exercise tolerance and dyspnea. In a three-armed comparison of 12-week hospital-based outpatient pulmonary rehabilitation, home-based pulmonary rehabilitation, and no pulmonary rehabilitation, Strijbos et al.[39] showed equivalent improvements in exercise tolerance, Borg dyspnea ratings, and well being in patients undergoing home pulmonary rehabilitation and those enrolled in a hospital-based program. This benefit was more sustained in the home-based pulmonary rehabilitation group compared with those participating in the hospital-based program.

Maltais et al.[40••] have conducted a larger scale study comparing self-monitored, home-based to outpatient hospital-based pulmonary rehabilitation programs in a randomized multicenter trial including both academic and community medical centers. The 252 patient trial successfully demonstrated noninferiority in the primary endpoint of change in Chronic Respiratory Questionnaire dyspnea score at one year. After a single home-based demonstration by a physiotherapist, patients in the home setting underwent a prescribed exercise course on leased ergometers to a predetermined target intensity. This target was set slightly below that for the patients in the supervised setting to maximize safety, but was compensated for by a 10-min extension in exercise duration. This investigation represents one of the largest trials directly comparing self-monitored home-based pulmonary rehabilitation and outpatient facility-based pulmonary rehabilitation. The results suggest that a self-monitored program can be both effective and well tolerated.

A Cochrane review that predates these recent investigations compared the more general category of home-based versus center-based ‘physical activity programs’ in older adults [41] with inconclusive results. The comparative efficacy of the intervention in this review was in part related to the underlying disease, with center-based studies showing short-term superiority in patients with peripheral vascular disease and mixed results in patients with COPD. In a CHF population, home-based exercise training was associated with a lower incidence of rehospitalization, but no sustained impact on functional status and quality of life [42].

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Patient population: disease severity

At present, palliative-care referral tends to occur primarily for patients with advanced disease. There are a number of recent studies that specifically examine pulmonary rehabilitation in this population. In the Maugeri study, a large multicenter investigation, the effects of inpatient pulmonary rehabilitation on patients with chronic respiratory failure (defined as resting pO2 below 60 mmHg or pCO2 above 45 mmHg) were compared with the effects in those without. The authors demonstrated equivalent and statistically significant improvement in indices of exercise capacity, dyspnea, and HRQOL, with modest improvements also noted in lung function [43]. Significant benefit has also been demonstrated in the severely impaired patients participating in the National Emphysema Treatment Trial (NETT), which investigated the role of lung volume reduction surgery in patients with very severe COPD [44•]. By definition, these patients (mean FEV1, 26.9% predicted) were sufficiently dissatisfied with their symptom burden/quality of life to consider surgical intervention. The trial mandated participation in pulmonary rehabilitation prior to randomization for all patients being considered for surgery, and demonstrated that pulmonary rehabilitation was associated with statistically significant improvements in exercise capacity, dyspnea, and HRQOL. A small fraction of patients derived sufficient symptomatic relief to withdraw from the study and opt against surgery. Lizak et al.[45] evaluated the impact of outpatient pulmonary rehabilitation in patients with severe dyspnea and found comparable improvements in severely dyspneic patients compared with those less afflicted, reinforcing that severe, disabling disease does not preclude benefit from pulmonary rehabilitation. They and other investigators [46] have also shown that gender does not appear to influence outcome.

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Patient population: disease state

Several older studies have suggested that pulmonary rehabilitation may be of benefit in a variety of lung diseases other than COPD. Despite the prevalence of disabling dyspnea in patients with interstitial lung disease (ILD) [47,48], few studies have focused exclusively on this population. In an observational study of 31 patients with interstitial lung disease, Jastrzebski et al.[49] demonstrated that a 12-week combination of inpatient and home-based pulmonary rehabilitation was feasible in this population, and resulted in improvements in dyspnea and some of the domains of HRQOL. More recently, Holland et al.[50] studied patients with ILD in a single-blinded randomized trial comparing an 8-week BIW outpatient pulmonary rehabilitation program with weekly telephone contact providing health advice and support. Immediately following completion of pulmonary rehabilitation, there were significant improvements in functional exercise capacity (6-MWD, the primary outcome measure) and in dyspnea and fatigue. These benefits were not sustained at 6-month follow-up.

Both aerobic and resistive exercise training have been shown to be of benefit in patients with CHF [51,52]. In a study of 30 patients with New York Heart Association class III CHF, Arad et al.[53] demonstrated that a rehabilitation program is feasible, and results in marked improvements in functional exercise capacity. As is the case in primary lung disease, these benefits did not correlate with improvements in indices of organ function, here measured as change in serum level of brain natriuretic peptide.

Pulmonary rehabilitation has shown more variable benefit in patients with lung cancer, not surprisingly, given the heterogeneity of this population. In a Cochrane review assessing the impact of noninvasive interventions on HRQOL in lung-cancer patients, Sola et al.[54] found significant benefit to nursing interventions aimed at dyspnea self-management. The single study of exercise included in the review focused on the role of pulmonary rehabilitation in augmenting sense of hope in patients undergoing resectional therapy with curative intent. Although benefit was suggested, this limited measurement in a narrow population does not readily generalize to the needs likely to be seen in the palliative-care setting. Spruitt et al.[55] evaluated the impact of inpatient pulmonary rehabilitation on functional exercise capacity in a group of 10 patients with stage I-III lung cancer having undergone therapy. In this small group, the investigators demonstrated marked baseline impairment in exercise capacity and significant improvement in functional exercise capacity not correlated with improvements in lung function after pulmonary rehabilitation. Importantly, despite improved functional capacity, there was no improvement in dyspnea or HRQOL. Although these results indicate the magnitude of impairment, more research is needed to define whether the benefits balance the burdens, as well as the precise lung cancer population in which pulmonary rehabilitation may be effective.

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Conclusion

Pulmonary rehabilitation has consistently produced significant improvements in functional capacity, dyspnea, and HRQOL, with benefit extending even to those with severe baseline impairment. Recent innovations include lower intensity exercise regimens and home-based programs, both of which demonstrate promising results. Appropriately individualized incorporation of pulmonary rehabilitation into a palliative plan of care may offer additional opportunities to optimize functional capacity and reduce symptom burden. As palliative medicine specialists become more familiar and involved with pulmonary rehabilitation, the potential for enhanced communication regarding end-of-life choices may provide additional benefit. Several studies have confirmed that patients enrolled in pulmonary rehabilitation want to discuss the burden/benefit of mechanical ventilation and to participate in end-of-life planning [56,57]; however, these discussions take place in only 20% [58]. Greater involvement by palliative specialists may result in more pervasive incorporation of palliative communication strategies into pulmonary rehabilitation programs.

In this review, we have outlined the evidence suggesting the potential for a broader niche for pulmonary rehabilitation in the palliative-care setting, and the innovations that are rendering its inclusion more feasible. Further study is required to assess which disease states other than COPD lend themselves to routine incorporation of pulmonary rehabilitation, what further modifications of exercise protocols are feasible and effective in patients with limited reserve, and whether more routine incorporation of palliative medicine experts into pulmonary rehabilitation fosters expansion of the structured end-of-life decision-making desired by patients and families and required by the escalating societal cost of futile end-of-life care.

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Acknowledgements

The authors gratefully acknowledge the contributions of Dr J. Cameron Muir in reviewing this manuscript and the expert research assistance of the library staff at Inova Fairfax Hospital.

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References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest

•• of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 145).

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Keywords:

dyspnea; palliative care; pulmonary rehabilitation

© 2009 Lippincott Williams & Wilkins, Inc.