Societies are aging all over the world, and medical attention has focused on changes in body composition during the aging process. As aging progresses, lean body mass decreases and fat percentage increases.[1] These changes in metabolism cause the loss of muscle mass and lower functional status. In 1989, Rosenberg [2] first expressed medical interest in the changes in muscles that accompany aging and suggested the use of the term “sarcopenia” for aging-associated loss of muscle. Since then, sarcopenia has become a more comprehensive term that includes the concept of loss of muscle function as well as the amount of muscle.[3] If there is difficulty in moving, a gradual decline in health status, or a recent history of falls, an unintended weight loss of 5% or more may suggest sarcopenia. [4] Sarcopenia is frequently associated with chronic diseases such as type 2 diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease (COPD), chronic kidney disease, rheumatoid arthritis, and cancer. The cut-off value for muscle mass is slightly different depending on the working group, and the prevalence of sarcopenia (low muscle mass) in South Korea is reported to be quite different depending on which value is used. Although systematic domestic data are still lacking, 9.3% of elderly men and 0.2% to 22.1% of elderly women are considered to have sarcopenia using the appendicular skeletal muscle mass (ASM)/height² (ht²) index in the data from the Korean National Health and Nutrition Examination Survey (KNHANES).[56] According to the KNHANES, 13.4% of the population aged 40 years or older has COPD.[7] A relationship between sarcopenia and COPD is increasingly reported, and there is some overlap in clinical features and treatments. It is fascinating to be able to diagnose 2 diseases through similar physical performance tests and to improve both diseases through the same treatment, such as exercise. Therefore, this review summarizes the clinical relevance and integrative management of the 2 diseases.

Many diagnostic methods have been proposed at various conferences, but recently more detailed diagnostic criteria have been suggested. The European Working Group on Sarcopenia in Older People (EWGSOP) presented a European consensus on the definition and diagnosis of sarcopenia in 2010, which was updated in 2018 by EWGSOP2. EWGSOP2 used low muscle mass and muscle function (muscle strength and physical performance) as criteria for diagnosing sarcopenia. In EWGSOP2, low muscle strength is defined as the first parameter of sarcopenia, and diagnosis is confirmed by the presence of decreased muscle mass (quantity and quality). Physical performance was previously a core parameter for diagnosis, but it is now proposed as a parameter to categorize the severity of sarcopenia in the revised definition (Table 1).[18]

In EWGSOP2, it was confirmed that the previous cut-off values for muscle mass are difficult to memorize. For this reason, the working group decided to sacrifice precision and use cutoff points that are close to references to make them easy to remember. The Asian Working Group for Sarcopenia (AWGS) is similar to the EWGSOP, but its criteria provide other clinical guidelines. For Asian people, SMI is 7.0 kg/m² for men and 5.4 kg/m² for women when using dual energy X-ray absorptiometry (DXA), and 7.0 kg/m² for men and 5.7 kg/m² for women when using bioimpedence analysis (BIA). In principle, the AWGS follows the diagnostic approach of the EWGSOP and revises and adds cut points in some areas from the Asian perspective. The sarcopenia project of the Foundation for the National Institutes of Health (FNIH) is designed to determine muscle strength levels associated with mobility disability and then determine the level of muscle mass that would identify clinically appropriate muscle weakness. Therefore, the FNIH sarcopenia project recommends the ASM/body mass index (BMI) ratio, which is an indicator of muscle mass, divided by the BMI of ASM.[9] The cutoff values established by the international working groups are summarized in Table 2.

Sarcopenia is associated with loss of mobility, falls, osteoporosis, poor quality of life (QOL) due to fracture, hospitalization, and death.[10] In addition, the loss of muscle mass and function lead to decreases in physical activity and energy consumption, resulting in an increase in body weight.[11] As a result, pulmonary function is reduced, and cardiovascular and metabolic diseases are more likely to occur. A study of the elderly in their 70s to 90s revealed that mortality increased by 1.9 times for every 1 kg/m² reduction of lean body mass for 2 years.[12] In Korean studies, 500 elderly patients over 65 years of age were followed up for 6 years. The mortality rate for those with sarcopenia was 2.99 times higher in men and 3.22 times higher in women than that of the normal group, based on the EWGSOP criteria.[13]

COPD is now the fourth leading cause of death worldwide. In 2012, more than 3 million people worldwide died of COPD, accounting for 6% of all deaths.[14] COPD is an important disease in public health because it can be prevented and treated. Forced expiratory volume in one second (FEV₁), which can be confirmed by pulmonary function tests, is important for the evaluation of COPD patients. Worsening dyspnea reduces the patient's physical performance. As a result, life satisfaction is lowered and anxiety and depression may occur.[15] COPD characterized by irreversible airflow limitation exacerbates respiratory distress as the disease progresses. As the amount of activity decreases, muscle mass decreases and eventually oxygen cannot be used effectively, resulting in a vicious cycle of deterioration of exercise capacity (Fig. 1).[16] In the BODE index (BMI, FEV₁, dyspnea measured by the modified Medical Research Council, 6-min walk distance) designed for COPD mortality prediction, exercise capacity and muscle mass are the main prognostic factors.[17] In other words, the clinical significance of physical activity in COPD is as important as that of medical treatment.

Deconditioning due to decreased activity is a major cause of limb muscle dysfunction. In chronic diseases such as COPD, however, problems such as inflammation, oxidative stress, malnutrition, and hypoxemia may also cause skeletal muscle dysfunction.[18] The rate of malnutrition in patients with COPD increases with the severity of the disease, up to 30% in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4.[19] In addition, changes in body composition are reported in up to 35% of cases in which the fat free mass (FFM) index (FFMI) is significantly lower than normal.[20] Even if the BMI is normal, the evaluation of body composition is important because the FFMI is often low. One study revealed that low FFMI correlates strongly with mortality in COPD patients with normal weight. [21] In patients with COPD, atrophy of the legs, especially the thigh muscles, was dominant over the whole body.[22] In severe COPD, it was confirmed that muscle fiber shifted from type I to type IIx, unlike in the normal aging process.[23] These abnormal fiber shifts led to inefficiencies that result in high oxygen demand at submaximal workloads.[24] Systemic oxidative stress was found to be associated with endurance of the quadriceps muscle in patients with severe COPD.[25] More oxidative stress in the limb muscles and poor function of the quadriceps muscle were reported in patients with hypoxemia.[26] Quadriceps muscle strength was reported to be 20% to 30% lower in patients with COPD than in normal people.[27] Decreased muscle endurance of the quadriceps in patients with COPD has been reported.[252628] Muscle endurance was also significantly reduced with hypoxemia as well as muscle strength.[26] Many COPD patients complain of leg muscle fatigue before dyspnea, and exercise is stopped. Various studies have been conducted using subjective or objective methods. Objective methods include measuring muscle twitch after magnetic stimulation,[29] or measuring the median frequency of surface electromyography.[30] Systemic inflammation in patients with COPD has recently been identified as a cause of other complications such as cachexia and osteoporosis.[313233] Among them, chronic inflammation in stable COPD patients is suspected as the cause of sarcopenia, and several studies are underway. Byun et al.[32] reported that high levels of high-sensitivity tumor necrosis factor-α (hsTNF-α), an inflammatory biomarker, were significant predictors of the presence of sarcopenia (odds ratio, 1.99; 95% confidence interval, 1.04–3.81) in 80 stable COPD patients.

Acute exacerbation of COPD is a condition best avoided during the course of the disease, but it is common. If acute exacerbation occurs at any time and the patient is admitted to the hospital, deterioration of systemic function including limb muscle strength can easily occur. Quadriceps muscle weakness after acute exacerbation of COPD is frequently reported, and weakened muscles recover 3 months or more after discharge.[33] Limb muscle dysfunction during acute exacerbations may be due to various factors such as systemic inflammation, malnutrition, and steroid use, as well as physical inactivity. A decreased mid-thigh muscle cross-sectional area and decreased quadriceps muscle strength contribute to increased mortality in COPD.[34] In addition, mortality was almost doubled when FFMI was less than 16 kg/m² in men and less than 15 kg/m² in women.[21] In conclusion, muscle strength, endurance, and muscle mass of the thigh are clinically important in COPD patients. For diagnosis of sarcopenia, muscle strength is measured by grip strength, not knee extensor strength, as a consensus made to simplify the diagnosis. In other words, evaluation of limb muscle dysfunction in COPD is not completely consistent with the diagnosis of sarcopenia, but it can be expected that there will be high correlation between the 2 diseases.

The prevalence of sarcopenia in stable COPD was reported to be 15% to 25% in previous foreign studies and 25% in a Korean study.[323536] Sarcopenia prevalence was inversely related to the modified Medical Research Council Dyspnea Scale and BODE index scores, and a higher prevalence was observed with lower 6-min walking distance.[32] The prevalence of sarcopenia in COPD patients is higher than that in normal elderly people. Therefore, COPD may be one cause of sarcopenia.[37] Physical frailty is defined as “a medical syndrome that increases the vulnerability of an individual to dependence and death due to a reduction in physical strength, endurance, and physiological function due to various causes.” The frailty prevalence rate in stable COPD diagnosed with the fatigue, resistance, ambulation, illnesses, and loss of weight scale was 6.6%, 50% of which was diagnosed as sarcopenia. The prevalence of sarcopenia in the non-frail COPD group was 22.2%.[38] Frailty, sarcopenia and COPD tend to overlap some in some of their features and disease course.

In patients with COPD, the factors that decrease muscle strength and endurance include chronic inflammation, oxidative stress, inactivity, hypoxemia, hormone abnormality, deficits of nutrients including protein and vitamin D, and the use of systemic corticosteroid. Therefore, treatment and management should either inhibit this process or go in the direction of supplementing the deficient elements. Some approaches are summarized below.

The market is expected to expand rapidly, as a disease code (the International Classification of Diseases, Tenth Revision, Clinical Modification code, M62.84) for sarcopenia was granted in the United States in October 2016. As a result, further research on an international scale will be conducted. Already, the European Union's innovative medicine initiative has selected the development of drugs for sarcopenia as a major health topic. In other words, sarcopenia can be expected to have a status equivalent to that of the current osteoporosis market. The diagnosis and treatment of COPD is already systematized. In addition to vaccination and smoking cessation for the prevention and treatment of COPD, the PR has also gradually expanded in South Korea. In conclusion, if physicians are interested in COPD PR, it is possible to evaluate, prevent, and treat sarcopenia easily. In COPD patients, sarcopenia can be diagnosed through tests such as the grip test, DXA or BIA, and gait speed. Standardization of the evaluation guideline will facilitate investigation of the prevalence of sarcopenia in domestic COPD patients and enable effective exercise to be prescribed for the treatment of patients with sarcopenia with COPD.