Tuberc Respir Dis.  2010 Nov;69(5):323-330.

New Paradigms in the Pathogenesis of Chronic Obstructive Pulmonary Disease

• Kim HJ

Abstract

A key mechanism in the pathogenesis of chronic obstructive pulmonary disease is thought to be an abnormal inflammatory response in the lungs to the inhalation of toxic particles and gases, derived from tobacco smoke, air pollution, and/or occupational exposures. This review highlights the potential participation of several alternative pathogenetic processes, particularly involving the potential participation of biological and pathobiological processes related to aging, including oxidative stress and enhanced expression of markers of senescence/aging in emphysematous lungs, and the potential for enhanced tissue destruction involving alveolar cell apoptosis.

Keyword

Aging; Oxidative stress; Emphysema; Apoptosis

MeSH Terms

Aging
Air Pollution
Apoptosis
Emphysema
Gases
Inhalation
Lung
Occupational Exposure
Oxidative Stress
Pulmonary Disease, Chronic Obstructive
Smoke
Tobacco
Gases
Smoke

Figure

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  Figure 1 Stimulation of normal alveolar macrophages activates nuclear factor-κB (NF-κB) and other transcription. Corticosteroids reverses the histone acetylation induced by NF-κB and switches off the activated inflammatory genes. In patients with chronic obstructive pulmonary disease (COPD), antiinflammatory effect of corticosteroids as histone deacetylases 2 (HDAC2) is now unable to reverse histone acetylation.

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  Figure 2 Chronic obstructive pulmonary disease as a disease of accelerated lung aging.

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  Figure 3 Senescence hypothesis for the pathogenetic mechanism of chronic obstructive pulmonary disease (COPD).

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  Figure 4 Aging pathways in chronic obstructive pulmonary disease (COPD). Oxidative stress may reduce the activity and expression of SIRT-1 in lungs via activation of phosphoinositide-3-kinase (PI3K) pathways, resulting in acetylation of several key target proteins linked to aging and cancer, including the transcription factors forkhead box (FOX) O and nuclear factor-κB (NF-κB), the tumor suppressor p53, and matrix metalloproteinase (MMP)-9.

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