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Year : 2006  |  Volume : 23  |  Issue : 4  |  Page : 175-177 Table of Contents   

Weight loss and skeletal muscle dysfunction in chronic obstructive pulmonary disease

Emeritus Professor of Medicine & Director, M.R. Medical College, Gulbarga., India

Correspondence Address:
P S Shankar
Emeritus Professor of Medicine & Director, M.R. Medical College, Gulbarga.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-2113.44397

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How to cite this article:
Shankar P S. Weight loss and skeletal muscle dysfunction in chronic obstructive pulmonary disease. Lung India 2006;23:175-7

How to cite this URL:
Shankar P S. Weight loss and skeletal muscle dysfunction in chronic obstructive pulmonary disease. Lung India [serial online] 2006 [cited 2020 Aug 13];23:175-7. Available from: http://www.lungindia.com/text.asp?2006/23/4/175/44397

Chronic obstructive pulmonary disease (COPD) is a syndrome of progressive airflow limitation caused by chronic inflammation of airways and lung parenchyma [1] .

The persistent airflow limitation associated with airway collapse, edema and fibrosis, is responsible for the wide spectrum of disease. Chronic inflammation plays the dominant role in the pathogenesis of COPD. The inflammatory process initiated by tobacco smoking and other irritant substances in the environment, activate macrophages in the respiratory tract. They release neutrophil chemotactic factors such as interleukin (IL)-8 and leukotriene (LT)-B4. There is accumulation of neutrophils in the airways making it a neutrophilic inflammatory disorder. The inflammation is perpetuated by macrophages, epithelial cells, and cytotoxic CD8+ T­lymphocytes. Neutrophils release proteases that bring about parenchymal damage and disintegration of connective tissue.

The pathogenic process initiated in COPD is likely to have a variety of effects on target tissues. The pathologic changes such as peribronchial fibrosis and narrowing, destruction of alveolar walls, and loss of elastic recoil, lead to airflow limitation. These changes exhibit adverse systemic effects such as abnormal skeletal muscle function, and wasting of the body. COPD is to be recognized as a systemic disease, which has metabolic and musculoskeletal implications.

   Mechanisms Top

The mechanisms underlying the systemic effects are not clear. However a number of interrelated and multiple factors such as inactivity, systemic inflammation, tissue hypoxia and oxidant stress play an important role in causing skeletal muscle dysfunction [2] .

   Nutritional Abnormalities and Weight Loss Top

Wasting is a common manifestation of chronic disease like COPD. A significant number of patients with severe COPD exhibit weight loss. The body cell mass (BCM) is the actively metabolizing and contracting tissue. The former refers to the organs and the latter to the muscles by weight loss. The alteration in BCM is recognized clinically by weight loss. The weight loss in COPD is essentially due to loss of skeletal muscle mass and to some extent to loss of fat mass [3] . Weight loss essentially pertains to loss in fat--free mass (FFM). Loss of FFM adversely affects muscle aerobic capacity and exercise capacity [4],[5] .

Weight loss appears to arise from an increased basal metabolic rate occurring due to an increased work of breathing. Inhaled salbutamol, altered amino acid composition and tissue hypoxia may result in an increased metabolic rate [6],[8] . Acidosis, infection, alteration in body composition and changes in intermediate metabolism or inadequate caloric intake especially during acute exacerbations of the disease are associated with an increased breakdown of cell proteins especially in muscles.

There is preferential loss of skeletal muscles especially in the lower extremities in patients with COPD. The muscle wasting is increasingly noticed in quadriceps muscle. Physical inactivity leads to quadriceps muscle­ weakness in patients with advanced COPD. Van Vliet and colleagues have shown that quadriceps muscle weakness is related to low circulating levels of testosterone in men with COPD [9] . Histologic study of biopsy specimens obtained from the quadriceps of patients with COPD has shown a loss of aerobic type I fibres and a reduction in oxidative enzymes [10],[11] . Wouters and colleagues have hypothesized that inflammatory cytokines may contribute to muscle wasting through the inhibition of myogenic differentiation [12] .

   Skeletal Muscle Dysfunction Top

The patients with COPD exhibit skeletal muscle dysfunction [13] . The muscles undergo atrophy and their strength gets diminished. It results in marked reduction in exercise capacity [14] . Among the muscles, diaphragm is put into constant work and it has to work against an increased load. Other skeletal muscles are utilized less due to inactivity [2] .

Skeletal muscle dysfunction is likely to occur from sedentary life-style, tissue hypoxia and systemic inflammation [14] . Systemic inflammation is the result of the effects of cytokines, such as tumor necrosis factor (TNF)­alpha, IL-6 and IL-8, and oxidative and nitrosoactive stress [15] . They are likely to cause protein inactivation and degradation leading to dysfunction, atrophy and apoptosis16.It must be noted that an increased inflammation in the lung does not correlate with increased levels of circulating inflammatory markers.

The circulating neutrophils appear to be activated in patients with COPD and they show enhanced chemotaxis and extracellular proteolysis [17] . They produce greater amount of reactive oxygen species [18] . There is likelihood of spill over of inflammation from the lung into the circulation or activation of inflammatory cells during their transit through the pulmonary vasculature. The skeletal muscles may also be involved in the production of TNF-alpha and other proinflammatory cytokines.

   Clinical Implications Top

Weight loss and skeletal muscle dysfunction bring about limitation in the activities and the exercise capacity of the patient with COPD, and indirectly on the quality of life. There is no correlation between weight loss and the parameters of pulmonary dysfunction such as, forced expiratory volume in one second (FEV 1 ) or arterial oxygen tension (PaO 2 ). The attempts to improve the body weight could improve the well being.

Thus, while undertaking the management of patients with CPD, attempts are to be made to regain body weight. A new multi-dimensional approach based on the BODE index has been created. It includes body mass index (B), the degree of airflow obstruction (O), and functional dyspnoea (D) and exercise capacity (E) as assessed by the 6-minute walking test. BODE index has shown to be better than FEV 1 in prediction of risk of fatality from respiratory causes among patients with COPD [19] . This approach has found an important place in the management of patients with COPD. Since sedentary life due to shortness of breath and tissue hypoxia from hypoxaemia have significant role in the pathogenesis of the systemic effects of COPD. The therapy should include physical rehabilitation and domiciliary oxygen therapy. They are likely to exert beneficial effect on the systemic effects.

Since systemic inflammation has a significant pathogenic role in the pulmonary and systemic manifestations, use of the systemic anti-inflammatory agents especially inhaled corticosteroids may bring about some beneficial response. However their role in the management of COPD is yet to be conclusively established. Efforts are being made to produce specific therapeutic agents to improve skeletal muscle dysfunction.

   References Top

1.Barnes P1. Chronic obstructive pulmonary disease. N Engl J Med. 2000: 343; 269-80.  Back to cited text no. 1    
2.Agusti AGN, Noguera A, Sauleda l, Sala E, Pons 1, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2004; 23: 932-946.  Back to cited text no. 2    
3.Schols AM. Nutrition in chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2000; 6: 110-115.  Back to cited text no. 3    
4.Majori M, Corradi M, Caminati A, et al. Predominant Thl cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease. J Allergy Clin Immunol 1998; 103: 458-462.  Back to cited text no. 4    
5.Palange P, Forte S, Onorati P, et al. Effect of reduced body weight on muscle aerobic capacity in patients with chronic obstructive pulmonary disease. Chest 1998; 114: 12-18.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Amoroso P, Wilson SR, Moxham 1, Ponte J. Acute effects of inhaled salbutamol on the metabolic rate of normal subjects. Thorax 1993; 48: 882-885.  Back to cited text no. 6    
7.Pouw EM, Schols AM, Deutz NEP, Wouters EFM. Plasma and muscle amino acid levels in relation to resting energy expenditure and inflammation in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998; 158: 797-801.  Back to cited text no. 7    
8.Sridhar MK. Why do patients with emphysema lose weight? Lancet 1999; 345: 1190-1191.  Back to cited text no. 8    
9.Van Vliet M, Spruit MA, Verleden G, Kasran A, Van Herck E, Pitta F, Bovillon R, Decramer M. Hypogonadism, quadriceps weakness, and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005: 172; 1105-1111.  Back to cited text no. 9    
10.Jacobsson P, Jadeldt L, Brundin A. Skeletal muscle metabolites and five types in patients with advanced COPD with and without chronic respiratory failure. Eur Respir J. 1990; 3: 192-196.  Back to cited text no. 10    
11.Maltais F, Simard A-A, Simard C, et al. Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit Care Med. 1996; 153: 288-293.  Back to cited text no. 11    
12.Wouters EFM, Creutzberg EC, Schols AMWJ. Systemic effects in chronic obstructive pulmonary disease. Chest 2002; 121: 1275-1305.  Back to cited text no. 12    
13.American Thoracic Society, European Respiratory Society. Skeletal muscle dysfunction in chronic obstructive pulmonary disease: a statement of the American Thoracic Society and European Respiratory Society. Am J Respir Crit Care Med. 1999; 159: S1-540.  Back to cited text no. 13    
14.Agusti AGN. Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005; 2: 367-370.  Back to cited text no. 14    
15.Gan WO, Man SFP, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systemic review and a meta-analysis. Thorax 2004; 59: 574-580.  Back to cited text no. 15    
16.Li Y-P, Schwartz R1, Waddell ID, Holloway BR, Reid MB: Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-alpha B activation in response to tumor necrosis factor-alpha. FASEB J 1998; 12: 871-880.  Back to cited text no. 16    
17.Barnett D, Hill SL, Chamba A, Stockkey RA. Neutrophils from subjects with chronic obstructive pulmonary disease show enhanced chemotaxis and extracellular proteolysis. Lancet. 1987; 2: 1043-1046.  Back to cited text no. 17    
18.Noguera A, Batle S, Miralles C, Iglesas J, Busquets X, MacNee W, Agusti AGN. Enhanced neutrophil response in chronic obstructive pulmonary disease. Thorax 2001; 56: 432-437.  Back to cited text no. 18    
19.Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, Cabral HI. The body-mass index, airflow obstruction, dyspnoea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004; 350: 1005-1012.  Back to cited text no. 19    


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