ABSTRACT
Chronic inflammation and oxidative stress are important features in the pathogenesis of smoking-induced inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD). The sources of the increased oxidative stress in patients with COPD derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive
oxygen species (ROS) generated by several inflammatory, immune, and various structural cells of the airways. The presence of oxidative stress has important consequences on several events of lung physiology and for the pathogenesis of COPD. These include increased sequestration of neutrophils in the pulmonary microvasculature, oxidative inactivation of antiproteases and surfactants, mucus hypersecretion, membrane lipid peroxidation, mitochondrial respiration, alveolar epithelial injury=permeability, breakdown=remodeling of extracellular matrix, and apoptosis. Increased levels of ROS produced in the airways are reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs, and blood in patients with COPD. Reactive oxygen species may play a role in enhancing the inflammation through the activation of MAP kinases and redox sensitive transcription factors such as nuclear factor-kB and activator protein-1-either directly or via the formation of lipid peroxidation products, such as acrolein, 4-hydroxy-2-nonenal, and F2-isoprostanes. Oxidative stress may alter the chromatin remodeling, leading to imbalance of gene expression of proinflammatory mediators and antioxidant enzymes in favor of inflammatory mediators in the lung. An effective wide spectrum antioxidant therapy that has good bioavailability and potency is urgently needed to control the localized oxidative and inflammatory processes that occur in the pathogenesis of COPD. In addition, development of such novel antioxidant compounds would be therapeutically useful in monitoring the oxidative and inflammatory biomarkers in the progression=severity of COPD.
