Plasma concentrations of NOX4 are predictive of successful liberation from mechanical ventilation and 28-day mortality in critically ill patients

Abstract

Background: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzymes play important roles in generating reactive oxygen species; in particular, NOX4 plays a distinct role in regulating lung inflammation and apoptosis. Methods: We determined whether plasma NOX4 level can be used as a prognostic biomarker to guide weaning from mechanical ventilation. Plasma levels of NOX4 were measured at days 1 (NOX4d1) and 7(NOX4d7) after initiation of mechanical ventilation in 184 patients. Results: Median NOX4d7 levels in patients with extubation failure were significantly higher than those in patients with extubation success (24.2 ng/mL vs.15.2 ng/mL, P<0.001). On multivariate logistic regression, SOFA≥8 (odds ratio[OR]:2.66; 95% confidence interval [CI], 1.26–5.59), mechanical ventilation time>11 days (OR: 3.36; 95% CI: 1.62–6.99), APACHE score >21 (OR, 2.16; 95% CI, 1.03–4.52) and NOX4d7>18.2 ng/mL (OR: 3.13, 95% CI: 1.49–6.57) were associated with extubation failure.NOX4d7 level >18.2 ng/mL (hazard ratio[HR], 2.17; 95% CI, 1.19–3.97), coexisting cancer (HR: 2.22; 95% CI, 1.12–4.38), SOFA≥8 (HR: 2.06; 95% CI, 1.12–3.81) and APACHE>21 (HR, 1.82; 95% CI, 1.05–3.18) were independently associated with 28-day mortality. Conclusions: Plasma NOX4 levels may help predict successful liberation from mechanical ventilation and 28-day mortality.