Cachexia in chronic obstructive pulmonary disease: New insights and therapeutic perspective

Journal of Cachexia, Sarcopenia and Muscle

Volumn 7, Issue 1, 2016, Pages 5-22

  Sanders, Karin J C ^a   Kneppers, Anita E M ^a   van de Bool, Coby ^a   Langen, Ramon C J ^a   Schols, Annemie M W J ^a  

^a MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Cachexia; COPD; Emphysema; Energy balance; Lung cancer; Muscle

Indexed keywords

ATROGIN 1; BRANCHED CHAIN AMINO ACID; MUSCLE RING FINGER 1 PROTEIN; PROTEASOME; UBIQUITIN PROTEIN LIGASE NEDD4;

ADIPOSE TISSUE; ANOREXIA; AUTOPHAGY; CACHEXIA; CHRONIC OBSTRUCTIVE LUNG DISEASE; DIET SUPPLEMENTATION; DIETARY INTAKE; DUAL ENERGY X RAY ABSORPTIOMETRY; ENERGY BALANCE; HUMAN; LYSOSOME; META ANALYSIS (TOPIC); MUSCLE ATROPHY; MUSCLE MASS; MYONUCLEAR TURNOVER; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN METABOLISM; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; REWARD; SYNTHESIS; TISSUE METABOLISM; TURNOVER TIME;

EID: 84957729514     PISSN: 21905991     EISSN: 21906009     Source Type: Journal    
DOI: 10.1002/jcsm.12062     Document Type: Review

References (243)

1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:e442.
2. Prince MJ, Wu F, Guo Y, Gutierrez Robledo LM, O'Donnell M, Sullivan R, et al. The burden of disease in older people and implications for health policy and practice. Lancet 2015;385:549-562.
3. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013;187:347-365.
4. Vanfleteren LE, Spruit MA, Groenen M, Gaffron S, van Empel VP, Bruijnzeel PL, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013;187:728-735.
5. Burgel PR, Paillasseur JL, Peene B, Dusser D, Roche N, Coolen J, et al. Two distinct chronic obstructive pulmonary disease (COPD) phenotypes are associated with high risk of mortality. PLoS One 2012;7:e51048.
6. Romme EA, Murchison JT, Phang KF, Jansen FH, Rutten EP, Wouters EF, et al. Bone attenuation on routine chest CT correlates with bone mineral density on DXA in patients with COPD. J Bone Miner Res 2012;27:2338-2343.
7. Schols AM, Soeters PB, Dingemans AM, Mostert R, Frantzen PJ, Wouters EF. Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. Am Rev Respir Dis 1993;147:1151-1156.
8. Vestbo J, Prescott E, Almdal T, Dahl M, Nordestgaard BG, Andersen T, et al. Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings from the Copenhagen City Heart Study. Am J Respir Crit Care Med 2006;173:79-83.
9. Mostert R, Goris A, Weling-Scheepers C, Wouters EF, Schols AM. Tissue depletion and health related quality of life in patients with chronic obstructive pulmonary disease. Respir Med 2000;94:859-867.
10. Engelen MP, Schols AM, Baken WC, Wesseling GJ, Wouters EF. Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in out-patients with COPD. Eur Respir J 1994;7:1793-1797.
11. Schols AM, Broekhuizen R, Weling-Scheepers CA, Wouters EF. Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr 2005;82:53-59.
12. Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, et al. Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;158:629-634.
13. Engelen MP, Schols AM, Does JD, Wouters EF. Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2000;71:733-738.
14. Engelen MP, Schols AM, Lamers RJ, Wouters EF. Different patterns of chronic tissue wasting among patients with chronic obstructive pulmonary disease. Clin Nutr 1999;18:275-280.
15. Caron MA, Debigare R, Dekhuijzen PN, Maltais F. Comparative assessment of the quadriceps and the diaphragm in patients with COPD. J Appl Physiol (1985) 2009;107:952-961.
16. Gosker HR, Engelen MP, van Mameren H, van Dijk PJ, van der Vusse GJ, Wouters EF, 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 2002;76:113-119.
17. Mancini DM, Coyle E, Coggan A, Beltz J, Ferraro N, Montain S, et al. Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. Circulation 1989;80:1338-1346.
18. Gosker HR, van Mameren H, van Dijk PJ, Engelen MP, van der Vusse GJ, Wouters EF, et al. Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J 2002;19:617-625.
19. Maltais F, LeBlanc P, Whittom F, Simard C, Marquis K, Belanger M, et al. Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD. Thorax 2000;55:848-853.
20. Remels AH, Gosker HR, Langen RC, Schols AM. The mechanisms of cachexia underlying muscle dysfunction in COPD. J Appl Physiol (1985) 2013;114:1253-62.
21. Files DC, D'Alessio FR, Johnston LF, Kesari P, Aggarwal NR, Garibaldi BT, et al. A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting. Am J Respir Crit Care Med 2012;185:825-834.
22. de Theije CC, Langen RC, Lamers WH, Gosker HR, Schols AM, Koehler SE. Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy. J Appl Physiol (1985) 2015;118:200-211.
23. van de Bool C, Rutten EP, Franssen FM, Wouters EF, Schols AM. Antagonistic implications of sarcopenia and abdominal obesity on physical performance in COPD. Eur Respir J 2015. doi: 10.1183/09031936.00197314. [Epub ahead of print]
24. Schols AM, Ferreira IM, Franssen FM, Gosker HR, Janssens W, Muscaritoli M, et al. Nutritional assessment and therapy in COPD: a European Respiratory Society statement. Eur Respir J 2014;44:1504-1520.
25. Jones SE, Maddocks M, Kon SS, Canavan JL, Nolan CM, Clark AL, et al. Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation. Thorax 2015;70:213-218.
26. Cherin P, Voronska E, Fraoucene N, de Jaeger C. Prevalence of sarcopenia among healthy ambulatory subjects: the sarcopenia begins from 45 years. Aging Clin Exp Res 2014;26:137-146.
27. O'Donnell DE, Ciavaglia CE, Neder JA. When obesity and chronic obstructive pulmonary disease collide. Physiological and clinical consequences. Ann Am Thorac Soc 2014;11:635-644.
28. Guenette JA, Jensen D, O'Donnell DE. Respiratory function and the obesity paradox. Curr Opin Clin Nutr Metab Care 2010;13:618-624.
29. van den Borst B, Gosker HR, Koster A, Yu B, Kritchevsky SB, Liu Y, et al. The influence of abdominal visceral fat on inflammatory pathways and mortality risk in obstructive lung disease. Am J Clin Nutr 2012;96:516-526.
30. Furutate R, Ishii T, Wakabayashi R, Motegi T, Yamada K, Gemma A, et al. Excessive visceral fat accumulation in advanced chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011;6:423-430.
31. McDonald ML, Diaz AA, Ross JC. San Jose Estepar R, Zhou L, Regan EA et al. Quantitative computed tomography measures of pectoralis muscle area and disease severity in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc 2014;11:326-334.
32. Diaz AA, Zhou L, Young TP, McDonald ML, Harmouche R, Ross JC, et al. Chest CT measures of muscle and adipose tissue in COPD: gender-based differences in content and in relationships with blood biomarkers. Acad Radiol 2014;21:1255-1261.
33. Langen RC, Gosker HR, Remels AH, Schols AM. Triggers and mechanisms of skeletal muscle wasting in chronic obstructive pulmonary disease. Int J Biochem Cell Biol 2013;45:2245-2256.
34. Zuo L, He F, Sergakis GG, Koozehchian MS, Stimpfl JN, Rong Y, et al. Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments. Am J Physiol Lung Cell Mol Physiol 2014;307:L205-L218.
35. Rutten EP, Franssen FM, Engelen MP, Wouters EF, Deutz NE, Schols AM. Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2006;83:829-834.
36. Engelen MP, Deutz NE, Wouters EF, Schols AM. Enhanced levels of whole-body protein turnover in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1488-1492.
37. Morrison WL, Gibson JN, Scrimgeour C, Rennie MJ. Muscle wasting in emphysema. Clin Sci (Lond) 1988;75:415-420.
38. Fermoselle C, Rabinovich R, Ausin P, Puig-Vilanova E, Coronell C, Sanchez F, et al. Does oxidative stress modulate limb muscle atrophy in severe COPD patients? Eur Respir J 2012;40:851-862.
39. Puig-Vilanova E, Rodriguez DA, Lloreta J, Ausin P, Pascual-Guardia S, Broquetas J, et al. Oxidative Stress, Redox Signaling Pathways, And Autophagy In Cachectic Muscles Of Male Patients With Advanced Copd And Lung Cancer. Free Radic Biol Med 2014;79:91-108.
40. Vogiatzis I, Simoes DC, Stratakos G, Kourepini E, Terzis G, Manta P, et al. Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD. Eur Respir J 2010;36:301-310.
41. Op den Kamp CM, Langen RC, Snepvangers FJ, de Theije CC, Schellekens JM, Laugs F, et al. Nuclear transcription factor kappa B activation and protein turnover adaptations in skeletal muscle of patients with progressive stages of lung cancer cachexia. Am J Clin Nutr 2013;98:738-748.
42. Debigare R, Cote CH, Maltais F. Ubiquitination and proteolysis in limb and respiratory muscles of patients with chronic obstructive pulmonary disease. Proc Am Thorac Soc 2010;7:84-90.
43. Debigare R, Maltais F, Cote CH, Michaud A, Caron MA, Mofarrahi M, et al. Profiling of mRNA expression in quadriceps of patients with COPD and muscle wasting. COPD 2008;5:75-84.
44. Doucet M, Russell AP, Leger B, Debigare R, Joanisse DR, Caron MA, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:261-269.
45. Guo Y, Gosker HR, Schols AM, Kapchinsky S, Bourbeau J, Sandri M, et al. Autophagy in locomotor muscles of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013;188:1313-1320.
46. Doucet M, Dube A, Joanisse DR, Debigare R, Michaud A, Pare ME, et al. Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD. Thorax 2010;65:963-970.
47. Levine S, Gregory C, Nguyen T, Shrager J, Kaiser L, Rubinstein N, et al. Bioenergetic adaptation of individual human diaphragmatic myofibers to severe COPD. J Appl Physiol (1985) 2002;92:1205-1213.
48. Levine S, Kaiser L, Leferovich J, Tikunov B. Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease. N Engl J Med 1997;337:1799-1806.
49. Mofarrahi M, Guo Y, Haspel JA, Choi AM, Davis EC, Gouspillou G, et al. Autophagic flux and oxidative capacity of skeletal muscles during acute starvation. Autophagy 2013;9:1604-1620.
50. Gielen S, Sandri M, Kozarez I, Kratzsch J, Teupser D, Thiery J, et al. Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging catabolism study. Circulation 2012;125:2716-2727.
51. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004;117:399-412.
52. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 2007;6:458-471.
53. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002;82:373-428.
54. Pickart CM. Back to the future with ubiquitin. Cell 2004;116:181-190.
55. Ottenheijm CA, Heunks LM, Li YP, Jin B, Minnaard R, van Hees HW, et al. Activation of the ubiquitin-proteasome pathway in the diaphragm in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006;174:997-1002.
56. Lemire BB, Debigare R, Dube A, Theriault ME, Cote CH, Maltais F. MAPK signaling in the quadriceps of patients with chronic obstructive pulmonary disease. J Appl Physiol (1985) 2012;113:159-166.
57. Plant PJ, Brooks D, Faughnan M, Bayley T, Bain J, Singer L, et al. Cellular markers of muscle atrophy in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2010;42:461-471.
58. Petersen AM, Magkos F, Atherton P, Selby A, Smith K, Rennie MJ, et al. Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle. Am J Physiol Endocrinol Metab 2007;293:E843-E848.
59. Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 2009;335:1-32.
60. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol 2010;22:132-139.
61. Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy 2008;4:524-526.
62. Mai S, Muster B, Bereiter-Hahn J, Jendrach M. Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy 2012;8:47-62.
63. Rello-Varona S, Lissa D, Shen S, Niso-Santano M, Senovilla L, Marino G, et al. Autophagic removal of micronuclei. Cell Cycle 2012;11:170-176.
64. Lewis A, Riddoch-Contreras J, Natanek SA, Donaldson A, Man WD, Moxham J, et al. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax 2012;67:26-34.
65. Crul T, Spruit MA, Gayan-Ramirez G, Quarck R, Gosselink R, Troosters T, et al. Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest 2007;37:897-904.
66. Adams GR. Invited Review: Autocrine/paracrine IGF-I and skeletal muscle adaptation. J Appl Physiol (1985) 2002;93:1159-67.
67. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-1945.
68. Martinez-Llorens J, Casadevall C, Lloreta J, Orozco-Levi M, Barreiro E, Broquetas J, et al. Activation of satellite cells in the intercostal muscles of patients with chronic obstructive pulmonary disease. Arch Bronconeumol 2008;44:239-244.
69. Tannerstedt J, Apro W, Blomstrand E. Maximal lengthening contractions induce different signaling responses in the type I and type II fibers of human skeletal muscle. J Appl Physiol (1985) 2009;106:1412-1418.
70. Lepper C, Partridge TA, Fan CM. An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration. Development 2011;138:3639-3646.
71. Relaix F, Zammit PS. Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development 2012;139:2845-2856.
72. Adams GR, Caiozzo VJ, Haddad F, Baldwin KM. Cellular and molecular responses to increased skeletal muscle loading after irradiation. Am J Physiol Cell Physiol 2002;283:C1182-C1195.
73. Agusti AG, Sauleda J, Miralles C, Gomez C, Togores B, Sala E, et al. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:485-489.
74. Gosker HR, Kubat B, Schaart G, van der Vusse GJ, Wouters EF, Schols AM. Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease. Eur Respir J 2003;22:280-285.
75. Dupont-Versteegden EE. Apoptosis in skeletal muscle and its relevance to atrophy. World J Gastroenterol 2006;12:7463-7466.
76. Mijaljica D, Devenish RJ. Nucleophagy at a glance. J Cell Sci 2013;126:4325-4330.
77. Verdijk LB, Snijders T, Drost M, Delhaas T, Kadi F, van Loon LJ. Satellite cells in human skeletal muscle; from birth to old age. Age (Dordr) 2014;36:545-547.
78. Snijders T, Verdijk LB, van Loon LJ. The impact of sarcopenia and exercise training on skeletal muscle satellite cells. Ageing Res Rev 2009;8:328-338.
79. Eliason G, Abdel-Halim S, Arvidsson B, Kadi F, Piehl-Aulin K. Physical performance and muscular characteristics in different stages of COPD. Scand J Med Sci Sports 2009;19:865-870.
80. Theriault ME, Pare ME, Maltais F, Debigare R. Satellite cells senescence in limb muscle of severe patients with COPD. PLoS One 2012;7:e39124.
81. Menon MK, Houchen L, Singh SJ, Morgan MD, Bradding P, Steiner MC. Inflammatory and satellite cells in the quadriceps of patients with COPD and response to resistance training. Chest 2012;142:1134-1142.
82. Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, et al. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci 2014;71:4361-4371.
83. Man WD, Natanek SA, Riddoch-Contreras J, Lewis A, Marsh GS, Kemp PR, et al. Quadriceps myostatin expression in COPD. Eur Respir J 2010;36:686-688.
84. Ju CR, Chen RC. Serum myostatin levels and skeletal muscle wasting in chronic obstructive pulmonary disease. Respir Med 2012;106:102-108.
85. Snijders T, Verdijk LB, Smeets JS, McKay BR, Senden JM, Hartgens F, et al. The skeletal muscle satellite cell response to a single bout of resistance-type exercise is delayed with aging in men. Age (Dordr) 2014;36:e9699.
86. Malaguti C, Nery LE, Dal Corso S, Napolis L, De Fuccio MB, Castro M, et al. Scaling skeletal muscle function to mass in patients with moderate-to-severe COPD. Eur J Appl Physiol 2006;98:482-488.
87. Malaguti C, Napolis LM, Villaca D, Neder JA, Nery LE, Dal CS. Relationship between peripheral muscle structure and function in patients with chronic obstructive pulmonary disease with different nutritional status. J Strength Cond Res 2011;25:1795-1803.
88. van den Borst B, Slot IG, Hellwig VA, Vosse BA, Kelders MC, Barreiro E, et al. Loss of quadriceps muscle oxidative phenotype and decreased endurance in patients with mild-to-moderate COPD. J Appl Physiol (1985) 2013;114:1319-1328.
89. Gosker HR, Zeegers MP, Wouters EF, Schols AM. Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax 2007;62:944-949.
90. Barreiro E, de la Puente B, Minguella J, Corominas JM, Serrano S, Hussain SN, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:1116-1124.
91. Degens H, Gayan-Ramirez G, van Hees HW. Smoking-induced skeletal muscle dysfunction: from evidence to mechanisms. Am J Respir Crit Care Med 2015;191:620-625.
92. Gosker HR, Wouters EF, van der Vusse GJ, Schols AM. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr 2000;71:1033-1047.
93. Labeit S, Kohl CH, Witt CC, Labeit D, Jung J, Granzier H. Modulation of muscle atrophy, fatigue and MLC phosphorylation by MuRF1 as indicated by hindlimb suspension studies on MuRF1-KO mice. J Biomed Biotechnol 2010;2010:e693741.
94. Eddins MJ, Marblestone JG, Suresh Kumar KG, Leach CA, Sterner DE, Mattern MR, et al. Targeting the ubiquitin E3 ligase MuRF1 to inhibit muscle atrophy. Cell Biochem Biophys 2011;60:113-118.
95. Edelmann MJ, Nicholson B, Kessler BM. Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases. Expert Rev Mol Med 2011;13:e35.
96. Gosker HR, Lencer NH, Franssen FM, van der Vusse GJ, Wouters EF, Schols AM. Striking similarities in systemic factors contributing to decreased exercise capacity in patients with severe chronic heart failure or COPD. Chest 2003;123:1416-1424.
97. Borgenvik M, Apro W, Blomstrand E. Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle. Am J Physiol Endocrinol Metab 2012;302:E510-E521.
98. Constantin D, Menon MK, Houchen-Wolloff L, Morgan MD, Singh SJ, Greenhaff P, et al. Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD. Thorax 2013;68:625-633.
99. Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 1998;273:14484-14494.
100. Drummond MJ, Rasmussen BB. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care 2008;11:222-226.
101. Ditch S, Paull TT. The ATM protein kinase and cellular redox signaling: beyond the DNA damage response. Trends Biochem Sci 2012;37:15-22.
102. Sabatini DM. mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 2006;6:729-734.
103. Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, et al. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J 2013;27:4184-4193.
104. Sanchez AM, Bernardi H, Py G, Candau RB. Autophagy is essential to support skeletal muscle plasticity in response to endurance exercise. Am J Physiol Regul Integr Comp Physiol 2014;307:R956-R969.
105. Couillard A, Maltais F, Saey D, Debigare R, Michaud A, Koechlin C, et al. Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167:1664-1669.
106. Wilborn CD, Taylor LW, Greenwood M, Kreider RB, Willoughby DS. Effects of different intensities of resistance exercise on regulators of myogenesis. J Strength Cond Res 2009;23:2179-2187.
107. Hill M, Goldspink G. Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage. J Physiol 2003;549:409-418.
108. Snijders T, Verdijk LB, McKay BR, Smeets JS, van Kranenburg J, Groen BB, et al. Acute dietary protein intake restriction is associated with changes in myostatin expression after a single bout of resistance exercise in healthy young men. J Nutr 2014;144:137-145.
109. Zhang L, Rajan V, Lin E, Hu Z, Han HQ, Zhou X, et al. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2011;25:1653-1663.
110. Lach-Trifilieff E, Minetti GC, Sheppard K, Ibebunjo C, Feige JN, Hartmann S, et al. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy. Mol Cell Biol 2014;34:606-618.
111. Bonetto A, Penna F, Minero VG, Reffo P, Costamagna D, Bonelli G, et al. Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-alpha. Amino Acids 2011;40:585-594.
112. Pan L, Wang M, Xie X, Du C, Guo Y. Effects of anabolic steroids on chronic obstructive pulmonary disease: a meta-analysis of randomised controlled trials. PLoS One. 2014;9:e84855.
113. Schols AM. Nutrition as a metabolic modulator in COPD. Chest 2013;144:1340-1345.
114. Schoffelen PF, Westerterp KR, Saris WH, Ten Hoor F. A dual-respiration chamber system with automated calibration. J Appl Physiol (1985) 1997;83:2064-2072.
115. Roberts SB. Use of the doubly labeled water method for measurement of energy expenditure, total body water, water intake, and metabolizable energy intake in humans and small animals. Can J Physiol Pharmacol 1989;67:1190-1198.
116. Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Baertschi P, Jequier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol 1986;250:R823-R830.
117. Hugli O, Schutz Y, Fitting JW. The daily energy expenditure in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;153:294-300.
118. Slinde F, Ellegard L, Gronberg AM, Larsson S, Rossander-Hulthen L. Total energy expenditure in underweight patients with severe chronic obstructive pulmonary disease living at home. Clin Nutr 2003;22:159-165.
119. Baarends EM, Schols AM, Westerterp KR, Wouters EF. Total daily energy expenditure relative to resting energy expenditure in clinically stable patients with COPD. Thorax 1997;52:780-785.
120. Mineo TC, Pompeo E, Mineo D, Ambrogi V, Ciarapica D, Polito A. Resting energy expenditure and metabolic changes after lung volume reduction surgery for emphysema. Ann Thorac Surg 2006;82:1205-1211.
121. Kao CC, Hsu JW, Bandi V, Hanania NA, Kheradmand F, Jahoor F. Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease. Metabolism 2011;60:1449-1455.
122. Schols AM, Fredrix EW, Soeters PB, Westerterp KR, Wouters EF. Resting energy expenditure in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 1991;54:983-987.
123. Goldstein S, Askanazi J, Weissman C, Thomashow B, Kinney JM. Energy expenditure in patients with chronic obstructive pulmonary disease. Chest 1987;91:222-224.
124. Cohen RI, Marzouk K, Berkoski P, O'Donnell CP, Polotsky VY, Scharf SM. Body composition and resting energy expenditure in clinically stable, non-weight-losing patients with severe emphysema. Chest 2003;124:1365-1372.
125. Green JH, Muers MF. The thermic effect of food in underweight patients with emphysematous chronic obstructive pulmonary disease. Eur Respir J 1991;4:813-819.
126. Vermeeren MA, Schols AM, Wouters EF. Effects of an acute exacerbation on nutritional and metabolic profile of patients with COPD. Eur Respir J 1997;10:2264-2269.
127. Ryan CF, Road JD, Buckley PA, Ross C, Whittaker JS. Energy balance in stable malnourished patients with chronic obstructive pulmonary disease. Chest 1993;103:1038-1044.
128. Kurpad AV, Muthayya S, Vaz M. Consequences of inadequate food energy and negative energy balance in humans. Public Health Nutr 2005;8:1053-1076.
129. Fredrix EW. Staal-van den Brekel AJ, Wouters EF. Energy balance in nonsmall cell lung carcinoma patients before and after surgical resection of their tumors. Cancer 1997;79:717-723.
130. Harvie MN, Campbell IT, Thatcher N, Baildam A. Changes in body composition in men and women with advanced nonsmall cell lung cancer (NSCLC) undergoing chemotherapy. J Hum Nutr Diet 2003;16:323-326.
131. Staal-van den Brekel AJ, Schols AM, Dentener MA, ten Velde GP, Buurman WA, Wouters EF. Metabolism in patients with small cell lung carcinoma compared with patients with non-small cell lung carcinoma and healthy controls. Thorax 1997;52:338-341.
132. Cao DX, Wu GH, Zhang B, Quan YJ, Wei J, Jin H, et al. Resting energy expenditure and body composition in patients with newly detected cancer. Clin Nutr 2010;29:72-77.
133. Van Remoortel H, Hornikx M, Demeyer H, Langer D, Burtin C, Decramer M, et al. Daily physical activity in subjects with newly diagnosed COPD. Thorax 2013;68:962-963.
134. Andersson M, Slinde F, Gronberg AM, Svantesson U, Janson C, Emtner M. Physical activity level and its clinical correlates in chronic obstructive pulmonary disease: a cross-sectional study. Respir Res 2013;14:128.
135. Troosters T, Sciurba F, Battaglia S, Langer D, Valluri SR, Martino L, et al. Physical inactivity in patients with COPD, a controlled multi-center pilot-study. Respir Med 2010;104:1005-1011.
136. Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:972-977.
137. Ehsan M, Khan R, Wakefield D, Qureshi A, Murray L, Zuwallack R, et al. A longitudinal study evaluating the effect of exacerbations on physical activity in patients with chronic obstructive pulmonary disease. Ann Am Thorac Soc 2013;10:559-564.
138. Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R. Physical activity and hospitalization for exacerbation of COPD. Chest 2006;129:536-544.
139. Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, et al. Physical activity monitoring in COPD: compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012;106:522-530.
140. Ferguson GT, Fernandez E, Zamora MR, Pomerantz M, Buchholz J, Make BJ. Improved exercise performance following lung volume reduction surgery for emphysema. Am J Respir Crit Care Med 1998;157:1195-1203.
141. Hartman JE, Boezen HM, Heintzbergen S, de Greef MH, Klooster K, ten Hacken NH, et al. Daily physical activity after bronchoscopic lung volume reduction: a pilot study. Eur Respir J 2012;40:1566-1567.
142. Lahaije AJ, van Helvoort HA, Dekhuijzen PN, Heijdra YF. Physiologic limitations during daily life activities in COPD patients. Respir Med 2010;104:1152-1159.
143. Vaes AW, Wouters EF, Franssen FM, Uszko-Lencer NH, Stakenborg KH, Westra M, et al. Task-related oxygen uptake during domestic activities of daily life in patients with COPD and healthy elderly subjects. Chest 2011;140:970-979.
144. Calvert LD, Steiner MC, Morgan MD, Singh SJ. Plasma ammonia response to incremental cycling and walking tests in COPD. Respir Med 2010;104:675-681.
145. Criner GJ, Belt P, Sternberg AL, Mosenifar Z, Make BJ, Utz JP, et al. Effects of lung volume reduction surgery on gas exchange and breathing pattern during maximum exercise. Chest 2009;135:1268-1279.
146. Budweiser S, Heinemann F, Meyer K, Wild PJ, Pfeifer M. Weight gain in cachectic COPD patients receiving noninvasive positive-pressure ventilation. Respir Care 2006;51:126-132.
147. Granger CL, McDonald CF, Irving L, Clark RA, Gough K, Murnane A, et al. Low physical activity levels and functional decline in individuals with lung cancer. Lung Cancer 2014;83:292-299.
148. Hummler S, Thomas M, Hoffmann B, Gartner P, Zoz M, Huber G, et al. Physical performance and psychosocial status in lung cancer patients: results from a pilot study. Oncol Res Treat 2014;37:36-41.
149. Hugli O, Frascarolo P, Schutz Y, Jequier E, Leuenberger P, Fitting JW. Diet-induced thermogenesis in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993;148:1479-1483.
150. Dore MF, Laaban JP, Orvoen-Frija E, Kouchakji B, Joubert M, Rochemaure J. Role of the thermic effect of food in malnutrition of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155:1535-1540.
151. Tang NL, Chung ML, Elia M, Hui E, Lum CM, Luk JK, et al. Total daily energy expenditure in wasted chronic obstructive pulmonary disease patients. Eur J Clin Nutr 2002;56:282-287.
152. Schols A, Mostert R, Cobben N, Soeters P, Wouters E. Transcutaneous oxygen saturation and carbon dioxide tension during meals in patients with chronic obstructive pulmonary disease. Chest 1991;100:1287-1292.
153. Broekhuizen R, Wouters EF, Creutzberg EC, Schols AM. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax 2006;61:17-22.
154. Staal-van den Brekel AJ, Schols AM, ten Velde GP, Buurman WA, Wouters EF. Analysis of the energy balance in lung cancer patients. Cancer Res 1994;54:6430-6433.
155. Langen RC, Haegens A, Vernooy JH, Wouters EF, de Winther MP, Carlsen H, et al. NF-kappaB activation is required for the transition of pulmonary inflammation to muscle atrophy. Am J Respir Cell Mol Biol 2012;47:288-297.
156. Tkacova R, Ukropec J, Skyba P, Ukropcova B, Pobeha P, Kurdiova T, et al. Increased adipose tissue expression of proinflammatory CD40, MKK4 and JNK in patients with very severe chronic obstructive pulmonary disease. Respiration 2011;81:386-393.
157. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12:489-495.
158. Dahlman I, Mejhert N, Linder K, Agustsson T, Mutch DM, Kulyte A, et al. Adipose tissue pathways involved in weight loss of cancer cachexia. Br J Cancer 2010;102:1541-1548.
159. Schols AM, Creutzberg EC, Buurman WA, Campfield LA, Saris WH, Wouters EF. Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:1220-1226.
160. Brusik M, Ukropec J, Joppa P, Ukropcova B, Skyba P, Balaz M, et al. Circulatory and adipose tissue leptin and adiponectin in relationship to resting energy expenditure in patients with chronic obstructive pulmonary disease. Physiol Res 2012;61:469-480.
161. Kajimura S, Saito M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol 2014;76:225-249.
162. Cinti S. Transdifferentiation properties of adipocytes in the adipose organ. Am J Physiol Endocrinol Metab 2009;297:E977-E986.
163. Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab 2014;20:433-447.
164. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, van Marken Lichtenbelt WD. Brown adipose tissue in morbidly obese subjects. PLoS One 2011;6:e17247.
165. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, et al. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 2011;19:1755-1760.
166. Lee P, Greenfield JR, Ho KK, Fulham MJ. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2010;299:E601-E606.
167. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509-1517.
168. Shellock FG, Riedinger MS, Fishbein MC. Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J Cancer Res Clin Oncol 1986;111:82-85.
169. Huang YC, Chen TB, Hsu CC, Li SH, Wang PW, Lee BF, et al. The relationship between brown adipose tissue activity and neoplastic status: an (18)F-FDG PET/CT study in the tropics. Lipids Health Dis 2011;10:238.
170. Saure EW, Eagan TM, Jensen RL, Voll-Aanerud M, Aukrust P, Bakke PS, et al. Explained variance for blood gases in a population with COPD. Clin Respir J 2012;6:72-80.
171. Nakayama K, Frew IJ, Hagensen M, Skals M, Habelhah H, Bhoumik A, et al. Siah2 regulates stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia. Cell 2004;117:941-952.
172. van den Borst B, Schols AM, de Theije C, Boots AW, Kohler SE, Goossens GH, et al. Characterization of the inflammatory and metabolic profile of adipose tissue in a mouse model of chronic hypoxia. J Appl Physiol (1985). 2013;114:1619-1628.
173. Sun K, Wernstedt Asterholm I, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, et al. Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc Natl Acad Sci U S A 2012;109:5874-5879.
174. Elias I, Franckhauser S, Ferre T, Vila L, Tafuro S, Munoz S, et al. Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance. Diabetes 2012;61:1801-1813.
175. Franssen FM, Sauerwein HP, Ackermans MT, Rutten EP, Wouters EF, Schols AM. Increased postabsorptive and exercise-induced whole-body glucose production in patients with chronic obstructive pulmonary disease. Metabolism 2011;60:957-964.
176. Engelen MP, Schols AM, Does JD, Deutz NE, Wouters EF. Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema. Am J Respir Crit Care Med 2000;161:98-103.
177. Engelen MP, Schols AM, Does JD, Gosker HR, Deutz NE, Wouters EF. Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1697-1704.
178. Perez de Heredia F, Wood IS, Trayhurn P. Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Arch 2010;459:509-518.
179. Carriere A, Jeanson Y, Berger-Muller S, Andre M, Chenouard V, Arnaud E, et al. Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure. Diabetes 2014;63:3253-3265.
180. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360:1518-1525.
181. Soderlund V, Larsson SA, Jacobsson H. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol. Eur J Nucl Med Mol Imaging 2007;34:1018-1022.
182. Hofford JM, Milakofsky L, Vogel WH, Sacher RS, Savage GJ, Pell S. The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels. Am Rev Respir Dis 1990;141:902-908.
183. Schiffelers SL, Blaak EE, Baarends EM, Van Baak MA, Saris WH, Wouters EF, et al. beta-Adrenoceptor-mediated thermogenesis and lipolysis in patients with chronic obstructive pulmonary disease. Am J Physiol Endocrinol Metab 2001;280:E357-E364.
184. Vosselman MJ, van der Lans AA, Brans B, Wierts R, van Baak MA, Schrauwen P, et al. Systemic beta-adrenergic stimulation of thermogenesis is not accompanied by brown adipose tissue activity in humans. Diabetes 2012;61:3106-3113.
185. Parysow O, Mollerach AM, Jager V, Racioppi S, San Roman J, Gerbaudo VH. Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans. Clin Nucl Med 2007;32:351-357.
186. Lee H, Kim S, Lim Y, Gwon H, Kim Y, Ahn JJ, et al. Nutritional status and disease severity in patients with chronic obstructive pulmonary disease (COPD). Arch Gerontol Geriatr 2013;56:518-523.
187. Goris AH, Vermeeren MA, Wouters EF, Schols AM, Westerterp KR. Energy balance in depleted ambulatory patients with chronic obstructive pulmonary disease: the effect of physical activity and oral nutritional supplementation. Br J Nutr 2003;89:725-731.
188. Schols AM, Soeters PB, Mostert R, Saris WH, Wouters EF. Energy balance in chronic obstructive pulmonary disease. Am Rev Respir Dis 1991;143:1248-1252.
189. Creutzberg EC, Wouters EF, Vanderhoven-Augustin IM, Dentener MA, Schols AM. Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1239-1245.
190. Bruera E. ABC of palliative care. Anorexia, cachexia, and nutrition. BMJ 1997;315:1219-1222.
191. Pilhatsch M, Scheuing H, Kroemer N, Kobiella A, Bidlingmaier M, Farger G, et al. Nicotine administration in healthy non-smokers reduces appetite but does not alter plasma ghrelin. Hum Psychopharmacol 2014;29:384-387.
192. Eckerblad J, Todt K, Jakobsson P, Unosson M, Skargren E, Kentsson M, et al. Symptom burden in stable COPD patients with moderate or severe airflow limitation. Heart Lung 2014;43:351-357.
193. Hilmarsen CW, Wilke S, Engan H, Spruit MA, Rodenburg J, Janssen DJ, et al. Impact of symptoms of anxiety and depression on COPD Assessment Test scores. Eur Respir J 2014;43:898-900.
194. Gronberg AM, Slinde F, Engstrom CP, Hulthen L, Larsson S. Dietary problems in patients with severe chronic obstructive pulmonary disease. J Hum Nutr Diet 2005;18:445-452.
195. Sarna L, Lindsey AM, Dean H, Brecht ML, McCorkle R. Weight change and lung cancer: relationships with symptom distress, functional status, and smoking. Res Nurs Health 1994;17:371-379.
196. Lyer S, Roughley A, Rider A, Taylor-Stokes G. The symptom burden of non-small cell lung cancer in the USA: a real-world cross-sectional study. Support Care Cancer 2014;22:181-187.
197. Bentsen SB, Rustoen T, Miaskowski C. Prevalence and characteristics of pain in patients with chronic obstructive pulmonary disease compared to the Norwegian general population. J Pain 2011;12:539-545.
198. Roberts MH, Mapel DW, Hartry A, Von Worley A, Thomson H. Chronic pain and pain medication use in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc 2013;10:290-298.
199. Ketwaroo GA, Cheng V, Lembo A. Opioid-induced bowel dysfunction. Curr Gastroenterol Rep 2013;15:344.
200. Portenoy RK, Ahmed E. Principles of opioid use in cancer pain. J Clin Oncol 2014;32:1662-1670.
201. Jamshed N, Lee ZE, Olden KW. Diagnostic approach to chronic constipation in adults. Am Fam Physician 2011;84:299-306.
202. Tielemans MM, Jaspers Focks J, van Rossum LG, Eikendal T, Jansen JB, Laheij RJ, et al. Gastrointestinal symptoms are still prevalent and negatively impact health-related quality of life: a large cross-sectional population based study in The Netherlands. PLoS One 2013;8:e69876.
203. Veldhuizen MG, Albrecht J, Zelano C, Boesveldt S, Breslin P, Lundstrom JN. Identification of human gustatory cortex by activation likelihood estimation. Hum Brain Mapp 2011;32:2256-2266.
204. Oliveira-Maia AJ, Roberts CD, Simon SA, Nicolelis MA. Gustatory and reward brain circuits in the control of food intake. Adv Tech Stand Neurosurg 2011;36:31-59.
205. Norden J, Gronberg AM, Bosaeus I, Berteus Forslund H, Hulthen L, Rothenberg E, et al. Nutrition impact symptoms and body composition in patients with COPD. Eur J Clin Nutr 2015;69:256-261.
206. Dewan NA, Bell CW, Moore J, Anderson B, Kirchain W, O'Donohue WJ Jr. Smell and taste function in subjects with chronic obstructive pulmonary disease. Effect of long-term oxygen via nasal cannulas. Chest 1990;97:595-599.
207. Wardwell L, Chapman-Novakofski K, Brewer MS. Effects of age, gender and chronic obstructive pulmonary disease on taste acuity. Int J Food Sci Nutr 2009;60:84-97.
208. Janssen P, Vanden Berghe P, Verschueren S, Lehmann A, Depoortere I, Tack J. Review article: the role of gastric motility in the control of food intake. Aliment Pharmacol Ther 2011;33:880-894.
209. Karapanagiotou EM, Tsochatzis EA, Dilana KD, Tourkantonis I, Gratsias I, Syrigos KN. The significance of leptin, adiponectin, and resistin serum levels in non-small cell lung cancer (NSCLC). Lung Cancer 2008;61:391-397.
210. Terzidis A, Sergentanis TN, Antonopoulos G, Syrigos C, Efremidis A, Polyzos A, et al. Elevated serum leptin levels: a risk factor for non-small-cell lung cancer? Oncology 2009;76:19-25.
211. Itoh T, Nagaya N, Yoshikawa M, Fukuoka A, Takenaka H, Shimizu Y, et al. Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:879-882.
212. Karapanagiotou EM, Polyzos A, Dilana KD, Gratsias I, Boura P, Gkiozos I, et al. Increased serum levels of ghrelin at diagnosis mediate body weight loss in non-small cell lung cancer (NSCLC) patients. Lung Cancer 2009;66:393-398.
213. Sescousse G, Caldu X, Segura B, Dreher JC. Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies. Neurosci Biobehav Rev 2013;37:681-696.
214. Murdaugh DL, Cox JE, Cook EW 3rd, Weller RE. fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program. Neuroimage 2012;59:2709-2721.
215. Patra SK, Arora S. Integrative role of neuropeptides and cytokines in cancer anorexia-cachexia syndrome. Clin Chim Acta 2012;413:1025-1034.
216. Luo N, Marcelin G, Liu SM, Schwartz G, Chua S Jr. Neuropeptide Y and agouti-related peptide mediate complementary functions of hyperphagia and reduced energy expenditure in leptin receptor deficiency. Endocrinology 2011;152:883-889.
217. Briggs DI, Andrews ZB. Metabolic status regulates ghrelin function on energy homeostasis. Neuroendocrinology 2011;93:48-57.
218. Sanchez-Lara K, Arrieta O, Pasaye E, Laviano A, Mercadillo RE, Sosa-Sanchez R, et al. Brain activity correlated with food preferences: a functional study comparing advanced non-small cell lung cancer patients with and without anorexia. Nutrition 2013;29:1013-1019.
219. Sahebjami H, Vassallo CL. Influence of starvation on enzyme-induced emphysema. J Appl Physiol Respir Environ Exerc Physiol 1980;48:284-288.
220. Sahebjami H, MacGee J. Effects of starvation on lung mechanics and biochemistry in young and old rats. J Appl Physiol (1985) 1985;58:778-784.
221. Sahebjami H, Domino M. Effects of starvation and refeeding on elastase-induced emphysema. J Appl Physiol (1985). 1989;66:2611-2616.
222. Bishai JM, Mitzner W. Effect of severe calorie restriction on the lung in two strains of mice. Am J Physiol Lung Cell Mol Physiol 2008;295:L356-L362.
223. Coxson HO, Chan IH, Mayo JR, Hlynsky J, Nakano Y, Birmingham CL. Early emphysema in patients with anorexia nervosa. Am J Respir Crit Care Med 2004;170:748-752.
224. Thurlbeck WM. Diaphragm and body weight in emphysema. Thorax 1978;33:483-487.
225. Golgeli A, Ozesmi C, Suer C. Effect of acute starvation on rat diaphragm function. Jpn J Physiol 1994;44:743-747.
226. Efthimiou J, Fleming J, Gomes C, Spiro SG. The effect of supplementary oral nutrition in poorly nourished patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1988;137:1075-1082.
227. Weekes CE, Emery PW, Elia M. Dietary counselling and food fortification in stable COPD: a randomised trial. Thorax 2009;64:326-331.
228. Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Casein protein results in higher prandial and exercise induced whole body protein anabolism than whey protein in chronic obstructive pulmonary disease. Metabolism 2012;61:1289-1300.
229. Engelen MP, De Castro CL, Rutten EP, Wouters EF, Schols AM, Deutz NE. Enhanced anabolic response to milk protein sip feeding in elderly subjects with COPD is associated with a reduced splanchnic extraction of multiple amino acids. Clin Nutr 2012;31:616-624.
230. van de Bool C, Mattijssen-Verdonschot C, van Melick PP, Spruit MA, Franssen FM, Wouters EF, et al. Quality of dietary intake in relation to body composition in patients with chronic obstructive pulmonary disease eligible for pulmonary rehabilitation. Eur J Clin Nutr 2014;68:159-165.
231. Rutten EP, Lenaerts K, Buurman WA, Wouters EF. Disturbed intestinal integrity in patients with COPD: effects of activities of daily living. Chest 2014;145:245-252.
232. Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Altered interorgan response to feeding in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2005;82:366-372.
233. Pouw EM, Schols AM, Deutz NE, Wouters EF. 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.
234. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-660.
235. Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A 2004;101:4679-4684.
236. Miki K, Maekura R, Nagaya N, Kitada S, Miki M, Yoshimura K, et al. Effects of ghrelin treatment on exercise capacity in underweight COPD patients: a substudy of a multicenter, randomized, double-blind, placebo-controlled trial of ghrelin treatment. BMC Pulm Med 2013;13:37.
237. Garcia JM, Boccia RV, Graham CD, Yan Y, Duus EM, Allen S, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol 2015;16: 108-116.
238. Currow DC, Abernethy AP. Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome. Future Oncol 2014;10:789-802.
239. Ziauddeen H, Farooqi IS, Fletcher PC. Obesity and the brain: how convincing is the addiction model? Nat Rev Neurosci 2012;13:279-286.
240. Stice E, Yokum S, Burger KS, Epstein LH, Small DM. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. J Neurosci 2011;31:4360-4366.
241. Roefs A, Stapert D, Isabella LA, Wolters G, Wojciechowski F, Jansen A. Early associations with food in anorexia nervosa patients and obese people assessed in the affective priming paradigm. Eat Behav 2005;6:151-163.
242. Zipfel S, Wild B, Gross G, Friederich HC, Teufel M, Schellberg D, et al. Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in outpatients with anorexia nervosa (ANTOP study): randomised controlled trial. Lancet 2014;383:127-137.
243. Deckersbach T, Das SK, Urban LE, Salinardi T, Batra P, Rodman AM, et al. Pilot randomized trial demonstrating reversal of obesity-related abnormalities in reward system responsivity to food cues with a behavioral intervention. Nutr Diabetes 2014;4:e129.