Eur Respir J 2003; 21:347-360
Copyright ©ERS Journals Ltd 2003
Systemic effects of chronic obstructive pulmonary disease
A.G.N. Agustí1,
A. Noguera2,
J. Sauleda1,
E. Sala1,
J. Pons3 and
X. Busquets3
1 Servei de Pneumología, 2 Analisis Cliniques and 3 Unidad de Investigación, Hospital Universitari Son Dureta, Palma de Mallorca, Spain
CORRESPONDENCE: A.G.N. Agustí, Servei de Pneumología, Hospital Universitari Son Dureta, Andrea Doria 55, 07014, Palma de Mallorca, Spain. Fax: 34 971175228. E-mail: aagusti@hsd.es
Keywords: chronic bronchitis, chronic obstructive pulmonary disease, emphysema, inflammation
Received: May 11, 2001
Accepted August 20, 2002
This study was supported, in part, by Fondo de Investigación Sanitaria, Sociedad Española de Neumología y Cirugía Torácica (SEPAR) and Associació Balear per l'Estudi de les Malalties Respiratories (ABEMAR).
Abstract
Chronic obstructive pulmonary disease (COPD) is characterised by an inappropriate/excessive inflammatory response of the lungs to respiratory pollutants, mainly tobacco smoking.
Recently, besides the typical pulmonary pathology of COPD (i.e. chronic bronchitis and emphysema), several effects occurring outside the lungs have been described, the so-called systemic effects of COPD. These effects are clinically relevant because they modify and can help in the classification and management of the disease.
The present review discusses the following systemic effects of chronic obstructive pulmonary disease: 1) systemic inflammation; 2) nutritional abnormalities and weight loss; 3) skeletal muscle dysfunction; and 4) other potential systemic effects. For each of these, the potential mechanisms and clinical implications are discussed and areas requiring further research are highlighted.
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|
 |
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|
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|
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|
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|
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|
 |
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|
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|
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|
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|
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|
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|
 |
|

|
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|
 |
 
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|
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|
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|
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|
 |
|

|
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|
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|
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|
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|
 |
 
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Eur. Respir. J.,
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27(3):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Eur. Respir. J.,
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27(3):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Chest,
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129(3):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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The potential impact of anaemia of chronic disease in COPD
Eur. Respir. J.,
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Am. J. Clinical Nutrition,
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82(5):
1059 - 1064.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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November 1, 2005;
2(4):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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November 1, 2005;
172(9):
1097 - 1104.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Eur. Respir. J.,
October 1, 2005;
26(4):
703 - 719.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Reduced Intracellular Oxygen Radical Production in Whole Blood Leukocytes From COPD Patients and Asymptomatic Smokers
Chest,
October 1, 2005;
128(4):
2051 - 2058.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Functional coupling of adenine nucleotide translocase and mitochondrial creatine kinase is enhanced after exercise training in lung transplant skeletal muscle
Am J Physiol Regulatory Integrative Comp Physiol,
October 1, 2005;
289(4):
R1144 - R1154.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Skeletal muscle inflammation and nitric oxide in patients with COPD
Eur. Respir. J.,
September 1, 2005;
26(3):
390 - 397.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Barnes and R. A. Stockley
COPD: current therapeutic interventions and future approaches
Eur. Respir. J.,
June 1, 2005;
25(6):
1084 - 1106.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Systemic Response to Ambient Particulate Matter: Relevance to Chronic Obstructive Pulmonary Disease
Proceedings of the ATS,
April 1, 2005;
2(1):
61 - 67.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Chest,
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127(4):
1212 - 1218.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Skeletal muscle microbiopsy: a validation study of a minimally invasive technique
Eur. Respir. J.,
March 1, 2005;
25(3):
431 - 440.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Blunted {gamma}{delta} T-lymphocyte response in chronic obstructive pulmonary disease
Eur. Respir. J.,
March 1, 2005;
25(3):
441 - 446.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. John, S. Hoernig, W. Doehner, D. D. Okonko, C. Witt, and S. D. Anker
Anemia and Inflammation in COPD
Chest,
March 1, 2005;
127(3):
825 - 829.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Musculoskeletal Effects of Chronic Obstructive Pulmonary Disease: Prevalent, Linked, but Ignored
Am. J. Respir. Crit. Care Med.,
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170(12):
1267 - 1268.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Gene Expression Profiling of Human Lung Tissue from Smokers with Severe Emphysema
Am. J. Respir. Cell Mol. Biol.,
December 1, 2004;
31(6):
601 - 610.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C.C. Christensen, M.S. Ryg, A. Edvardsen, and O.H. Skjonsberg
Relationship between exercise desaturation and pulmonary haemodynamics in COPD patients
Eur. Respir. J.,
October 1, 2004;
24(4):
580 - 586.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Am. J. Respir. Crit. Care Med.,
October 1, 2004;
170(7):
721 - 722.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Thorax,
July 1, 2004;
59(7):
574 - 580.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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NF-{kappa}B activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight
Thorax,
June 1, 2004;
59(6):
483 - 487.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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169(9):
1022 - 1027.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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[Abstract]
[Full Text]
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|
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Copyright © 2003 by the European Respiratory Society.
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