RESUMO
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.
RESUMO
Bacterial pneumonia is a major cause of mechanical ventilation in intensive care units. We hypothesized that the presence of particular microbiota in endotracheal tube aspirates during the course of intubation was associated with clinical outcomes such as extubation failure or 28-day mortality. Sixty mechanically ventilated ICU (intensive care unit) patients (41 patients with pneumonia and 19 patients without pneumonia) were included, and tracheal aspirates were obtained on days 1, 3, and 7. Gene sequencing of 16S rRNA was used to measure the composition of the respiratory microbiome. A total of 216 endotracheal aspirates were obtained from 60 patients. A total of 22 patients were successfully extubatedwithin3 weeks, and 12 patients died within 28days. Microbiota profiles differed significantly between the pneumonia group and the non-pneumonia group (Adonis, p < 0.01). While α diversity (Shannon index) significantly decreased between day 1 and day 7 in the successful extubation group, it did not decrease in the failed extubation group among intubated patients with pneumonia. There was a significant difference in the change of ßdiversity between the successful extubation group and the failed extubation group for Bray-Curtis distances (p < 0.001). At the genus level, Rothia, Streptococcus, and Prevotella correlated with the change of ß diversity. A low relative abundance of Streptococci at the time of intubation was strongly associated with 28-day mortality. The dynamics of respiratory microbiome were associated with clinical outcomes such as extubation failure and mortality. Further large prospective studies are needed to test the predictive value of endotracheal aspirates in intubated patients.
