Oxidative stress and free radicals in COPD--implications and relevance for treatment

Abstract

Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.

Keywords: antioxidants; chronic obstructive pulmonary disease; reactive nitrogen species; reactive oxygen species.

Figure 1

Generating reactive oxygen and nitrogen species and defending against them. Notes: Homeostasis of pro- and antioxidative processes is a prerequisite for normal growth and metabolism. Increased as well as suppressed formation of reactive species may be harmful. An elevated formation of reactive species may lead to random cellular damage causing aging and disease, but also to specific signaling pathways. Adapted by permission from Macmillan Publishers Ltd: NATURE. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of aging. Nature. 2000;408(6809):239–247, copyright 2000. Available from: http://www.nature.com/nature/index.html. Abbreviations: CAT, catalases; GPx, peroxidases; NADPH, ; RNS, reactive nitrogen species; SOD, superoxide dismutases.