TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis.

Background: Chronic tissue injury was shown to induce progressive scarring in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), while an array of repair/regeneration and stress responses come to equilibrium to determine the outcome of injury at the organ level. In the lung, type I alveolar epithelial (ATI) cells constitute the epithelial barrier, while type II alveolar epithelial (ATII) cells play a pivotal role in regenerating the injured distal lungs. It had been demonstrated that eukaryotic cells possess repair machinery that can quickly patch the damaged plasma membrane after injury, and our previous studies discovered the membrane-mending role of Tripartite motif containing 72 (TRIM72) that expresses in a limited number of tissues including the lung.

Hypercapnia Alters Alveolar Epithelial Repair by a pH-Dependent and Adenylate Cyclase-Mediated Mechanism.

Lung cell injury and repair is a hallmark of the acute respiratory distress syndrome (ARDS). Lung protective mechanical ventilation strategies in these patients may lead to hypercapnia (HC). Although HC has been explored in the clinical context of ARDS, its effect upon alveolar epithelial cell (AEC) wounding and repair remains poorly understood.

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data.

Purpose: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.

Methods: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016.

Inhaled TRIM72 Protein Protects Ventilation Injury to the Lung through Injury-guided Cell Repair.

Studies showed that TRIM72 is essential for repair of alveolar cell membrane disruptions, and exogenous recombinant human TRIM72 protein (rhT72) demonstrated tissue-mending properties in animal models of tissue injury. Here we examine the mechanisms of rhT72-mediated lung cell protection in vitro and test the efficacy of inhaled rhT72 in reducing tissue pathology in a mouse model of ventilator-induced lung injury. In vitro lung cell injury was induced by glass beads and stretching.

Understanding Pulmonary Stress-Strain Relationships in Severe ARDS and Its Implications for Designing a Safer Approach to Setting the Ventilator.

This review describes the current understanding of the lungs' response to deforming stress under conditions of both normal physiology and acute lung injury. Several limiting assumptions are needed to infer lung parenchymal stress and strain from airway pressure, volume, and flow data from mechanically ventilated patients with injured lungs. These assumptions include the effects of the chest wall on lung-surface pressure, its topographical distribution, and the effects of non-uniform tissue properties on local parenchymal stresses.

Differentiating pulmonary transfusion reactions using recipient and transfusion factors.

Background: It is increasingly recognized that recipient risk factors play a prominent role in possible transfusion-related acute lung injury (pTRALI) and transfusion-associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI.

Study Design And Methods: We performed a post hoc analysis of a case-control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester.

Quantitative assessment of lung stiffness in patients with interstitial lung disease using MR elastography.

Purpose: To investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls.

Materials And Methods: A 1.5T spin-echo, echo planar imaging MRE (SE-EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls.

Plasma membrane wounding and repair in pulmonary diseases.

Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures, and gastric acid aspiration stress lung cells, and the compromise of plasma membranes occurs as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. Because it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes and discuss relevant genetic, physical, and biological injury mechanisms, as well as mechanisms used by lung cells for cell survival and membrane repair.

Transpulmonary Pressure: The Importance of Precise Definitions and Limiting Assumptions.

Recent studies applying the principles of respiratory mechanics to respiratory disease have used inconsistent and mutually exclusive definitions of the term "transpulmonary pressure." By the traditional definition, transpulmonary pressure is the pressure across the whole lung, including the intrapulmonary airways, (i.e.

TRIM72 modulates caveolar endocytosis in repair of lung cells.

Alveolar epithelial and endothelial cell injury is a major feature of the acute respiratory distress syndrome, in particular when in conjunction with ventilation therapies. Previously we showed [Kim SC, Kellett T, Wang S, Nishi M, Nagre N, Zhou B, Flodby P, Shilo K, Ghadiali SN, Takeshima H, Hubmayr RD, Zhao X. Am J Physiol Lung Cell Mol Physiol 307: L449-L459, 2014.

Volume Delivered During Recruitment Maneuver Predicts Lung Stress in Acute Respiratory Distress Syndrome.

Objective: Global lung stress varies considerably with low tidal volume ventilation for acute respiratory distress syndrome. High stress despite low tidal volumes may worsen lung injury and increase risk of death. No widely available parameter exists to assess global lung stress.

Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions.

Background: Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and possible TRALI.

Study Design And Methods: In a nested case-control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147).

Extravascular lung water and pulmonary vascular permeability index as markers predictive of postoperative acute respiratory distress syndrome: a prospective cohort investigation.

Objective: Robust markers of subclinical perioperative lung injury are lacking. Extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index are two promising early markers of lung edema. We aimed to evaluate whether extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index would identify patients at risk for clinically significant postoperative pulmonary edema, particularly resulting from the acute respiratory distress syndrome.

Recipient clinical risk factors predominate in possible transfusion-related acute lung injury.

Background: Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI.

Study Design And Methods: In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year period at the University of California at San Francisco and the Mayo Clinic (Rochester, Minnesota).

Predictive value of plasma biomarkers for mortality and organ failure development in patients with acute respiratory distress syndrome.

Purpose: To evaluate the predictive value of 6 different biomarkers in the development of multiple-organ failure (MOF) and mortality in a contemporary prospective cohort of acute respiratory distress syndrome (ARDS).

Methods: Patients with ARDS admitted to a tertiary referral center during an 8-month period were included. Plasma sample collection of 6 different biomarkers on days 1, 3, and 5 after ARDS onset was performed (von Willebrand factor, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, interleukin 8, receptor for advanced glycation end-products, and club cell secretory protein).

The hidden consequences of ventilator management decisions.

In the following perspective, we will highlight seemingly remote, downstream consequences of common ventilator management decisions. For example, a change in PEEP may alter venous return, blood pressure, cardiac output, arterial and venous blood gas tensions, metabolic rate, respiratory sensations, breathing pattern, and the work of breathing. If providers consider any of these changes dangerous or maladaptive, they may initiate additional interventions in the form of vasoactive agents, intravenous fluids, and/or sedatives, all of which have their own risk/benefit profile.

TRIM72 is required for effective repair of alveolar epithelial cell wounding.

The molecular mechanisms for lung cell repair are largely unknown. Previous studies identified tripartite motif protein 72 (TRIM72) from striated muscle and linked its function to tissue repair. In this study, we characterized TRIM72 expression in lung tissues and investigated the role of TRIM72 in repair of alveolar epithelial cells.

Prospective study on the clinical course and outcomes in transfusion-related acute lung injury*.

Objective: Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases.

Design: Prospective case study with controls.