Oxidants/antioxidants and COPD

Oxidative stress results from an oxidant/antioxidant imbalance, an excess o f oxidants and/or a depletion of antioxidants. Oxidative stress is thought to play an important role in the pathogenesis of a number of lung diseases, not only through direct injurious effects, but by involvement in the molec ular mechanisms that control lung inflammation. A number of studies have sh own an increased oxidant burden and consequently increased markers of oxida tive stress in the airspaces, breath, blood, and urine in smokers and in pa tients with COPD. The presence of oxidative stress has important consequenc es for the pathogenesis of COPD. These include oxidative inactivation of an tiproteinases, airspace epithelial injury, increased sequestration of neutr ophils in the pulmonary microvasculature, and gene expression of proinflamm atory mediators. With regard to the latter, oxidative stress has a role in enhancing the inflammation that occurs in smokers and patients with COPD, t hrough the activation of redox-sensitive transcriptions factors such as nuc lear factor-kappa B and activator protein-1, which regulate the genes for p roinflammatory mediators and protective antioxidant gene expression. The sources of the increased oxidative stress in patients with COPD are der ived from the increased burden of oxidants present in cigarette smoke, or f rom the increased amounts of reactive oxygen species released from leukocyt es, both in the airspaces and in the blood. Antioxidant depletion or defici ency in antioxidants may contribute to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants, and h ence dietary supplementation may be a beneficial therapeutic intervention i n this condition. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity may be therapies that not only protec t against the direct injurious effects of oxidants, but may fundamentally a lter the inflammatory events that play an important part in the pathogenesi s of COPD.