Systemic Inflammation and Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease: State of the Art and Novel Insights in Regulation of Muscle Plasticity

Clinics in Chest Medicine

Volumn 28, Issue 3, 2007, Pages 537-552

  Remels, Alexander H ^a   Gosker, Harry R ^a   van der Velden, Jos ^a   Langen, Ramon C ^a   Schols, Annemie M ^a  

^a MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE DEPENDENT PROTEINASE; CASPASE; ENDONUCLEASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; MESSENGER RNA; MUSCLE PROTEIN; MYOD PROTEIN; SOMATOMEDIN C; TUMOR NECROSIS FACTOR ALPHA;

APOPTOSIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; DISEASE ASSOCIATION; HEALTH STATUS; HUMAN; MUSCLE ATROPHY; MUSCLE CELL; MUSCLE DISEASE; MUSCLE FUNCTION; MUSCLE GROWTH; MUSCLE MASS; MUSCLE REGENERATION; MUSCLE STRENGTH; NONHUMAN; OXIDATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN METABOLISM; PROTEIN SYNTHESIS; REVIEW; SKELETAL MUSCLE; TREATMENT OUTCOME;

APOPTOSIS; HUMANS; INFLAMMATION; MUSCLE, SKELETAL; MUSCULAR ATROPHY; MUSCULAR DISEASES; OXIDATIVE STRESS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

EID: 34548034704     PISSN: 02725231     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ccm.2007.06.003     Document Type: Review

References (129)

1. Agusti A.G. Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2 (2005) 367-370 [discussion: 71-2]
2. Balasubramanian V.P., and Varkey B. Chronic obstructive pulmonary disease: effects beyond the lungs. Curr Opin Pulm Med 12 (2006) 106-112
3. Mador M.J. Muscle mass, not body weight, predicts outcome in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 166 (2002) 787-789
4. Gosker H.R., Wouters E.F., van der Vusse G.J., et al. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr 71 (2000) 1033-1047
5. Satta A., Migliori G.B., Spanevello A., et al. Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance. Eur Respir J 10 (1997) 2853-2860
6. Gosker H.R., Engelen M.P., van Mameren H., et al. Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease. Am J Clin Nutr 76 (2002) 113-119
7. Jagoe R.T., and Engelen M.P. Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease. Eur Respir J 46 Suppl (2003) 52s-63s
8. Morrison W.L., Gibson J.N., Scrimgeour C., et al. Muscle wasting in emphysema. Clin Sci (Lond) 75 (1988) 415-420
9. Rutten E.P., Franssen F.M., Engelen M.P., et al. Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease. Am J Clin Nutr 83 (2006) 829-834
10. Agusti A.G., Sauleda J., Miralles C., et al. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 166 (2002) 485-489
11. Gosker H.R., Kubat B., Schaart G., et al. Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease. Eur Respir J 22 (2003) 280-285
12. Gosker H.R., van Mameren H., van Dijk P.J., et al. Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J 19 (2002) 617-625
13. Jakobsson P., Jorfeldt L., and Henriksson J. Metabolic enzyme activity in the quadriceps femoris muscle in patients with severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 151 (1995) 374-377
14. Essen-Gustavsson B., and Henriksson J. Enzyme levels in pools of microdissected human muscle fibres of identified type: adaptive response to exercise. Acta Physiol Scand 120 (1984) 505-515
15. Pouw E.M., Schols A.M., van der Vusse G.J., et al. Elevated inosine monophosphate levels in resting muscle of patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 157 (1998) 453-457
16. Kutsuzawa T., Shioya S., Kurita D., et al. Muscle energy metabolism and nutritional status in patients with chronic obstructive pulmonary disease: a 31P magnetic resonance study. Am J Respir Crit Care Med 152 (1995) 647-652
17. 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 153 (1996) 288-293
18. Franssen F.M., Broekhuizen R., Janssen P.P., et al. Limb muscle dysfunction in COPD: effects of muscle wasting and exercise training. Med Sci Sports Exerc 37 (2005) 2-9
19. Baarends E.M., Schols A.M., Akkermans M.A., et al. Decreased mechanical efficiency in clinically stable patients with COPD. Thorax 52 (1997) 981-986
20. Gosker H.R., Schrauwen P., Hesselink M.K., et al. Uncoupling protein-3 content is decreased in peripheral skeletal muscle of patients with COPD. Eur Respir J 22 (2003) 88-93
21. Bezaire V., Seifert E.L., and Harper M.E. Uncoupling protein-3: clues in an ongoing mitochondrial mystery. FASEB J 21 (2007) 312-324
22. Rabinovich R.A., Ardite E., Troosters T., et al. Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164 (2001) 1114-1118
23. Couillard A., Maltais F., Saey D., et al. Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 167 (2003) 1664-1669
24. Donaldson G.C., Seemungal T.A., Patel I.S., et al. Airway and systemic inflammation and decline in lung function in patients with COPD. Chest 128 (2005) 1995-2004
25. Wouters E.F., Creutzberg E.C., and Schols A.M. Systemic effects in COPD. Chest 121 (2002) 127S-130S
26. Yanbaeva D.G., Dentener M.A., Creutzberg E.C., et al. Systemic inflammation in COPD: is genetic susceptibility a key factor?. COPD 3 (2006) 51-61
27. Pinto-Plata V.M., Mullerova H., Toso J.F., et al. C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax 61 (2006) 23-28
28. Broekhuizen R., Wouters E.F., Creutzberg E.C., et al. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax 61 (2006) 17-22
29. Yende S., Waterer G.W., Tolley E.A., et al. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax 61 (2006) 10-16
30. Vernooy J.H., Kucukaycan M., Jacobs J.A., et al. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 166 (2002) 1218-1224
31. Noguera A., Busquets X., Sauleda J., et al. Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 158 (1998) 1664-1668
32. Takabatake N., Nakamura H., Abe S., et al. The relationship between chronic hypoxemia and activation of the tumor necrosis factor-alpha system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161 (2000) 1179-1184
33. Bartoccioni E., Michaelis D., and Hohlfeld R. Constitutive and cytokine-induced production of interleukin-6 by human myoblasts. Immunol Lett 42 (1994) 135-138
34. Tews D.S., and Goebel H.H. Expression of cell adhesion molecules in inflammatory myopathies. J Neuroimmunol 59 (1995) 185-194
35. Langen R.C., Schols A.M., Kelders M.C., et al. Muscle wasting and impaired muscle regeneration in a murine model of chronic pulmonary inflammation. Am J Respir Cell Mol Biol 35 (2006) 689-696
36. Montes de Oca M., Torres S.H., De Sanctis J., et al. Skeletal muscle inflammation and nitric oxide in patients with COPD. Eur Respir J 26 (2005) 390-397
37. Agusti A., Morla M., Sauleda J., et al. NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax 59 (2004) 483-487
38. Broekhuizen R., Grimble R.F., Howell W.M., et al. Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism. Am J Clin Nutr 82 (2005) 1059-1064
39. Buck M., and Chojkier M. Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J 15 (1996) 1753-1765
40. Guttridge D.C., Mayo M.W., Madrid L.V., et al. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 289 (2000) 2363-2366
41. Li Y.P., Schwartz R.J., Waddell I.D., et al. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. FASEB J 12 (1998) 871-880
42. Smith B.K., Conn C.A., and Kluger M.J. Experimental cachexia: effects of MCA sarcoma in the Fischer rat. Am J Physiol 265 (1993) R376-R384
43. Pahl H.L. Signal transduction from the endoplasmic reticulum to the cell nucleus. Physiol Rev 79 (1999) 683-701
44. Reid M.B., and Li Y.P. Tumor necrosis factor-alpha and muscle wasting: a cellular perspective. Respir Res 2 (2001) 269-272
45. Ling P.R., Schwartz J.H., and Bistrian B.R. Mechanisms of host wasting induced by administration of cytokines in rats. Am J Physiol 272 (1997) E333-E339
46. Ventadour S., and Attaix D. Mechanisms of skeletal muscle atrophy. Curr Opin Rheumatol 18 (2006) 631-635
47. Li Y.P., Lecker S.H., Chen Y., et al. TNF-alpha increases ubiquitin-conjugating activity in skeletal muscle by up-regulating UbcH2/E220k. FASEB J 17 (2003) 1048-1057
48. Ladner K.J., Caligiuri M.A., and Guttridge D.C. Tumor necrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products. J Biol Chem 278 (2003) 2294-2303
49. Garcia-Martinez C., Llovera M., Agell N., et al. Ubiquitin gene expression in skeletal muscle is increased by tumour necrosis factor-alpha. Biochem Biophys Res Commun 201 (1994) 682-686
50. Gomes M.D., Lecker S.H., Jagoe R.T., et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 98 (2001) 14440-14445
51. Lecker S.H., Jagoe R.T., Gilbert A., et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 18 (2004) 39-51
52. Wray C.J., Mammen J.M., Hershko D.D., et al. Sepsis upregulates the gene expression of multiple ubiquitin ligases in skeletal muscle. Int J Biochem Cell Biol 35 (2003) 698-705
53. Drexler H., Riede U., Munzel T., et al. Alterations of skeletal muscle in chronic heart failure. Circulation 85 (1992) 1751-1759
54. Inoue I., and Katayama S. The possible therapeutic actions of peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists, PPAR gamma agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, angiotensin converting enzyme (ACE) inhibitors and calcium (Ca)-antagonists on vascular endothelial cells. Curr Drug Targets Cardiovasc Haematol Disord 4 (2004) 35-52
55. Cai D., Frantz J.D., Tawa Jr. N.E., et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119 (2004) 285-298
56. Hunter R.B., and Kandarian S.C. Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. J Clin Invest 114 (2004) 1504-1511
57. Lang C.H., and Frost R.A. Sepsis-induced suppression of skeletal muscle translation initiation mediated by tumor necrosis factor alpha. Metabolism 56 (2007) 49-57
58. Garcia-Martinez C., Lopez-Soriano F.J., and Argiles J.M. Acute treatment with tumour necrosis factor-alpha induces changes in protein metabolism in rat skeletal muscle. Mol Cell Biochem 125 (1993) 11-18
59. Lang C.H., Frost R.A., Nairn A.C., et al. TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab 282 (2002) E336-E347
60. Cooney R.N., Maish III G.O., Gilpin T., et al. Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle. Shock 11 (1999) 235-241
61. Thissen J.P. How proinflammatory cytokines may impair growth and cause muscle wasting. Horm Res 67 Suppl 1 (2007) 64-70
62. Glass D.J. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37 (2005) 1974-1984
63. Broussard S.R., McCusker R.H., Novakofski J.E., et al. Cytokine-hormone interactions: tumor necrosis factor alpha impairs biologic activity and downstream activation signals of the insulin-like growth factor I receptor in myoblasts. Endocrinology 144 (2003) 2988-2996
64. Strle K., Broussard S.R., McCusker R.H., et al. Proinflammatory cytokine impairment of insulin-like growth factor I-induced protein synthesis in skeletal muscle myoblasts requires ceramide. Endocrinology 145 (2004) 4592-4602
65. Allen D.L., Roy R.R., and Edgerton V.R. Myonuclear domains in muscle adaptation and disease. Muscle Nerve 22 (1999) 1350-1360
66. Danial N.N., and Korsmeyer S.J. Cell death: critical control points. Cell 116 (2004) 205-219
67. Almendro V., Carbo N., Busquets S., et al. Sepsis induces DNA fragmentation in rat skeletal muscle. Eur Cytokine Netw 14 (2003) 256-259
68. Phillips T., and Leeuwenburgh C. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J 19 (2005) 668-670
69. Stewart C.E., Newcomb P.V., and Holly J.M. Multifaceted roles of TNF-alpha in myoblast destruction: a multitude of signal transduction pathways. J Cell Physiol 198 (2004) 237-247
70. Mitch W.E., and Du J. Cellular mechanisms causing loss of muscle mass in kidney disease. Semin Nephrol 24 (2004) 484-487
71. Callahan L.A., and Supinski G.S. Diaphragm and cardiac mitochondrial creatine kinases are impaired in sepsis. J Appl Physiol 102 (2007) 44-53
72. Setsuta K., Seino Y., Ogawa T., et al. Ongoing myocardial damage in chronic heart failure is related to activated tumor necrosis factor and Fas/Fas ligand system. Circ J 68 (2004) 747-750
73. van der Velden J., Langen R., Kelders M., et al. Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3{beta}. Am J Physiol Cell Physiol 292 5 (2007) C1636-44
74. Hawke T.J., and Garry D.J. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 91 (2001) 534-551
75. Langen R.C., Schols A.M., Kelders M.C., et al. Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB. FASEB J 15 (2001) 1169-1180
76. Dogra C., Changotra H., Wedhas N., et al. TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. FASEB J 21 8 (2007) 1857-1869
77. Broussard S.R., McCusker R.H., Novakofski J.E., et al. IL-1beta impairs insulin-like growth factor i-induced differentiation and downstream activation signals of the insulin-like growth factor i receptor in myoblasts. J Immunol 172 (2004) 7713-7720
78. Langen R.C., Van Der Velden J.L., Schols A.M., et al. Tumor necrosis factor-alpha inhibits myogenic differentiation through MyoD protein destabilization. FASEB J 18 (2004) 227-237
79. Tolosa L., Morla M., Iglesias A., et al. IFN-gamma prevents TNF-alpha-induced apoptosis in C2C12 myotubes through down-regulation of TNF-R2 and increased NF-kappaB activity. Cell Signal 17 (2005) 1333-1342
80. Fredenrich A., and Grimaldi P.A. Roles of peroxisome proliferator-activated receptor delta in skeletal muscle function and adaptation. Curr Opin Clin Nutr Metab Care 7 (2004) 377-381
81. Lefebvre P., Chinetti G., Fruchart J.C., et al. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 116 (2006) 571-580
82. Cresci S., Wright L.D., Spratt J.A., et al. Activation of a novel metabolic gene regulatory pathway by chronic stimulation of skeletal muscle. Am J Physiol 270 (1996) C1413-C1420
83. Horowitz J.F., Leone T.C., Feng W., et al. Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. Am J Physiol Endocrinol Metab 279 (2000) E348-E355
84. Minnich A., Tian N., Byan L., et al. A potent PPARalpha agonist stimulates mitochondrial fatty acid beta-oxidation in liver and skeletal muscle. Am J Physiol Endocrinol Metab 280 (2001) E270-E279
85. Muoio D.M., MacLean P.S., Lang D.B., et al. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice: evidence for compensatory regulation by PPAR delta. J Biol Chem 277 (2002) 26089-26097
86. Fritz T., Kramer D.K., Karlsson H.K., et al. Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients. Diabetes Metab Res Rev 22 (2006) 492-498
87. Brunmair B., Staniek K., Dorig J., et al. Activation of PPAR-delta in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids. Diabetologia 49 (2006) 2713-2722
88. Luquet S., Lopez-Soriano J., Holst D., et al. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB J 17 (2003) 2299-2301
89. Furnsinn C., Willson T.M., and Brunmair B. Peroxisome proliferator-activated receptor-delta, a regulator of oxidative capacity, fuel switching and cholesterol transport. Diabetologia 50 (2007) 8-17
90. St-Pierre J., Lin J., Krauss S., et al. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 278 (2003) 26597-26603
91. Wu Z., Puigserver P., Andersson U., et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98 (1999) 115-124
92. Scarpulla R.C. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576 (2002) 1-14
93. Lin J., Wu H., Tarr P.T., et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418 (2002) 797-801
94. Talmadge R.J., Otis J.S., Rittler M.R., et al. Calcineurin activation influences muscle phenotype in a muscle-specific fashion. BMC Cell Biol 5 (2004) 28
95. Chin E.R., Olson E.N., Richardson J.A., et al. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev 12 (1998) 2499-2509
96. Handschin C., Rhee J., Lin J., et al. An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci U S A 100 (2003) 7111-7116
97. Chin E.R. Role of Ca2+/calmodulin-dependent kinases in skeletal muscle plasticity. J Appl Physiol 99 (2005) 414-423
98. Wu H., Kanatous S.B., Thurmond F.A., et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296 (2002) 349-352
99. Aschenbach W.G., Sakamoto K., and Goodyear L.J. 5′ adenosine monophosphate-activated protein kinase, metabolism and exercise. Sports Med 34 (2004) 91-103
100. Reznick R.M., and Shulman G.I. The role of AMP-activated protein kinase in mitochondrial biogenesis. J Physiol 574 (2006) 33-39
101. Ai H., Ihlemann J., Hellsten Y., et al. Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle. Am J Physiol Endocrinol Metab 282 (2002) E1291-E1300
102. Zong H., Ren J.M., Young L.H., et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 99 (2002) 15983-15987
103. Ameln H., Gustafsson T., Sundberg C.J., et al. Physiological activation of hypoxia inducible factor-1 in human skeletal muscle. FASEB J 19 (2005) 1009-1011
104. Semenza G.L. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell 107 (2001) 1-3
105. Semenza G.L. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88 (2000) 1474-1480
106. Hoppeler H., and Vogt M. Muscle tissue adaptations to hypoxia. J Exp Biol 204 (2001) 3133-3139
107. Narravula S., and Colgan S.P. Hypoxia-inducible factor 1-mediated inhibition of peroxisome proliferator-activated receptor alpha expression during hypoxia. J Immunol 166 (2001) 7543-7548
108. Delerive P., De Bosscher K., Besnard S., et al. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274 (1999) 32048-32054
109. Sung C.K., She H., Xiong S., et al. Tumor necrosis factor-alpha inhibits peroxisome proliferator-activated receptor gamma activity at a posttranslational level in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 286 (2004) G722-G729
110. Tham D.M., Martin-McNulty B., Wang Y.X., et al. Angiotensin II is associated with activation of NF-kappaB-mediated genes and downregulation of PPARs. Physiol Genomics 11 (2002) 21-30
111. Remels A.H., Schrauwen P., Broekhuizen R., et al. Expression and contents of PPARs is reduced in skeletal muscles of COPD patients. Eur Respir J 30 2 (2007)
112. Bernard S., Whittom F., Leblanc P., et al. Aerobic and strength training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 159 (1999) 896-901
113. Franssen F.M., Broekhuizen R., Janssen P.P., et al. Effects of whole-body exercise training on body composition and functional capacity in normal-weight patients with COPD. Chest 125 (2004) 2021-2028
114. Casaburi R. Anabolic therapies in chronic obstructive pulmonary disease. Monaldi Arch Chest Dis 53 (1998) 454-459
115. Creutzberg E.C., and Casaburi R. Endocrinological disturbances in chronic obstructive pulmonary disease. Eur Respir J 46 Suppl (2003) 76s-80s
116. Ferreira I., Brooks D., Lacasse Y., et al. Nutritional intervention in COPD: a systematic overview. Chest 119 (2001) 353-363
117. Schols A.M., Soeters P.B., Mostert R., et al. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease: a placebo-controlled randomized trial. Am J Respir Crit Care Med 152 (1995) 1268-1274
118. Anthony J.C., Anthony T.G., Kimball S.R., et al. Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 131 (2001) 856S-860S
119. Bolton C.E., Broekhuizen R., Ionescu A.A., et al. Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD. Thorax 62 (2007) 109-114
120. Creutzberg E.C., Schols A.M., Weling-Scheepers C.A., et al. Characterization of nonresponse to high caloric oral nutritional therapy in depleted patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161 (2000) 745-752
121. Mourkioti F., Kratsios P., Luedde T., et al. Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. J Clin Invest 116 (2006) 2945-2954
122. Guttridge D.C., Albanese C., Reuther J.Y., et al. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19 (1999) 5785-5799
123. Pelosi L., Giacinti C., Nardis C., et al. Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines. FASEB J 21 7 (2007) 1393-1402
124. Puente-Maestu L., Tena T., Trascasa C., et al. Training improves muscle oxidative capacity and oxygenation recovery kinetics in patients with chronic obstructive pulmonary disease. Eur J Appl Physiol 88 (2003) 580-587
125. Gosker H.R., Schrauwen P., Broekhuizen R., et al. Exercise training restores uncoupling protein-3 content in limb muscles of patients with chronic obstructive pulmonary disease. Am J Physiol Endocrinol Metab 290 5 (2006) E976-E981
126. Rabinovich R.A., Bastos R., Ardite E., et al. Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J 29 (2007) 643-650
127. Broekhuizen R., Wouters E.F., Creutzberg E.C., et al. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 60 (2005) 376-382
128. Birrell M.A., Patel H.J., McCluskie K., et al. PPAR-gamma agonists as therapy for diseases involving airway neutrophilia. Eur Respir J 24 (2004) 18-23
129. Patel H.J., Belvisi M.G., Bishop-Bailey D., et al. Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol 170 (2003) 2663-2669