Updates in Chronic Obstructive Pulmonary Disease for the Year 2014

Chronic Obstructive Pulmonary Disease as an Inflammatory DiseaseChronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of the airways and lung parenchyma that is characterized by increased numbers of neutrophils, activated macrophages, and activated T-lymphocytes (Tc1 and Th1 cells) [1].The inflammation is amplified in COPD compared with smokers without COPD, and the molecular basis for this amplification is now better understood, providing novel targets for future therapies.Macrophages are markedly increased in COPD, and these cells play a key role in recruiting other inflammatory cells and in releasing mediators and proteases.Macrophages in the lungs are recruited from circulating monocytes by chemotactic factors such as CXCLI (GRO-a) and CCL2 (MCP1).The inflammatory changes in COPD are due to the release of multiple inflammatory mediators, including lipid mediators, cytokines, and chemokines [2].Many of these mediators are regulated by the proinflammatory transcription factor nuclear factor-κB (NF-κB), which is activated in epithelial cells and macrophages of COPD patients [2].Activated macrophages and neutrophils release elastolytic enzymes, particularly matrix metalloproteinase (MMP)-9, that contribute to the development of emphysema.In addition, cytotoxic Tc1 cells may induce the destruction of alveolar cells.Small airway narrowing and fibrosis appear to be the major mechanisms contributing to airflow limitation and air trapping, but the mechanisms of fibrosis are poorly understood.Th17 cells may play a role in orchestrating neutrophilic inflammation in COPD [3]. Corticosteroid ResistanceIn sharp contrast to asthma, the inflammation in COPD shows little response to corticosteroids.This steroid resistance may be explained by the reduced activity of a key nuclear enzyme, histone deacetylase 2 (HDAC2), which also accounts for the amplified inflammation in COPD [4].The reduction in HDAC2 is driven by increased oxidative stress through the activation of the enzyme phosphoinositide-3-kinase-δ (PI3Kδ), which is inhibited by low concentrations of theophylline [5].Clinical trials with low dose theophylline as a means of reversing corticosteroid-resistance in COPD are currently underway. Reduced Bacterial PhagocytosisAlveolar macrophages normally phagocytose inhaled microorganisms and keep the respiratory tract sterile, but in COPD, there is a defect in bacterial phagocytosis by macrophages that may result in chronic bacterial colonization [6].