Pulmonary Rehabilitation Nicholas S. Hill Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts–New England Medical Center, Boston, Massachusetts Pulmonary rehabilitation programs use multidisciplinary teams to logic defect that gives rise to a disability (i.e., some loss of optimize physical and social functioning of patients with chronic function). This begets a handicap, which is the disadvantage respiratory impairment. These programs provide rehabilitation in caused by the disability, leading to a lower than desired level inpatient, outpatient, or home settings, using at least three sessions of functioning within the societal context. Thus, the goals of weekly (one may be unsupervised) for at least 6 wk. The programs pulmonary rehabilitation are to (1 ) alleviate symptoms, (2 ) re- usually consist of exercise training, education, and psychosocial/ store functional capabilities as much as possible, and (3 ) reduce behavioral components. Upper extremity exercises and instruction handicap, thus enhancing overall quality of life. on breathing technique are included in most rehabilitation pro- grams and reduce dyspnea, but the contribution of these to im- These beg the question: Shouldn’t all medical care for patients proved functional capacity remains unproven. Decreases in the sen- with chronic illnesses share these goals of a rehabilitation program? sation of dyspnea, increased functional exercise capacity, and If so, then how does rehabilitation differ from optimal compre- enhanced quality of life of patients with chronic obstructive pulmo- hensive care administered by any physician? The answer is that nary disease (COPD) are established benefits of pulmonary rehabili- although all medical care of chronic illnesses should aim to tation. Evidence is lacking for the efficacy of rehabilitation for pa- optimize overall patient function and quality of life, pulmonary tients with non-COPD causes of pulmonary impairment, but many rehabilitation programs are structured to bring about speciﬁc of these patients probably benefit. Despite the availability of strong enhancements by applying a multidisciplinary approach within evidence to support the efficacy of pulmonary rehabilitation pro- the context of a focused program. The essential components grams in patients with severe COPD, third-party reimbursement include exercise training, education, other possible interventions, policies have been inconsistent. Nonetheless, enrollment in a pul- and outcomes assessment. To achieve the above goals, profes- monary rehabilitation program is encouraged for all appropriate sionals from a variety of disciplines, as shown in Table 1, directly candidates with chronic respiratory impairment, particularly for participate in pulmonary rehabilitation programs, or at least are those with severe COPD. readily available for consultation. Keywords: chronic obstructive pulmonary disease; rehabilitation exercise training STRUCTURE OF A PULMONARY REHABILITATION PROGRAM Pulmonary rehabilitation has been advocated for several decades as a way to provide comprehensive care and improve the func- A physician, usually a pulmonologist, serves as medical director. tional status of patients with chronic respiratory diseases. How- This individual is responsible for overall medical direction of ever, convincing evidence in the form of randomized controlled the program and should perform an initial assessment on all trials to support the efﬁcacy of this intervention has been avail- prospective patients to ascertain their appropriateness for the able only for the past decade (1). In addition, many questions program, as well as to ensure that the medical regimen has been remain about pulmonary rehabilitation, including its effect on optimized. The physician can also identify comorbidities that important outcomes like resource utilization or survival, responses might necessitate modiﬁcations in the patient’s individualized of non–chronic obstructive pulmonary disease (non-COPD), opti- program. A physician should be readily available to help with mal structure and essential components of a rehabilitation pro- medical emergencies, or a plan should be in place for prompt gram, the best ways to assess outcomes, and reimbursement issues. action (i.e., calling 911) should a medical emergency arise. A According to the ofﬁcial statement of the American Thoracic physiatrist may also participate in the program, to assist with Society, “pulmonary rehabilitation is a multidisciplinary pro- management of nonpulmonary handicaps. gram of care for patients with chronic respiratory impairment Physical, educational, and respiratory therapists are also es- that is individually tailored and designed to optimize physical sential to the program. The physical therapist prescribes a spe- and social performance and autonomy” (2). This article describes ciﬁc exercise regimen tailored to the individual patient’s handi- the structure and essential components of a typical rehabilitation caps and goals, whereas the occupational therapist teaches program, examines evidence supporting efﬁcacy and probable conservation measures and assesses needs for prosthetic devices mechanisms of action, and discusses reimbursement issues and or wheelchairs. The respiratory therapist also helps to oversee questions for the future. the exercise program, and teaches breathing exercises, as well as proper use of aerosolized medications and oxygen. In some GOALS OF PULMONARY REHABILITATION programs, nurses with special expertise in respiratory disorders Patients who are candidates for pulmonary rehabilitation have help to oversee the exercise and educational components, partic- respiratory impairment, deﬁned as an underlying pathophysio- ularly for inpatient programs. In others, an exercise physiologist prescribes and monitors the exercise program. A nutritionist should help patients formulate nutritional goals and educate on proper diet. A social worker assesses needs for home services, (Received in original form November 23, 2005; accepted in final form December 5, 2005) works with third-party payers to help patients obtain needed Correspondence and requests for reprints should be addressed to Nicholas beneﬁts, and may provide counseling. A psychologist may also S. Hill, M.D., Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts–New be available to provide counseling as well as instruction in coping England Medical Center, 750 Washington Street #257, Boston, MA 02111. E-mail: strategies and relaxation exercises. Professionals helping to run firstname.lastname@example.org the rehabilitation program should meet on a regular basis to go Proc Am Thorac Soc Vol 3. pp 66–74, 2006 DOI: 10.1513/pats.200511-121JH over individual patient progress and discuss program modiﬁca- Internet address: www.atsjournals.org tions to help patients meet their goals. The speciﬁc professionals Hill: Pulmonary Rehabilitation 67 TABLE 1. MULTIDISCIPLINARY TEAM PARTICIPATING ON A TABLE 3. INDICATIONS AND CONTRAINDICATIONS TO PULMONARY REHABILITATION TEAM PULMONARY REHABILITATION Physicians Indications Pulmonologist Symptomatic impairment attributable to pulmonary disability Physiatrist Failure of standard medical regimen to achieve adequate symptomatic relief Therapists Motivated, adherent patient Physical Contraindications Occupational Lack of motivation Respiratory Nonadherence Nurse or exercise physiologist Inadequate financial resources Nutritionist Severe cognitive dysfunction or psychiatric illness Social worker Unstable comorbidity (unstable angina, uncompensated congestive heart failure) Psychologist Severe exercise-induced hypoxemia, not correctable with O2 supplementation Inability to exercise due to severe lung or other disease (arthritis, stroke) Cigarette smoking* * Only as per some insurers; Medicare requires smoking abstinence for at least involved vary from program to program and no one blueprint 3 mo before it will cover pulmonary rehabilitation. applies to all. Programs can run successfully with a physician and one or two therapists (2), but individuals representing other disciplines should be available at least on a consultative basis. pulmonary function impairment or the need for chronic oxygen SETTING FOR PULMONARY REHABILITATION therapy will be reimbursed. Contraindications to participation include the lack of motivation, signiﬁcant cognitive impairment, Pulmonary rehabilitation is administered in inpatient, outpa- inability to attend the program consistently, unstable medical tient, or home settings, or some combination of these. In the conditions that may pose risks, or the inability to participate in United States (but not in Europe), inpatient rehabilitation is an exercise program because of a severe arthritic or other limiting usually reserved for patients who are too disabled to travel to condition. Although cigarette smoking is sometimes considered and from an outpatient program and the focus of these programs a contraindication, smokers and nonsmokers have similar re- is more often on optimizing medical or ventilator regimens than sponses to rehabilitation. Active smokers should be encouraged on the exercise components. In Europe, ambulatory patients to quit, and participation in a smoking cessation program can may be admitted to an inpatient program to undergo intensive be made a condition of their participation. A number of studies therapy and to avoid the inconvenience of daily travel. Possible have examined predictors of a favorable response to rehabilita- indications for inpatient pulmonary rehabilitation in the United tion. Zuwallach and coworkers (11) found that those with the States are listed in Table 2. lowest maximal oxygen uptakes at baseline had the largest pro- Most studies on pulmonary rehabilitation have focused on portionate improvements, whereas baseline pulmonary function the outpatient setting, sometimes with the expectation that pa- was not predictive. Troosters and colleagues (12) found that tients will perform some of their exercises at home, and encour- patients with no ventilatory reserve and normal skeletal muscle aging patients to continue exercise regimens at home after com- strength (inspiratory muscles, handgrip, and quadriceps) were pletion of the program. A number of studies have demonstrated least likely to improve. Thus, the candidate most likely to beneﬁt improved endurance and/or quality of life after completion of is a previously sedentary (and presumably deconditioned) pa- home-based rehabilitation programs (4–8). A multicenter ran- tient with no more than moderately severe disease. domized controlled trial of home-based pulmonary rehabilita- tion is currently underway in Canada (9). One study found that INITIAL ASSESSMENT a home-based program achieved more durable beneﬁts than a hospital-based program (10), but direct comparisons between The physician director performs a screening assessment to deter- home-based and outpatient programs are lacking. mine the suitability of prospective rehabilitation candidates. The physician takes a medical history and examines the patient, seek- CANDIDATES FOR PULMONARY REHABILITATION ing underlying conditions that might alter or even preclude par- ticipation in a rehabilitation program. For example, patients at Candidates for pulmonary rehabilitation are patients with symp- risk for coronary artery disease who have not yet undergone an tomatic impairment attributable to their respiratory condition adequate evaluation may be asked to complete an exercise stress (Table 3). Patients should be motivated, not have signiﬁcant test before being enrolled into the program. The physician should transportation problems, and be capable of understanding the also ascertain that the patient is on an optimal medical regimen, purpose and educational content of the program. Though some including bronchodilators, antiinﬂammatory drugs, and oxygen randomized controlled trials suggest that even patients with mild supplementation as indicated. impairment may beneﬁt from rehabilitation, Medicare guidelines (see below) specify that only those with moderate to severe ESSENTIAL COMPONENTS OF A PULMONARY REHABILITATION PROGRAM Exercise Training TABLE 2. INDICATIONS FOR INPATIENT AS OPPOSED TO OUTPATIENT PULMONARY REHABILITATION Virtually every pulmonary rehabilitation program includes exercise Severe impairment training as a centerpiece. In general, improvements in exercise Multiple comorbidities performance can occur only if patients exercise on a regular basis. Chronic invasive mechanical ventilation This is usually accomplished in a group setting using individually Slow convalescence from an acute respiratory illness tailored exercise prescriptions supervised by therapists. Some Preparing a debilitated or chronically ventilated patient for discharge home programs offer one-to-one exercise supervision by a therapist, Transportation problems, too distant from program but the cost-effectiveness of this approach is dubious. Most 68 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006 programs offer a variety of exercise regimens aimed at improving strength and endurance. The frequency, intensity, and speciﬁcity Figure 2. Effect of individual- of exercise sessions are considered the main determinants of the ized training (open circles) and training effect. standard training (closed squares) Frequency. For pragmatic reasons, most pulmonary rehabili- regimens on lactate accumula- tation programs hold sessions only two or three times weekly. tion in seven patients with severe Some evidence indicates that two sessions per week may be chronic obstructive pulmonary inadequate for a training effect (13), but most programs meeting disease. Horizontal axis is per- centage of pretraining maximal only twice weekly instruct patients to exercise at home in be- oxygen uptake. Individualized tween sessions. The frequency of exercise sessions to obtain an training decreases lactate accu- optimal training effect has not been established, but the regimen mulation at higher intensity exer- of twice-weekly supervised sessions with additional unsupervised cise levels. *p 0.05, **p 0.01, sessions at home has been advocated by at least one consensus ***p 0.001 between groups. group (14). Reproduced by permission from Intensity. Most studies indicate that there is a threshold for Reference 17. the training effect. If a level of intensity corresponding to 60 to 75% of the maximum oxygen uptake can be sustained for at least 20 to 30 min for a few days per week, an improvement in endurance is a virtual certainty (2), although concerns have been Speciﬁcity. Training regimens are speciﬁc in that the type of raised about patients’ ability to adhere to a high-intensity regi- exercise determines the nature of the gain. For example, walking men. Clark and colleagues (15) examined the efﬁcacy of low- endurance increases after training of the lower extremities but intensity isotonic exercises of the upper and lower extremities not upper extremities (19). Furthermore, endurance exercises performed at home in a group of 40 patients with COPD. These improve endurance capabilities more than strength, whereas authors demonstrated a dramatic improvement in treadmill strength training (i.e., weightlifting) increases strength but not walking time (Figure 1) and suggested that their program would necessarily endurance (20) or other outcomes such as exercise be applicable in patients with COPD with a wide range of func- capacity or health status (21). Therefore, most programs incorpo- tional defects. Punzal and coworkers (16) used a high-intensity rate a variety of training regimens. Gradually increasing the exercise program, exercising patients at approximately 85% of duration and intensity of workouts on a track, treadmill, or cycle their maximal baseline treadmill walking speed, and also demon- ergometer increases lower extremity endurance. strated signiﬁcant endurance beneﬁts. Vallet and coworkers (17) Some patients with COPD become uncomfortably dyspneic compared an individually tailored exercise regimen that targeted while using the upper extremities for reaching or personal hy- the heart rate at anaerobic threshold to a standard lower intensity giene because this diverts shoulder girdle muscles that the patient regimen that targeted 50% of the maximal heart rate. The indi- is using to assist breathing. Upper extremity muscle training vidually tailored regimen increased O2 pulse and reduced lactate using unsupported weightlifting techniques (22), stretching of accumulation compared with the standard regimen (Figure 2). elastic bands (Ther-a-bands; Hygenic Corp., Akron, OH) or hand However, many programs lack the facilities to monitor oxygen cranks (for endurance) can alleviate symptoms related to the use uptake and use symptom guidance instead (18). Patients exercise of the upper extremities. An arm-training program decreases the at a level that gives them moderate dyspnea (Borg 3) but at work effort, level of dyspnea, and dynamic hyperinﬂation associ- sustainable levels of exercise. Training at such levels has been ated with a given level of arm exercise (23). shown to increase endurance at the end of a program (18). Some programs also incorporate speciﬁc exercises aimed at improving respiratory muscle strength, such as inspiratory threshold training, a largely isometric exercise in which a device permits inspiratory ﬂow only if a threshold negative pressure is reached, or inspiratory resistive training, in which patients in- spire through a resistor. It is unclear whether one technique is superior to the other (24), perhaps partly because adherence to inspiratory threshold training has been a problem. In a meta- analysis, Lotters and colleagues (25) found a nonsigniﬁcant trend for improved exercise capacity after inspiratory muscle training (IMT) alone or as an adjunct to general exercise training. A subgroup analysis showed that patients with greater inspiratory muscle weakness at baseline had signiﬁcantly more beneﬁt than those with normal inspiratory muscle strength. They concluded that IMT is an important component of rehabilitation in patients with COPD with inspiratory muscle weakness, but failed to con- sider that this result could also be attributed to regression toward the mean. More recently, Weiner and colleagues (26) demonstrated that resistance training of expiratory muscles might be useful as an adjunct to rehabilitation. Not only did patients with trained Figure 1. Total work performed on a treadmill (endurance walk test) is expiratory muscles have greater expiratory muscle strength and shown before and after exercise program in the training group (open endurance than control subjects but they also had signiﬁcantly circles) and in the control group (closed circles). The mean difference in greater 6-min walk distances. Another recent study found that the training group (before–after) was 6,372 J versus 430 J in the control hyperpnea training improved respiratory muscle endurance but group (p 0.001 by Student’s t test). Reproduced by permission from did not translate into improved overall function (27). Given the Reference 15. lack of evidence for improvement in overall function attributable Hill: Pulmonary Rehabilitation 69 to strength or endurance training of the respiratory muscles, the fat-free muscle mass, strength, and quality of life score in patients place of respiratory muscle training in rehabilitation programs whose diets were supplemented with creatine (35). remains controversial (28). Outcome Assessment Education Pulmonary rehabilitation programs monitor outcomes partly as Pulmonary rehabilitation programs include an educational com- indicators of performance and to ensure quality, but also because ponent usually provided during group teaching and discussion many third-party payers now require such assessments to qualify sessions, but sometimes to individuals (29). These group sessions for reimbursement. Outcome measures usually include a func- are typically scheduled immediately before or after exercise ses- tional assessment. Many programs use the 6-min walk test or sions. Different topics are addressed, often on a weekly basis the 10-m shuttle test (36, 37). Both are widely applied tests of (Table 4). The effectiveness of the educational component has functional endurance that are of prognostic value. The shuttle not been tested in controlled studies, and the importance of walk test is an incremental test, but both it and the 6-min walk education as a component of a pulmonary rehabilitation program test are effort-dependent and subject to nonrespiratory limita- has not been established. tions such as weakness, pain, or arthritis. Some programs per- form maximal cardiopulmonary exercise tests that test maximal Psychosocial and Behavioral Component capacity rather than endurance. These tests are usually combined Because of the psychologic and emotional stress patients experi- with a dyspnea assessment as a rough gauge of effort, such as ence as part of their chronic illness as well as the high rate of the Borg score or rating on a visual analog scale. depression, most pulmonary rehabilitation programs incorporate Many programs also use dyspnea scales such as the Baseline psychosocial and behavioral interventions (30). Psychologists or and Transitional Dyspnea indices that assess dyspnea as related social workers may administer these during educational sessions, to function, effort, and task (38). In addition, most programs teaching coping and stress reduction strategies as well as relax- use questionnaires to assess overall quality of life (or health ation techniques (31). In a recent controlled trial, an occupa- status). The Short Form-36 is a commonly used proprietary in- tional therapist taught controlled breathing and energy conserva- strument that tests overall health status. Disease-speciﬁc ques- tion techniques during speciﬁc activities such as bed making or tionnaires such as the St. George’s Respiratory Questionnaire table setting, and was able to show improved dyspnea and overall (SGRQ) (39) or the Chronic Respiratory Disease Questionnaire functional scores compared with didactic lectures (32). Sexual (CRQ) (40) are also commonly used. Both are validated ques- dysfunction may be addressed and sexual counseling offered. tionnaires in patients with COPD, and some evidence suggests Patients with incapacitating stress, anxiety, or depression may that the CRQ is a bit more sensitive than the SGRQ in detecting warrant individual counseling or referral to a psychiatrist for improvements (41). A composite index has recently been de- medical therapy. scribed that combines body mass index (B), severity of airway obstruction (O), dyspnea index (D), and exercise capacity (E) Other Interventions (BODE index) and correlates with prognosis of patients with Breathing techniques have traditionally been taught as part of COPD (34). This has registered improvement after completion pulmonary rehabilitation programs including pursed lip breath- of a pulmonary rehabilitation program and was associated with ing and diaphragmatic breathing (33). Pursed lip breathing can improved outcomes (42). Whether this composite index adds to improve oxygenation and relieve the sensation of dyspnea, al- the value of traditional single-outcome indices remains to be though studies demonstrating that these gains translate into im- determined. proved functional status or state of well-being are lacking. Bene- ﬁcial effects of diaphragmatic breathing exercises have not been EVIDENCE FOR THE EFFICACY OF demonstrated (33). PULMONARY REHABILITATION Nutritional intervention is another important aspect of pul- Patients with COPD monary rehabilitation, although most programs use nutritional consultants rather than include nutritionists as full-time mem- Numerous randomized controlled trials have established the bers of the rehabilitation team. Patients with chronic respiratory efﬁcacy of pulmonary rehabilitation for COPD (3, 4, 43–48) (see conditions are frequently either over- or underweight, and a low Table 5). One of the most comprehensive is that by Ries and body mass index correlates with a worse prognosis (34). Few coworkers (49) on 119 patients randomized to receive education studies have demonstrated that nutritional interventions im- plus exercise training or education alone. In this study, tests of prove outcomes, but one recently showed improvements in both maximal and endurance exercise showed signiﬁcant beneﬁts that persisted for 1 yr. Dyspnea and self-efﬁcacy were also im- proved, but lung function and quality of well-being did not change. There were trends for improved survival (67 vs. 56% TABLE 4. TOPICS OFTEN COVERED DURING GROUP EDUCATION SESSIONS What’s wrong in common lung diseases TABLE 5. SIGNIFICANT BENEFITS OF PULMONARY Breathing medications REHABILITATION Oxygen therapy Energy conservation techniques Established by multiple randomized controlled trials (Level A evidence) Relaxation techniques 1. Improved functional capacity (6-min walk or Shuttle Walk Test) Breathing techniques 2. Reduced dyspnea* Pursed lip breathing 3. Improved health-specific quality of life* Diaphragmatic breathing Nutrition Observed in some randomized controlled trials (Level B evidence) What to do in emergencies 1. Reduced need for hospitalization* Traveling with lung disease * Only in patients with chronic obstructive pulmonary disease with severe airway End-of-life issues obstruction. 70 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006 after up to 6 yr of follow-up) and reduced hospital days per Non-COPD Disorders patient per year ( 2.3 vs. 1.3 d/patient/yr), but these did not Most evidence and all of the randomized controlled trials pertain reach statistical signiﬁcance. to the efﬁcacy of pulmonary rehabilitation for patients with More recently, a Cochrane meta-analysis assessed the efﬁcacy COPD. However, rehabilitation is still of potential beneﬁt for of pulmonary rehabilitation for COPD (50), but the Ries study patients with many non-COPD disorders (Table 6). As long as was excluded because it had an educational intervention in its patients have enough reserve to perform some exercise, it is control group, not just conventional therapy. The Cochrane anal- likely that they can obtain a training effect. Furthermore, educa- ysis examined results of 23 randomized controlled trials, con- tion about their disease may enhance coping abilities as well as cluding that rehabilitation of patients with COPD signiﬁcantly adherence to their medical regimen. (both statistically and clinically) improves dyspnea and disease- Because patients with non-COPD disorders may have unique speciﬁc quality of life, including scales of fatigue and mastery. requirements, the pulmonary rehabilitation program needs to Functional exercise capacity as assessed by the 6-min walk dis- be individually tailored for them. For example, patients with tance also increased signiﬁcantly, an average of 49 m, which asthma may not have as much exercise impairment as most is at the margin of the estimated minimal clinically signiﬁcant patients with COPD, but for them, education about the proper difference of 54 m (51). The greatest beneﬁt was apparent in use of medication, especially during emergencies, as well as patients with severe as opposed to mild to moderate COPD; environmental controls deserves more emphasis. Patients with beneﬁt was maintained for at least 6 mo; and supervised pro- asthma enrolled in a swim training program increased their grams tended to offer greater beneﬁt than unsupervised pro- 12-min walk distance after 10 wk of training, with a decrease in grams. Although the Cochrane analysis found no overall reduc- the occurrence of exercise-induced bronchospasm (59). Patients tion in the need for hospitalization after rehabilitation, some with certain neuromuscular diseases, such as post-polio syn- individual studies have found signiﬁcant reductions in hospital drome, may beneﬁt from comprehensive rehabilitation (60), days per year (52) as well as annual health care use and direct demonstrating increased strength and endurance of affected costs (53). A recent study also found reductions in patients with muscles (61). However, muscle strengthening or conditioning COPD with anxiety and depression after pulmonary rehabilita- exercises are unlikely to be helpful in patients with advanced tion compared with matched control subjects (54). A follow- progressive neuromuscular diseases, such as muscular dystro- up meta-analysis focusing just on patients with mild–moderate phies (62). Such patients may still beneﬁt from ﬂexibility exer- COPD concluded that exercise can improve conditioning in cises to minimize contractures or programs to optimize their these patients, but that studies are lacking to support the idea use of ventilator assistance regimens. Patients with lung cancer that rehabilitation favorably inﬂuences dyspnea, quality of life, require different kinds of education and may be recovering from or disease progression in the mild–moderate subgroup (55). the effects of radiation or chemotherapy (63). They may also An important limitation inherent to all of the controlled stud- have pain management problems that demand special attention. ies is the inability to blind patients or investigators to treatment Those with interstitial ﬁbrosis may experience profound exer- group, leaving the results open to bias. Nonetheless, the authors cise-induced oxygen desaturations that pose challenges for the of the Cochrane review concluded that no additional trials are delivery of high-ﬂow oxygen during exercise, and patients with needed comparing pulmonary rehabilitation with conventional cystic ﬁbrosis may need coaching on secretion removal or special therapy in patients with COPD. However, they opined that addi- precautions if they are harboring highly resistant organisms, such tional study is needed to determine what components of a reha- as Burkholderia cepacia. Small, uncontrolled series of patients bilitation program are essential, the ideal program length, the with cystic ﬁbrosis indicate that they respond favorably to exer- best combination of intensity, frequency and speciﬁc exercises cise programs (64, 65). Patients with bronchiectasis also respond for the training program, the value of breathing exercises, and to exercise training, but without added beneﬁt from IMT (66). how best to maintain beneﬁts. With the advent of new and more effective therapies for pulmo- Several recent studies have shed light on some of these ques- nary arterial hypertension, the initiation of an exercise program tions. A study in the United Kingdom found that early rehabilita- to coincide with the initiation of new medical therapy may tion (within 10 d) after a hospitalization for a COPD exacerbation enhance functional improvement in such patients. Pulmonary improved exercise capacity and health status at the 3-mo time rehabilitation has also been used pre- and postoperatively for point compared with standard care (56). A Danish group using lung resection, lung transplantation (67), and lung volume reduc- hour-long exercise sessions twice weekly for 8 wk found no tion surgeries, and was included as standard therapy in both the signiﬁcant improvement in 6-min walk distance or health-related quality of life, and speculated that two sessions weekly might be too few to produce a training effect (13). However, there was TABLE 6. NON–CHRONIC OBSTRUCTIVE PULMONARY a high dropout rate and adherence with the exercise program DISEASE CHRONIC RESPIRATORY CONDITIONS THAT MAY was not speciﬁed. Clearly, there must be a minimum threshold BENEFIT FROM A PULMONARY REHABILITATION PROGRAM of exercise frequency if a training effect is to be achieved, and Asthma two sessions/wk may be close to that threshold, but exercise Chest wall disease duration (each session as well as the duration of the program) Cystic fibrosis as well as exercise intensity must also be factored in. With regard Interstitial lung disease; post-ARDS pulmonary fibrosis to the optimal duration of a pulmonary rehabilitation program, Lung cancer Green and colleagues (57) found that 7 wk of rehabilitation was Neuromuscular diseases such as post–polio syndrome Exercise program may not be appropriate for advanced disease better than 4 wk. Another recent study found that 6-min walk Flexibility training distance of patients with severe COPD increased between 12 Optimization of ventilator assistance re: and 24 wk of pulmonary rehabilitation and recommended that Perioperative states (e.g., thoracic, abominal surgery) supervised programs extend for at least 24 wk to optimize bene- Pre- and post–lung transplantation, LVRS ﬁts, but this study was uncontrolled (58). For pragmatic reasons, Pulmonary vascular disease including the reimbursement policies of insurers, however, most Definition of abbreviations: ARDS adult respiratory distress syndrome; programs last between 6 and 12 wk. LVRS lung volume reduction surgery. Hill: Pulmonary Rehabilitation 71 surgery and control arms in the National Emphysema Therapy gram. Optimization of and improved adherence to the medical Trial, which evaluated the efﬁcacy of lung volume reduction regimen, weight loss, and smoking cessation, and better treatment surgery (68). of comorbidities, such as cardiovascular disease or obstructive sleep apnea, are other possible but unsubstantiated mechanisms MAINTENANCE OF BENEFIT of beneﬁt. The increased attention from professionals as well as Some studies have monitored patients for up to 2 yr (47, 49). the educational component in rehabilitation programs may also Ries and colleagues (49) found that improvements in functional be important in improving overall health status, but this has not exercise capacity are sustained for at least 12 mo. Troosters and been established. Thus, although conditioning of peripheral (i.e., coworkers (69) later demonstrated that improvements in the quadriceps) muscle appears to be an important mechanism of 6-min walk test and quality of life exceeded minimal clinically rehabilitation beneﬁt in many patients with COPD, identiﬁcation signiﬁcant differences for 18 mo. Ideally, patients are to apply of a single mechanism that applies to all patients seems unlikely; what they have learned in the rehabilitation phase of the pro- rather, multiple factors appear to play a role in limiting patient gram, undergoing a lifestyle change that includes regular exer- function and a multipronged approach is most likely to be suc- cise. Unfortunately, many if not most patients fail to adhere to cessful in effecting improvement, with speciﬁc reversible factors this ideal, and programmatic beneﬁts are eventually lost. Some varying from one individual patient to another. programs encourage patients to return to the rehabilitation cen- ter two or three times weekly after completion of the formal program so that the exercise program can be maintained. They USE OF OXYGEN SUPPLEMENTATION IN offer continued but less intense supervision and usually charge PULMONARY REHABILITATION a small fee because such maintenance programs are not covered Oxygen supplementation has long been considered routine in by insurance. pulmonary rehabilitation to maintain O2 saturation of more than Whether formal maintenance programs after completion of 88%, on the basis of studies showing that O2 supplementation the rehabilitation program extend or enhance initial beneﬁts has used in this fashion improves exercise performance. Recently, not been established. Ries and colleagues (70) tested a mainte- Emtner and colleagues (78) demonstrated that even patients nance program consisting of weekly phone calls and monthly reinforcement sessions. Functional exercise capacity and overall with COPD who do not desaturate during exercise still have health status were better sustained by maintenance than conven- signiﬁcant gains with O2 supplementation, including greater exer- tional management for 12 mo, but the advantage disappeared cise endurance (30% prolongation) and improved health quality. by 24 mo. In another study, once-weekly training sessions after a The mechanism of this beneﬁt is unclear, and this ﬁnding must 3-mo intensive rehabilitation period failed to sustain the beneﬁts be conﬁrmed before routine adoption can be recommended. achieved, but 2 to 3 h of exercise weekly during the maintenance Heliox, the mixture of oxygen (up to 40%) and helium, reduces period prevented some of the deterioration (71). Distractive gas density compared with air and lowers resistance to airﬂow stimuli during exercise sessions (music via earphones) have been in regions of turbulence. It can reduce air trapping and enhance found to improve maintenance of the beneﬁcial effects of a exercise tolerance in patients with COPD and could serve as an rehabilitation program (72). additional way to augment the training effect (79). MECHANISM OF BENEFIT NONINVASIVE VENTILATION AS AN ADJUNCT For years, physiologists have pointed to the mechanical dis- TO REHABILITATION advantages and propensity to fatigue of the respiratory muscles in patients with COPD and have speculated that therapies aimed The use of long-term use of noninvasive positive-pressure venti- at increasing the strength and endurance of inspiratory muscles lation to improve functional and health status of patients with would improve overall function (73). Numerous studies demon- severe, stable COPD has long been controversial. A recent ran- strate that speciﬁc muscle training can enhance strength and/or domized study from Italy (80) has demonstrated that noninvasive endurance of the inspiratory muscles in patients with COPD, ventilation used for 2 yr in patients with severe COPD and but these speciﬁc improvements have not been shown to contrib- chronic CO2 retention prevented the deterioration in daytime ute to enhancements in overall functional or health status. More- gas exchange and health status that was observed among control over, the improvements in dyspnea scores, functional exercise subjects, and tended to reduce hospital days per patient per capacity, and health status that accrue from participation in a year. Noninvasive positive-pressure techniques can also be used pulmonary rehabilitation program do not correlate with im- during exercise training to permit the attainment of a higher provements in pulmonary function. level of intensity during training, potentially augmenting the Alternative possible mechanisms for the beneﬁts of rehabili- training effect (81, 82). Continuous positive airway pressure, tation include improved cardiovascular conditioning and efﬁ- pressure support (83), and proportional assist ventilation (84) ˙ ciency as demonstrated by increased Vo2max, lower heart rate ˙ ˙ all augment the level of exercise intensity attainable, with the for a given Vo2 and lower Vo2 for a given work load (74), and greatest effect attributable to proportional assist ventilation. strengthening and conditioning of weakened peripheral muscles However, no study has yet demonstrated that this greater exer- (75). Saey and colleagues (76) recently demonstrated that mech- anisms of exercise limitation differ between patients with COPD: cise intensity actually translates into improved functional exer- some (fatiguers) had evidence of quadriceps muscle fatigue and cise capacity, and one study suggests otherwise (85). had no improvement after inhalation of ipratropium, whereas Another way to use noninvasive ventilation as an adjunct to others (nonfatiguers) had no evidence of quadriceps fatigue but rehabilitation is to rest respiratory muscles between exercise rather had ventilatory limitation and responded to ipratropium periods. Garrod and coworkers (86) used this approach in a by increasing exercise endurance. Mador and coworkers (77) controlled trial of patients with severe, stable COPD undergoing have shown that quadriceps muscles of patients with COPD are rehabilitation. They found that the noninvasive positive-pressure more resistant to fatigue after completion of a rehabilitation pro- ventilation–treated group improved its performance on the 72 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006 shuttle walk test (Figure 3) and had an improved quality of of life of patients with severe COPD and probably in those life (CRQ), even though the average patient used noninvasive with other chronic non-COPD causes of pulmonary impairment. positive-pressure ventilation for only 2 h daily. However, because Multidisciplinary programs provide rehabilitation in inpatient, this study was not blinded, the possibility of bias could not be outpatient, or home settings using at least three sessions weekly entirely excluded. (one may be unsupervised) over at least 6 wk. The programs Although some of the above studies are promising, noninva- usually consist of exercise training, education, and psychosocial/ sive ventilation is not yet a standard component of pulmonary behavioral components, but lower extremity conditioning is the rehabilitation and should remain an investigational technique only component with established beneﬁt. Upper extremity exer- pending further study. cises and instruction on breathing technique are included in most rehabilitation programs, but the contribution of these to REIMBURSEMENT ISSUES improved functional exercise capacity remains unproven. The value of IMT is likewise unclear and such training is not consid- Third-party payers have long been ambivalent about reimburs- ered a routine component of rehabilitation. ing for pulmonary rehabilitation. Reimbursement policies have Despite the availability of strong evidence to support the varied from time to time, payer to payer, and region to region. efﬁcacy of pulmonary rehabilitation programs in patients with Although the Center for Medicaid and Medicare Services has created codes for pulmonary rehabilitation, there is no national severe COPD, third-party reimbursement policies have been policy on reimbursement, and regional Medicare providers often inconsistent, and there is currently no national policy. Despite deny payment. this impediment, enrollment in a pulmonary rehabilitation pro- Pending a national policy, most providers of pulmonary reha- gram is encouraged for all appropriate candidates with chronic bilitation rely on collections for physical therapy and billable respiratory impairment, particularly for those with severe COPD. tests. Several physical therapy codes can be used and are often Investigators are encouraged to accumulate evidence to ﬁll current reimbursed as long as patients meet certain criteria. These in- knowledge gaps, including the establishment of what mecha- clude an International Classiﬁcation of Diseases–9 diagnosis of nisms and components of pulmonary rehabilitation are essential emphysema, COPD, or chronic bronchitis, and having a reduced to success, what speciﬁc exercise prescriptions bring about the FEV1 (ranging from 50 to 65% of predicted depending on the largest beneﬁt, how best to sustain beneﬁts over the long-term, state) or meeting the criteria for oxygen therapy. In addition, and what non-COPD causes of respiratory impairment respond patients must have ceased smoking for at least 3 mo. favorably to rehabilitation. These guidelines are not based on scientiﬁc evidence but must Conflict of Interest Statement : N.S.H. does not have a financial relationship with be met nonetheless. Many managed-care plans pattern their a commercial entity that has an interest in the subject of this manuscript. reimbursement policies after Medicare guidelines, but others may be willing to pay global rates. Plans that use case managers References for patients with chronic illnesses are often willing to negotiate 1. Troosters T, Casaburi R, Gosselink R, Decramer M. Pulmonary rehabili- on an individual patient basis. tation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;172:19–38. CONCLUSIONS 2. American Thoracic Society. Ofﬁcial statement of the American Thoracic Society: pulmonary rehabilitation. Am J Respir Crit Care Med 1999; Pulmonary rehabilitation decreases the sensation of dyspnea, 159:1666–1682. increases functional exercise capacity, and improves the quality 3. Hui KP, Hewitt AB. A simple pulmonary rehabilitation program im- proves health outcomes and reduces hospital utilization in patients with COPD. Chest 2003;124:94–97. 4. Wijkstra PJ, Van Altena R, Krann J, Otten V, Postma DS, Koeter GH. Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home. Eur Respir J 1994;7:269–273. 5. Wijkstra PJ, van der Mark TW, Kraan J, Van Altena R, Koeter GH, Postma D. Effects of home rehabilitation on physical performance in patients with chronic obstructive pulmonary disease (COPD). Eur Respir J 1996;9:104–110. 6. Wijkstra PJ, van der Mark TW, Kraan J, Van Altena R, Koeter GH, Postma DS. Long-term effects of home rehabilitation on physical per- formance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;153:1234–1241. 7. Hernandez MTE, Rubio TM, Ruiz FO, et al. Results of a home-based training program for patients with COPD. Chest 2000;118:106–114. 8. Na JO, Kim DS, Yoon SH, Jegal YJ, Kim WS, Kim ES, Kim MW. A simple and easy home-based pulmonary rehabilitation programme for patients with chronic lung diseases. Monaldi Arch Chest Dis 2005;63: 30–36. 9. Maltais F, Bourbeau J, Lacasse Y, Shapiro S, Perrault H, Penrod JR, Baltzan M, Rouleau M, Julien M, Paradis B, et al. Canadian, multicen- Figure 3. Changes in shuttle walk test (SWT) in noninvasive ventilation tre, randomized clinical trial of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease: rationale and methods. Can plus exercise (NPPV ET) and exercise therapy (ET) groups at each Respir J 2005;12:193–198. assessment. p 0.009 difference between the groups in final 4 wk of 10. Strijbos JH, Postma DS, Van Altena R, Gimeno F, Koeter GH. A com- training (A3 and A4); p 0.01 difference between the groups over parison between an outpatient hospital-based pulmonary rehabilita- 12-wk period (A1 and A4). Open circles represent the ET group; closed tion program and a home-care pulmonary rehabilitation program in circles represent the NPPV ET group. A1: baseline assessment; A2: patients with COPD. Chest 1996;109:366–372. prerehabilitation assessment (4 wk); A3: midrehabilitation assessment 11. Zuwallach RL, Patel K, Reardon JZ, et al. Predictors of improvement (8 wk); A4: postrehabilitation assessment (12 wk). Reproduced by per- in the 12-minute walking distance following a 6-week outpatiemt pul- mission from Reference 86. monary rehabilitation program. Chest 1991;99:805–808. Hill: Pulmonary Rehabilitation 73 12. Troosters T, Gosselink R, Decramer M. Exercise training in COPD: how 38. Mahler DA, Wells CK. Evaluation of clinical methods for rating dyspnea. to distinguish responders from nonresponders. J Cardiopulm Rehabil Chest 1988;93:580–586. 2001;21:10–17. 39. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete 13. Ringbaek TJ, Broendum E, Hemmingsen L, et al. Rehabilitation of measure of health status for chronic airﬂow limitation: the St. George’s patients with chronic obstructive pulmonary disease: exercise twice a 2 Respiratory Questionnaire. Am Rev Respir Dis 1992;145:1321–1327. week is not sufﬁcient. Respir Med 2000;94:150–154. 40. Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A 14. British Thoracic Society Subcommittee. Pulmonary rehabilitation. measure of quality of life for clinical trials in chronic lung disease. Thorax 2001;56:827–834. Thorax 1987;42:773–778. 15. Clark CJ, Cochrane JE, Mackay E. Low intensity peripheral muscle 41. Singh SJ, Sodergren SC, Hyland ME, et al. A comparison of three disease- conditioning improves exercise tolerance and breathlessness in COPD. speciﬁc and two generic health-status measures to evaluate the out- Eur Respir J 1996;9:2590–2596. come of pulmonary rehabilitation in COPD. Respir Med 2001;95: 16. Punzal PA, Ries AL, Kaplan RM, Prewitt LM. Maximum intensity exer- 71–77. cise training in patients with chronic obstructive pulmonary disease. 42. Cote CG, Celli BR. Pulmonary rehabilitation and the BODE index in Chest 1991;100:618–623. COPD. Eur Respir J 2005;26:630–636. 17. Vallet G. Ahmaidi S, Serres I, Fabre C, Bourgouin D, Desplan J, Varray 43. Goldstein RS, Gort EH, Stubbing D, Avendado MA, Guyatt GH. Ran- A, Prefaut C. Comparison of two training programmes in chronic domised controlled trial of respiratory rehabilitation. Lancet 1994;344: airway limitation patients: standardized versus individualized proto- 1394–1397. cols. Eur Respir J 1997;10:114–122. 44. Reardon J, Awad E, Normandin E, Vale F, Clark B, ZuWallack RL. 18. Horowitz MB, Littenberg B, Mahler DA. Dyspnea ratings for prescribing The effect of comprehensive outpatient pulmonary rehabilitation on exercise intensity in patients with COPD. Chest 1996;109:1169–1175. dyspnea. Chest 1994;105:1046–1052. 19. Lake FR, Henderson K, Briffa T, Openshaw J, Musk AW. Upper-limb 45. Bendstrup K, Ingemann E, Jensen J, Holm S, Bengtsson B. Out-patient and lower-limb exercise training in patients with chronic airﬂow ob- rehabilitation improves activities of daily living, quality of life and struction. Chest 1990;97:1077–1082. exercise tolerance in chronic obstructive pulmonary disease. Eur 20. Bernard S, Whittom F, Le Blanc P, et al. Aerobic and strength training Respir J 1997;10:2801–2806. in patients with chronic obstructive pulmonary disease. Am J Respir 46. Wedzicha JA, Bestall JC, Garrod R, Garnham R, Paul EA, Jones PW. Crit Care Med 1999;159:896–901. Randomized controlled trial of pulmonary rehabilitation in severe 21. Mador MJ, Bozkanat E, Aggarwal A, Shaffer M, Kufel TJ. Endurance chronic obstructive pulmonary disease patients, stratiﬁed with the and strength training in patients with COPD. Chest 2004;125:2036– MRC dyspnoea scale. Eur Respir J 1998;12:363–369. 2045. 47. Guell R, Casan P, Belda J, Sangenis M, Morante F, Guyatt GF, Sanchis J. ¨ 22. Martinez FJ, Vogel DP, Dupont DN, Stanopoulos I, Gray A, Beamis Long-term effects of outpatient rehabilitation of COPD: a randomized JF. Supported arm exercise vs unsupported arm exercise in the rehabil- trial. Chest 2000;117:976–983. itation of patients with severe chronic airﬂow obstruction. Chest 48. Troosters T, Gosselink R, Decmer M. Short- and long-term effects of 1993;103:1397–1402. outpatient rehabilitation in patients with COPD: a randomized trial. 23. Gigliotti F, Coli C, Bianchi R, Grazzini M, Stendardi L, Castellani C, Am J Respir Crit Care Med 2000;109:207–212. Scano G. Arm exercise and hyperinﬂation in patients with COPD: 49. Ries AL, Kaplan RM, Limberg TM, Prewitt LM. Effects of pulmonary effect of arm training. Chest 2005;128:1225–1232. rehabilitation on physiologic and psychosocial outcomes in patients 24. Harver A, Mahler DA, Daubenspeck JA. Targeted inspiratory muscle with chronic obstructive pulmonary disease. Ann Intern Med 1995;122: training improves respiratory muscle function and reduces dyspnea in 823–832. patients with chronic obstructive pulmonary disease. Ann Intern Med 50. Lacasse Y, Brosseau S, Milne S, et al. Pulmonary rehabilitation for COPD. 1989;111:117–124. Cochrane Database Syst Rev 2002(3):CD003793. 25. Lotters F, van Tol B, Keakkel G, Gosselink R. Effects of controlled 51. Redelmeier DA, Bayoumi AM, Goldstein RS, Guyatt GH. Interpreting inspiratory muscle training in patients with COPD: a meta-analysis. small differences in functional status: the six minute walk test in chronic Eur Respir J 2002;20:570–576. lung disease patients. Am J Respir Crit Care Med 1997;155:1278–1282. 26. Weiner P, Magadle R, Beckerman M, Weiner M, Berar-yanay N. Speciﬁc 52. Grifﬁths TL, Burrr ML, Campbell IA, et al. Results at 1 year of outpatient expiratory muscle training in COPD. Chest 2003;124:468–473. multidisciplinary pulmonary rehabilitation: a randomized controlled 27. Mador MJ, Deniz O, Aggarwal A, Shaffer M, Kufel TJ, Spengler CM. trial. Lancet 2000;355:362–368. Effect of respiratory muscle endurance training in patients with COPD 53. Golmohammadi K, Jacobs P, Sin DD. Economic evaluation of a undergoing pulmonary rehabilitation. Chest 2005;128:1216–1224. community-based pulmonary rehabilitation program for chronic ob- 28. Gosselink R. Breathing techniques in patients with chronic obstructive structive pulmonary disease. Lung 2004;182:187–196. pulmonary disease (COPD). Chronic Respir Dis 2004;1:163–172. 54. Kayahan B, Karapolat H, Atyntoprak E, Atasever A, Ozturk O. Psycho- 29. Nelsh CM, Hopp JW. The role of education in pulmonary rehabilitation. logical outcomes of an outpatient pulmonary rehabilitation program J Cardiopulm Rehabil 1988;11:439–441. 30. Agle DP, Baum GL. Psychosocial aspects of chronic obstructive pulmo- in patients with chronic obstructive pulmonary disease. Respir Med nary disease. Med Clin North Am 1977;61:749–758. (In press) 31. Renfroe KL. Effect of progressive relaxation on dyspnea and state anxiety 55. Chavannes N, Vollenberg JJ, van Schayck CP, Wouters EF. Effects of in patients with chronic obstructive pulmonary disease. Heart Lung physical activity in mild to moderate COPD: a systematic review. 1988;17:408–413. Br J Gen Pract 2002;52:574–578. 32. Norweg AM, Whiteson J, Malgady R, Mola A, Rey M. The effectiveness 56. Man WD, Polkey MI, Donaldson N, Gray BJ, Moxham J. Community of different combinations of pulmonary rehabilitation program pulmonary rehabilitation after hospitalisation for acute exacerbations components: a randomized controlled trial. Chest 2005;128:663–672. of chronic obstructive pulmonary disease: randomised controlled 33. ACCP/AACVPR Pulmonary Rehabilitation Guideline Panel. Pulmo- study. BMJ 2004;329:1209. nary rehabilitation: joint ACCP/AACVPR evidence-based guidelines. 57. Green RH, Singh SJ, Williams J, Morgan MD. A randomized trial of Chest 1997;112:1363–1396. four weeks versus seven weeks of pulmonary rehbilitation in COPD. 34. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez Thorax 2001;56:143–145. RA, Pinto Plata V, Cabral HJ. The body-mass index, airﬂow obstruc- 58. Verrill D, Barton C, Beasley W, Lippard WM. The effects of short- tion, dyspnea, and exercise capacity index in chronic obstructive pul- term and long-term pulmonary rehabilitation on functional capacity, monary disease. N Engl J Med 2004;350:1005–1012. perceived dyspnea, and quality of life. Chest 2005;128:673–683. 35. Fuld JP, Kilduff LP, Neder JA, Pitsiladis Y, Lean ME, Ward SA, Cotton 59. Emtner M, Herala M, Stalenheim G. High-intensity physical training in MM. Creatine supplementation during pulmonary rehabilitation in adults with asthma. Chest 1996;109:323–330. chronic obstructive pulmonary disease. Thorax 2005;60:531–537. 60. Birk TJ. Poliomyelitis and the post-polio syndrome: exercise capacities 36. Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor and adaptation current research, future directions, and widespread DW, Berman LB. The 6-minute walk: a new measure of exercise applicability. Med Sci Sports Exerc 1993;25:466–472. capacity in patients with chronic heart failure. Can Med Assoc J 1985; 61. Einarsson G. Muscle conditioning in late poliomyelitis. Arch Phys Med 132:919–923 Rehabil 1991;72:11–14. 37. Singh SJ, Morgan MDL, Scott S, Walters D, Hardman AE. Development 62. Bach JR. Pulmonary rehabilitation considerations for Duchenne muscu- of a shuttle walking test of disability in patients with chronic airways lar dystrophy: the prolongation of life by respiratory muscle aids. Crit obstruction. Thorax 1992;47:1019–1024. Rev Phys Rehabil Med 1992;3:239–269. 74 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006 63. Bernhard J, Ganz PA. Psychosocial issues in lung cancer patients (part 1). reconditioning on breathlessness in severe airﬂow limitation. Am J Chest 1991;99:216–223. Respir Crit Care Med 1995;152:2005–2013. 64. DeJong W, Grevink RG, Roorda RJ, Kaptein AA, van der Schans CP. 75. Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness Effect of a home exercise training program in patients with cystic contributes to exercise limitation in COPD. Am J Respir Crit Care ﬁbrosis. Chest 1994;105:463–468. Med 1996;153:976–980. 65. Blau H, Mussafﬁ-Georgy H, Fink G, Kaye C, Szeinberg A, Spitzer SA, 76. Saey D, Debigare R, LeBlanc P, Mador MJ, Cote CH, Jobin J, Maltais F. Yahav J. Effects of an intensive 4-week summer camp on cystic ﬁbrosis: Contractile leg fatigue after cycle exercise; a factor limiting exercise pulmonary function, exercise tolerance, and nutrition. Chest 2002;121: in patients with COPD. Am J Respir Crit Care Med 2003;168:425–430. 1117–1122. 77. Modor MJ, Kufel TJ, Pineda LA, et al. Effect of pulmonary rehabilitation 66. Newall C, Stockley RA, Hill SL. Exercise training and inspiratory muscle on quadriceps fatiguability during exercise. Am J Respir Crit Care Med 2001;163:930–935. training in patients with bronchiectasis. Thorax 2005;60:943–948. 78. Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R. Beneﬁts of 67. Biggar D, Malen J, Trulock E, Cooper J. Pulmonary rehabilitation before supplemental oxygen in exercise training in nonhypoxemic COPD and after lung transplantation. In: Casaburi R, Petty T, editors. Princi- patients. Am J Respir Crit Care Med 2003;168:1034–1042. ples and practice of pulmonary rehabilitation. Philadelphia: W.S. 79. Palange P, Crimi E, Pellegrino R, Brusasco V. Supplemental oxygen Saunders; 1993. pp. 459–467. and heliox: “new” tools for exercise training in chronic obstructive 68. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, pulmonary disease. Curr Opin Pulm Med 2005;11:145–148. Weinmann G, Wood DE; National Emphysema Treatment Trial Re- 80. Clini E, Sturani C, Rossi A, Viaggi S, Corrado A, Donner CF, Ambrosino search Group. A randomized trial comparing lung-volume-reduction N. The Italian multicentre study on noninvasive ventilation in COPD surgery with medical therapy for severe emphysema. N Engl J Med patients. Eur Respir J 2002;20:529–538. 2003;348:2059–2073. 81. Ambrosino N. Exercise and noninvasive ventilatory support. Monaldi 69. Troosters T, Gosselink R, Decramer M. Short- and long-term effects of Arch Chest Dis 2000;55:242–246. outpatient rehabilitation in patients with chronic obstructive pulmo- 82. Dolmage TE, Goldstein RS. Proportional assist ventilation and exercise nary disease: a randomized trial. Am J Med 2000;109:207–212. tolerance in subjects with COPD. Chest 1997;111:948–954. 70. Ries AL, Kaplan RM, Myers R, Prewitt LM. Maintenance after pulmo- 83. Maltais F, Reissmann H, Gottfried SB. Pressure support reduces inspira- nary rehabilitation in chronic lung disease: a randomized trial. Am J tory effort and dyspnea during exercise in chronic airﬂow obstruction. Respir Crit Care Med 2003;167:880–888. Respir Med 2002;96:359–367. 71. Wadell K, Henriksson-Larsen K, Lundgren R, Sundelin G. Group train- 84. Bianchi L, Foglio K, Pagani M, Vitacca M, Rossi A, Ambrosino N. Effects of proportional assist ventilation on exercise tolerance in ing in patients with COPD: long-term effects after decreased training COPD patients with chronic hypercapnia. Eur Respir J 1998;11:422– frequency. Disabil Rehabil 2005;27:571–581. 427. 72. Bauldoff GS, Hoffman LA, Zullo TG, Sciurba FC. Exercise maintenance 85. Bianchi L, Foglio K, Porta R, Baiardi R, Vitacca M, Ambrosino N. Lack following pulmonary rehabilitation: effect of distractive stimuli. Chest of additional effect of adjunct of assisted ventilation to pulmonary 2002;122:948–954. rehabilitation in mild COPD patients. Respir Med 2002;96:359–367. 73. Rochester DF. Physiological basis for pulmonary rehabilitation. In: 86. Garrod R, Mikelsons C, Paul EA, Wedzicha JA. Randomized controlled Fishman AP, editor. Pulmonary rehabilitation. Series on Lung Biology trial of domiciliary noninvasive positive pressure ventilation and physi- in Health and Disease. New York: Marcel Dekker; 1996. pp. 67–96. cal training in severe COPD. Am J Respir Crit Care Med 2000;162: 74. O’Donnell DE, McGuire MA, Samis L, et al. The impact of exercise 1335–1341.