Daily Ards Research Analysis

OBJECTIVES: Ventilatory ratio (VR) could be a useful marker of COVID-19 acute respiratory distress syndrome (ARDS) worsening, since its value has been shown to correlate with dead space and severity of non-COVID-19 ARDS. In this study, we sought to: 1) compare VR to the estimated intrapulmonary shunt and the Pao2/Fio2 ratio for the association with the risk of intubation and 2) define the best VR threshold to discriminate between intubated patients and nonintubated patients. DESIGN: Multicenter, prospective experimental study. SETTING: ICUs from University and General Hospitals. PATIENTS: Patients with moderate-to-severe COVID-19 ARDS. INTERVENTIONS: We conducted standardized continuous positive airway pressure sessions with an Fio2 of 100% and positive end-expiratory pressure of 5 cm H2O to calculate the Pao2/Fio2 ratio, the estimated intrapulmonary shunt (indexed on cardiac output), and VR. These sessions were repeated until intubation or ICU discharge. A time-dependent joint multivariable model was performed. MEASUREMENTS AND MAIN RESULTS: Fifty-two patients were included, 25 of whom required intubation (48%). Among studied variables including the Pao2/Fio2 ratio and the estimated intrapulmonary shunt, VR was most associated with the longitudinal risk of intubation with a hazard ratio (HR, 3.30; 97.5% CI, 1.42-8.91; p = 0.001) compare to the Pao2/Fio2 ratio with HR (0.98; 97.5% CI, 0.97-0.99; p = 0.002) and the estimated intrapulmonary shunt with HR (2.31; 97.5% CI, 0.37-24.01; p = 0.394). The best VR threshold values were identified at day 1 (VR = 2.1, sensitivity, 85.7%; specificity, 60.1%; area under the receiver operating characteristic curve [AUC] = 0.810), day 3 (VR = 2.3; sensitivity, 92.0%; specificity, 91.2%; AUC = 0.973), and day 5 (VR = 2; sensitivity, 92%; specificity, 97%; AUC = 0.979) to discriminate intubated and nonintubated patients. CONCLUSIONS: The study provides valuable insights into COVID-19 ARDS, highlighting VR as a reliable and objective predictor of intubation. Increased VR could be a critical marker of lung injury progression in patients with ARDS.

RATIONALE: Tidal recruitment/derecruitment (R/D) is a well-known mechanism of lung injury in ARDS patients, but its bedside identification is challenging during assisted ventilation. OBJECTIVES: To investigate bedside determinants of tidal R/D assessed by electrical impedance tomography (EIT) in spontaneously breathing ARDS patients on pressure support ventilation (PSV). METHODS: Secondary analysis of a previous study including lightly sedated ARDS patients ventilated on PSV at two PEEP levels selected by EIT (PEEPEIT) and low PEEP/FiO2 table (PEEPTABLE). Detailed physiological assessment was performed, including respiratory mechanics, inspiratory drive and effort, regional mechanics and tidal R/D measured by EIT. MEASUREMENTS AND MAIN RESULTS: Of 30 original patients, one was excluded due to unstable end-expiratory lung impedance, leaving 29 patients for analysis. Median PEEP was 10.0 [8.0-12.0] cmH2O with PEEPEIT and 8.0 [5.0-10.0] cmH2O with PEEPTABLE. Overall, tidal R/D was 14.3% [9.0-33.0], but it was lower at PEEPEIT vs. PEEPTABLE (11.3% [4.8-20.5] vs. 21.9% [6.8-31.7]; P = .008). R/D reduction with PEEPEIT correlated with decreases in collapse (rho = 0.72; P < .001) and pendelluft (rho = 0.57; P = .002).Analyzing data from both randomized PEEP together, mixed-effects models showed higher tidal R/D at lower PEEP (P < .001), more negative end-expiratory transpulmonary pressure (PLEnd-Exp) (P < .001), larger collapse (P < .001) and lower lung compliance (P = .002). Higher respiratory drive (P = .001), effort (P = .009), and dynamic driving transpulmonary pressure (P = .009) correlated with higher tidal R/D. Patients with non-focal infiltrates presented higher tidal R/D (P = .005).At multivariable analysis, PLEnd-Exp, lung collapse and non-focal pattern were independently associated tidal R/D. CONCLUSION: In spontaneously breathing ARDS patients on PSV, the main determinants of tidal R/D are more negative PLEnd-Exp, higher lung collapse and non-focal infiltrates.

Pseudomonas aeruginosa, an opportunistic pathogen, is a primary cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in immunocompromised individuals. Isoliquiritigenin (ISL), a natural flavonoid primarily found in liquorice (Glycyrrhiza glabra), has demonstrated protective effects against infection-induced ALI. However, the therapeutic potential and molecular mechanisms of ISL against P. aeruginosa-induced ALI remain unclear. In this study, we established a mouse model of acute bacterial pneumonia and an in vitro lung epithelial cell infection model to assess the therapeutic efficacy and underlying mechanisms of ISL. Results showed that ISL improved the survival and alleviated the P. aeruginosa-induced ALI in mice by reducing neutrophil recruitment, pulmonary cell death and bacterial load. Transcriptomic and enrichment analyses revealed that ISL reversed infection-induced inflammation and oxidative stress, while also providing supporting evidence for ferroptosis-related alterations. Moreover, ISL treatment significantly preserved the structural and functional integrity of the pulmonary epithelial barrier by attenuating pulmonary edema, reducing pulmonary epithelial permeability, and restoring tight junction protein expression. Network pharmacology identified AKT1, EGFR, PPARG and COX-2 as candidate targets of ISL. SPR, molecular docking and molecular dynamics simulation further verified the interaction between ISL and PPARγ. Subsequent mechanistic investigations demonstrated that ISL activated the PPARγ/Nrf2/GPX4 signaling axis and inhibited lung epithelial cell ferroptosis both in vivo and in vitro. Altogether, ISL protects against P. aeruginosa-induced ALI by activating PPARγ/Nrf2/GPX4 axis and suppressing lung epithelial cell ferroptosis, thereby preserving lung epithelial barrier integrity and reducing inflammatory responses.