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Published in: Respiratory Research 1/2012

Open Access 01-12-2012 | Research

TNF-α is associated with loss of lean body mass only in already cachectic COPD patients

Authors: Tomas ML Eagan, Esteban C Gabazza, Corina D’Alessandro-Gabazza, Paloma Gil-Bernabe, Shinya Aoki, Jon A Hardie, Per S Bakke, Peter D Wagner

Published in: Respiratory Research | Issue 1/2012

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Abstract

Background

Systemic inflammation may contribute to cachexia in patients with chronic obstructive pulmonary disease (COPD). In this longitudinal study we assessed the association between circulating C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels and subsequent loss of fat free mass and fat mass in more than 400 COPD patients over three years.

Methods

The patients, aged 40–76, GOLD stage II-IV, were enrolled in 2006/07, and followed annually. Fat free mass and fat mass indexes (FFMI & FMI) were calculated using bioelectrical impedance, and CRP, TNF-α, IL-1ß, and IL-6 were measured using enzyme immunoassays. Associations with mean change in FFMI and FMI of the four inflammatory plasma markers, sex, age, smoking, FEV1, inhaled steroids, arterial hypoxemia, and Charlson comorbidity score were analyzed with linear mixed models.

Results

At baseline, only CRP was significantly (but weakly) associated with FFMI (r = 0.18, p < 0.01) and FMI (r = 0.27, p < 0.01). Univariately, higher age, lower FEV1, and use of beta2-agonists were the only significant predictors of decline in FFMI, whereas smoking, hypoxemia, Charlson score, and use of inhaled steroids predicted increased loss in FMI. Multivariately, high levels of TNF-α (but not CRP, IL-1ß or IL-6) significantly predicted loss of FFMI, however only in patients with established cachexia at entry.

Conclusion

This study does not support the hypothesis that systemic inflammation is the cause of accelerated loss of fat free mass in COPD patients, but suggests a role for TNF-α in already cachectic COPD patients.
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Literature
1.
go back to reference Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM: Global burden of COPD: systematic review and meta-analysis. Eur Respir J. 2006, 28: 523-532. 10.1183/09031936.06.00124605.PubMedCrossRef Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM: Global burden of COPD: systematic review and meta-analysis. Eur Respir J. 2006, 28: 523-532. 10.1183/09031936.06.00124605.PubMedCrossRef
2.
go back to reference Berry CE, Wise RA: Mortality in COPD: causes, risk factors, and prevention. COPD. 2010, 7: 375-382. 10.3109/15412555.2010.510160.PubMedCrossRef Berry CE, Wise RA: Mortality in COPD: causes, risk factors, and prevention. COPD. 2010, 7: 375-382. 10.3109/15412555.2010.510160.PubMedCrossRef
3.
go back to reference Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ: Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008, 5: 549-555. 10.1513/pats.200709-148ET.PubMedPubMedCentralCrossRef Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ: Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008, 5: 549-555. 10.1513/pats.200709-148ET.PubMedPubMedCentralCrossRef
4.
go back to reference Wagner PD: Possible mechanisms underlying the development of cachexia in COPD. Eur Respir J. 2008, 31: 492-501. 10.1183/09031936.00074807.PubMedCrossRef Wagner PD: Possible mechanisms underlying the development of cachexia in COPD. Eur Respir J. 2008, 31: 492-501. 10.1183/09031936.00074807.PubMedCrossRef
5.
go back to reference 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.PubMed 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.PubMed
6.
go back to reference Bolton CE, Ionescu AA, Shiels KM, Pettit RJ, Edwards PH, Stone MD, Nixon LS, Evans WD, Griffiths TL, Shale DJ: Associated loss of fat-free mass and bone mineral density in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004, 170: 1286-1293. 10.1164/rccm.200406-754OC.PubMedCrossRef Bolton CE, Ionescu AA, Shiels KM, Pettit RJ, Edwards PH, Stone MD, Nixon LS, Evans WD, Griffiths TL, Shale DJ: Associated loss of fat-free mass and bone mineral density in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004, 170: 1286-1293. 10.1164/rccm.200406-754OC.PubMedCrossRef
7.
go back to reference Eagan TM, Ueland T, Wagner PD, Hardie JA, Mollnes TE, Damas JK, Aukrust P, Bakke PS: Systemic inflammatory markers in chronic obstructive pulmonary disease - results from the Bergen COPD Cohort Study. Eur Respir J. 2010, 35: 540-548. 10.1183/09031936.00088209.PubMedCrossRef Eagan TM, Ueland T, Wagner PD, Hardie JA, Mollnes TE, Damas JK, Aukrust P, Bakke PS: Systemic inflammatory markers in chronic obstructive pulmonary disease - results from the Bergen COPD Cohort Study. Eur Respir J. 2010, 35: 540-548. 10.1183/09031936.00088209.PubMedCrossRef
8.
go back to reference Mannino DM, Ford ES, Redd SC: Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Am J Med. 2003, 114: 758-762. 10.1016/S0002-9343(03)00185-2.PubMedCrossRef Mannino DM, Ford ES, Redd SC: Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Am J Med. 2003, 114: 758-762. 10.1016/S0002-9343(03)00185-2.PubMedCrossRef
9.
go back to reference Pinto-Plata VM, Mullerova H, Toso JF, Feudjo-Tepie M, Soriano JB, Vessey RS, Celli BR: C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax. 2006, 61: 23-28.PubMedPubMedCentralCrossRef Pinto-Plata VM, Mullerova H, Toso JF, Feudjo-Tepie M, Soriano JB, Vessey RS, Celli BR: C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax. 2006, 61: 23-28.PubMedPubMedCentralCrossRef
10.
go back to reference Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X: Systemic effects of chronic obstructive pulmonary disease. Eur Respir J. 2003, 21: 347-360. 10.1183/09031936.03.00405703.PubMedCrossRef Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X: Systemic effects of chronic obstructive pulmonary disease. Eur Respir J. 2003, 21: 347-360. 10.1183/09031936.03.00405703.PubMedCrossRef
11.
go back to reference Barnes PJ, Celli BR: Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009, 33: 1165-1185. 10.1183/09031936.00128008.PubMedCrossRef Barnes PJ, Celli BR: Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009, 33: 1165-1185. 10.1183/09031936.00128008.PubMedCrossRef
12.
go back to reference Nussbaumer-Ochsner Y, Rabe KF: Systemic manifestations of COPD. Chest. 2011, 139: 165-173. 10.1378/chest.10-1252.PubMedCrossRef Nussbaumer-Ochsner Y, Rabe KF: Systemic manifestations of COPD. Chest. 2011, 139: 165-173. 10.1378/chest.10-1252.PubMedCrossRef
13.
go back to reference Sinden NJ, Stockley RA: Systemic inflammation and comorbidity in COPD: a result of 'overspill' of inflammatory mediators from the lungs? Review of the evidence. Thorax. 2010, 65: 930-936. 10.1136/thx.2009.130260.PubMedCrossRef Sinden NJ, Stockley RA: Systemic inflammation and comorbidity in COPD: a result of 'overspill' of inflammatory mediators from the lungs? Review of the evidence. Thorax. 2010, 65: 930-936. 10.1136/thx.2009.130260.PubMedCrossRef
14.
go back to reference Tisdale MJ: Mechanisms of cancer cachexia. Physiol Rev. 2009, 89: 381-410. 10.1152/physrev.00016.2008.PubMedCrossRef Tisdale MJ: Mechanisms of cancer cachexia. Physiol Rev. 2009, 89: 381-410. 10.1152/physrev.00016.2008.PubMedCrossRef
15.
go back to reference Di Francia M, Barbier D, Mege JL, Orehek J: Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994, 150: 1453-1455.PubMedCrossRef Di Francia M, Barbier D, Mege JL, Orehek J: Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994, 150: 1453-1455.PubMedCrossRef
16.
go back to reference Eid AA, Ionescu AA, Nixon LS, Lewis-Jenkins V, Matthews SB, Griffiths TL, Shale DJ: Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001, 164: 1414-1418.PubMedCrossRef Eid AA, Ionescu AA, Nixon LS, Lewis-Jenkins V, Matthews SB, Griffiths TL, Shale DJ: Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001, 164: 1414-1418.PubMedCrossRef
17.
go back to reference Itoh T, Nagaya N, Yoshikawa M, Fukuoka A, Takenaka H, Shimizu Y, Haruta Y, Oya H, Yamagishi M, Hosoda H, Kangawa K, Kimura H: Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004, 170: 879-882. 10.1164/rccm.200310-1404OC.PubMedCrossRef Itoh T, Nagaya N, Yoshikawa M, Fukuoka A, Takenaka H, Shimizu Y, Haruta Y, Oya H, Yamagishi M, Hosoda H, Kangawa K, Kimura H: Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004, 170: 879-882. 10.1164/rccm.200310-1404OC.PubMedCrossRef
18.
go back to reference Takabatake N, Nakamura H, Abe S, Hino T, Saito H, Yuki H, Kato S, Tomoike H: Circulating leptin in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999, 159: 1215-1219.PubMedCrossRef Takabatake N, Nakamura H, Abe S, Hino T, Saito H, Yuki H, Kato S, Tomoike H: Circulating leptin in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999, 159: 1215-1219.PubMedCrossRef
19.
go back to reference Broekhuizen R, Grimble RF, Howell WM, Shale DJ, Creutzberg EC, Wouters EF, Schols AM: Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta −511 single nucleotide polymorphism. Am J Clin Nutr. 2005, 82: 1059-1064.PubMed Broekhuizen R, Grimble RF, Howell WM, Shale DJ, Creutzberg EC, Wouters EF, Schols AM: Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta −511 single nucleotide polymorphism. Am J Clin Nutr. 2005, 82: 1059-1064.PubMed
20.
go back to reference Shin KC, Chung JH, Lee KH: Effects of TNF-alpha and leptin on weight loss in patients with stable chronic obstructive pulmonary disease. Korean J Intern Med. 2007, 22: 249-255. 10.3904/kjim.2007.22.4.249.PubMedPubMedCentralCrossRef Shin KC, Chung JH, Lee KH: Effects of TNF-alpha and leptin on weight loss in patients with stable chronic obstructive pulmonary disease. Korean J Intern Med. 2007, 22: 249-255. 10.3904/kjim.2007.22.4.249.PubMedPubMedCentralCrossRef
21.
go back to reference Tanni SE, Pelegrino NR, Angeleli AY, Correa C, Godoy I: Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients. J Inflamm (Lond). 2010, 7: 29-10.1186/1476-9255-7-29.CrossRef Tanni SE, Pelegrino NR, Angeleli AY, Correa C, Godoy I: Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients. J Inflamm (Lond). 2010, 7: 29-10.1186/1476-9255-7-29.CrossRef
22.
go back to reference Van Helvoort HA, Heijdra YF, Thijs HM, Vina J, Wanten GJ, Dekhuijzen PN: Exercise-induced systemic effects in muscle-wasted patients with COPD. Med Sci Sports Exerc. 2006, 38: 1543-1552. 10.1249/01.mss.0000228331.13123.53.PubMedCrossRef Van Helvoort HA, Heijdra YF, Thijs HM, Vina J, Wanten GJ, Dekhuijzen PN: Exercise-induced systemic effects in muscle-wasted patients with COPD. Med Sci Sports Exerc. 2006, 38: 1543-1552. 10.1249/01.mss.0000228331.13123.53.PubMedCrossRef
23.
go back to reference Schols AM, Dingemans AM, Soeters PB, Wouters EF: Within-day variation of bioelectrical resistance measurements in patients with chronic obstructive pulmonary disease. Clin Nutr. 1990, 9: 266-271. 10.1016/0261-5614(90)90035-Q.PubMedCrossRef Schols AM, Dingemans AM, Soeters PB, Wouters EF: Within-day variation of bioelectrical resistance measurements in patients with chronic obstructive pulmonary disease. Clin Nutr. 1990, 9: 266-271. 10.1016/0261-5614(90)90035-Q.PubMedCrossRef
24.
go back to reference Schutz Y, Kyle UU, Pichard C: Fat-free mass index and fat mass index percentiles in Caucasians aged 18–98 y. Int J Obes Relat Metab Disord. 2002, 26: 953-960.PubMedCrossRef Schutz Y, Kyle UU, Pichard C: Fat-free mass index and fat mass index percentiles in Caucasians aged 18–98 y. Int J Obes Relat Metab Disord. 2002, 26: 953-960.PubMedCrossRef
25.
go back to reference Vittinghoff E, Glidden DV, Shiboski SC, McCulloch CE: Repeated Measures and Longitudinal Data Analysis. Regression Methods in Biostatistics - Linear, Logistic, Survival, and Repeated Measures Models. Edited by: Dietz K, Gail M, Krickeberg J, Samet A, Tsiatis A. 2005, New York: Springer, 253-289. Vittinghoff E, Glidden DV, Shiboski SC, McCulloch CE: Repeated Measures and Longitudinal Data Analysis. Regression Methods in Biostatistics - Linear, Logistic, Survival, and Repeated Measures Models. Edited by: Dietz K, Gail M, Krickeberg J, Samet A, Tsiatis A. 2005, New York: Springer, 253-289.
26.
go back to reference Foschino Barbaro MP, Carpagnano GE, Spanevello A, Cagnazzo MG, Barnes PJ: Inflammation, oxidative stress and systemic effects in mild chronic obstructive pulmonary disease. Int J Immunopathol Pharmacol. 2007, 20: 753-763.PubMed Foschino Barbaro MP, Carpagnano GE, Spanevello A, Cagnazzo MG, Barnes PJ: Inflammation, oxidative stress and systemic effects in mild chronic obstructive pulmonary disease. Int J Immunopathol Pharmacol. 2007, 20: 753-763.PubMed
27.
go back to reference Gan WQ, Man SF, Senthilselvan A, Sin DD: Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004, 59: 574-580. 10.1136/thx.2003.019588.PubMedPubMedCentralCrossRef Gan WQ, Man SF, Senthilselvan A, Sin DD: Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004, 59: 574-580. 10.1136/thx.2003.019588.PubMedPubMedCentralCrossRef
28.
go back to reference Frey DJ, Fleshner M, Wright KPJ: The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. 2007, 21: 1050-1057. 10.1016/j.bbi.2007.04.003.PubMedCrossRef Frey DJ, Fleshner M, Wright KPJ: The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. 2007, 21: 1050-1057. 10.1016/j.bbi.2007.04.003.PubMedCrossRef
29.
go back to reference Naya M, Tsukamoto T, Morita K, Katoh C, Furumoto T, Fujii S, Tamaki N, Tsutsui H: Plasma interleukin-6 and tumor necrosis factor-alpha can predict coronary endothelial dysfunction in hypertensive patients. Hypertens Res. 2007, 30: 541-548. 10.1291/hypres.30.541.PubMedCrossRef Naya M, Tsukamoto T, Morita K, Katoh C, Furumoto T, Fujii S, Tamaki N, Tsutsui H: Plasma interleukin-6 and tumor necrosis factor-alpha can predict coronary endothelial dysfunction in hypertensive patients. Hypertens Res. 2007, 30: 541-548. 10.1291/hypres.30.541.PubMedCrossRef
30.
go back to reference Dossus L, Becker S, Achaintre D, Kaaks R, Rinaldi S: Validity of multiplex-based assays for cytokine measurements in serum and plasma from "non-diseased" subjects: comparison with ELISA. J Immunol Methods. 2009, 350: 125-132. 10.1016/j.jim.2009.09.001.PubMedCrossRef Dossus L, Becker S, Achaintre D, Kaaks R, Rinaldi S: Validity of multiplex-based assays for cytokine measurements in serum and plasma from "non-diseased" subjects: comparison with ELISA. J Immunol Methods. 2009, 350: 125-132. 10.1016/j.jim.2009.09.001.PubMedCrossRef
31.
go back to reference Eagan TM, Aukrust P, Ueland T, Hardie JA, Johannessen A, Mollnes TE, Damas JK, Bakke PS, Wagner PD: Body composition and plasma levels of inflammatory biomarkers in COPD. Eur Respir J. 2010, 36: 1027-1033. 10.1183/09031936.00194209.PubMedCrossRef Eagan TM, Aukrust P, Ueland T, Hardie JA, Johannessen A, Mollnes TE, Damas JK, Bakke PS, Wagner PD: Body composition and plasma levels of inflammatory biomarkers in COPD. Eur Respir J. 2010, 36: 1027-1033. 10.1183/09031936.00194209.PubMedCrossRef
32.
go back to reference Wiedenmann B, Malfertheiner P, Friess H, Ritch P, Arseneau J, Mantovani G, Caprioni F, Van Cutsem E, Richel D, DeWitte M, Qi M, Robinson DJ, Zhong B, De Boer C, Lu JD, Prabhakar U, Corringham R, Von Hoff D: A multicenter, phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia. J Support Oncol. 2008, 6: 18-25.PubMed Wiedenmann B, Malfertheiner P, Friess H, Ritch P, Arseneau J, Mantovani G, Caprioni F, Van Cutsem E, Richel D, DeWitte M, Qi M, Robinson DJ, Zhong B, De Boer C, Lu JD, Prabhakar U, Corringham R, Von Hoff D: A multicenter, phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia. J Support Oncol. 2008, 6: 18-25.PubMed
33.
go back to reference Marcora SM, Chester KR, Mittal G, Lemmey AB, Maddison PJ: Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis. Am J Clin Nutr. 2006, 84: 1463-1472.PubMed Marcora SM, Chester KR, Mittal G, Lemmey AB, Maddison PJ: Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis. Am J Clin Nutr. 2006, 84: 1463-1472.PubMed
34.
go back to reference Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J: The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007, 175: 926-934. 10.1164/rccm.200607-995OC.PubMedCrossRef Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J: The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007, 175: 926-934. 10.1164/rccm.200607-995OC.PubMedCrossRef
35.
go back to reference Bolton CE, Broekhuizen R, Ionescu AA, Nixon LS, Wouters EF, Shale DJ, Schols AM: Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD. Thorax. 2007, 62: 109-114. 10.1136/thx.2006.060368.PubMedPubMedCentralCrossRef Bolton CE, Broekhuizen R, Ionescu AA, Nixon LS, Wouters EF, Shale DJ, Schols AM: Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD. Thorax. 2007, 62: 109-114. 10.1136/thx.2006.060368.PubMedPubMedCentralCrossRef
Metadata
Title
TNF-α is associated with loss of lean body mass only in already cachectic COPD patients
Authors
Tomas ML Eagan
Esteban C Gabazza
Corina D’Alessandro-Gabazza
Paloma Gil-Bernabe
Shinya Aoki
Jon A Hardie
Per S Bakke
Peter D Wagner
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2012
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-13-48

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