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

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzymes play important roles in generating reactive oxygen species (ROS); 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 and to predict mortality in intubated patients. Plasma levels of NOX4 were measured at days 1 (NOX4 D1) and 7 (NOX4 D7) after initiation of mechanical ventilation in 184 patients. RESULTS: With increase in day 7 NOX4 quartile, the success of weaning tended to decrease and 28-day mortality tended to increase. On multivariate logistic regression, Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) [odds ratio (OR): 1.10; 95% CI, 1.02–1.18], duration of mechanical ventilation (OR: 1.12; 95% CI: 1.06–1.18), and NOX4 D7 levels >18.2 ng/mL (OR: 4.40; 95% CI: 1.91–10.06) were independently associated with weaning failure. Also, Cox-hazard proportional model showed that NOX4 D7 level >18.2 ng/mL (hazard ratio [HR], 2.29; 95% CI, 1.26–4.16), APACHE II (HR: 1.07; 95% CI: 1.02–1.14), Sequential Organ Failure Assessment (SOFA) (HR: 1.10; 95% CI: 1.01–1.20) and coexisting cancer (HR: 1.99; 95% CI, 1.01–3.94), were independently associated with 28-day mortality. The longitudinal trend of NOX4 level varied according to the clinical outcomes. CONCLUSIONS: An increased plasma NOX4 D7 level was associated with weaning failure and 28-day mortality in patients with mechanical ventilation. Our results suggest that NOX4-directed management may lead to improved outcomes in patients with mechanical ventilation.