Bronchial epithelial gene expression of NOX isoforms are related to important clinical characteristics in COPD

Chronic Obstructive Pulmonary Disease (COPD) is characterised by persistent airflow obstruction, airway inflammation and increased oxidative stress. The Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidases (NOX1-5 and DUOX1-2) are implicated in the generation of reactive oxygen species, but their role in COPD is uncertain. As part of the EvA study bronchial brushings were obtained from 279 COPD subjects and 215 healthy controls. Gene expression of the NOX isoforms was analysed; compared between COPD and health and multiple regression analyses of NOX expression and clinical, physiological, and quantitative (q)CT parameters were performed in COPD cases. Gene expression of NOX2, 4 and DUOX2 was increased significantly and NOX1 decreased in COPD compared to controls, whereas NOX5 and DUOX1 expression was not different between groups and NOX3 was not present. Multiple regression analyses identified independent associations between: NOX1 and DUOX2 with airflow obstruction (FEV1/FVC ratio) (β=0.006[0.003]; P=0.046 and β=-0.016[0.008]; P=0.035 respectively); NOX1 and NOX2 with airway inflammation (NOX1 with sputum neutrophil and eosinophil % β=0.004[0.002]; P=0.016 and β=-0.056[0.028]; P=0.047 and NOX2 with sputum eosinophils % β=0.004[0.002]; P=0.016); and NOX4 with body mass index (β=0.022[0.005]; P In conclusion, NOX1, 2 and 4, and DUOX2 are differentially expressed between COPD and health. Associations between these NOX isoforms and important clinical characteristics suggest a potential role for NOX in the pathogenesis of COPD.