Significance: NADPH oxidase (NOX) enzymes, which are widely expressed in different airway cell types, not only contribute to the maintenance of physiological processes in the airways but also participate in the pathogenesis of many acute and chronic diseases. Therefore, the understanding of NOX isoform regulation, expression, and the manner of their potent inhibition might lead to effective therapeutic approaches.
Recent advances: The study of the role of NADPH oxidases family in airway physiology and pathophysiology should be considered as a work in progress. While key questions still remain unresolved, there is significant progress in terms of our understanding of NOX importance in airway diseases as well as a more efficient way of using NOX modifiers in human settings.
Critical issues: Agents that modify the activity of NADPH enzyme components would be considered useful tools in the treatment of various airway diseases. Nevertheless, profound knowledge of airway pathology, as well as the mechanisms of NOX regulation is needed to develop potent but safe NOX modifiers.
Future directions: Many compounds seem to be promising candidates for development into useful therapeutic agents, but their clinical potential is yet to be demonstrated. Further analysis of basic mechanisms in human settings, high-throughput compound scanning, clinical trials with new and existing molecules, and the development of new drug delivery approaches are the main directions of future studies on NOX modifiers. In this article, we discuss the current knowledge with regard to NOX isoform expression and regulation in airway inflammatory diseases as well as the aptitudes and therapeutic potential of NOX modifiers.