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Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction

Section of Airways Disease, National Heart and Lung Institute, Imperial College London, London, UK.

CORRESPONDENCE: K. F. Chung, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. Fax: 44 2073518126. E-mail: f.chung{at}imperial.ac.uk

Keywords: Autoimmunity, chronic obstructive pulmonary disease, macrophages, neutrophil, oxidative stress, senescence

Received: February 7, 2008
Accepted February 15, 2008

Chronic obstructive pulmonary disease is a leading global cause of morbidity and mortality that is characterised by inexorable deterioration of small airways obstruction with emphysema associated with cellular inflammation and structural remodelling. Other features include apoptosis as well as proliferation of cells, and both tissue repair and lack of tissue repair.

Metalloprotease release, together with that of apoptotic factors, may underlie the emphysema, and, conversely, fibrosis of the small airways may be accounted for by the effects of growth factor activation. In advanced disease, influential factors include the development of autoimmunity, with activation of dendritic cells and T-helper cells of both type 1 and 2, and the senescence response.

An inability of macrophages to ingest apoptosed cells and bacteria may exacerbate inflammatory responses. Systemic inflammation with concomitant cardiovascular disease and metabolic syndrome may reflect the effect of cigarette smoke on nonpulmonary cells. Corticosteroid resistance may be secondary to oxidative stress mechanisms, such as inactivation of histone deacetylases.

The mechanisms of chronic obstructive pulmonary disease may be heterogeneous, according to severity, and clinical phenotypes need to be correlated with cellular and pathological processes. Treatments may be targeted to patients with specific mechanisms.