A decremental PEEP trial for determining open-lung PEEP in a rabbit model of acute lung injury

A positive end-expiratory pressure (PEEP) above the lower inflection point (LIP) of the pressure-volume curve has been thought necessary to maintain recruited lung volume in acute lung injury (ALI). We used a strategy to identify the level of open-lung PEEP (OLP) by detecting the maximum tidal compliance during a decremental PEEP trial (DPT). We performed a randomized controlled study to compare the effect of the OLP to PEEP above LIP and zero PEEP on pulmonary mechanics, gas exchange, hemodynamic change, and lung injury in 26 rabbits with ALI. After recruitment maneuver, the lavage-injured rabbits received DPTs to identify the OLP. Animals were randomized to receive volume controlled ventilation with either: (a) PEEP = 0 cm H2O (ZEEP); (b) PEEP = 2 cm H2O above OLP (OLP + 2); or (c) PEEP = 2 cm H2O above LIP (LIP + 2). Peak inspiratory pressure and mean airway pressure were recorded and arterial blood gases were analyzed every 30 min. Mean blood pressure and heart rate were monitored continuously. Lung injury severity was assessed by lung wet/dry weight ratio. Animals in OLP + 2 group had less lung injury as well as relatively better compliance, more stable pH, and less hypercapnia compared to the LIP + 2 and ZEEP groups. We concluded that setting PEEP according to the OLP identified by DPTs is an effective method to attenuate lung injury. This strategy could be used as an indicator for optimal PEEP. The approach is simple and noninvasive and may be of clinical interest.     

SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants as potential clinical biomarkers for personalized treatment strategy selection in patients with severe COVID-19 pneumonia

BackgroundExploring the pathogenetic mechanisms behind severe lung damage in COVID-19 is crucial. In this study, we decided to focus on two molecular markers that affect surfactant metabolism and lung development: the surfactant protein B (SFTPB) and the glucocorticoid receptor (NR3C1) genes. The aim of our study was to determine the effect of SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the course of the disease in patients with COVID-19, and the treatment measures they required.MethodsThe study group included 58 patients with a diagnosis of severe “viral COVID-19 pneumonia.” Determination of SFTPB and NR3C1 gene variants was performed using the PCR-RFLP method.ResultsOur results indicate that the presence of the SFTPB gene CC genotype increases the risk of developing acute respiratory distress syndrome in patients with COVID-19 (χ² = 4.03, p = 0.045, OR = 3.90 [1.19–12.78]). However, patients with the SFTPB gene TT genotype required respiratory support for a shorter period of time. Patients with the NR3C1 gene CC genotype underwent a longer glucocorticoid therapy. Moreover, for patients with the CC genotype, a longer stay in the intensive care unit was detected before lethal outcome.ConclusionsThe obtained results confirm the influence of the SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the therapy, course, and severity of the disease in patients with COVID-19. Of course, these results require further study, analysis, and larger, complex, systematic research.