Journal Information
Vol. 46. Issue S4.
EPOC: de la etiopatogenia al tratamiento
Pages 9-15 (September 2010)
Share
Share
Download PDF
More article options
Vol. 46. Issue S4.
EPOC: de la etiopatogenia al tratamiento
Pages 9-15 (September 2010)
Full text access
EPOC: inflamación bronquial y sistémica
COPD: bronchial and systemic inflammation
Visits
11487
Ciro Casanova Macarioa,
Corresponding author
ccasanova@canarias.org

Autor para correspondencia.
, Juan Pablo de Torres Tajesb, Elizabeth Córdoba Lanusc
a Servicio de Neumología, Unidad de Investigación, Hospital Universitario La Candelaria, Santa Cruz de Tenerife, España
b Servicio de Neumología, Clínica Universitaria de Navarra, Pamplona, España
c Unidad de Investigación, Hospital Universitario La Candelaria, Santa Cruz de Tenerife, España
This item has received
Article information
Resumen

La enfermedad pulmonar obstructiva crónica (EPOC) se considera una enfermedad inflamatoria de la vía aérea, en la que puede coexistir una inflamación sistémica de bajo grado. La etiología es multifactorial, pero, fundamentalmente, condicionada por una respuesta inflamatoria amplificada y anómala al humo del tabaco. En esta respuesta están involucradas la inmunidad innata y la adquirida. Esta última es de característica linfocitaria tipo Th1 (CD8) y su presencia parece asociarse a la progresión a estadios avanzado de la enfermedad. En la actualidad, desconocemos si la inflamación bronquial y sistémica están relacionadas o si actúan como compartimentos independientes. La mayor parte de los datos que tenemos sobre la EPOC se obtienen de estudios transversales, por lo que no se puede establecer una relación de causalidad entre los posibles mediadores inflamatorios y los factores genéticos involucrados en la afectación pulmonar y extrapulmonar de esta enfermedad. Necesitamos nuevos estudios que nos permitan categorizar la respuesta inflamatoria con los diferentes fenotipos de la EPOC.

Palabras clave:
Enfermedad pulmonar obstructiva crónica
Inflamación
Inmunidad
Genética
Abstract

Chronic obstructive pulmonary disease (COPD) is considered to be an inflammatory disease of the airways, in which there can be low-grade systemic inflammation. The etiology of this disease is multifactorial but is mainly due to an anomalous and amplified inflammatory response to tobacco smoke. This inflammatory response involves innate and acquired immunity. The latter is characterized by a Th1-type (CD8) response and its presence seems to be associated with progression to advanced stages of the disease. Currently, it is unknown whether bronchial and systemic inflammation are related or whether they act as independent compartments. Most of the available data on COPD are drawn from cross-sectional studies and consequently a causal relation between the possible inflammatory mediators and the genetic factors involved in pulmonary and extrapulmonary involvement in this disease cannot be established. Further studies are required that would allow the inflammatory response to be correlated with the distinct COPD phenotypes.

Keywords:
Chronic obstructive pulmonary disease
Inflammation
Immunity
Genetics
Full text is only aviable in PDF
Bibliografía
[1.]
G. Peces-Barba, J.A. Barberá, A. Agusti, C. Casanova, A. Casas, J.L. Izquierdo, et al.
Guía de práctica clínica de diagnóstico y tratamiento de la enfermedad pulmonar obstructiva crónica. Normativa SEPAR-ALAT.
Arch Bronconeumol, 44 (2008), pp. 271-281
[2.]
K.F. Rabe, S. Hurd, A. Anzueto, P.J. Barnes, A.S. Buist, P. Calverley, et al.
Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for chronic obstructive pulmonary disease (GOLD). Workshop summary.
Am J Respir Crit Care Med, 176 (2007), pp. 532-555
[3.]
J.C. Hogg.
Pathophysiology of airflow limitation in chronic obstructive pulmonary disease.
[4.]
J.C. Hogg, F. Chu, B. Utokaparch, R. Woods, W.M. Elliot, L. Buzatu, et al.
The natures of small-airway obstruction in chronic obstructive pulmonary disease.
New Engl J Med, 350 (2004), pp. 2645-2653
[5.]
P.J. Barnes, B. Chowdhury, S.A. Kharitonov, H. Magnussen, C.P. Page, D. Postma, M. Saetta.
Pulmonary biomarkers in COPD.
Am J Respir Crit Care Med, 174 (2006), pp. 6-14
[6.]
T.C. O'Shaughnessy, T.W. Ansari, N.C. Barnes, P.K. Jeffery.
Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ Tlymphocytes with FEV1.
Am J Respir Crit Care Med, 155 (1997), pp. 852-857
[7.]
M. Saetta, A.D. Stefano, G. Turato, F.M. Facchini, L. Corbino, C.E. Mapp, et al.
CD8+ T-lymphocites in peripheral airways of smokers with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 158 (1998), pp. 822-826
[8.]
L. Fabbri, M. Romagnoli, L. Corbetta, G. Casoni, K. Busljetic, G. Turato, et al.
Differences in airway inflammmation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease.
AM J Respir Crit Care Med, 167 (2003), pp. 418-424
[9.]
M.G. Cosio, M. Saetta, A. Agusti.
Immunologic aspects of chronic obstructive pulmonary disease.
New Engl J Med, 360 (2009), pp. 2445-2454
[10.]
S.L. Traves, S.V. Culpitt, R.E. Russell, P.J. Barnes, L.E. Donelly.
Increased level of chemokines GROalpha and MCP-1 insputum samples from patients with COPD.
Thorax, 57 (2002), pp. 590-595
[11.]
E.F.M. Wouters, N.L. Reynaert, M.A. Dentener, J.HJ. Vernooy.
Systemic and local inflammation in asthma and chronic obstructive pulmonary disease.
Proc Am Thorac Soc, 6 (2009), pp. 638-647
[12.]
R.W. Chapman, M. Minnicozzi, C.S. Celly, J.E. Phillips, T.T. Kung, R.W. Hipkin, et al.
A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation.
J Pharmacol Exp Ther, 322 (2007), pp. 486-493
[13.]
L.M. Ebert, P. Schaerli, B. Moser.
Chemokine-mediated control on T cell traffic in lymphoid and peripheral tissues.
Mol Inmunol, 42 (2005), pp. 799-809
[14.]
P. Boschetto, S. Quintavalle, E. Zeni, S. Leprotti, A. Potena, L. Ballerin, et al.
Association between markers of emphysema and more severe chronic obstructive pulmonary disease Thorax, 61 (2006), pp. 1037-1042
[15.]
L. Núñez-Naveira, C. Montero-Martinez, Ramos-Borbón.
Oxidación, inflamación y modificaciones estructurales.
Arch Bronconeumol, 43 (2007), pp. 18-29
[16.]
C. Costa, R. Rufino, S.L. Traves, J.R.L. Silva, P.J. Barnes, L.E. Donnelly.
CXCR3 and CCR5 chemokines in induced sputum from patients with COPD.
Chest, 133 (2008), pp. 26-33
[17.]
S.G. Kelsen, M.O. Aksoy, R. Hershman, R. Ji, X. Li, M. Hurford, et al.
Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.
Am J Respir Crit Care Med, 179 (2009), pp. 799-805
[18.]
J.L. Curtis, C.M. Freeman, J.C. Hogg.
The immunopathogenesis of chronic obstructive pulmonary disease.
Proc Am Thorac Soc, 4 (2007), pp. 512-521
[19.]
T.S. Lapperre, S.D. Postma, M.M.E. Gosman, J.B. Snoeck-Stroband, N.H.T. Ten Hacken, et al.
Relation between duration of smoking cessation and bronchial inflammation in COPD.
Thorax, 61 (2006), pp. 115-121
[20.]
E. Gamble, D.C. Grootendorst, K. Hattotuwa, T. O'Shaughanessy, F.S.F. Ram, Y. Qiu, et al.
Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis.
Eur Respir J, 30 (2007), pp. 467-471
[21.]
A. Marin, E. Monso, M. García, J. Sauleda, A. Noguera, J. Pons, et al.
Variability and effects of bronchial colonization in patients with moderate COPD.
Eur Respir J, 35 (2010), pp. 295-302
[22.]
A. Di Stefano, A. Capelli, M. Lusuardi, P. Balbo, C. Vecchio, P. Maestrelli, et al.
Severity of airflow limitation is associated with severity of airway inflammation in smokers.
Am J Respir Crit Care Med, 158 (1998), pp. 1277-1285
[23.]
C.M. Freeman, F.J. Martinez, M.K. Han, T.M. Ames, S.W. Chensue, J.C. Todt, et al.
Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 180 (2009), pp. 1179-1188
[24.]
G. Turato, R. Zuin, M. Miniati, S. Baraldo, F. Rea, B. Beghé, et al.
Airway inflammation in severe chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 166 (2002), pp. 105-110
[25.]
V.M. Keatings, P.D. Collins, D.M. Scott, P.J. Barnes.
Differences in iterleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.
Am J Respir Crit Care Med, 153 (1996), pp. 530-534
[26.]
J.H. Vernooy, M. Kucukaycan, J.A. Jacobs, N.H. Chavannes, W.A. Buurman, M.A. Dentener, et al.
Local and systemic inflammation in patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 166 (2002), pp. 1218-1224
[27.]
J.R. Hurst, T.M.A. Wilkinson, W.R. Perera, G.C. Donaldson, J.A. Wedzicha.
Relationships among bacteria, upper airway, lower airway, and systemic inflammation in COPD.
Chest, 127 (2005), pp. 1219-1226
[28.]
G.C. Donaldson, T.A.R. Seemungal, I.S. Patel, A. Bhowmik, T.M.A. Wilkinson, J.R. Hurst, et al.
Airway and systemic inflammation and decline in lung function in patients with COPD.
Chest, 128 (2005), pp. 1995-2004
[29.]
J.C. Hogg, F.S.F. Chu, W.C. Tan, D.C. Sin, S.A. Patel, P.D. Pare, et al.
Survival after lung volumen reduction in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 176 (2007), pp. 454-459
[30.]
A. Agustí.
Systemic effects of chronic obstructive pulmonary disease.
Proc Am Thorac Soc, 2 (2005), pp. 367-370
[31.]
W.Q. Gan, S.F. Man, A. Senthilselvan, D.D. Sin.
Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a metaanalysis.
Thorax, 59 (2004), pp. 574-580
[32.]
A. Agustí.
EPOC e inflamación sistémica. Una vía de enlace para la comorbilidad.
Arch Bronconeumol, 45 (2009), pp. 14-17
[33.]
S. Guerra, D.L. Sherrill, C. Venker, C.M. Ceccato, M. Halonen, F.D. Martinez.
Chronic bronchitis befote age 50 years predicts incident airflow limitation and mortality risk.
Thorax, 64 (2009), pp. 894-900
[34.]
K.H. Groenewegen, D.S. Postma, W.C. Hop, P.L. Wielders, N.J. Schlösser, E.F. Wouters, COSMIC Study Group.
Increased systemic inflammation is a risk factor for COPD exacerbations.
Chest, 133 (2008), pp. 350-357
[35.]
P.J. Barnes.
The cytokine network in chronic obstructive pulmonary disease.
Am J Respir Cell Mol Biol, 41 (2009), pp. 631-638
[36.]
V. Pinto-Plata, J. Toso, K. Lee, D. Park, J. Bilello, H. Mullerova, et al.
Profiling serum biomarkers in patients with COPD: associations with clinical parameters.
Thorax, 62 (2007), pp. 595-601
[37.]
S.J. Thorleifsson, O.B. Margretardottir, G. Gudmundsson, I. Olafsson, B. Benediktsdottir, C. Janson, et al.
Chronic airflow obstruction and markers of systemic inflammation: results from the BOLD study in Iceland.
Respir Med, 103 (2009), pp. 1548-1553
[38.]
Y. Higashimoto, T. Iwata, M. Okada, H. Satoh, K. Fukuda, Y. Tohda.
Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease.
Respir Med, 103 (2009), pp. 1231-1238
[39.]
J.P. De Torres, E. Cordoba-Lanus, C. Lopez-Aguilar, M. Muros de Fuentes, A. Montejo de Garcini, A. Aguirre-Jaime, et al.
C-reactive protein levels and clinically important predictive outcomes in stable COPD patients.
Eur Respir J, 27 (2006), pp. 902-907
[40.]
C. Casanova, J.P. De Torres, M. Montes de Oca.
Enfermedad pulmonar obstructiva crónica: aspectos sistémicos y factores pronósticos.
Arch Bronconeumol, 43 (2007), pp. 25-34
[41.]
J. Vestbo, E. Prescott, T. Almdal, M. Dahl, B.G. Nordestgaard, T. Andersen, 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, 173 (2006), pp. 79-83
[42.]
P.D. Wagner.
Possible mechanisms underlying the development of cachexia in COPD.
Eur Respir J, 31 (2008), pp. 492-501
[43.]
C. Casanova, J.P. De Torres, M.A. Martín.
EPOC y malnutrición.
Arch Bronconeumol, 45 (2009), pp. 31-35
[44.]
E. Barreiro, A.M. Schols, M.I. Polkey, J.B. Galdiz, H.R. Gosker, E.B. Swallow, et al.
Cytokine profile in quadriceps muscles of patients with severe COPD.
Thorax, 63 (2008), pp. 100-107
[45.]
C.E. Bolton, A.A. Ionescu, K.M. Shiels, R.J. Pettit, P.H. Edwards, M.D. Stone, et al.
Associated loss of fat-free mass and bone mineral density in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 170 (2004), pp. 1286-1293
[46.]
C.E. Bolton, M.D. Stone, P.H. Edwards, J.M. Duckers, W.D. Evans, D.J. Shale.
Circulating matrix metalloproteinase-9 and osteoporosis in patients with chronic obstructive pulmonary disease.
Chron Respir Dis, 6 (2009), pp. 81-87
[47.]
R. Jimenez, J. De Miguel, J. Rejas, A. Martín, E. Gobartt, V. Hernandez, et al.
Health, treatment and health care resources consumption profile among spanish adults with diabetes and chronic obstructive pulmonary disease.
Prim Care Diabetes, 3 (2009), pp. 141-148
[48.]
S.F. Van Eeden, D.D. Sin.
Chronic obstructive pulmonary disease: a chronic systemic inflammatory disease.
Respiration, 75 (2008), pp. 224-238
[49.]
F. Di Marco, M. Verga, M. Reggente, F. María Casanova, P. Santus, F. Blasi, et al.
Anxiety and depression in COPD patients: The roles of gender and disease severity.
Respir Med, 100 (2006), pp. 1767-1774
[50.]
T.M. Eagan, T. Ueland, P.D. Wagner, J.A. Hardie, T.E. Mollnes, J.K. Damås, et al.
Systemic inflammatory markers in chronic obstructive pulmonary disease -results from the Bergen COPD Cohort Study, 35 (2010), pp. 540-548
[51.]
M. John, S. Hoernig, W. Doehner, D.D. Okonko, C. Witt, S.D. Anker.
Anemia and inflammation in COPD.
Chest, 127 (2005), pp. 825-829
[52.]
D.D. Sin, S.F. Man.
Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease.
Circulation, 107 (2003), pp. 1514-1519
[53.]
M.A. Gibbons, T. Sethi.
Chronic obstructive pulmonary disease and lung cancer: inflammation the missing link.
Therapy, 6 (2009), pp. 805-820
[54.]
J.P. De Torres, G. Bastarrika, J.P. Wisnivesky, A.B. Alcaide, A. Campo, L.M. Seijo, et al.
Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest.
Chest, 132 (2007), pp. 1932-1938
[55.]
S.F. Man, J.E. Connett, N.R. Anthonisen, R.A. Wise, D.P. Tashkin, D.D. Sin.
C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease.
Thorax, 61 (2006), pp. 849-853
[56.]
M. Dahl, J. Vestbo, P. Lange, S.E. Bojesen, A. Tybjaerg-Hansen, B.G. Nordestgaard.
C-reactive protein as a predictor of prognosis in COPD.
Am J Respir Crit Care Med, 175 (2007), pp. 250-255
[57.]
J.P. De Torres, V. Pinto-Plata, C. Casanova, H. Mullerova, E. Córdoba-Lanús, M. Muros de Fuentes, et al.
C-reactive protein levels and survival in patients with moderate to very severe COPD.
Chest, 133 (2008), pp. 1336-1343
[58.]
D.A. Lomas, E.K. Silverman, L.D. Edwards, N.W. Locantore, B.E. Miller, D.H. Horstman, R. Tal-Singer.
Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD.
Eur Respir J, 34 (2009), pp. 95-102
[59.]
M.W. Sims, R.M. Tal-Singer, S. Kierstein, A.I. Musani, M.F. Beers, R.A. Panettieri, A. Haczku.
Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study.
Respir Res, 9 (2008), pp. 13
[60.]
B. Gooptu, D.A. Lomas.
Polymers and inflammation: disease mechanisms of the serpinopathies.
J Exp Med, 205 (2008), pp. 1529-1534
[61.]
W. Ning, C.J. Li, N. Kaminski, C.A. Feghali-Bostwick, S.M. Alber, Y.P. Di, et al.
Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease.
Proc Natl Acad Sci USA, 101 (2004), pp. 14895-14900
[62.]
A.G. Wilson, J.A. Symons, T.L. McDowell, H.O. McDevitt, G.W. Duff.
Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.
Proc Natl Acad Sci USA, 94 (1997), pp. 3195-3199
[63.]
M.R. Gingo, L.J. Silveira, Y.E. Miller, A.L. Friedlander, G.P. Cosgrove, E.D. Chan, et al.
Tumour necrosis factor gene polymorphisms are associated with COPD.
Eur Respir J, 31 (2008), pp. 1005-1012
[64.]
J. Smolonska, C. Wijmenga, D.S. Postma, H.M. Boezen.
Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years’ research.
Am J Respir Crit Care Med, 180 (2009), pp. 618-631
[65.]
G. Tanaka, A.J. Sandford, K. Burkett, J.E. Connett, N.R. Anthonisen, P.D. Paré, et al.
Tumour necrosis factor and lymphotoxin a polymorphisms and lung function in smokers.
Eur Respir J, 29 (2007), pp. 34-41
[66.]
D. Fishman, G. Faulds, R. Jeffery, V. Mohamed-Ali, J.S. Yudkin, S. Humphries, P. Woo.
The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.
J Clin Invest, 102 (1998), pp. 1369-1376
[67.]
C. Seifart, A. Dempfle, A. Plagens, U. Seifart, U. Clostermann, B. Müller.
TNF-a-, TNF-b-, IL- 6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease.
Tissue Antigens, 65 (2005), pp. 93-100
[68.]
R. Broekhuizen, E.F. Wouters, E.C. Creutzberg, A.M. Schols.
Elevated CRP levels mark metabolic and functional impairment in advanced COPD.
Thorax, 61 (2006), pp. 17-22
[69.]
J.Q. He, M.G. Foreman, K. Shumansky, X. Zhang, L. Akhabir, D.D. Sin, et al.
Associations of IL6 polymorphisms with lung function decline and COPD.
Thorax, 64 (2009), pp. 698-704
[70.]
E. Cordoba-Lanus, J.P. De Torres, Lopez-Aguilar, C. Rodriguez-Perez M-, N. Maca-Meyer, A. Montejo-de-Garcini, et al.
Association of IL-6 gene polymorphism and COPD in a Spanish population.
Resp Med, 102 (2008), pp. 1805-1811
[71.]
D.G. Yanbaeva, M.A. Dentener, M.A. Spruit, J.J. Houwing-Duistermaat, D. Kotz, V.L. Passos, et al.
IL6 and CRP haplotypes are associated with COPD risk and systemic inflammation: a case-control study.
BMC Med Genet, 10 (2009), pp. 23
[72.]
Y.M. Van Durme, K.M. Verhamme, A.J. Aarnoudse, G.R. Van Pottelberge, A. Hofman, J.C. Witteman, et al.
C-reactive protein levels, haplotypes, and the risk of incident chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 179 (2009), pp. 375-382
[73.]
J. Hull, A. Thomson, D. Kwiatkowski.
Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
Thorax, 55 (2000), pp. 1023-1027
[74.]
U. Arinir, W. Klein, G. Rodhe, S. Stemmler, J. Epplen, G. Schulte-Werninghaus.
Polymorphisms in the interleukin-8 gene in patientes with chronic obstructive pulmonary disease.
Electrophoresis, 26 (2005), pp. 2888-2891
[75.]
M. Matheson, J. Ellis, J. Raven, E. Walters, M. Abramson.
Association of IL-8, CXCR2 and TNF-a polimorphisms and airway disease.
J Hum Genet, 51 (2006), pp. 196-203
[76.]
P.J. Barnes, I.M. Adcock, K. Ito.
Histone acetylation and deacetylation: importance in inflammatory lung diseases.
Eur Respir J, 25 (2005), pp. 552-563
[77.]
K. Ito, M. Ito, W.M. Elliott, B. Cosio, G. Caramori, O.M. Kon, et al.
Decreased histone deacetylase activity in chronic obstructive pulmonary disease.
N Engl J Med, 352 (2005), pp. 1967-1976
Copyright © 2010. Sociedad Española de Neumología y Cirugía Torácica
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?