Role of Nitrosative Stress: What Is the Potential Clinical Implication?

In the airways of COPD and asthma, NO is excessively produced by inducible NO synthesis (iNOS) during inflammation, which can react with concurrently produced superoxide, leading to the formation of peroxynitrite, a highly reactive nitrogen species (RNS). Peroxynitrite can cause tissue injury, lipid peroxidation and the nitration of tyrosine residues. Thus, RNS induces nitrosative stress in lung tissue and contributes to the pathophysiology such as airway remodeling, enhanced airway inflammation and corticosteroid resistance in severe asthma and COPD. Asthma-COPD overlap (ACO) has the physiological and clinical features of both asthma and COPD. It has been demonstrated that RNS is more enhanced in the airways of ACO than in asthma or COPD as confirmed by the formation of nitrotyrosine, a marker of nitrosative stress. Furthermore, the degree of nitrotyrosine in the airways is also known to be associated with the clinical course of patients with ACO. This chapter describes the basic mechanism of RNS formation and pathophysiological action of RNS in airway diseases. In addition, the clinical utility of nitrotyrosine as a biomarker for nirosative stress in ACO and the future potential of targeting nitrosative stress as a therapeutic strategy for ACO are discussed.