The Main Clinical Indicators of Sarcopenia in Patients with Chronic Respiratory Disease: Skeletal Muscle Dysfunction Approach

*Esmaeil Alibakhshi, Raffaele Fiorillo, Luis Lores Obradors, Ana María Sánchez-Laforga, Amparo Villar Cánovas, Mostafa Ghanei and Ali Qazvini*

### **Abstract**

Patients with chronic respiratory diseases (CRDs) have a disorder in muscle structure and function, but their function increases with physical progress and decreases the risk of general, and muscular weakness are more likely to develop sarcopenia. We randomly selected patients (N = 38) with mean age of 72 1.0 years old men and women elderly with chronic respiratory diseases such as asthma, COPD, bronchiectasis and obesity with dyspnea score ≥ 2 in MRC index. All patients after receiving research information and signing informed consent have gone through performing clinical assessments. They performed femur bone mineral density (FBMD) and ultrasound on the rectus femoris muscle mid-tight crosssectional area (RFMTCSA) in the quadriceps muscle. The significant changes in BMI were seen in all patients, pre-rehabilitation, BMI <sup>=</sup> <sup>30</sup> 1.06 kg/m<sup>2</sup> and postrehabilitation, BMI <sup>=</sup> <sup>29</sup> 1.00 kg/m2 . In Pearson's correlation of r = 0.607 between T-score and Z-score in FBMD and RFMTCSA in pre-rehabilitation, there is a little bit significant correlation between the variables than in the Pearson's correlation of r = 0.910 in post-rehabilitation, P < 0.00. Comparing femur bone and rectus femoris muscle parameters as indicators for diagnosis of sarcopenia in chronic respiratory patients, we observed that in rectus femoris muscle, ultrasound is the most effective foot muscle detector.

**Keywords:** sarcopenia, femoral bone mineral density, rectus femoris muscle phenotype, quadriceps muscles, chronic respiratory disease, quality of life

### **1. Introduction**

Chronic respiratory disease (CRDs) is widespread worldwide. It was reported to be the sixth leading cause of death in the world in 1990 and is now the fourth leading cause of death and is projected to be the third leading cause of death in the

world by 2020 [1]. Chronic obstruction of airflow is an important feature of these patients. CRDs have impaired airway function and lung structures. Some of the most common chronic obstructive pulmonary diseases, COPD, asthma, occupational lung disease, pulmonary hypertension and respiratory problems associated with the patient are due to adverse physical conditions such as for overweight and obesity. Patients with chronic respiratory illness can suffer from other symptoms such as frailty, depression, heart attack, fatigue, decreased exercise capacity, and kidney pain. Exercise is in many cases a strategic way to improve the symptoms of these diseases. It is now widely reported that proper exercise can be an effective prevention and treatment strategy for respiratory patients, and this is very important in the management of elderly people with chronic respiratory diseases. Recent studies of extra-pulmonary issues in chronic respiratory patients have shown that quadriceps muscle is the most important muscle for these patients due to involvement in movement and activities [2, 3]**.** But accurate and reliable equipment must be used to evaluate the quadriceps. New scientific studies have used ultrasound technology as an important and valid device for an accurate evaluation of quadriceps function and structure.

The mechanism that disrupts musculoskeletal function can have negative consequences through the progression of the so-called "healthy age" to sarcopenia and weakness. Sarcopenia has been described as a decrease in skeletal muscle and a decrease in physical function dependence, which requires knowledge of current conditions of the musculoskeletal system to reduce muscle mass and muscle weakness in chronic respiratory patients. Skeletal muscle function is often considered in common diagnostic criteria, due to muscle weakness and a history of weight loss, which is often a product of muscle wasting. Both syndromes indicate skeletal muscle dysfunction, which affects more of these syndromes, the broader effects of the disease, both inside and outside the lungs, affecting morbidity and mortality in these patients [8]. Therefore, the presence of sarcopenia may be considered and provide additional prognostic information provided by skeletal muscle function markers. Previous studies have reported that a decrease in skeletal muscle mass is associated with a decrease lung function in patients with COPD. More recently, in studies of nursing home residents, Carlson et al. [6] showed that peripheral muscle strength, including hand-grip strength, was associated with maximal stimulating muscle strength. However, there is a paucity of information on how skeletal muscle mass changes are associated with pulmonary function in adults without lung

*The Main Clinical Indicators of Sarcopenia in Patients with Chronic Respiratory Disease…*

Some scientific reports suggest that one of the systemic effects of COPD is sarcopenia. The term is described as an age-related decline in muscle volume and function. This situation is associated with negative health consequences such as falling, disability, hospitalization, poor quality of life and mortality. The cause of sarcopenia is in addition to the consequences of the disease, nutrition, and activities caused by physiological changes. Sarcopenia can be classified as a physical impairment associated with adverse health consequences. These findings suggest that sarcopenia is associated with decreased lung function in COPD patients. These patients also have a relative or absolute increase in fat mass, which can lead to systemic inflammation, and insulin resistance [9, 14]**.** In a recent study, body mass index (BMI) was not significantly associated with lung function, the severity of

Skeletal muscle dysfunction is a well-known clinical manifestation in COPD patients. Key features include quadriceps weakness, atrophy, and type II fiber alteration, all of which are associated with a poor prognosis independent of lung function. Sarcopenia describes age-related skeletal muscle loss, leading to an increased risk of physical disability, poor health, and mortality. Sarcopenia is increasingly recognized as a clinical syndrome with its contributing factors, including physical inactivity, malnutrition, and chronic illness. Since COPD is in some ways an accelerated disease in the aging process, it is proposed the hypothesis that sarcopenia is related to COPD patients [10]**.** In patients with COPD, most studies addressing skeletal muscle dysfunction have focused on one aspect of sarcopenia, mainly in the lower limbs. This contradicts international consensus statements on sarcopenia, which emphasizes the loss of both muscle mass and function in diagnostic criteria, and emphasizes the importance of general muscle function. In particular, evaluation of one aspect of sarcopenia is not sufficient, as the relationship between muscle mass and strength is nonlinear, and muscle atrophy does not always lead to dysfunction and there are no functional status weaknesses. The European Working Group on Sarcopenia in the Elderly (EWGSOP) has developed practical clinical diagnostic criteria for sarcopenia approved by international organizations and used to assess the prevalence and impact of this syndrome on disease

dyspnea, quality of life, and decreased skeletal muscle mass.

disease.

**31**

**1.2 Recognizing sarcopenia in CRDs**

*DOI: http://dx.doi.org/10.5772/intechopen.91333*

According to the latest scientific reports [4, 5], the rate of sarcopenia in COPD patients is about 25%. Severe sarcopenia was 2.5% and only 0.8% obesity associated with sarcopenia. The incidence of sarcopenia in COPD patients is 15%. It is well known that respiratory disorders are a very common disease. It is also quite evident that respiratory distress is a very common disease that affects up to 10% of adults over 40 years of age and causes high levels of illness and mortality. It is associated with additional respiratory disorders, such as cardiovascular disease, osteoporosis, depression, and anemia. Besides, other non-pulmonary complications, such as cardiovascular disease, bone loss, musculoskeletal disorders, and muscle weakness, can also adversely affect their health outcomes. Increasing different comorbidities can damage lung function, decrease quality of life, and increase mortality. In all of these problems, muscle weakness and osteoporosis is a major problem that needs more therapeutic intervention. In the general population, osteoporosis risk factors include female gender, age, low body weight, glucocorticoid intake in chronic patients, and endocrine problems such as hyperthyroidism and primary hyperparathyroidism. Recently, reduced skeletal muscle as sarcopenia parameter has been identified as a risk factor [6]**.** The major risk factors for osteoporosis in respiratory patients are not yet clearly understood, but factors such as aging, female gender, low body weight, and body mass index (BMI) have been associated with reduced BMD in patients with COPD [6]**.** But compared to skeletal muscle index, body weight and BMI do not provide a more accurate reflection of body composition. In one study of aging and body composition, the prevalence of sarcopenia in the overweight group (BMI = 25–29) was 8.9% and in the obese group (BMI > 30) 7.1%. Overweight and obesity are often symptoms of sarcopenia and gradually increase with the prevalence of chronic respiratory disease. Low body mass index is associated with osteoporosis risk factors in patients with COPD including low body weight and low BMD [7]**.** Sarcopenia is a major complication of chronic obstructive pulmonary disease, which is often seen even without low BMI. However, few studies have been published on the relationship between sarcopenia and BMD.

#### **1.1 Skeletal muscle dysfunction in CRDs**

Musculoskeletal disorders are an important clinical examination that is recognized in chronic respiratory patients. For example, in people with COPD, common changes in the musculoskeletal system, including quadriceps weakness, atrophy, and fiber-type shift, each provide independent predictive information of the lung.

*The Main Clinical Indicators of Sarcopenia in Patients with Chronic Respiratory Disease… DOI: http://dx.doi.org/10.5772/intechopen.91333*

The mechanism that disrupts musculoskeletal function can have negative consequences through the progression of the so-called "healthy age" to sarcopenia and weakness. Sarcopenia has been described as a decrease in skeletal muscle and a decrease in physical function dependence, which requires knowledge of current conditions of the musculoskeletal system to reduce muscle mass and muscle weakness in chronic respiratory patients. Skeletal muscle function is often considered in common diagnostic criteria, due to muscle weakness and a history of weight loss, which is often a product of muscle wasting. Both syndromes indicate skeletal muscle dysfunction, which affects more of these syndromes, the broader effects of the disease, both inside and outside the lungs, affecting morbidity and mortality in these patients [8]. Therefore, the presence of sarcopenia may be considered and provide additional prognostic information provided by skeletal muscle function markers. Previous studies have reported that a decrease in skeletal muscle mass is associated with a decrease lung function in patients with COPD. More recently, in studies of nursing home residents, Carlson et al. [6] showed that peripheral muscle strength, including hand-grip strength, was associated with maximal stimulating muscle strength. However, there is a paucity of information on how skeletal muscle mass changes are associated with pulmonary function in adults without lung disease.

#### **1.2 Recognizing sarcopenia in CRDs**

Some scientific reports suggest that one of the systemic effects of COPD is sarcopenia. The term is described as an age-related decline in muscle volume and function. This situation is associated with negative health consequences such as falling, disability, hospitalization, poor quality of life and mortality. The cause of sarcopenia is in addition to the consequences of the disease, nutrition, and activities caused by physiological changes. Sarcopenia can be classified as a physical impairment associated with adverse health consequences. These findings suggest that sarcopenia is associated with decreased lung function in COPD patients. These patients also have a relative or absolute increase in fat mass, which can lead to systemic inflammation, and insulin resistance [9, 14]**.** In a recent study, body mass index (BMI) was not significantly associated with lung function, the severity of dyspnea, quality of life, and decreased skeletal muscle mass.

Skeletal muscle dysfunction is a well-known clinical manifestation in COPD patients. Key features include quadriceps weakness, atrophy, and type II fiber alteration, all of which are associated with a poor prognosis independent of lung function. Sarcopenia describes age-related skeletal muscle loss, leading to an increased risk of physical disability, poor health, and mortality. Sarcopenia is increasingly recognized as a clinical syndrome with its contributing factors, including physical inactivity, malnutrition, and chronic illness. Since COPD is in some ways an accelerated disease in the aging process, it is proposed the hypothesis that sarcopenia is related to COPD patients [10]**.** In patients with COPD, most studies addressing skeletal muscle dysfunction have focused on one aspect of sarcopenia, mainly in the lower limbs. This contradicts international consensus statements on sarcopenia, which emphasizes the loss of both muscle mass and function in diagnostic criteria, and emphasizes the importance of general muscle function. In particular, evaluation of one aspect of sarcopenia is not sufficient, as the relationship between muscle mass and strength is nonlinear, and muscle atrophy does not always lead to dysfunction and there are no functional status weaknesses. The European Working Group on Sarcopenia in the Elderly (EWGSOP) has developed practical clinical diagnostic criteria for sarcopenia approved by international organizations and used to assess the prevalence and impact of this syndrome on disease

settings and states. Although commonly used in COPD, it is necessary to understand the magnitude and nature of the problem in the disease associated with atrophy and muscle weakness [11]**.** Sarcopenia is associated with many common disease management strategies, including exercise training and nutritional aspects. Given the emergence of drugs directed to sarcopenia in other disease conditions, such data may be useful for drug production [12]**.** In this study, we evaluated the prevalence and risk factors of sarcopenia in respiratory patients and the effect of sarcopenia on functional exercise capacity and health status. We also seek to examine the relationship between sarcopenia and quadriceps strength and to examine whether exercise training as part of pulmonary rehabilitation can reverse sarcopenia.

the elderly is quite clear. But none of the current indicators of sarcopenia include its diagnostic algorithm. Bonsignore [17] and Marmorato et al. [18] believe that the use of muscle ultrasound is also potential in this area and is largely based on pioneering studies in which muscle mass and its architecture are evaluated using this method in

*The Main Clinical Indicators of Sarcopenia in Patients with Chronic Respiratory Disease…*

Body mass index (BMI) should be mounted on a wall using standard hospital calibration scales, because these parameters are very useful and fruitful in respiratory treatment as an indicator of health status. BMI is calculated as body mass (kg)

severe COPD where an increasing BMI is linearly associated with better survival, while in patients with mild to moderate COPD the lowest mortality risk occurs in normal to overweight or weight loss in these patients. The World Health Organization criteria were used to classify the subjects as low-weight (BMI < 18.5), eutrophic (18.5 < BMI ≤ 24.99), overweight (25 ≤ BMI ≤ 29.99) or obese (BMI ≥ 30.00) [19]**.** This index and division for respiratory patients can also be cited and so for all population recognized. The biggest problem with BMI is that when patients with chronic respiratory disease have a normal weight, they are unable to recognize the percentage of the muscles of this patient, which is the main cause of her movement and activity, and in this situation, we need to use more precise equipment the body composition by BIA (Bioelectrical Impedance Analysis), including the percentage of muscle, fat, bone, lean mass, hole body mass, is more accurately measured, and this can be useful in a more accurate diagnosis of sarcopenia in these patients [20]**.**

One of the most important indicators of sarcopenia in chronic respiratory patients is the skeletal muscle index (SMI), which is measured by factors such as age, height, weight, ethnicity, gender, and BMI in a valid and reliable formula, and its rate in an evaluation table according to gender and age is measurable. This index is the most important factor in the diagnosis of sarcopenia in chronic patients, especially in patients with respiratory disease. SMI is calculated as a function of weight and height as follows: (height [m]\_0.244\_body mass) + (7.8\_height) + (6.6\_gender) – (0.098\_age) + (ethnicity – 3.3). The SMI index is then calculated by

dividing an individual's SMI (kg) by his or her height squared (m<sup>2</sup>

can be used as the main factor in the diagnosis of a respiratory patient with

The gold standard of research for evaluating sarcopenia relies on complete techniques, cross-sectional imaging, a non-functional, and more structured approach to routine care. A more practical alternative indicator of lumbar muscle density in L3 using a normalized computed tomography (CT) is called skeletal muscle index (SMI). While evidence suggests that decreased lumbar SMI is associated with adverse clinical outcomes, such as deaths in the lung or colorectal cancers, little research has investigated how this measure of sarcopenia relates to dyspnea or decreased exercise tolerance. Although lung cancer patients and respiratory patients often use chest CT scans as part of their care, fewer respiratory patients receive lumbar scans. This limits the ability to evaluate sarcopenia using the lumbar SMI and therefore requires the discovery of the quadriceps SMI instrument as a more accurate sarcopenia measure. Besides, the measurement of thoracic skeletal muscle,

). However, this mostly applies to patients with

). This indicator

healthy subjects and respiratory patients.

*DOI: http://dx.doi.org/10.5772/intechopen.91333*

**1.3 Sarcopenia indexes in CRDs**

divided by squared body height (m<sup>2</sup>

*1.3.2 Skeletal muscle index (SMI)*

sarcopenia [21]**.**

**33**

*1.3.1 Body mass index (BMI)*

Patients with respiratory disorders have musculoskeletal disorders, but their function increases with the progression of physical activity and reduces the risk of general and muscular weakness. Respiratory patients with general and muscular weakness have higher mortality rates than non-weak patients and are more likely to have sarcopenia and an increased incidence of the disease. In one study at a British hospital (2015) [13], the prevalence of sarcopenia was reported to be 14.5% of COPD patients in British country compared to other European countries. In chronic respiratory patients, both risk factors (smoking, aging) and their causal mechanisms (endocrine dysfunction and inflammatory cytokines) are common and be high prevalence. These causes have increased with age and the global prevalence of recurrent respiratory diseases. Muscle structure and function must be considered for the diagnosis of sarcopenia. Clinically, the current definition of sarcopenia may show several defects, especially for quantitative measurement of muscle volume. Firstly, muscle mass thresholds are defined differently, and this causes patients to be classified correctly or incorrectly for sarcopenia. The prevalence of sarcopenia in the elderly also depends on the accepted definition for evaluation. However, the role of skeletal muscle ultrasound for screening and diagnosis of sarcopenia in the elderly remains and is important. None of the current definitions of sarcopenia include it in the diagnostic algorithms currently in the category of specialists. However, some experts [14–16] believe that using ultrasound in this field is also useful and this technique is recognizable based on pioneering studies of muscle mass in healthy individuals and patients with an aging approach. Therefore, most studies support the use of potentially validated muscle ultrasound to identify sarcopenia in the elderly. However, since it has been performed in small samples and a variety of clinical conditions (from healthy subjects to patients with chronic diseases), no significant recommendations have been made regarding the use of large-scale muscle ultrasound. In smaller cases, so in the same patients, some muscles may be affected by sarcopenia and other muscles not affected. Innovative muscle ultrasound studies have been conducted by Abe et al. [19] and his colleagues have contributed to the development of knowledge of this phenomenon and have developed specific concepts. They also developed and validated the equations, and calculated the total body mass index from ultrasound muscle thickness measurements in Japanese and Caucasian subjects, and achieved significant results. However, the relationship between full-body sarcopenia and specific sarcopenia is not fully understood and needs further research to identify the indicators. In this capture, in a small group of healthy adults, the researchers showed that the ratio of anterior or posterior muscle to ultrasound was not consistent with abdominal lumbar mass measured by DEXA. However, according to the researchers' findings, it can be concluded that using ultrasound and DEXA to predict sarcopenia indices in chronic respiratory patients is valid and reliable, but which parameter has the most impact? It is not clear yet and we need to investigate more in the future. However, the role of skeletal muscle ultrasound for screening and diagnosis of sarcopenia in

the elderly is quite clear. But none of the current indicators of sarcopenia include its diagnostic algorithm. Bonsignore [17] and Marmorato et al. [18] believe that the use of muscle ultrasound is also potential in this area and is largely based on pioneering studies in which muscle mass and its architecture are evaluated using this method in healthy subjects and respiratory patients.
