Convincing evidence suggests that oxidative stress and reactive oxygen species (ROS) play an important role in the etiology and progression of a number of human diseases. The normal, noninflamed lung is well adapted to the relatively high ambient oxygen concentration, but the extremely high generation of ROS during inflammation overwhelms the protective mechanisms of the lung, and it becomes a particularly vulnerable target during inflammatory processes. Generation of oxidative species is a principal contributor to inflammatory injury, and failure to control inflammation may lead to continuing inflammation and organ dysfunction progressing to organ failure. comments
Cystic fibrosis (CF) is the most frequent hereditary disease in white subjects, leading to early death, mainly from respiratory insufficiency. Mutations of the CF transmembrane regulator lead to progressive pulmonary damage and fibrosis. The sequence of events leading from defects in CF transmembrane regulator function to marked inflammation and tissue destruction is not yet precisely known. Mechanisms include viscous mucous and chronic bacterial infection of the airways. The endobronchial inflammation in CF is characterized by large numbers of polymorphonuclear neutrophils (PMNs). In the airspaces, free radicals generated by these cells can be deleterious for structure and function of many pro-teins. In addition, redox-regulated signal transduction can contribute to the apoptosis of lung cells, which is partly determined by cross-talk between the cellular signaling pathways and the redox state. Thus, the prevention of excessive oxidative stress through antioxidant therapies may be useful in the prevention and treatment of CF lung disease.
Increased oxidative stress in CF patients has been estimated by measurement of serum parameters. Measurement of sputum samples from CF patients who spontaneously produced sputum due to a significant degree of lung damage demonstrated the formation of myeloperoxidase-derived oxidizing and possibly nitrating species within the respiratory tract. Expectorated sputum originates mainly from the large airways and contains large amounts of cellular debris releasing proteolytic enzymes and oxidative species, partially leading to secondary oxidative damage within sputum, prior to expectoration, and thus may not be representative for the assessment of protein oxidation in the lung.