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Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic condition that negatively affects several patient-centered outcomes. Among these, exercise capacity, dyspnea, and quality of life are the most relevant. In this article, factors contributing to exercise limitation, increase in exercise-induced dyspnea, quality of life deterioration, and other pathophysiological aspects in patients with COPD are analyzed in detail. Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. PR has been clearly shown to induce favorable and long-lasting effects on all patient-centered outcomes. In addition, PR appears to have positive (even if not conclusively demonstrated) effects on other important outcomes in patients with COPD: number and severity of exacerbations, healthcare resource utilization, and survival. The organization of PR treatment, its components, outcome assessment, and future directions are discussed in light of the most robust scientific evidence.

Keywords

comorbidities muscle dysfunction phenotypes pulmonary rehabilitation

Definition of pulmonary rehabilitation

The American Thoracic Society and the European Respiratory Society have recently adopted the following definition: pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. Integrated into the individualized treatment of the patient, PR is designed to reduce symptoms, optimize functional status, increase participation, and reduce healthcare costs through stabilizing or reversing systemic manifestations of the disease. Comprehensive PR programs include patient assessment, exercise training, education, and psychosocial support [Nici et al. 2006].

We will first address the pathophysiology and main consequences of chronic obstructive pulmonary disease (COPD), since it is a disease not only characterized by pulmonary inflammation and structural abnormalities leading to airflow obstructions, exercise limitation and symptoms of dispnea and fatigue, but also extended to a variety of systemic alterations. These extrapulmonary effects include systemic inflammation, nutritional abnormalities and weight loss, skeletal muscle dysfunction, and additional organ effects. The high burden of COPD is further contributed to by systemic effects, leading to a pronounced deterioration in health status and a diminished quality of life (QoL).

Chronic obstructive pulmonary disease: pathophysiology and consequences

Peripheral and respiratory muscles dysfunction

The principal symptom limiting exercise in patients with COPD is dyspnea, due to changes in the respiratory mechanics and impaired pulmonary gas exchange (Table 1). Hamilton and colleagues [Hamilton et al. 1996] noted that lower limb fatigue in isolation was greater than the sensation of dyspnea in 43% of patients with COPD who had maximal exercise testing. Although lower limb muscles are largely responsible for limiting activities such as walking and going up inclines or flights of stairs, it is recognized that the activities of daily living (ADL) that involve the upper limbs, especially those that involve unsupported upper limbs (upper limbs at shoulder level without support), are also poorly tolerated by patients with COPD [Dolmage et al. 1993].

Table 1.

Chronic obstructive pulmonary disease (COPD): pathophysiology and consequences.

Peripheral and respiratory muscles dysfunction

COPD phenotypes

Nutritional abnormalities

Cardiac impairment

Cognitive impairment

Other comorbid diseases

Therefore, since the 1990s, growing attention has been paid to muscle dysfunction in COPD. All striated muscles have two basic functional properties, strength and endurance. Strength is the mechanical expression of the maximum contractile force of the muscle. Endurance, however, is the ability to sustain a submaximal force over time. Strength and endurance depend on different structural and biological elements. While strength is, above all, a function of muscle mass, endurance depends on the aerobic capacity of the muscle because aerobic metabolism is more efficient and sustainable than anaerobic metabolism [Gea and Barreiro, 2008].

COPD is one of the diseases associated with more functionally deficient muscle contraction (dysfunction). Peripheral muscle dysfunction (and weight loss) may be observed in patients with COPD, irrespective of the degree of airflow limitation, and atrophy of skeletal muscle is their main cause. The precise cellular and molecular mechanisms leading to skeletal muscle atrophy in these patients are unclear [Reid, 2001]. Inactivity, systemic inflammation, oxidative stress, tissue hypoxia, and enhanced skeletal muscle apoptosis have been considered, among others, to be potential pathogenic factors [Agusti et al. 2003]. In particular, systemic inflammation is likely to be an important pathogenetic mechanism of skeletal muscle diseases. This implies important clinical implications because it worsens prognosis [Schols et al. 1998] and QoL of patients with COPD [Mostert et al. 2000]. It is therefore important to develop rational and effective new treatments to palliate skeletal muscle diseases in COPD [Debigare et al. 2001].

Chronic inflammatory states such as COPD can profoundly affect skeletal muscle function [Ottenheijm et al. 2005]. This is related to systemic inflammatory mediators that are persistently elevated in this chronic disease state and to various other physiological effects and comorbidity. Systemic inflammation may impair the oxygen transport through the cytoplasm and into the mitochondria and directly impair mitochondrial oxygen utilization [Naeije, 2005]. This event produces muscle cell hypoxia and thus a conversion to anaerobic metabolism at low levels of exercise. The final outcome is lactate accumulation coupled with an earlier muscle fatigability.

The expiratory airflow limitation in COPD leads to air trapping (hyperinflation) because there is insufficient time for adequate lung emptying. The impact on symptoms and impairment at rest and during exertion is increasingly recognized to be fundamental in COPD. The consequences of hyperinflation include a shortened diaphragm with less efficient neuromechanical coupling,and constraints on inspiratory reserve volume within the limitations of the thoracic cage expansion. Both short-acting and long-acting bronchodilators have been shown to reduce lung hyperinflation at rest and during exercise with associated improvements in exercise endurance time [Maltais et al. 2005; O’Donnell et al. 2004].

The hyperinflation of COPD reduces the flow and pressure-generating capacity of the diaphragm. This is compensated by a threefold increase in neural drive, adaptations of the chest wall and diaphragm shape to accommodate the increased volume, and adaptations of muscle fibers to preserve strength and increase endurance. Paradoxical indrawing of the lower costal margin during inspiration in severe COPD (Hoover’s sign) correlates with high inspiratory drive and severe airflow obstruction rather than contraction of radially oriented diaphragm fibers. The inspiratory muscles remain highly resistant to fatigue in patients with COPD, and the ultimate development of ventilatory failure is associated with insufficient central drive [McKenzie et al. 2009].

Moreover, there are two mechanisms to which upper limb mechanical efficiency and exercise capacity are impaired: neuromechanical dysfunction (thoracoabdominal asynchrony) of respiratory muscles: diaphragm and accessory muscles [Franssen et al. 2002; Tangri and Woolf, 1973]; and changes in lung volume during activities involving the upper limbs [Baarends et al. 1995; Celli et al. 1986; Criner and Celli, 1988; Epstein et al. 1995; Gigliotti et al. 2005; Martinez et al. 1991].

Regarding lower limb muscle dysfunction, reduced quadriceps muscle strength, as assessed by isometric peak torque (PT), has been documented [Gosselink et al. 1996]. This impairment was a predictor of reduced maximal oxygen consumption. In addition, patients present with decreased muscle endurance compared with healthy individuals. A plausible explanation for this reduction is abnormal muscle metabolism in which the oxidative activity is lower [Serres et al. 1998]. It is of note that there is an association between muscle endurance and the level of physical ADL performance, as well as between muscle endurance and the degree of airflow obstruction [Janaudis-Ferreira et al. 2006]. Certain factors, such as reduced muscle strength, decreased aerobic capacity, dependence on glycolytic metabolism, and rapid accumulation of lactate during exercise, might be responsible for early muscle fatigue in patients with COPD.

Muscle atrophy is one component building the concept of muscle dysfunction. Muscle atrophy has a significant impact on patient clinical status, independent of the impairment in lung function. A lot of effort has been devoted lately to increasing our understanding of the relationship between COPD and the initiation and the development of muscle atrophy. A growing body of evidence is showing that the ubiquitin–proteasome system, an adenosine-triphosphate-dependent proteolytic pathway, is playing a crucial role in the cascade leading to degradation of contractile proteins, thus promoting the development of muscle atrophy. Interestingly, this system is also involved in essential cellular processes such as response to hypoxemia and muscle tissue regeneration [Debigare et al. 2010].

An association between risk for hospital admission due to exacerbations and baseline muscle function, irrespective of body weight and body mass index (BMI) has been confirmed [Vilaro et al. 2010]. The authors postulate that this impairment in muscle function is associated with the inflammatory burst and therapy of exacerbations. In fact, the same authors have documented that patients with COPD who require admission for exacerbation suffer a global, progressive and linear deterioration of muscle function [Martinez-Llorens et al. 2004]. The prevalence and severity of respiratory and peripheral muscle dysfunction remain elevated even while recovering clinical stability. These data are consistent with the study which was able to demonstrate that at hospital discharge, noninvasively measured respiratory muscle overload was associated with an increased risk of hospital readmission for exacerbation in patients with moderate to severe COPD [Gonzalez et al. 2008].

Chronic obstructive pulmonary disease phenotypes

Recently a direct correlation has been demonstrated between cachexia and the Global Initiative for Obstructive Lung Disease (GOLD) stage of disease severity [Schols et al. 2005]. GOLD classification is based on the degree of obstruction, as revealed by forced expiratory volume in 1 s (FEV₁) and FEV₁/forced vital capacity (FVC) ratio decrease, but there has been some debate about the use of FEV₁ as the main single evaluative parameter for COPD [Nishimura et al. 2002]. In the literature a systemic evaluation of patients with COPD has been proposed, stressing that thereis a need to seek candidates for multidimensional disease staging [Celli et al. 2004]. According to that, actually COPD can be viewed as a ‘basket’ that encompasses a range of pulmonary and systemic manifestations, and which is characterized by a narrow pattern of symptoms, exposure to certain risk factors, variable patterns of airflow obstruction and airway hyperresponsiveness, and different types of airways inflammation with structural changes [Celli, 2006; Hargreave and Parameswaran, 2006]. The increase over time of the knowledge in the pathogenesis and in clinical characteristics has led to the awareness of an overlap of phenotypes resulting in difficulties differentiating the disorders from each other. These phenotypes are also difficult to frame due to potential differing responses to therapeutic interventions, since a disease-modifying treatment has the potential to modify clinical variables [Mannino, 2002]. Recognizing the different phenotypes within COPD is important for understanding the underlying disease processes, and to determine whether the phenotypes vary in their response to different pharmacological treatments: this knowledge could lead to treatment specifically targeted for defined phenotypic groups, rather than a ‘syndromic disease’ or asthma/COPD in general. An obvious limitation is the lack of a gold standard against which to assess phenotypic definitions of COPD [Polverino and Cosio, 2009].

Nutritional abnormalities

Weight loss results from negative net energy balance, that is, less energy intake than energy output. Daily energy expenditure is composed of three parts: resting energy expenditure (REE) accounting for about 60%; diet-induced thermogenesis accounting for less than 10%; and energy consumed for physical activity making up the rest. REE is elevated (>120% normal) in patients with COPD. In patients who are malnourished, the oxygen cost of breathing is significantly higher than in the normally nourished and control group subjects [Donahoe et al. 1989]. It has been postulated that increased REE is at least in part due to increased oxygen cost of breathing. The consequence is that patients with severe airflow obstruction who are also ‘underweight’ have an increased mortality risk. Indeed, BMI is a component in the calculation of the BMI obstruction dyspnea exercise (BODE) index [Celli et al. 2004], a prognostic indicator of mortality. Tumor necrosis factor α (TNFα) is a key proinflammatory cytokine associated with weight loss in malignancy, infections, inflammatory diseases, and severe heart failure. TNFα levels are elevated in underweight compared with normal weight patients with COPD [Di Francia et al. 1994]. Mean TNFα levels in the underweight group were tenfold higher than in the normal weight group. However, being underweight per se does not seem to be a predictor of systemic inflammation in patients with emphysema. TNFα may also mediate muscle wasting by stimulating catecholamine secretion and muscle protein lysis.

At the local level, the vastus lateralis of patients with severe COPD with normal weight and no signs of muscle atrophy exhibited greater protein content of TNFα and larger inflammatory cell counts [Montes de Oca et al. 2005], as well as increased levels of apoptosis [Agusti et al. 2002] than control subjects. Interestingly, no significant differences were found in the levels of molecular or cellular inflammation of the vastus lateralis muscle between low and normal weight patients with COPD [Montes de Oca et al. 2005]. Other studies, however, have shown no TNFα expression in limb muscles of patients with COPD.

The inconsistency of TNFα levels in COPD suggests that this cytokine cannot be the only factor leading to weight loss. It appears that the mechanisms for weight loss in COPD, and specifically in patients with emphysema, are multifactorial, and that the factors may affect different COPD phenotypes differently [King et al. 2008].

Cardiac impairment

Cardiovascular diseases are the leading causes of death in patients with mild to moderate COPD, chief among which is ischemic heart disease. In a pooled analysis of two large population-based epidemiological studies [Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, n = 20,296 adults >44 years old], the prevalence of cardiovascular disease (defined as ischemic heart disease, heart failure, stroke, and transient ischemic attack) in patients with COPD was found to be 20–22% compared with 9% in subjects without COPD [Mannino et al. 2008]. As was the case in patients with COPD and diabetes or hypertension, the presence of cardiovascular disease conferred a significantly higher risk of hospital admission and mortality within 5 years. Unsurprisingly, these increases were particularly amplified in patients with GOLD stage III and IV COPD rather than those with mild to moderate COPD. Recently it has been demonstrated that ischemic echocardiogram changes (considered as major or minor Q or QS pattern, ST junction and segment depression, T-wave items, or left bundle branch block) are common in patients with COPD and associated with poor clinical outcome irrespective of FEV₁ [Vanfleteren et al. 2011]. Chronic low-grade systemic inflammation is a major pathophysiological link between COPD and atherosclerotic diseases. Impaired vascular reactivity is an independent and early feature of atherosclerosis and a risk factor for the condition even before structural plaque changes are present [Patel and Hurst, 2011]. Endothelium dependent and independent vasodilatation has been found to be impaired in patients with COPD without known cardiovascular disease compared with control subjects and the degree of endothelial dysfunction was related to lung function and serum C-reactive protein, providing another inflammatory link between COPD and atherosclerosis [Eickhoff et al. 2008]. Subclinical atherosclerosis is likely to start early in the course of COPD, as suggested by the findings of increased carotid artery intima-media thickness in middle-aged smokers with airflow limitation [Iwamoto et al. 2009].

There are many causes of heart failure but the most common are ischemic heart disease and longstanding poorly controlled hypertension, both of which are common in patients with COPD. Isolated right heart failure in patients with COPD is usually cor pulmonale mediated by the increased right-sided outflow pressures due to raised pulmonary vascular resistance often found in severe lung disease. In addition to intrinsic myocardial dysfunction, there is evidence of impaired ventricular filling associated with the severity of emphysema, raising the possibility of heart failure secondary to lung hyperinflation physically restricting cardiac preload [Patel and Hurst, 2011]. Hyperinflated lungs in COPD push the diaphragm caudally; such increased intrathoracic pressure can impair low pressure ventricular filling [Watz et al. 2010]. This mechanism can lead to reduced physical activity.

Cognitive impairment

Cognitive impairment has been demonstrated in 77% of patients with COPD and hypoxaemia [Grant et al. 1982]. Furthermore, it has been suggested that impaired performance in neuropsychological tests may be a predictor of mortality and disability in certain COPD populations [Antonelli-Incalzi et al. 2006; Fix et al. 1985; Incalzi et al. 2005]. However, despite their potential importance, understanding of cognitive problems in COPD remains incomplete. Anxiety and depression impede PR, exacerbate problems with dyspnea, and affect smoking cessation [Borson et al. 1998]. Depression may lead to early addictive smoking, and recurrent depression impedes smoking cessation [Borson et al. 1998]. Depression has been found to negatively affect exercise capacity, health perception/wellbeing, the use of inpatient and outpatient health services, and hospital admissions – first admission and total number of admissions – in patients with COPD [Ng et al. 2007]. Future research needs to include practical methods for improving provider and patient recognition of depression and anxiety as targets for intervention. This could be accomplished by using self-report measures as part of regular screening in primary care and pulmonary clinics. On the basis of a long-term, mounting body of evidence, pharmacological and psychological interventions require further large-scale clinical trials to determine which interventions are most efficacious [Putman-Casdorph and McCrone, 2009].

Other comorbid diseases

COPD has also been linked to other comorbid conditions, often disregarded, such as gastroesophageal reflux, renal insufficiency, osteoporosis, psychiatric illness and cognitive dysfunction.

A consequence of the hyperinflation, often disregarded, is gastroesophageal reflux disease (GERD). GERD occurs in 30–60% of patients with COPD [Johnston et al. 2008; Mokhlesi et al. 2001] and the relative risk of patients accruing a diagnosis of GERD is 1.46 in the year following COPD diagnosis [Garcia Rodriguez et al. 2008]. The key underlying mechanism of GERD is transient relaxations of the lower esophageal sphincter allowing stomach contents to move into the esophagus and often as high as the larynx and mouth, particularly when intra-abdominal pressure is raised. There are reasons why reflux may be more prevalent in COPD, including a low lying diaphragm from hyperinflation, coughing, and increased use of abdominal muscles for ventilation. Once liquid refluxate lies within the esophagus, increased extrinsic (intrathoracic) pressure that is evident in COPD may potentiate the movement of fluid against gravity towards the larynx. Given the anatomical arrangement and innervations of the human larynx, it is possible for small amounts of liquid refluxate to spill over into the airway where its constituents may cause an inflammatory response and potentially increase susceptibility to infection [Patel and Hurst, 2011].

Renal insufficiency, detected by low glomerular filtration rate (GFR), was detected in 43% of a series of 356 older adults compared with 23% of older adults without COPD [Incalzi et al. 2010]. Half of the patients with COPD and a reduced GFR had a normal serum creatinine. This latter group of patients with ‘covert’ renal insufficiency was more likely to have a low serum albumin and low muscle mass.

A 3-year observational study, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, examined the prevalence of depression among 2118 patients with COPD, 335 smokers without COPD, and 243 nonsmokers [Hanania et al. 2011]. Depression was more prevalent among patients with COPD (26%) than smokers without COPD (12%) or nonsmokers (7%) and was associated with worse health and functional status. Cognition impairment was evaluated in a survey of 4150 older adults [Hung et al. 2009]. The adjusted mean cognition scores of those with severe COPD were significantly lower than those with nonsevere or absent COPD.

Goals and benefits of pulmonary rehabilitation

First, we would like to underline that in the long-term management of chronic diseases such as COPD, rehabilitation treatment aims to accompany the patient throughout the whole course of the disease.

PR aims to reduce symptoms, decrease disability, increase participation in physical and social activities, and improve the overall QOL of patients with chronic respiratory disease. These goals are achieved through patient and family education, exercise training, psychosocial and behavioral intervention. The rehabilitation intervention is geared toward the problems and needs of each patient and is implemented by a multidisciplinary team of healthcare professionals [Haave and Hyland, 2008].

The primary goal of PR is to restore patients to the highest possible level of independent function that is obtained by helping them become more physically active, by allowing them to learn more about their disease, treatment options, and how to deal with their respiratory impairment. Patients are stimulated to become actively involved in providing their own healthcare, to become more independent in daily activities, and less dependent on healthcare professionals and medical resources. Rather than focusing only on reversing the disease process, rehabilitation attempts to reduce symptoms and reduce disability from the disease. Several rehabilitation strategies have been developed for patients with disabling COPD. As stated above, programs typically include components such as patient assessment, exercise training, education, nutritional intervention, and psychosocial support. PR is appropriate for any patient with chronic lung disease that is stable but the respiratory symptoms are disabling. Patients with advanced disease can benefit if they are selected appropriately and if realistic goals are set [Ries et al. 2007].

It should be underlined that the benefits of PR can be obtained even in irreversible pulmonary disorders because much of the disability and handicap results not from the respiratory disorder per se but mostly from secondary morbidities that are often treatable if recognized. Although the degree of airway obstruction or hyperinflation of COPD does not change appreciably with PR, reversal of muscle deconditioning and better pacing enables patients to walk longer distances and with less dyspnea [Hill, 2006].

A successful rehabilitation program identifies and differentiates the disease process (ie, impairments, disabilities, handicaps) so that remedial strategies can be determined. The functional consequences of these impairments are addressed so that the person with chronic respiratory impairment is returned to the fullest possible physical, mental, social, and economic independence. Several impairments, such as weakness, dysfunction of peripheral and respiratory muscles, anxiety and depression, and abnormalities of nutrition have responded to treatment. Improvements in overall and exertional dyspnea, as well as health-related QOL, have been documented. Significant increases in maximal exercise capacity, as measured during exercise testing have been observed [Casaburi and ZuWallack, 2009; Nici et al. 2006; Puhan et al. 2008].

Many clinical trials have examined the benefits of PR, although virtually all of them were single-center trials of modest size. Demonstrations of benefit are based on randomized, controlled (though unblinded) studies. For three outcomes, the benefit is unequivocal: exercise capacity (in incremental, constant work rate, and timed walking tests), severity of dyspnea, and health-related QoL. For these three outcomes, the magnitude of benefit is generally superior to any other COPD therapy [Ries et al. 2007].

A meta-analysis by Lacasse and colleagues summarized 31 randomized, controlled trials of PR [Lacasse et al. 2006]. In 11 trials involving 618 participants, health-related QoL was evaluated with the use of the Chronic Respiratory Disease Questionnaire (CRQ). Improvements were demonstrated in the four domains evaluated by this instrument: dyspnea, fatigue, emotional function, and mastery (the patient’s feeling of control over the disease). The average effect size was 1.5 to 2.1 times the estimated minimum clinically important difference between the treatment and control groups. In 16 trials involving 669 participants, the weighted mean improvement in functional exercise capacity, assessed on the basis of the distance walked in 6 min, was 48 m. This approximated the estimated minimum clinically important difference of 50 m [Guyatt et al. 1987; Lacasse et al. 2006].

It should be underlined that in some studies PR has been shown to reduce hospitalization and other measures of healthcare use, and to improve cost effectiveness. Reductions in depression and anxiety and improvements in cognitive function and self-efficacy have been reported in trials specifically investigating these outcomes. A survival benefit of PR has not been clearly demonstrated, although the randomized trials that have examined survival were relatively small and were underpowered to detect this effect [California Pulmonary Rehabilitation Collaborative Group, 2004; Griffiths et al. 2000, 2001; Troosters et al. 2005].

Setting and staffing

Despite a substantial variability in program structure, the efficacy of PR performed in inpatient, outpatient, or home settings has been well documented. The structure and components of the program, rather than the setting itself, determine the effectiveness of PR. The choice of setting often depends on the variability and distance to the program, insurance payer coverage, patient preference, and the physical, functional, and psychosocial status of the patient. Inpatient rehabilitation is generally recommended for patients affected the most because intensive rehabilitative services and specialized training for patients and families are available. Outpatient rehabilitation, which can be hospital or community based, has the potential to benefit most patients but requires a certain level of functional ability. Although outcomes have not been well studied, home-based PR is convenient for patients and family members and may provide sustained motivation for continued exercise training [du Moulin et al. 2009; Griffiths et al. 2000; Guell et al. 2000; Neder et al. 2002; Sewell et al. 2006; Votto et al. 1996].

According to the well accepted definition given above, rehabilitation offers a comprehensive approach to medical care. For this reason, the combined expertise of an interdisciplinary team is highly desired. PR is delivered by a multidisciplinary team whose structure varies according to patient population, program budget, reimbursement, and the availability of team members and resources. The rehabilitation team must be headed by a pulmonary physician specialist who coordinates other physicians skilled in evaluating the neuromuscular, musculoskeletal, cognitive, and cardiopulmonary systems. Moreover the team leader physician should be skilled in working with a team of professionals, because he/she is responsible for the medical treatment and rehabilitation program. The other members of the rehabilitation team include respiratory and physical therapists, an occupational therapist, a rehabilitation nurse, a vocational counselor, a social worker, a dietician, and a psychologist. Each member also needs to have knowledge of the general principles of other members’ disciplines [ZuWallack and Crouch, 2004a].

The environment in which the PR program is carried out is of pivotal importance. Preferably it should be a large, quiet, and comfortable fitness facility in which all the people involved in the therapeutic process can be accommodated (Figure 1). Separate rooms should be available to offer discretion to patients who have undergone bronchial drainage procedures that may induce even copious expectoration (Figure 2).

Figure 1.

Environment to perform pulmonary rehabilitation.

Figure 2.

Bronchial Drainage Procedure.

Pulmonary rehabilitation: program components

Exercise training

Patients with COPD have reduction in functional exercise capacity as the disease progresses (Table 2). In these patients, dyspnea may become so disabling that they lead a sedentary lifestyle, which results in further deconditioning, worsening of symptoms, and reduced QoL. It is therefore evident that the exercise program is the foundation of PR. Endurance exercise of the leg muscles is the main focus, with walking, stationary cycling, and treadmill exercise commonly performed. Exercise does not alter underlying respiratory impairment, but it does ameliorate dyspnea and improve other outcome measures like exercise capacity and QoL. Generally, this training is well tolerated. An interval training regimen consisting of 2–3 min of high-intensity training alternating with equal periods of rest might be a substitute for patients who cannot tolerate sustained activity [Kortianou et al. 2010].

Table 2.

Pulmonary rehabilitation: program components.

Exercise training

Education and psychosocial/behavioral intervention

Chest physical therapy and breathing techniques

Nutritional intervention

Dyspnea ratings during maximal graded exercise testing may offer reliable predictions of exercise intensity during training. Consequently, most pulmonary programs for the improvement of aerobic capacity use dyspnea targeting to guide training intensity. Once again, high-intensity regimens are generally preferred, with initial targets of at least 60% of the maximum exercise tolerance repeated two to five times a week, although lower-intensity exercise is also beneficial. Exercise intensity is increased as tolerated under the observation of rehabilitation staff members. A resistance-exercise component is often included, and so improved leg strength aids in some ADL.

As peripheral muscle weakness contributes to exercise limitation in patients with lung disease, strength training is a rational component of exercise training during PR. Hence, resistance training that involves the upper arms is also useful because it facilitates the ability to carry out the ADL and some of the upper-arm muscles also serve as auxiliary muscles of respiration. Respiratory-muscle training was once common, but it is now known that even with improvement of respiratory muscle strength, functional capacity usually does not improve [Butcher and Jones, 2006; Celli et al. 2004; Nici et al. 2006].

Reversibility of training effects is well known. Although the benefits of PR have been demonstrated up to 2 years following a short-term intervention, most studies suggest that the clinical benefits of PR tend to decline gradually over time. Thus it is important to implement strategies to maintain the benefits of PR over time, such as repeated courses of rehabilitation treatment or maintenance interventions. In one study by Foglio and colleagues, although repeated PR interventions spaced 1 year apart led to significant short-term gains similar to those seen following an initial 8-week outpatient program, no additive, long-term physiological benefits were noted. Another study by Ries and colleagues demonstrated that a 12-month maintenance intervention (consisting of monthly supervised exercise and educational reinforcement sessions and weekly telephone contacts) following an initial 8-week outpatient PR program led to modest improvements in the maintenance of walking endurance, health status, and healthcare utilization compared with usual care following PR over a 1-year follow-up period. Ultimately, the effects of training are specifically maintained as long as exercise is continued. Therefore, efforts at improving long-term adherence with exercise training at home are necessary for the long-term effectiveness of PR [Foglio et al. 2001; Ries et al. 2007].

It is noteworthy that walking represents a fundamental ability to perform several ADL. Furthermore, PR programs aim to encourage walking as an important, useful, and preferred form of exercise for many patients with COPD [Troosters et al. 2005]. Wheeled walking aids are sometimes prescribed for patients with COPD to improve their functional exercise capacity. More recently, it has been shown that walking with a rollator (which supports the upper arms) is effective in improving both physical performance and reducing dyspnea in patients with COPD who are severely disabled [Solway et al. 2002]. Another study showed that walking with a wheeled cart is able to improve distance, symptoms, and cardiopulmonary parameters in patients with COPD receiving long term oxygen therapy (LTOT) and performing PR. These results are of particular relevance among the subgroup of patients who are more disabled [Crisafulli et al. 2007] (Figure 3).

Figure 3.

Patient with respiratory insufficiency and treated with oxygen therapy while performing exercise training: (A) the oxygen canister is carried on the patient’s shoulder; (B) the oxygen canister is transported using a small, light, wheeled cart.

Education and psychosocial/behavioral intervention

Education and psychosocial/behavioral intervention is an integral part of PR programs. It encourages active participation in healthcare and determines a better understanding of the physical and psychological modifications that occur in chronic illnesses [Casaburi and ZuWallack, 2009]. With this approach, patients can become more collaborative in self-management and may develop better compliance. Furthermore, this intervention has been demonstrated to induce a reduction in dyspnea sensation [Haas et al. 1993]. Factors hypothesized to contribute to this desensitization include the antidepressant effect of exercise and the social interaction and distraction from dyspneic sensations that occur during exercise with a group of patients who have the same condition (Figure 4). In addition, this approach promotes adaptive behaviors, such as abstinence from smoking, better adherence to pharmacological and exercise therapy, and earlier recognition and treatment of COPD exacerbations. Self-management education has been shown to reduce the use of healthcare services and costs among patients with moderate to severe COPD and a history of hospitalizations [Bourbeau et al. 2003]. Other interventions, including psychotherapy, may also be effective but additional evidence is needed before their effectiveness can be proven [Norwood, 2006].

Figure 4.

Social interaction in a group of patients.

Chest physical therapy and breathing techniques

Chest physical therapy, including postural drainage, improves mucus clearance from airways. The value of this therapy in patients with stable COPD and with acute COPD exacerbation is uncertain. Nonetheless, for patients who produce more than 30 ml of sputum every 24 h or who have difficulties with sputum elimination, chest physical therapy combined with postural drainage and effective coughing techniques enhance sputum expectoration; the actual benefit, however, has not been determined [Fagevik and Westerdahl, 2009]. Nowadays, chest physiotherapy represents a nonessential component of PR, to be used in a small percentage of patients with chronic respiratory disease who are affected by a marked hypersecretory component [de Blasio, 2009].

Nutritional intervention

Body composition abnormalities are probably prevalent in all cases of advanced respiratory disease. However, to date, most literature has focused on patients with COPD. Patients with moderate to severe COPD are frequently underweight, including up to one third of outpatients and 32–63% of those referred for PR or those participating in clinical trials [de Benedetto et al. 2000]. Undernourishment (i.e. BMI < 21) in a patient with chronic respiratory disease is a poor prognostic indicator. Approximately 50% of hospitalized patients with COPD are reported to suffer from protein and calorie malnutrition [Celli et al. 2008]. Progressive weight loss occurs from inadequate dietary intake, diet-induced thermogenesis, increased REE, and failure of normal adaptive response to undernutrition. These mechanisms lead to energy imbalance and weight loss. Maintenance of adequate nutritional status by timely screening and appropriate management is essential [Annegarn et al. 2011]. Obtaining optimal nutritional status in PR should help to maximize the patient’s state of health, respiratory muscle function, and overall sense of wellbeing; it also may improve disease outcome [Decramer, 2008].

Pulmonary rehabilitation: outcome assessment

Like many other treatment modalities, PR has made significant progress in evaluating patient outcomes. However, understanding outcome evaluations continues to require careful examination. For example, programs should not only determine how much individual patients benefit from rehabilitation but should also identify what components of the process led to these benefits. Meaningful conclusions regarding the benefits of the program require robust evaluative instruments. Measurement of outcomes is essential in PR as it directly relates to its effectiveness. It is generally recommended that outcomes such as dyspnea, activity, and exercise capabilities should be evaluated because these areas should improve with PR (Table 3).

Table 3.

Pulmonary rehabilitation: outcome assessment.

Symptoms evaluation

Performance evaluation

Exercise capacity

Quality-of-life evaluation

Practical recommendations on outcome’s assessment

Symptom evaluation

The two major symptoms in patients referred to PR are dyspnea and fatigue. These symptoms are complex, with multiple mechanisms of action [Meek et al. 2001]. By nature, symptoms are subjective and require self-reporting. In the PR setting, dyspnea or fatigue can be assessed in two ways: in ‘real time’ or through recall [ZuWallack et al. 2004b]. Each approach may yield differing results. Real-time evaluation of symptoms will only answer the question of how short of breath or fatigued the patient is at the moment of testing. The Borg scale and the visual analog scale (VAS) are most commonly used for this purpose, which are either useful in assessing dyspnea or fatigue during exercise testing or training. Recall of symptoms, such as dyspnea or fatigue, is usually accomplished through the use of questionnaires. Some questionnaires require patients to rate their overall dyspnea experience, whereas others ask about dyspnea related to activities. Although most have adequate psychometric properties, some were initially developed for research purposes and thus are not ‘user friendly’ in the PR setting. Other considerations should be the context in which the symptoms are measured, how the questions about symptoms are worded, and the timeframe over which the symptom is measured (ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002).

Performance evaluation

An important goal of rehabilitation is to improve the patient’s ability to engage in ADL. Because improvements in exercise capacity do not necessarily translate into increases in ADL, assessment of functional performance is important. Assessment of performance can be accomplished by direct observation or by patient report. Most PR programs rely on patient self-reports to assess activity levels using both the patient’s report on the intensity of dyspnea with activities and the degree to which a patient may perform activities in a real-life situation [Lareau et al. 1998]. An emerging method of evaluating activities in the nonlaboratory setting is the use of activity monitors or motion detectors. Activity monitors can be used in the rehabilitation setting to provide an objective measure of patients’ daily activities [Steele et al. 2000]. Monitors range from simple, such as a pedometer, which evaluates the number of steps a patient takes, to more complex devices that measure movement in three planes, such as a triaxial accelerometer [Pitta et al. 2005].

Exercise capacity

Measurement of exercise capacity can be accomplished in several ways, including field tests, activity monitors, and cardiopulmonary exercise testing. Field tests have several advantages: they are simple to perform with little additional equipment, are conducted in a nonlaboratory setting, and are responsive to the PR intervention. They are either self-paced, such as the 6 min walk test [ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002], or externally paced tests, such as the incremental and endurance shuttle walk tests [Singh et al. 1992]. Both tests measure distance walked. Although cardiopulmonary exercise testing can be of considerable help in the initial assessment of exercise limitation and formulating the exercise prescription, it can also be useful in outcome assessment. Physiological measurements provide valuable insight into mechanisms of exercise intolerance. Cardiopulmonary exercise testing can be incremental to maximal symptom limitation or at a constant work rate [Nici et al. 2006].

Quality of life evaluation

QOL has been described as a person’s satisfaction or happiness with life in demands that the patient considers important and may be considered a balance between what is desired in life and what is achieved (although these indicators are difficult to measure). In rehabilitation, the following instruments have been used: general health questionnaires, such as sickness impact profile and short form; disease-specific scales, such as the CRQ; the St George Respiratory Questionnaire (SGRQ). Disease-specific measures have demonstrated greater sensitivity to change from baseline after rehabilitation intervention [Ringbaek et al. 2012].

Practical recommendations on outcome assessment

In conclusion, healthcare professionals dealing with PR must consider the most useful indicators of outcome to use in their clinical practice. Symptoms, exercise capacity, and health-related QOL must be objectively measured before and after the PR protocol and used as indicators of outcome. Symptoms can be measured with dyspnea and fatigue scales (i.e. Borg scale or VAS scale). Exercise capacity can be measured with field tests (i.e. 6MWD) and health-related QoL can be measured with self-administered disease specific questionnaires (i.e. CRQ or SGRQ).

Possible future directions

In a relatively short period of time, PR has become recognized as a cornerstone in the comprehensive management of patients with COPD. Despite the progress already made in its understanding, more information is needed to determine appropriate treatment for the increasing number of patients with chronic respiratory disease. The science and implementation of PR need to develop along several lines in the next few years.

PR positively impacts exercise capacity, health-related QoL, dyspnea and fatigue, as well as reducing healthcare utilization. Recent interest in the systemic nature of COPD has resulted in the use of multidimensional indices. There are exciting novel approaches to optimize training in patients with marked ventilatory limitation to exercise and evidence is increasing to support PR in respiratory conditions other than COPD. Issues that continue to challenge us include the following: optimizing access to PR; translating gains in exercise capacity into increased physical activity; strategies to maintain the gains made during PR; minimizing the deleterious effects of acute exacerbations of COPD; and establishing whether PR confers a survival benefit.

Other areas for future research are the impact of PR on healthcare costs; the additional benefit of psychosocial support, education, behavioral intervention and group therapy; the ideal intensity, duration and optimum form of exercise training; the possible benefit of strength training; the efficacy of maintenance programs; and the benefits of respiratory muscle rest obtained with noninvasive positive-pressure ventilation.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

The authors declare no conflicts of interest in preparing this article.

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Current best practice in pulmonary rehabilitation for chronic obstructive pulmonary disease

Abstract

Keywords

Definition of pulmonary rehabilitation

Chronic obstructive pulmonary disease: pathophysiology and consequences

Peripheral and respiratory muscles dysfunction

Chronic obstructive pulmonary disease phenotypes

Nutritional abnormalities

Cardiac impairment

Cognitive impairment

Other comorbid diseases

Goals and benefits of pulmonary rehabilitation

Setting and staffing

Pulmonary rehabilitation: program components

Exercise training

Education and psychosocial/behavioral intervention

Chest physical therapy and breathing techniques

Nutritional intervention

Pulmonary rehabilitation: outcome assessment

Symptom evaluation

Performance evaluation

Exercise capacity

Quality of life evaluation

Practical recommendations on outcome assessment

Possible future directions

Footnotes

Funding

Conflict of interest statement

References