Comparison of the Oxygenation Factor and the Oxygenation Ratio in Subjects With ARDS.

BACKGROUND: The oxygenation ratio (ie, [Formula: see text]/[Formula: see text]) remains the most commonly used index for assessing oxygenation and disease severity in patients with acute ARDS. However, the oxygenation ratio does not account for mechanical ventilation settings. We hypothesized that the oxygenation factor (ie, oxygenation ratio/mean airway pressure) is superior to the oxygenation ratio in reflecting oxygenation in patients with ARDS and results in a different classification of ARDS severity. METHODS: In 150 subjects with ARDS (50 severe, 50 moderate, and 50 mild), arterial blood gas, mean airway pressure, static lung compliance, driving pressure, and mechanical power were obtained. The oxygenation ratio and the oxygenation factor were then calculated. Receiver operating characteristic curves were constructed for oxygenation ratio and oxygenation factor at lung compliance > 40 mL/cm H2O, driving pressure < 15 cm H2O, and mechanical power < 17 J/min, thresholds that are known to predict survival in patients with ARDS. Subjects were reclassified for ARDS severity on the basis of the oxygenation factor and compared to classification on the basis of the oxygenation ratio. RESULTS: Areas under the receiver operating characteristic curves for the oxygenation factor were significantly higher than for the oxygenation ratio. Reclassification of ARDS severity using the oxygenation factor did not affect subjects classified as having severe ARDS per the oxygenation ratio. However, 52% of subjects with moderate ARDS per the oxygenation ratio criteria were reclassified as either severe (25 subjects) or mild ARDS (1 subject) on the basis of oxygenation factor criteria. Also, 54% of subjects with mild ARDS per the oxygenation ratio criteria were reclassified as severe (4 subjects), moderate (21 subjects), or non-ARDS (2 subjects) on the basis of oxygenation factor criteria. CONCLUSIONS: The oxygenation factor was a superior ARDS oxygenation index compared to the oxygenation ratio and should be considered as a substitute criteria for classification of the severity of ARDS. (ClinicalTrials.gov registration NCT03946189.).

Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release.

Macrophage responses to Francisella infection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. Therefore, we studied the ability of fresh human blood monocytes to engulf and respond to Francisella by using the live vaccine strain variant and Francisella novicida. Because Francisella organisms have been reported to escape from the phagolysosome into the cytosol, we hypothesized that this escape may trigger the activation of caspase-1. Francisella tularensis variants were readily taken up by fresh human CD14(+) monocytes, inducing the release of IL-1beta, as well as IL-8, in a time- and dose-dependent fashion. Importantly, whereas live and dead Escherichia coli, F. novicida, and live vaccine strain, as well as the LPS of E. coli, were able to induce abundant IL-1beta mRNA synthesis and intracellular pro-IL-1beta production, only live Francisella induced enhanced IL-1beta processing and release (51 +/- 10 vs. 7.1 +/- 2.1 ng/ml, for F. novicida vs. E. coli LPS; P = 0.0032). Cytochalasin D blocked the Francisella internalization and the Francisella-induced monocyte IL-1beta processing and release but not that induced by the exogenous stimulus E. coli LPS. Also, killing bacteria did not block uptake but significantly diminished the IL-1beta processing and release that was induced by Francisella. Blocking bacterial escape from the phagosome into the cytosol also decreased IL-1beta but not IL-8 release. These findings demonstrate that Francisella organisms efficiently induce IL-1beta processing and release in fresh monocytes by means of a sensing system that requires the uptake of live bacteria capable of phagosome escape.