Pulmonary rehabilitation

INTRODUCTION — Pulmonary rehabilitation improves symptoms, quality of life, pulmonary function, health care utilization, and may improve survival in patients with chronic respiratory disease. Most of the evidence supporting the benefit of pulmonary rehabilitation has been derived from studies of patients with chronic obstructive pulmonary disease (COPD). However, results obtained in patients with respiratory diseases different from COPD have provided evidence that the benefits from pulmonary rehabilitation are also observed in symptomatic patients with other respiratory diseases.

The indications, goals, and components of pulmonary rehabilitation and the potential benefits for patients with chronic lung disease will be reviewed here [1]. Other therapeutic modalities, such as smoking cessation, oxygen therapy, bronchodilators, antibiotics, nutritional support, respiratory muscle training and resting, and cardiac rehabilitation, are discussed separately. (See "Stable COPD: Initial pharmacologic management" and "Overview of smoking cessation management in adults" and "Long-term supplemental oxygen therapy" and "Malnutrition in advanced lung disease" and "Respiratory muscle training and resting in COPD" and "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary heart disease".)

DEFINITION — Pulmonary rehabilitation is a broad therapeutic concept. It is defined by the American Thoracic Society and the European Respiratory Society as a "comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors" [2,3]. This definition remains unchanged after a thorough review by the American Thoracic Society Assembly on Pulmonary Rehabilitation [4].

PATIENT SELECTION — Pulmonary rehabilitation is appropriate for most symptomatic patients with respiratory disease that is impairing their quality of life. The vast majority of studies have evaluated pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD).

The Global Initiative for Chronic Obstructive Disease recommends that pulmonary rehabilitation be included in the management of patients with chronic obstructive pulmonary disease (COPD) who are symptomatic with functional limitations (Group B) and suffering from moderate or severe exacerbations (Group E) (algorithm 1) [5]. Based on improvement in exercise capacity and likely improvement in dyspnea and quality of life, the American Thoracic Society also recommends pulmonary rehabilitation for patients with interstitial lung diseases and suggests that patients with pulmonary hypertension may also benefit [6].

Frailty affects approximately one-fourth of patients with COPD and is a predictor of noncompletion of pulmonary rehabilitation. However, a study of 816 patients with stable COPD of whom 212 (26 percent) met criteria for frailty found that those who completed pulmonary rehabilitation experienced reduced dyspnea, improved exercise performance and physical activity level, and 61 percent no longer met criteria for frailty [7]. Thus, frailty is not necessarily a contraindication. Similarly, chronic hypercapnia due to advanced COPD is not a contraindication, as benefit has been demonstrated in these patients [8].

Contraindications to pulmonary rehabilitation are infrequent, but include conditions that would place the patient at increased risk during exercise (eg, uncontrolled cardiac disease) or present obstacles to participation (eg, severe arthritis, neurologic impairment, cognitive or psychosocial disorders) [2].

Some patients with comorbid COPD and cardiac disease may be better suited to a cardiac rehabilitation program. (See "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary heart disease".)

PREPROGRAM EVALUATION — Prior to participation in a pulmonary rehabilitation program, each patient is assessed individually for severity of respiratory impairment, exercise tolerance, presence of comorbidities (especially cardiac, musculoskeletal, and neurologic disease), and cognitive-language-psychosocial problems [5,9].

Most pulmonary rehabilitation programs obtain preparticipation spirometry before and after bronchodilator, diffusing capacity for carbon monoxide, and exercise capacity testing. These tests are used to enable an appropriate exercise prescription for the program and to provide a baseline for post program comparisons. For physical training to be successful, it must exceed the physical loads that the patient already encounters in daily life and, therefore, exercise programs need to be tailored to the individual.

One of several clinical tests of exercise capacity may be used, such as the six-minute walk test, the shuttle walk test, or cardiopulmonary exercise testing [10,11]:

●In a six-minute walk test, the patient walks as far as possible during a period of six minutes; the total distance walked (in meters), oxygen saturation during the walk, and dyspnea are monitored [12]. In a systematic analysis of four trials that measured six-minute walk distance before and after pulmonary rehabilitation, the mean improvement in the six-minute walk test was 107 meters (95% CI 84-129) [13]. An increase of 35 meters or more is considered significant [14]. (See "Overview of pulmonary function testing in adults", section on 'Six-minute walk test'.)

●For a shuttle walk test, the patient walks back and forth between two cones using either a progressive increase in speed or a constant speed at 85 percent of a previous maximal speed [10,15]. In an analysis of two trials that measured shuttle walk distance before and after pulmonary rehabilitation, the mean improvement in the shuttle walk test was 81 meters (95% CI 48-115) [13]. (See "Overview of pulmonary function testing in adults", section on 'Incremental shuttle walk test' and "Overview of pulmonary function testing in adults", section on 'Endurance shuttle walk test'.)

●Cardiopulmonary exercise testing (CPET) is the most comprehensive of the three tests and uses either a cycle ergometer or a treadmill to measure physiologic outcomes such as oxygen uptake, carbon dioxide output, tidal volume, minute ventilation, electrocardiographic tracings, and pulse oximetry [10,16]. In the rehabilitation setting, it is typically reserved for patients in whom the cause of dyspnea is unclear and for research studies. The peak oxygen uptake (mL/min) or the peak work power (Watts) achieved during a CPET can serve as a guide to determine the intensity of the training workload to target in individual exercise training. (See "Exercise physiology".)

PRACTICAL ASPECTS

Setting — Pulmonary rehabilitation programs may be conducted in a hospital, outpatient, or home setting. Most of the research has involved outpatient pulmonary rehabilitation programs with one to three visits per week. The optimal setting has not been determined and may vary with the patient and community. Increased exercise endurance following lower extremity exercise has been demonstrated in both hospital and home settings [17-31].

For some patients, pulmonary rehabilitation is initiated during a hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (COPD). While ventilatory limitations may limit aerobic exercise, resistive muscle training has been well-tolerated in this setting and is associated with improved muscle strength and six-minute walk distance [2,32,33]. Although there has been interest in starting rehabilitation early in patients admitted to intensive care units with respiratory failure, randomized trials have shown similar results for most outcomes in the group of patients receiving early pulmonary rehabilitation compared with those receiving usual care [34]. One study that enrolled 389 patients found an increased risk of death in those patients randomized to the rehabilitation arm [35]. Other studies have found that enrollment within 14 or 90 days, respectively, after discharge improved outcomes compared with later or no enrollment [36,37]. Thus, it may be best to wait until the patient is stable to maximize the benefits of exercise training. Transportation issues and frailty may limit participation after discharge.

The number of sessions per week offered by the different types of programs varies; outpatient programs commonly meet two or three days/week, while inpatient programs are usually planned for five days/week [2].

Preliminary evidence suggests that an eight week, home-based rehabilitation with telephone calls from a physiotherapist may achieve short-term improvements comparable to outpatient programs [38]. Web-based programs and telemedicine offer another attractive alternative, and the results of initial studies appear promising [31,39,40].

Monitoring — During exercise training, dyspnea, breath sounds, diaphoresis, blood pressure, heart rate, and oxygen saturation are monitored [2]. Continuous telemetry is generally not used. If necessary, supplemental oxygen is added and titrated to an oxygen saturation >88 percent. Blood glucose monitoring before and after exercise is prudent for patients with diabetes.

Exercise is interrupted if the patient develops severe dyspnea (eg, Borg score ≥7), chest pain, lightheadedness, palpitations, tachycardia, hypotension, or refractory hypoxemia.

Duration — The optimal duration of a pulmonary rehabilitation program is uncertain. In one randomized trial, there was little difference between a four and seven week program [41]. It is generally believed, however, that longer programs (eg, 8 to 12 weeks) confer more durable benefits with a minimum of eight weeks advised to achieve a substantial effect [2,42,43].

Improvement in functional exercise capacity seems to plateau within 12 weeks of the start of the pulmonary rehabilitation program, despite continued training [44-46].

Maintenance — Observational trials and common sense suggest that a program of exercise maintenance should provide additional benefits compared with a return to a pre-rehabilitation lifestyle. A multicenter trial randomly assigned 143 patients with moderate/severe COPD to a weekly maintenance program or clinical follow-up for over three years, after an eight week conventional pulmonary rehabilitation program [47]. All patients improved significantly their exercise capacity, dyspnea, and health status after the basic eight-week program. Marginal but significant differences were noted between the maintenance and control groups in BODE index and six-minute walk distance up to two years, but the benefit vanished after that time. Interestingly, no difference was found in mortality between the groups over the three years.

A novel option used to maintain the symptomatic and functional gains obtained after formal rehabilitation programs of patients with COPD is the use of digital means to promote physical activity. Recently, a randomized control trial was completed in 67 patients with symptomatic COPD [48]. The intervention group consisted of 33 patients who were instructed and monitored in the use of a smartphone application (app) consisting of an exercise training program, breathing exercises, and educational instructions. The patients used an activity tracker to monitor step counts and were followed for six months with quality-of-life and dyspnea scales. The control group also wore the activity tracker every day and used a smartphone for the step count and functional assessments but had no access to the COPD app. At the end of the study, the step count was significantly higher in the intervention group (5000 steps; 95% CI, 2900-10,200) compared with the control group (3100 steps; 95% CI, 600-4400). The intervention group also showed significant improvement in the COPD Assessment Test (CAT) and in dyspnea and fatigue scores. These results suggest that digital interventions may be useful to maintain the gains obtained after pulmonary rehabilitation, which usually reverse over time as patients tend to return to pre-rehabilitation activity levels.

Attendance — Regular attendance during a rehabilitation program is desirable, but not always possible. Factors found to decrease attendance include: current smoking, greater breathlessness, higher frequency of hospital admissions, shorter walked distance in the six-minute walk distance, longer duration of the program (eg, 18 versus 6 weeks), and longer journey time [49].

COMPONENTS — Pulmonary rehabilitation consists of exercise training, promotion of healthy behaviors (eg, smoking cessation, regular exercise, healthy nutrition, proper medication use, adherence to prescribed medications, and disease self-management), and psychological support (eg, improving self-efficacy and providing coping strategies for chronic illness). A summary of the desired components needed for a pulmonary rehabilitation program is provided in the figure (figure 1).

Exercise limitation in patients with chronic obstructive pulmonary disease (COPD) and other respiratory diseases is multifactorial and includes ventilatory limitation, gas transfer abnormalities, pulmonary vascular and cardiac dysfunction, limb muscle dysfunction, and comorbid impairments such as those due to peripheral arterial disease and arthritis. Overall, pulmonary rehabilitation aims to improve cardiorespiratory and skeletal muscle function (eg, ambulation) and thereby reduce dyspnea and fatigue and improve quality of life.

Exercise training — The optimal type of training for patients with lung disease has not been determined and may vary among individuals, but the majority of studies and programs have utilized endurance training. Interval training, and resistance/strength training have also shown benefits and could be used in combination with or instead of endurance training.

Endurance training — Endurance training (also known as conditioning) is the most common exercise training method employed in pulmonary rehabilitation programs. Endurance exercise can be performed using lower or upper extremity exercise, although lower extremity training (eg, stationary cycling, treadmill, or free walking) has been better studied and is at the center of most pulmonary rehabilitation programs. In general, the training load must be greater than the loads the patient experiences in daily life and should progress as the patient's endurance improves. Improving skeletal muscle function reduces the ventilatory demands of exercise and improve exercise capacity.

Endurance exercise training with an arm or leg ergometer is typically prescribed three to five times a week with continuous exercise for 20 to 30 minutes at 60 percent of the individual's maximal work rate or greater [2]. As an example, a patient who can achieve a maximal workload of 100 watts may target exercise at a workload of 60 to 70 watts continuously for the entire session. This intensity of exercise is usually associated with a dyspnea Borg score of 4 to 6, correlating with moderate to severe dyspnea or fatigue (table 1).

Lower extremity exercise — Increased exercise endurance has been demonstrated following lower extremity exercise programs in multiple controlled and uncontrolled studies performed in both hospital and home settings [17-27].

While the weight of evidence supports a role for lower extremity exercise in improving the functional status of patients with COPD, the optimal duration of the activity, frequency of the exercise sessions, and intensity of the task remain poorly defined [50,51]. In general, studies demonstrating physiologic improvement tend to have the most intense exercise prescriptions. However, even patients with the most severe COPD and poor exercise performance can undergo exercise training. One study evaluated 50 patients with COPD who had a range of forced expiratory volume in one second (FEV₁) from 0.38 to 3.24 L [52]. An inverse relationship was observed between the baseline 12-minute walk distance and the improvement following exercise training.

The mechanism by which exercise improves endurance remains unclear. The benefits generally occur without change in pulmonary function tests or static respiratory muscle mechanics. Because of these observations, it was thought for many years that desensitization to dyspnea was the most important mechanism responsible for the observed benefit [53]. However, rigorous studies have proven that exercise training leads to biological and physiological changes in the skeletal muscles and the pattern of breathing of these patients that are responsible for the observed improvement.

One study with 11 participants demonstrated a true training effect based on the finding that an endurance training program led to skeletal muscle adaptation, characterized by an increased concentration of skeletal muscle oxidative enzymes [54]. Another report showed reductions in exercise-induced lactic acidosis and ventilation after training [55]. The improvement was proportional to the intensity of the training, with a 12 percent lower rise in lactic acidosis in patients trained at a low work rate versus a 32 percent lower rise in patients trained at a high work rate.

That the benefits of endurance training extend to the dynamics of breathing was borne out in a detailed physiological study of the respiratory pattern of breathing during exercise in patients with COPD. In that study [56], at the same level of physical work (watts) before and after rehabilitation, patients who underwent exercise training had a lower respiratory rate, lower ventilatory requirement, and less dynamic lung hyperinflation. This allowed them to perceive less dyspnea and to increase their exercise endurance.

The absence of significant lactic acidosis during exercise does not preclude achieving a training effect. In a study of 25 patients with COPD who underwent a six week cycle ergometry exercise program, rehabilitation resulted in a mean increase of 36 percent in peak work rate and 77 percent in endurance on a constant work rate test despite the absence of significant metabolic acidosis during baseline testing [57]. A physiologic training effect was demonstrated by a lower heart rate response during constant work rate testing and evidence of faster kinetics of oxygen consumption and carbon dioxide production, ie, the steady-state values were achieved sooner during exercise.

Upper extremity exercise — Most of our knowledge about exercise conditioning is derived from programs emphasizing leg training. This is unfortunate, because the performance of many everyday tasks requires the use of hands plus the concerted action of other muscle groups that are used in upper torso and arm positioning. Some of these muscle groups serve a dual function (respiratory and postural), and use of the muscles for arm exercise decreases their capacity to participate in ventilation [58]. Arm training results in improved performance, which is mostly task specific [58-60]. Although some studies suggest a possible effect of arm training on respiratory muscle function [58], others found no change in ventilatory muscle performance [53,59,60].

In a study comparing different types of upper extremity exercise, unsupported arm training (against gravity) decreased oxygen uptake more than arm cranking training at the same workload [61]. Thus, unsupported arm exercise may be a more effective way of training patients in activities that resemble those of daily living [62]. In a meta-analysis, unsupported upper extremity exercise decreased dyspnea and arm fatigue during activities of daily living, but did not result in a clinically important difference in the Borg scale (table 1) [63]. Like lower extremity exercise, the optimal duration of the activity, frequency of the exercise sessions, and intensity of the task remain poorly defined for upper extremity exercise.

Interval exercise training — During interval training, intervals of high intensity exercise are alternated with periods of rest or lower intensity exercise. An advantage of interval training is that individuals who are not able to reach the prescribed intensity or duration of endurance training due to severe dyspnea or oxygen desaturation may derive benefit from interval exercise training [64-67]. Regimens of interval training in pulmonary rehabilitation typically achieve a similar total work amount compared to continuous training and produce similar results [2].

This was best illustrated by a trial that randomly assigned 98 patients with severe COPD to receive interval or continuous exercise training for three weeks, followed by exercise at home [64]. At the end of the three weeks, the groups had similar improvement in quality of life and six-minute walking distance. However, adherence to the assigned protocol was higher in the interval training group (48 versus 24 percent).

In addition, a randomized trial of 42 patients with moderately severe COPD found that interval load exercise had a similar effect on BODE improvement compared with constant load exercise (calculator 1) [68].

The optimal durations of high intensity and rest/low intensity intervals are not known; intervals of high intensity exertion may need to be shorter than one minute to achieve a decreased dyspnea relative to endurance exercise [66].

Resistance/strength training — Resistance/strength training has a greater potential to improve muscle mass and strength than endurance training. During resistance/strength training, individual muscle groups are trained by repetitive lifting of weights, selected based on the individual's capacity. The optimal approach to resistance training in pulmonary rehabilitation has not been determined, but preliminary evidence suggests that it provides additive benefit to endurance training. One potential benefit is that resistance exercise results in lower oxygen consumption and minute ventilation and evokes less dyspnea, which may be advantageous for patients who are less tolerant of endurance training.

Light weight training may provide additional benefit to endurance training. One report, for example, evaluated 14 patients with COPD enrolled in a home program [23]. The patients were randomly assigned to daily walking while carrying a light backpack (controls) or the same regimen with additional weight lifting (wrist and arms curls, partial leg squats, calf raises, and supine dumbbell press) [23]. After training, weight lifters had reduced their minute ventilation and increased their ergometry endurance by 16 percent, when compared with controls.

Alternative exercise training modalities — Less conventional forms of exercise or muscle training may offer new avenues of therapy, such as breathing retraining, ventilatory muscle training, neuromuscular electrical stimulation, Tai Chi, and flexibility training. Studies are less robust, and the role of these therapies in pulmonary rehabilitation is less clear.

Breathing retraining — Patients with lung disease may have a rapid shallow breathing pattern, and it is thought that rapid shallow breathing is deleterious to ventilation and gas exchange due to the potential increase in dead space ventilation and progressive air trapping. Interventions designed to change the breathing pattern have produced conflicting results [9]:

●Retraining with breathing techniques that decrease breathing frequency, such as yoga and pursed lip breathing have in some studies led to increases in tidal volume and oxygen saturation, and a reduction in dyspnea [69]. In a meta-analysis that included sixteen studies with a total of 1233 participants, three months of yoga with timed breathing techniques were associated with a significant improvement in six-minute walk distance, but there was no consistent improvement in dyspnea or health-related quality of life [70].

●Diaphragmatic breathing, a technique that aims to increase tidal volume through focusing on diaphragmatic descent, has yielded variable results [70]. In one study with 30 participants, four weeks of supervised diaphragmatic breathing reduced dyspnea and increased six minute walk distance compared with usual care [71]. On the other hand, a smaller study found that diaphragmatic breathing increased the work of breathing and dyspnea in patients with COPD compared with natural breathing [72]. It is very difficult to individually train specific respiratory muscles because they are all required to function synchronously, so the results of these studies have to be interpreted with caution. Theoretically, any decrease in breathing rate and prolongation of the expiratory time should be of benefit to patients with COPD and hyperinflation. On the other hand, for patients with restrictive disease, the respiratory constraints differ, and the same techniques may not apply.

Ventilatory muscle training — Hyperinflation in COPD leads to flattening and shortening of the diaphragm, anatomically reducing its pressure-generating capacity. Attempts to increase the strength and/or endurance of the ventilatory muscles have had mixed results. As examples:

●A meta-analysis of 25 studies that assessed the efficacy of inspiratory muscle training in patients with stable COPD found significant increases in inspiratory muscle strength, exercise capacity, and one measure of quality of life and a significant decrease in dyspnea [73]. However, two randomized trials with over 750 patients enrolled showed improvement in respiratory muscle strength, but no improvement in patient reported outcomes [74,75].

●A meta-analysis of 17 randomized studies of ventilatory muscle training (VMT) revealed nonsignificant changes in muscle strength in 11 studies and in respiratory muscle endurance in the nine studies in which that outcome was assessed [76]. However, in five studies in which there were improvements in strength or endurance of the breathing muscles, gains in functional capacity were noted.

As with upper and lower extremity exercise training, the optimal duration, frequency, and intensity of VMT remain to be defined. Furthermore, an effective response may be dependent upon controlling the pattern of breathing during the inspiratory maneuver to ensure that an adequate training stimulus has been achieved, ie, 30 percent of maximal inspiratory pressure [77]. While VMT is not recommended as a routine element in pulmonary rehabilitation programs, it may be considered in selected patients with COPD and ventilatory muscle weakness [50].

Other — Other types of exercise training that may eventually have a role in pulmonary rehabilitation include transcutaneous neuromuscular electrical stimulation, Tai Chi, and flexibility training.

●Transcutaneous neuromuscular electrical stimulation (NMES) – NMES involves electrical stimulation and contraction of individual muscles with minimal cardiorespiratory involvement. NMES may be appropriate for selected patients with severe respiratory or cardiac limitations to exercise. NMES appears to improve limb muscle strength and exercise capacity and reduce dyspnea [2,78]. Contraindications based on expert opinion include implanted pacemaker or defibrillator, seizure disorder, uncontrolled cardiac arrhythmias, unstable angina, and knee or hip osteoarthritis or joint replacement.

●Tai Chi involves a series of slow and rhythmic movements performed in a focused manner and accompanied by deep breathing. Based on two systematic reviews, on average, patients trained with Tai Chi improved functional capacity and pulmonary function when compared with usual care [79,80]. Its benefit compared with standard pulmonary rehabilitation exercise programs is less clear [2], although a randomized trial of 120 patients observed improved scores in health status 12 weeks after program completion in the Tai-Chi group compared with standard pulmonary rehabilitation [81].

●Flexibility training – Flexibility training may improve respiratory function through better posture and thoracic mobility, but is not well-studied [2].

Education — Education about lung disease and its management has long been a component of pulmonary rehabilitation (table 2) [82]. Collaborative approaches to improve self-efficacy may be more effective in achieving behavior change than didactic approaches [2].

Promotion of healthy behaviors — All patients should receive education to improve lung disease self-management. Useful topics include smoking cessation, oxygen therapy, nutrition, physical activity, proper use of medications, and health preservation (eg, vaccinations). Several studies show that patients instructed about the nature of their disease and the implications of therapy can better understand, recognize, and treat the symptoms of their disease [83].

●Smoking cessation – Smoking cessation may be difficult to achieve because of the strong psychological and physiologic dependence. Nonetheless, it should be at the center of any rehabilitation program, since smoking cessation is the most beneficial therapy for long-term outcomes in any patient with respiratory disease. Some approaches that may be helpful include patient education about the risks of continued smoking, referral to smoking cessation group programs, nicotine replacement therapy, and other pharmacotherapy. However, caution and diplomacy are needed when approaching this topic in the context of pulmonary rehabilitation as cigarette smoking is an independent predictor of lack of successful completion of pulmonary rehabilitation [84]. (See "Overview of smoking cessation management in adults" and "Pharmacotherapy for smoking cessation in adults".)

●Long term oxygen therapy (LTOT) – Education about the indications for LTOT, importance of not smoking when oxygen is in use, types of oxygen delivery devices, and logistics of travelling with oxygen are standard components of pulmonary rehabilitation education. (See "Long-term supplemental oxygen therapy" and "Portable oxygen delivery and oxygen conserving devices" and "Evaluation of patients for supplemental oxygen during air travel".)

●Nutritional counseling and weight management – Attention to a healthy diet is particularly important in lung disease. Patients with lung disease are at risk for obesity due to limitations to physical activity and adverse effects of oral glucocorticoids given for exacerbations; weight loss can help reduce the work of breathing. Other patients, typically those with advanced lung disease may suffer from progressive weight loss and malnutrition. (See "Healthy diet in adults" and "Malnutrition in advanced lung disease".)

●Proper use of medications – With the broad spectrum of inhaled medications for COPD, it is helpful to review how the various medications work in COPD and the correct techniques for using inhalers and nebulizers. (See "The use of inhaler devices in adults" and "Delivery of inhaled medication in adults".)

●Health preservation – Other components of health preservation include disease self-management (eg, action plan), strategies for symptom control, avoidance of respiratory irritants, importance of maintaining physical activity, and obtaining appropriate vaccinations. (See "Seasonal influenza vaccination in adults" and "Pneumococcal vaccination in adults".)

While helpful, education alone does not appear to be an effective substitute for exercise training (table 2).

●In one study, 76 patients with COPD were randomized to three treatment groups that included behavior modification, cognitive modification, and behavior-cognitive modification [85]. They were compared with two control groups. After three months, the treatment groups increased their exercise endurance and an index of quality of life, compared to controls. Unfortunately, some patients in the treatment groups were encouraged to perform walking and breathing exercises, thereby confounding the results.

●Four studies in which education alone was used as a control intervention, and the results compared to treatment with exercise, found that education alone was of little benefit [17,22,86,87]. In one report, for example, 119 patients with COPD were randomized to a comprehensive rehabilitation program or to education alone [86]. The comprehensive program was associated with increases in exercise tolerance and endurance (+10.3 versus +1.3 min with education) and in a dyspnea score (-7.0 versus +0.6 with education).

Advance care planning — Education about advance care planning is an accepted component of pulmonary rehabilitation programs [88-90]. Specific topics may include the following:

●Understanding your disease and prognosis

●Discussing goals of care and advance care planning with health care provider and family/caregivers

●Life-sustaining treatments

●Surrogate decision-making

●Advance directive documents (eg, a durable power of attorney for health care, also known as health care proxy, and a living will)

●Process of dying and end-of-life care

●Prevention of suffering

Ideally, the discussion will enable patients to feel more comfortable discussing these issues with their family/caregivers and significant others. The patient may be able to use the process of designating a health care proxy to provide family/caregivers with a clear sense of their goals for treatment and preferences regarding the use of life-sustaining treatments, such as mechanical ventilation, cardiopulmonary resuscitation, feeding tubes, and dialysis. (See "Advance care planning and advance directives" and "Patient education: Advance directives (The Basics)" and "Palliative care for adults with nonmalignant chronic lung disease".)

Psychological support — Severe pulmonary disease is a risk factor for the development of anxiety and depression, which may contribute to fatigue and activity avoidance [2,5,91]. This can result in decreased participation in social activities, often including sexual activity.

These problems are likely to improve as patients become involved in a pulmonary rehabilitation program [92], and protracted psychologic counseling is usually not necessary. It has been shown, for example, that 15 to 20 rehabilitation sessions that include education, exercise breathing techniques, and relaxation techniques are more effective in reducing anxiety than a similar number of psychotherapy sessions [93]. A meta-analysis of 11 studies comprising 734 participants showed that pulmonary rehabilitation conferred significant benefits of a moderate magnitude for anxiety symptoms and large magnitude for depression symptoms [94], likely contributing to the significant increase in health status scores that this therapy provides.

Loss of dignity has been identified as a concern among patients with advanced COPD and correlates with anxiety and depression. Among 195 patients with COPD participating in an inpatient pulmonary rehabilitation program, loss of dignity was noted by 25 (13 percent) at the start of the program, but was substantially improved or resolved at completion of the program [95].

One randomized trial of 20 patients with severe COPD showed that pulmonary rehabilitation improved depression scores independent of changes in quality of life and dyspnea [96]. However, in some patients it may be necessary to administer short courses of antidepressant medications. Issues about sexuality should be raised and discussed and, when necessary, sexual counseling should be initiated. (See "Generalized anxiety disorder in adults: Management" and "Unipolar depression in adults and initial treatment: General principles and prognosis".)

BENEFITS — Patients with chronic obstructive pulmonary disease (COPD) often decrease their physical activity because exercise can induce or worsen dyspnea. The progressive deconditioning associated with inactivity initiates a vicious cycle, with dyspnea becoming problematic at ever lower physical demands. Pulmonary rehabilitation aims to break the cycle. Patient-related outcome benefits of pulmonary rehabilitation include decreased dyspnea, improved health-related quality of life, fewer days of hospitalization, and decreased health-care utilization (table 3) [13,97-99].

Initiation of exercise rehabilitation during or immediately after admission to a medical ward for acute or chronic respiratory failure reduces the extent of functional decline and hastens recovery [100]. It may also reduce health care costs, readmissions, and mortality [13,17,101], as long as the patient is not so ill that pulmonary rehabilitation may not offer any benefit [34]. Indeed, one multicenter trial of 389 patients admitted to the intensive care unit observed an increased mortality risk in patients randomized to pulmonary rehabilitation within 48 hours of admission to the unit [35]. More studies are needed in patients sick enough to be admitted to intensive care before this issue is clarified.

Mortality — Studies of pulmonary rehabilitation increasingly support a mortality benefit [13,97,102-105]. In a systematic review that included 670 participants with COPD, the meta-analysis did not find a statistically significant reduction in mortality (pooled OR 0.68, 95% CI 0.28-1.67) based on low quality evidence [13]. A subsequent retrospective cohort study of 197,376 Medicare beneficiaries hospitalized for COPD found that initiation of pulmonary rehabilitation within 90 days of discharge was associated with a reduction in all-cause mortality at one year (absolute risk difference -6.7 percent; 95% CI -7.9 to -5.6 percent) [37]. As this was not a randomized trial, factors other than pulmonary rehabilitation participation may have contributed to the observed effect. A subsequent randomized trial of 150 patients found greater benefit in exercise capacity, but not in overall one year mortality in patients enrolled within two weeks after discharge or the same rehabilitation program initiated two months after discharge [36]. Taken together these results suggest that the program can be started as early as two weeks after an admission for COPD exacerbation.

Exercise capacity and lung function — Pulmonary rehabilitation has been associated with improvements in exercise capacity and dynamic mechanics of breathing during exercise.

A meta-analysis of 65 randomized controlled trials concluded that pulmonary rehabilitation was more effective than standard community-based care with respect to functional exercise capacity (figure 2) [99]. The six-minute walk distance was greater following pulmonary rehabilitation than with community care and exceeded the threshold of clinical significance (mean difference [MD] 43.93 meters, 95% CI 32.64 to 55.21; participants = 1879; studies = 38). Maximal exercise testing in participants allocated to pulmonary rehabilitation compared with usual care revealed an increase in maximal workload (MD 6.77, 95% CI 1.89 to 11.65; N = 779; studies = 16).

Findings from individual studies include the following: In a prospective observational study of 1218 participants, pulmonary rehabilitation was associated with improved exercise capacity [102]. A three-year prospective case control study of 80 patients with moderate to severe COPD showed improvements in body mass index (BMI), lung function, and health status with pulmonary rehabilitation compared with usual care [104]. One trial randomized 89 stable patients with COPD to an eight-week in hospital rehabilitation program (including leg and upper extremity exercise) followed by 16 weeks of outpatient supervision or conventional community care [25]. Dyspnea, six-minute walk distance, and submaximal cycling time improved significantly with the hospital-based program. In a randomized trial, exercise training in a pulmonary rehabilitation program followed by a maintenance program improved the BODE index and the six-minute walk distance for two years compared to usual medical care, but the benefits seemed to vanish after that time [47].

Quality of life — The effectiveness of medical interventions is increasingly being judged by their impact on a patient's quality of life, a criterion that requires data on a range of patient symptoms, activities, social interactions, and psychological state. Several studies have demonstrated improved quality of life following both inpatient [102,103,105] and outpatient [17,106-108] pulmonary rehabilitation programs.

A meta-analysis of 65 randomized controlled trials concluded that pulmonary rehabilitation was more effective than standard community-based care in the four important domains of quality of life based on scores on the Chronic Respiratory Questionnaire (CRQ) [99]. Scores for dyspnea, fatigue, emotional function and mastery were greater than the minimal clinically important difference (MCID) of 0.5 units (dyspnea: MD 0.79, 95% CI 0.56-1.03, N = 1283; studies = 19; fatigue: MD 0.68, 95% CI 0.4-0.92, N = 1291; studies = 19; emotional function: MD 0.56, 95% CI 0.34-0.78, N = 1291; studies = 19; mastery: MD 0.71, 95% CI 0.47-0.95, N = 1212; studies = 19). Statistically significant improvements were noted in all domains of the St. George's Respiratory Questionnaire (SGRQ; MD -6.89, 95% CI -9.26 to -4.52, N = 1146; studies = 19).

Robustness — Pulmonary rehabilitation improves markers of frailty in patients with respiratory disease in large part by increasing physical performance of the lower limb muscles [109]. Patients with frailty who complete rehabilitation also benefit in terms of symptom burden and quality of life, as described above, with some studies showing that they derive even more benefit than the average COPD patient [7,110]. However, patients with frailty are more likely to experience comorbidities, unplanned hospital admissions, and clinical deterioration that prevents them from regular participation in rehabilitation programs [111].

In one study of 816 patients with COPD, over 60 percent of frail patients who subsequently completed an eight-week pulmonary rehabilitation program (n = 115) no longer met criteria for frailty [7]. Patients who were initially frail showed greater improvements in dyspnea (MMRC score), handgrip strength, incremental shuttle walk test, Chronic Respiratory Disease Questionnaire score (fatigue, emotional and mastery domains), COPD Assessment Test (CAT) score, and anxiety and depression (HADS score) than patients without frailty, even after adjusting for age and sex. However, being frail nearly doubled the odds of program noncompletion (adjusted OR 2.20, 95% CI 1.39-3.46), most often due to exacerbation and/or hospital admission.

This "frailty rehabilitation paradox," whereby those with frailty are both the most likely to benefit and least likely to complete rehabilitation, is a challenge in the field. Adaptive and flexible approaches to rehabilitation delivery, including robust outreach to frail patients and opportunities to return for supervised training or catch-up sessions, may improve the ability of programs to help this patient population [109].

Health care utilization — Several uncontrolled studies suggest that pulmonary rehabilitation decreases total hospital stay and recurrent hospitalization rates in patients with COPD. The average decrease was 23 days per year per patient for the studies analyzed [112-114]. The longest study thus far included 64 patients followed for four years [114]. For the 44 patients alive at the end of the study, hospitalization had decreased from a cumulative level of 529 days (12 days per patient per year) in the year prior to therapy to an average of 145, 270, 278, and 207 days (an average of five days per patient per year) for the four years of follow-up.

The benefits have been less clear in controlled studies [86,101,115,116]. One report found a decrease in hospitalization over six months in a group of treated patients when compared with controls [115]. In contrast, a subsequent large study found only a modest (-2.4 days per patient per year) and not statistically significant decrease in hospitalization rate in the in patients participating in a comprehensive rehabilitation program [86]. A subsequent study randomly assigned 99 patients to a six-week program of pulmonary rehabilitation, while 101 patients received usual care [116]. After one year, there were no differences in the number of patients hospitalized, although the length of stay was significantly shorter among hospitalized patients who had been randomized to rehabilitation.

Effect of comorbidities — Patients with COPD are likely to have additional comorbid diseases, such as hypertension, diabetes, heart failure, and coronary heart disease [117,118]. Among 2962 patients with COPD enrolled in a pulmonary rehabilitation program, the presence of comorbidities, particularly metabolic diseases and heart disease, reduced the likelihood of an improved outcome [117]. However, a prospective study in 316 patients with moderate to severe COPD, performed by the same investigators, found that only functional disability at baseline and coexisting osteoporosis resulted in a poorer outcome from pulmonary rehabilitation [118]. While the numbers are small, the presence of coronary artery disease in 11 percent did not adversely affect the likelihood of achieving improved exercise tolerance and quality of life.

Durability of benefits — The benefits of pulmonary rehabilitation decline over time [2,119]; however, the optimal role, intensity, and timing of periodic retraining of patients to sustain the initial gains has yet to be defined [2,106,120].

An observational study evaluated 48 patients who participated in five successive hospital-based rehabilitation programs over a seven-year period [119]. The patients showed improvement in exercise capacity, health status, dyspnea, and the BODE index (calculator 1) at the end of each program, although the degree of improvement decreased with successive programs. Exercise tolerance, dyspnea, and health-related quality of life did not worsen over the seven years despite progressive worsening in forced expiratory volume in one second.

Maintenance with a simplified program, including self-monitoring, helped to maintain improvements in exercise tolerance and health status in an observational study [121], while repeat programs reproduced the initial gains in another [122]. Results from a randomized trial in 143 patients showed that the benefits of maintenance were maintained for two years, after which the difference between treated and controls waned [47]. (See 'Maintenance' above.)

PULMONARY REHABILITATION IN CONDITIONS OTHER THAN COPD — While individuals with chronic obstructive pulmonary disease (COPD) comprise the highest proportion of referrals for pulmonary rehabilitation and study participants, individuals with other chronic lung diseases, including interstitial lung disease, bronchiectasis, cystic fibrosis, asthma, pulmonary artery hypertension, lung cancer, and lung transplantation, also derive benefit [2,3].

●Interstitial lung disease – Dyspnea on exertion and poor exercise tolerance are key features of interstitial lung disease (ILD). Increased exercise tolerance, decreased dyspnea, and improved quality of life have been demonstrated in trials of pulmonary rehabilitation [123,124]. It has been suggested that ILD-focused educational content regarding the disease process, symptom management, oxygen use, medications, and end-of-life counselling would be helpful to participants with ILD [125]. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Pulmonary rehabilitation'.)

●Bronchiectasis – Bronchiectasis is associated with cough, purulent sputum production, recurrent respiratory infection, airflow limitation, and dyspnea, leading to reduced conditioning. A few small trials found that pulmonary rehabilitation led to improvements in outcomes such as inspiratory muscle strength, incremental shuttle walking distance, and endurance exercise capacity, compared with control. The role of pulmonary rehabilitation in bronchiectasis is discussed separately. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Pulmonary rehabilitation'.)

●Cystic fibrosis – Exercise training has an established role in the management of patients with cystic fibrosis [2]. To minimize the risk of transmission of resistant organisms between patients, certain infection control guidelines should be followed. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Infection prevention and control' and "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Exercise'.)

●Asthma – Exercise training can improve asthma symptoms, anxiety, depression, and quality of life [126,127]. Pre-exercise use of bronchodilators and gradual warm-up may reduce exercise-induced bronchoconstriction [2]. (See "Exercise-induced bronchoconstriction".)

●Pulmonary arterial hypertension (PAH) – Muscular deconditioning is common in PAH due to abnormal pulmonary vascular responses to exercise. The role of exercise training in PAH is less well-established than in other lung diseases due to concerns about syncope and sudden death. For patients with a good response to targeted therapy for PAH, low level (submaximal) exercise appears safe in a monitored setting and can lead to improvement in exertional dyspnea and in the six minute walk test distance [128]. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)", section on 'General measures and supportive therapy'.)

●Lung cancer – Patients with lung cancer often experience muscle weakness, deconditioning, fatigue, and anxiety, which may be compounded by the effects of underlying COPD [2,129]. Limited data suggest that pulmonary rehabilitation is associated with benefits in walking endurance, peak exercise capacity, dyspnea, and fatigue [2,130].

●Lung transplantation – Pulmonary rehabilitation plays an essential role in the management of individuals both before and after lung transplantation [2]. Increased exercise tolerance achieved in pulmonary rehabilitation has the potential to improve surgical outcomes and postoperative rehabilitation improves recovery [131,132].

●COVID-19 – Many patients who have survived COVID-19 infection have developed so-called "long-COVID" characterized by symptoms such as dyspnea, headaches, fatigue, muscle weakness, and depression with important impairment in functional capacity. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")".)

Several studies suggest that pulmonary rehabilitation may be of benefit in patients with respiratory involvement from COVID-19 who remain symptomatic after the acute episode:

•A systematic review of five randomized trials of pulmonary rehabilitation in patients recovering from COVID-19 infection included 512 participants aged 49 to 69 years (of whom 65 percent were males) [133]. Three of the randomized control trials compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two different active rehabilitation interventions. Improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. These findings support the use of rehabilitation to lessen the disability frequently affecting patients after important COVID-19 infections.

•In a prospective study of older adults in China, 36 patients underwent a six-week respiratory rehabilitation training after COVID-19 infection and 36 formed the control group with no formal rehabilitation. Significant improvements were observed in lung function and six-minute walk test between the two groups. The SF-36 scores, in 8 dimensions, were significantly improved in the rehabilitation group. Although some favorable differences were observed in anxiety scores, there was no difference in the depression scale [134].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic obstructive pulmonary disease" and "Society guideline links: Pulmonary rehabilitation".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Pulmonary rehabilitation (The Basics)" and "Patient education: Medicines for COPD (The Basics)" and "Patient education: Advance directives (The Basics)")

●Beyond the Basics topics (see "Patient education: Chronic obstructive pulmonary disease (COPD) (Beyond the Basics)" and "Patient education: Chronic obstructive pulmonary disease (COPD) treatments (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Pulmonary rehabilitation is defined as a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors. (See 'Definition' above.)

●Patient selection – Pulmonary rehabilitation, when coupled with smoking cessation, optimization of blood gases, and medication, is part of the optimal treatment program for patients with symptomatic airflow obstruction, particularly patients with chronic obstructive pulmonary disease (COPD) categories B and E (algorithm 1). (See 'Patient selection' above.)

●Preprogram evaluation – Prior to participation in a pulmonary rehabilitation program, each patient is assessed individually for severity of respiratory impairment, exercise tolerance, presence of comorbidities (especially cardiac, musculoskeletal, and neurologic disease), and cognitive-language-psychosocial problems. (See 'Preprogram evaluation' above.)

●Components of pulmonary rehabilitation

•Lower extremity endurance training – Lower extremity endurance training (eg, cycling, walking) is of benefit in several areas of importance to patients with COPD, including exercise endurance (figure 2), perception of dyspnea, and quality of life (figure 3). Therefore, lower extremity endurance training should be part of all programs of pulmonary rehabilitation. (See 'Lower extremity exercise' above.)

•Upper extremity endurance training – Evidence from several small studies suggests that arm training is beneficial to patients who complain of symptoms when performing upper extremity exercise. (See 'Endurance training' above.)

•Resistance/strength training – Resistance/strength training has the potential to improve muscle mass and strength beyond the gains achieved with endurance training, but the optimal regimen has not been established. (See 'Resistance/strength training' above.)

•Alternative regimens – Less conventional forms of exercise or muscle training, such as breathing retraining, ventilatory muscle training (but not inspiratory muscle training), neuromuscular electrical stimulation, Tai Chi, and flexibility training, may offer new avenues of therapy. Further study is needed to define the role of these therapies in pulmonary rehabilitation. (See 'Alternative exercise training modalities' above.)

●Patient education – Education and psychologic support improve patients' awareness and understanding of their disease but are of limited value in improving exercise tolerance in the absence of an exercise training program. (See 'Education' above.)

●Benefits – In appropriately selected patients, pulmonary rehabilitation has demonstrated improvements in exercise capacity, frailty, and quality of life and may decrease mortality. Most of the benefits of pulmonary rehabilitation appear to wane over time; how best to extend these benefits is an area of active investigation.

●Pulmonary rehabilitation in other lung diseases – Individuals with other chronic lung diseases, such as interstitial lung disease, bronchiectasis, cystic fibrosis, asthma, pulmonary artery hypertension, lung cancer, persistent respiratory symptoms post COVID-19, and lung transplantation, may also derive benefit from pulmonary rehabilitation, although supportive data is more limited. (See 'Pulmonary rehabilitation in conditions other than COPD' above.)