Daily Ards Research Analysis

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury whose pathogenesis is characterized by excessive lung inflammation and alveolar-capillary barrier permeability. Matrix metalloproteinase 7 (MMP7) can regulate leukocyte recruitment and the production of pro-inflammatory cytokines, but whether it plays a role in acute lung injury (ALI) is an unanswered question. We hypothesized that global loss of MMP7 would attenuate sepsis-induced ALI and systemic inflammation. To test this, male and female MMP7 knockout (MMP7KO) mice and wild-type (WT) littermates were exposed to a two-hit model of ALI (sepsis+hyperoxia). Sepsis was induced through intraperitoneal injection of cecal slurry (CS; 1.6mg/g) or 5% dextrose (control) followed by exposure to hyperoxia (HO; FiO2=0.95) or room air (control, FiO2=0.21). At 24-hours post-CS+HO, we measured weight loss, illness severity, and body temperature. The mice were then sacrificed, and samples from the lungs, kidneys, spleen, blood, peritoneal wash, and bronchoalveolar lavage (BAL) fluid were collected for analysis. Bacterial burden was assessed in the peritoneum, lung, and spleen. Lung inflammation was assessed by BAL inflammatory cell recruitment and pro-inflammatory cytokine concentrations as well as lung tissue mRNA expression of pro-inflammatory cytokines. Alveolar-capillary barrier disruption was quantified by BAL total protein, BAL immunoglobulin M, and lung wet-to-dry weight ratios. Histologic evidence of lung injury was evaluated using a histological scoring system. Systemic inflammation was measured through plasma pro-inflammatory cytokines and peritoneal inflammatory cells. Kidney function, inflammation, and injury were assessed through plasma urea nitrogen concentrations, as well as tissue levels of pro-inflammatory cytokines, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1). Relative mRNA expression of MMP-7, MMP-9, and MMP-2 was also quantified in both lung and kidney tissue through qPCR. At 24-hours post-CS+HO all mice developed ALI. Septic mice also had increased systemic inflammation, kidney inflammation, kidney injury, and kidney dysfunction compared to controls. Loss of MMP7 did not affect markers of inflammation, organ injury, or organ dysfunction. Interestingly, septic male mice exhibited more severe illness, systemic and lung inflammation, lung injury, and lung expression of matrix metalloproteinases, while septic female mice exhibited more kidney inflammation, kidney injury, and kidney expression of matrix metalloproteinases. In conclusion, MMP7 is not essential for the development or resolution of sepsis-induced ALI in this model and likely plays a limited role in the condition.

Acute respiratory distress syndrome (ARDS) is a disease of the lung and/or extrapulmonary system characterized by acute, progressive breathing difficulty and refractory hypoxemia. After years of revision, the 2012 International Expert Conference developed a new diagnostic standard for ARDS, known as the Berlin definition, which provides good guidance on how to define and judge the disease in clinical practice. Despite the establishment of diagnostic standards and treatment improvements, ARDS mortality rate still remains high. The primary reason is that the pathophysiology has not been fully elucidated. In patients with ARDS, damage to the alveolar capillary membrane may occur, leading to increased vascular permeability and the occurrence of pulmonary edema. Therefore, exploring the pathogenesis of ARDS from the perspective of microvascular permeability and identification of effective targets may be key factors in the diagnosis and treatment of ARDS. This review presents the current literature regarding the role of miRNAs (micro ribonucleic acids) in early detection and prediction of ARDS outcome.

We report one of the first known cases of transbronchial lung cryobiopsy (TBLC) performed in a patient with severe acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO). After transient stopping of anticoagulation, TBLCs were performed in a controlled environment at the bedside in the intensive care unit (ICU). The ECMO avoided severe oxygenation deterioration, and bleeding was controlled by Fogarty balloon inflation. No major complications occurred, and the pulmonary biopsies helped obtain prognostic information and decide the most appropriate management. Nevertheless, the safety of this technique in such high-risk patients should be further investigated in larger case series, as it can be harmful if not performed in an appropriate environment.