Ming Zhong, Pengfei Liu, Yiran Chen, Danqing Wang, Xipeng Qiu, Xuanjing Huang. Proceedings of the 58th Annual Meeting of the Association for Computational Linguistics. 2020.

Unchecked inflammation is a hallmark of inflammatory tissue injury in diseases such as acute respiratory distress syndrome (ARDS). Yet the mechanisms of inflammatory lung injury remain largely unknown. Here we showed that bacterial endotoxin lipopolysaccharide (LPS) and cecal ligation and puncture–induced (CLP-induced) polymicrobial sepsis decreased the expression of transcription factor cAMP response element binding (CREB) in lung endothelial cells. We demonstrated that endothelial CREB was crucial for VE-cadherin transcription and the formation of the normal restrictive endothelial adherens junctions. The inflammatory cytokine IL-1β reduced cAMP generation and CREB-mediated transcription of VE-cadherin. Furthermore, endothelial cell–specific deletion of CREB induced lung vascular injury whereas ectopic expression of CREB in the endothelium prevented the injury. We also observed that rolipram, which inhibits type 4 cyclic nucleotide phosphodiesterase–mediated (PDE4-mediated) hydrolysis of cAMP, prevented endotoxemia-induced lung vascular injury since it preserved CREB-mediated VE-cadherin expression. These data demonstrate the fundamental role of the endothelial cAMP-CREB axis in promoting lung vascular integrity and suppressing inflammatory injury. Therefore, strategies aimed at enhancing endothelial CREB-mediated VE-cadherin transcription are potentially useful in preventing sepsis-induced lung vascular injury in ARDS.

Background: The physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation–perfusion matching by contrast-enhanced EIT in patients with ARDS. Design: Monocenter prospective physiologic study. Setting: University medical ICU. Patients: Ten mechanically ventilated ARDS patients who underwent PP. Interventions: We performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session. Measurements and main results: The regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation–perfusion matched region was found to increase and correlate with the increased PaO₂/FiO₂ by PP, which was attributed mainly to reduced shunt in the lung. Conclusions: Prolonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation–perfusion matching and oxygenation. Trial registration: ClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.