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Eur Respir J 2003; 22:672-688
Copyright ©ERS Journals Ltd 2003

Chronic obstructive pulmonary disease: molecular and cellularmechanisms

P.J. Barnes1, S.D. Shapiro2 and R.A. Pauwels3

1 National Heart and Lung Institute, ImperialCollege, London, UK, 2 Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 3 Dept of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium

CORRESPONDENCE: P.J. Barnes, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, London, SW3 6LY, UK. Fax: 44 2073515675. E-mail: p.j.barnes@imperial.ac.uk

Keywords: chemokine, cytokine, emphysema, macrophage, oxidative stress, protease

Received: April 10, 2003
Accepted June 12, 2003

The meeting "COPD: the important questions" held in Malta in November 2002 was sponsored by AstraZeneca.

Abstract

Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective.

There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases.

The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.




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Altered expression of the Smad signalling pathway: implications for COPD pathogenesis
Eur. Respir. J., September 1, 2006; 28(3): 533 - 541.
[Abstract] [Full Text] [PDF]

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M. I. Zervou, E. G. Tzortzaki, D. Makris, M. Gaga, E. Zervas, E. Economidou, M. Tsoumakidou, N. Tzanakis, J. Milic-Emili, and N. M. Siafakas
Differences in microsatellite DNA level between asthma and chronic obstructive pulmonary disease
Eur. Respir. J., September 1, 2006; 28(3): 472 - 478.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. J. Barnes
Against the dutch hypothesis: asthma and chronic obstructive pulmonary disease are distinct diseases.
Am. J. Respir. Crit. Care Med., August 1, 2006; 174(3): 240 - 243.
[Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
T. K. Baginski, K. Dabbagh, C. Satjawatcharaphong, and D. C. Swinney
Cigarette Smoke Synergistically Enhances Respiratory Mucin Induction by Proinflammatory Stimuli
Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 165 - 174.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
A. Shifren and R. P. Mecham
The stumbling block in lung repair of emphysema: elastic fiber assembly.
Proceedings of the ATS, July 1, 2006; 3(5): 428 - 433.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. I. D'hulst, K. R. Bracke, T. Maes, J. L. De Bleecker, R. A. Pauwels, G. F. Joos, and G. G. Brusselle
Role of tumour necrosis factor-{alpha} receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema
Eur. Respir. J., July 1, 2006; 28(1): 102 - 112.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. Zandvoort, Y. M. van der Geld, M. R. Jonker, J. A. Noordhoek, J. T. W. M. Vos, J. Wesseling, H. F. Kauffman, W. Timens, and D. S. Postma
High ICAM-1 gene expression in pulmonary fibroblasts of COPD patients: a reflection of an enhanced immunological function
Eur. Respir. J., July 1, 2006; 28(1): 113 - 122.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. J. Barnes, B. Chowdhury, S. A. Kharitonov, H. Magnussen, C. P. Page, D. Postma, and M. Saetta
Pulmonary Biomarkers in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 6 - 14.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S.-R. Yang, A. S. Chida, M. R. Bauter, N. Shafiq, K. Seweryniak, S. B. Maggirwar, I. Kilty, and I. Rahman
Cigarette smoke induces proinflammatory cytokine release by activation of NF-{kappa}B and posttranslational modifications of histone deacetylase in macrophages
Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L46 - L57.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
O. Leclerc, V. Lagente, J-M. Planquois, C. Berthelier, M. Artola, T. Eichholtz, C. P. Bertrand, and F. Schmidlin
Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice
Eur. Respir. J., June 1, 2006; 27(6): 1102 - 1109.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
M A Dentener, R Louis, R H E Cloots, M Henket, and E F M Wouters
Differences in local versus systemic TNF{alpha} production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNF{alpha} release
Thorax, June 1, 2006; 61(6): 478 - 484.
[Abstract] [Full Text] [PDF]

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J. P. de Torres, E. Cordoba-Lanus, C. Lopez-Aguilar, M. Muros de Fuentes, A. Montejo de Garcini, A. Aguirre-Jaime, B. R. Celli, and C. Casanova
C-reactive protein levels and clinically important predictive outcomes in stable COPD patients
Eur. Respir. J., May 1, 2006; 27(5): 902 - 907.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. O. Aksoy, Y. Yang, R. Ji, P. J. Reddy, S. Shahabuddin, J. Litvin, T. J. Rogers, and S. G. Kelsen
CXCR3 surface expression in human airway epithelial cells: cell cycle dependence and effect on cell proliferation
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L909 - L918.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. A. Marwick, C. S. Stevenson, J. Giddings, W. MacNee, K. Butler, I. Rahman, and P. A. Kirkham
Cigarette smoke disrupts VEGF165-VEGFR-2 receptor signaling complex in rat lungs and patients with COPD: morphological impact of VEGFR-2 inhibition
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L897 - L908.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. Vlahos, S. Bozinovski, J. E. Jones, J. Powell, J. Gras, A. Lilja, M. J. Hansen, R. C. Gualano, L. Irving, and G. P. Anderson
Differential protease, innate immunity, and NF-{kappa}B induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L931 - L945.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
H. Slevogt, B. Schmeck, C. Jonatat, J. Zahlten, W. Beermann, V. van Laak, B. Opitz, S. Dietel, P. D. N'Guessan, S. Hippenstiel, et al.
Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-{kappa}B activation and histone deacetylase activity reduction
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L818 - L826.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
M. Chignard and D. Pidard
Neutrophil and Pathogen Proteinases versus Proteinase-Activated Receptor-2 Lung Epithelial Cells: More Terminators than Activators.
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 394 - 398.
[Abstract] [Full Text] [PDF]

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D. M. Mannino, G. Watt, D. Hole, C. Gillis, C. Hart, A. McConnachie, G. Davey Smith, M. Upton, V. Hawthorne, D. D. Sin, et al.
The natural history of chronic obstructive pulmonary disease.
Eur. Respir. J., March 1, 2006; 27(3): 627 - 643.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
D. D. Sin, S. F. P. Man, A. McWilliams, and S. Lam
Progression of Airway Dysplasia and C-Reactive Protein in Smokers at High Risk of Lung Cancer
Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 535 - 539.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
I K Demedts, A Morel-Montero, S Lebecque, Y Pacheco, D Cataldo, G F Joos, R A Pauwels, and G G Brusselle
Elevated MMP-12 protein levels in induced sputum from patients with COPD
Thorax, March 1, 2006; 61(3): 196 - 201.
[Abstract] [Full Text] [PDF]

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 ChestHome page
P. J. Barnes
Reduced Histone Deacetylase in COPD: Clinical Implications
Chest, January 1, 2006; 129(1): 151 - 155.
[Abstract] [Full Text] [PDF]

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 Exp Biol MedHome page
J. O. Cantor, B. Shteyngart, J. M. Cerreta, S. Ma, and G. M. Turino
Synergistic Effect of Hydrogen Peroxide and Elastase on Elastic Fiber Injury In Vitro
Exp Biol Med, January 1, 2006; 231(1): 107 - 111.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
V M Pinto-Plata, H Mullerova, J F Toso, M Feudjo-Tepie, J B Soriano, R S Vessey, and B R Celli
C-reactive protein in patients with COPD, control smokers and non-smokers
Thorax, January 1, 2006; 61(1): 23 - 28.
[Abstract] [Full Text] [PDF]

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 ChestHome page
S. S. Braman
Chronic Cough Due to Chronic Bronchitis: ACCP Evidence-Based Clinical Practice Guidelines
Chest, January 1, 2006; 129(1_suppl): 104S - 115S.
[Abstract] [Full Text] [PDF]

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 ChestHome page
W. Matsuyama, H. Mitsuyama, M. Watanabe, K.-i. Oonakahara, I. Higashimoto, M. Osame, and K. Arimura
Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Markers in COPD
Chest, December 1, 2005; 128(6): 3817 - 3827.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. G. Woodruff, L. L. Koth, Y. H. Yang, M. W. Rodriguez, S. Favoreto, G. M. Dolganov, A. C. Paquet, and D. J. Erle
A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking
Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1383 - 1392.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
D D Sin, L Wu, J A Anderson, N R Anthonisen, A S Buist, P S Burge, P M Calverley, J E Connett, B Lindmark, R A Pauwels, et al.
Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease
Thorax, December 1, 2005; 60(12): 992 - 997.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
I. M. Adcock and K. Ito
Glucocorticoid Pathways in Chronic Obstructive Pulmonary Disease Therapy
Proceedings of the ATS, November 1, 2005; 2(4): 313 - 319.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
S. I. Rennard and J. A. Stoner
Challenges and Opportunities for Combination Therapy in Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2005; 2(4): 391 - 393.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. Couillard and C. Prefaut
From muscle disuse to myopathy in COPD: potential contribution of oxidative stress
Eur. Respir. J., October 1, 2005; 26(4): 703 - 719.
[Abstract] [Full Text] [PDF]

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 ChestHome page
T. L. Petty
Are COPD and Lung Cancer Two Manifestations of the Same Disease?
Chest, October 1, 2005; 128(4): 1895 - 1897.
[Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
R. D. Wang, J. L. Wright, and A. Churg
Transforming Growth Factor-{beta}1 Drives Airway Remodeling in Cigarette Smoke-Exposed Tracheal Explants
Am. J. Respir. Cell Mol. Biol., October 1, 2005; 33(4): 387 - 393.
[Abstract] [Full Text] [PDF]

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 ERRHome page
P. J. Barnes
New approaches to COPD
Eur. Respir. Rev., September 1, 2005; 14(94): 2 - 11.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. I. D'hulst, K. Y. Vermaelen, G. G. Brusselle, G. F. Joos, and R. A. Pauwels
Time course of cigarette smoke-induced pulmonary inflammation in mice
Eur. Respir. J., August 1, 2005; 26(2): 204 - 213.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
V L Kinnula
Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases
Thorax, August 1, 2005; 60(8): 693 - 700.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
S Wasswa-Kintu, W Q Gan, S F P Man, P D Pare, and D D Sin
Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis
Thorax, July 1, 2005; 60(7): 570 - 575.
[Abstract] [Full Text] [PDF]

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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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 Am. J. Respir. Crit. Care Med.Home page
T. S. Lapperre and P. J. Sterk
Dissociation of Lung Function and Airway Inflammation in Chronic Obstructive Pulmonary Disease: Is It a Real or Statistical Phenomenon?
Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1317 - 1318.
[Full Text] [PDF]


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