Catabolic/anabolic balance and muscle wasting in patients with COPD.

BACKGROUND The mechanisms leading to muscle wasting in patients with COPD are still uncertain. This study was undertaken to evaluate the relationships among circulating levels of catabolic factors (ie, interleukin [IL]-6 and cortisol), anabolic factors (ie, bioavailable testosterone [Tbio], dehydroepiandrosterone sulfate [DHEAS], and insulin-like growth factor [IGF]-I), and mid-thigh muscle cross-sectional area (MTCSA) in patients with COPD. METHODS Serum levels of the above factors were measured in 45 men with COPD (mean [+/- SEM] FEV(1), 43 +/- 3% predicted; mean age, 67 +/- 1 years) and 16 sedentary healthy men of similar age. MTCSA was quantified using CT scanning. Patients with COPD were subdivided into two groups according to the MTCSA (< 70 or >or= 70 cm(2)). RESULTS There was a greater prevalence of hypogonadism (ie, Tbio, < 2 nmol/L) in patients with COPD compared to control subjects (22% vs 0%, respectively). Patients with an MTCSA of < 70 cm(2) had significantly reduced levels of DHEAS compared to those in healthy subjects (p < 0.01). IL-6 levels were significantly higher in both subgroups of COPD patients compared to those in control subjects (p < 0.005). The cortisol/DHEAS, IL-6/DHEAS, IL-6/Tbio, and IL-6/IGF-I ratios were significantly greater in COPD patients with an MTCSA of < 70 cm(2) compared to those in control subjects (p < 0.05). The cortisol/DHEAS and IL-6/DHEAS ratios were also significantly greater in COPD patients with an MTCSA of < 70 cm(2) than in COPD patients with an MTCSA of >or= 70 cm(2) (p < 0.05). In a stepwise multiple regression analysis, the IL-6/DHEAS ratio explained 20% of the variance in MTCSA (p < 0.005). CONCLUSION Catabolic/anabolic disturbances were found in COPD patients leading to a shift toward catabolism and possibly to the development of peripheral muscle wasting.

[1]  Y. Lacasse,et al.  Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. , 2002, American journal of respiratory and critical care medicine.

[2]  E. Bozkanat,et al.  Skeletal muscle dysfunction in chronic obstructive pulmonary disease , 2001, Respiratory research.

[3]  R. Casaburi.  Skeletal muscle dysfunction in chronic obstructive pulmonary disease. , 1999, Medicine and science in sports and exercise.

[4]  O. Ukkola.  [Cachexia]. , 2020, Duodecim; laaketieteellinen aikakauskirja.

[5]  B. Sjödin,et al.  Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies , 2000, The Journal of physiology.

[6]  A. Ionescu,et al.  Bone density, body composition, and inflammatory status in cystic fibrosis. , 2000, American journal of respiratory and critical care medicine.

[7]  A. Goris,et al.  Tissue depletion and health related quality of life in patients with chronic obstructive pulmonary disease. , 2000, Respiratory medicine.

[8]  E. Keller,et al.  Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. , 2000, Annual review of medicine.

[9]  D. Furutama,et al.  Specific binding and effects of dehydroepiandrosterone sulfate (DHEA-S) on skeletal muscle cells: possible implication for DHEA-S replacement therapy in patients with myotonic dystrophy. , 1999, Life sciences.

[10]  F. Maltais,et al.  Aerobic and strength training in patients with chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[11]  L. Moldawer,et al.  Interleukin-1α (IL-1α) and Tumor Necrosis Factor α (TNFα) Regulate Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Levels and mRNA Abundance In Vivo and In Vitro* , 1999 .

[12]  R. Tremblay,et al.  Usefulness and limitation of bioavailable testosterone in assessment of androgenicity during the process of aging in men , 1999 .

[13]  L. Moldawer,et al.  Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) regulate insulin-like growth factor binding protein-1 (IGFBP-1) levels and mRNA abundance in vivo and in vitro. , 1999, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[14]  F. Maltais,et al.  Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. , 1998, Medicine and science in sports and exercise.

[15]  R. Haubrich,et al.  The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age‐advanced men and women , 1998, Clinical endocrinology.

[16]  F. Maltais,et al.  Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[17]  P. Poole‐Wilson,et al.  Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. , 1998, Journal of the American College of Cardiology.

[18]  H. Magnussen,et al.  Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy. , 1998, The European respiratory journal.

[19]  R. Wolfe,et al.  Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. , 1998, American journal of physiology. Endocrinology and metabolism.

[20]  S. Lamberts,et al.  The endocrinology of aging. , 1997, Science.

[21]  S. Anker,et al.  Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. , 1997, Journal of the American College of Cardiology.

[22]  H. Turner,et al.  Gonadal function in men with chronic illness , 1997, Clinical endocrinology.

[23]  P. Ponikowski,et al.  Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. , 1997, Circulation.

[24]  C. Benbassat,et al.  Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures. , 1997, The Journal of clinical endocrinology and metabolism.

[25]  E. Wouters,et al.  Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. , 1996, Thorax.

[26]  M. Buck,et al.  Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. , 1996, The EMBO journal.

[27]  N. Jones,et al.  Muscle strength, symptom intensity, and exercise capacity in patients with cardiorespiratory disorders. , 1995, American journal of respiratory and critical care medicine.

[28]  M. Yano,et al.  Interleukin-6 induces proteolysis by activating intracellular proteases (cathepsins B and L, proteasome) in C2C12 myotubes. , 1995, Clinical science.

[29]  E. Wouters,et al.  Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. A placebo-controlled randomized trial. , 1995, American journal of respiratory and critical care medicine.

[30]  H. Fillit,et al.  Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. , 1990, The New England journal of medicine.

[31]  K. Mealy,et al.  The testicular effects of tumor necrosis factor. , 1990, Annals of surgery.

[32]  J. Snick,et al.  Interleukin-6: an overview. , 1990, Annual review of immunology.

[33]  J. Morley,et al.  Endocrinology in aging. , 1988, Disease-a-month : DM.

[34]  J. Gosney.  Atrophy of Leydig cells in the testes of men with longstanding chronic bronchitis and emphysema. , 1987, Thorax.

[35]  Phillips Yy,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. , 1987, The American review of respiratory disease.

[36]  R. Hume,et al.  Hypothalamic-pituitary dysfunction in respiratory hypoxia. , 1981, Thorax.

[37]  R B Douglas,et al.  The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. , 1980, The American review of respiratory disease.

[38]  Goldman Hi,et al.  Respiratory function tests; normal values at median altitudes and the prediction of normal results. , 1959 .