scholarly journals Coagulation Dysfunction in Acute Respiratory Distress Syndrome and Its Potential Impact in Inflammatory Subphenotypes

2021 ◽  
Vol 8 ◽  
Author(s):  
Samantha A. Livingstone ◽  
Karin S. Wildi ◽  
Heidi J. Dalton ◽  
Asad Usman ◽  
Katrina K. Ki ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
The United States ◽  
The Body ◽  
Pulmonary Mechanics ◽  
Holistic Understanding ◽  
Coagulation Dysfunction

The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes.

Nitric oxide and interval hypoxic training in COVID-19 rehabilitation— new research direction

2021 ◽  
pp. 30-41
Author(s):  
Tatyana Nikolaevna Tsyganova ◽  
Egor Egorov ◽  
Tamara Nikolaevna Voronina
Keyword(s):  
Nitric Oxide ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Viral Infection ◽  
Distress Syndrome ◽  
The Body ◽  
Lung Damage ◽  
Specific Method ◽  
Hypoxic Training

COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, primarily affects lung tissue and disrupts gas exchange, leading to acute respiratory distress syndrome, systemic hypoxia, and lung damage. The search for methods of prevention and rehabilitation, especially after suffering from pneumonia caused by COVID-19, is on the agenda. This article discusses the possibilities of the interval hypoxic training (IHT) method for preventing infections by initiating nitric oxide production in the body. One of the main effects of IHT is the balanced stimulation of nitric oxide (NO) secretion. Over the past two decades, there has been an increasing interest in the function of nitric oxide (NO) in the human body. Nitric oxide plays a key role in maintaining normal vascular function and regulating inflammatory processes, including those leading to lung damage and the development of acute respiratory distress syndrome (ARDS). Our immune system destroys bacteria and viruses by oxidative burst, i.e. when oxygen accumulates inside the cell. This process also involves nitric oxide, a signaling molecule that has an antibacterial and antiviral effect, as well as regulates vascular tone and affects the permeability of the cell wall. Interval hypoxytherapy enhances endogenous oxidative protection and increases the amount of nitric oxide, thus allowing the body’s cells to resist infection more effectively. Mitochondrial NOS induction and mitochondrial NO synthesis increase under the action of pathogenic factors on the cell. By modulating the activity of mtNOS and the synthesis of mitochondrial NO, it is possible to increase the resistance to hypoxic effects. Interval hypo-hyperoxic training as an effective non-specific method of increasing the body’s defenses is indispensable not only in the prevention of viral infection, but also in rehabilitation after viral pneumonia, as well as as a method that reduces the severity of viral infection in the event of infection.

scholarly journals Basic and clinical research progress in acute lung injury/acute respiratory distress syndrome

2018 ◽  
Vol 7 (2) ◽  
pp. 38-43 ◽  
Author(s):  
Tong Wang
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
Severe Infection ◽  
Research Progress ◽  
Severe Stage

Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathological obstetrics. ALI and ARDS demonstrate similar pathophysiological changes. The severe stage of ALI is defined as ARDS. At present, a significant progress has been achieved in the study of the pathogenesis and pathophysiology of ALI/ARDS. Whether or not ALI/ARDS patients can recover depends on the degree of lung injury, extra-pulmonary organ damage, original primary disease of a patient, and adequacy in supportive care. Conservative infusion strategies and protective lung ventilation reduce ARDS disability and mortality. In this study, the pathogenesis of ALI/ARDS, lung injury, molecular mechanisms of lung repair, and conservative infusion strategies and pulmonary protective ventilation are reviewed comprehensively.

scholarly journals Extracellular histones in lung dysfunction: a new biomarker and therapeutic target?

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402096535
Author(s):  
Pratap Karki ◽  
Konstantin G. Birukov ◽  
Anna A. Birukova
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Therapeutic Effects ◽  
Lung Dysfunction ◽  
Extracellular Histones

Extracellular histones released from injured or dying cells following trauma and other severe insults can act as potent damage-associated molecular patterns. In fact, elevated levels of histones are present in human circulation in hyperinflammatory states such as acute respiratory distress syndrome and sepsis. The molecular mechanisms owing to histone-induced pathologies are at the very beginning of elucidating. However, neutralization of histones with antibodies, histone-binding or histone-degrading proteins, and heparan sulfates have shown promising therapeutic effects in pre-clinical acute respiratory distress syndrome and sepsis models. Various cell types undergoing necrosis and apoptosis or activated neutrophils forming neutrophil extracellular traps have been implicated in excessive release of histones which further augments tissue injury and may culminate in multiple organ failure. At the molecular level, an uncontrolled inflammatory cascade has been considered as the major event; however, histone-activated coagulation and thrombosis represent additional pathologic events reflecting coagulopathy. Furthermore, epigenetic regulation and chemical modifications of circulating histones appear to be critically important in their biological functions as evidenced by increased cytotoxicity associated with citrullinated histone. Herein, we will briefly review the current knowledge on the role of histones in acute respiratory distress syndrome and sepsis, and discuss the future potential of anti-histone therapy for treatment of these life-threatening disorders.

scholarly journals Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection

2009 ◽  
Vol 83 (14) ◽  
pp. 7062-7074 ◽  
Author(s):  
Barry Rockx ◽  
Tracey Baas ◽  
Gregory A. Zornetzer ◽  
Bart Haagmans ◽  
Timothy Sheahan ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Host Response ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
Aged Mice ◽  
Young Mice

ABSTRACT Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.

scholarly journals Trends in Extracorporeal Membrane Oxygenation for the Treatment of Acute Respiratory Distress Syndrome in the United States

2016 ◽  
Vol 32 (9) ◽  
pp. 535-539 ◽  
Author(s):  
Barret Rush ◽  
Katie Wiskar ◽  
Landon Berger ◽  
Donald Griesdale
Keyword(s):  
United States ◽  
Acute Respiratory Distress Syndrome ◽  
Extracorporeal Membrane Oxygenation ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
International Classification Of Diseases ◽  
The United States ◽  
Relative Increase ◽  
Membrane Oxygenation

Objectives: Our aim was to describe patient characteristics and trends in the use of extracorporeal membrane oxygenation (ECMO) for the treatment of acute respiratory distress syndrome (ARDS) in the United States from 2006 to 2011. Methods: We used the Nationwide Inpatient Sample to isolate all patients aged 18 years who had a discharge International Classification of Diseases, Ninth Revision diagnosis of ARDS, with and without procedure codes for ECMO, between 2006 and 2011. Results: We examined a total of 47 911 414 hospital discharges, representing 235 911 271 hospitalizations using national weights. Of the 1 479 022 patients meeting the definition of ARDS (representing 7 281 206 discharges), 775 underwent ECMO. There was a 409% relative increase in the use of ECMO for ARDS in the United States between 2006 and 2011, from 0.0178% to 0.090% ( P = .0041). Patients treated with ECMO had higher in-hospital mortality (58.6% vs 25.1%, P < .0001) and longer hospital stays (15.8 days vs 6.9 days, P < .0001). They were also younger (47.9 vs 66.4 years, P < .0001) and more likely to be male (62.2% vs 49.6%, P < .0001). The median time to initiate ECMO from the time of admission was 0.5 days (interquartile range [IQR] 4.9 days). Conclusion: There has been a dramatic increase in ECMO use for the treatment of ARDS in the United States.

scholarly journals Gene Therapy for Acute Respiratory Distress Syndrome

2022 ◽  
Vol 12 ◽  
Author(s):  
Jing Liu ◽  
David A. Dean
Keyword(s):  
Gene Therapy ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Single Gene ◽  
Treatment Strategies ◽  
The United States ◽  
Clinical Syndrome ◽  
Underlying Mechanisms

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.

A case of vaping-induced acute respiratory distress syndrome requiring extracorporeal life support

Perfusion ◽  
2020 ◽  
pp. 026765912092563
Author(s):  
Sudhir Krishnan ◽  
Guramrinder Singh Thind ◽  
Mona Soliman ◽  
Leslie Tolle ◽  
Eduardo Mireles-Cabodevila ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
The United States ◽  
Product Use

Introduction: An upsurge of e-cigarette, or vaping, product use–associated lung injury has been reported in the United States. The potential role of extracorporeal life support in e-cigarette, or vaping, product use–associated lung injury merits consideration. Case report: We present a case of vaping-induced severe acute respiratory distress syndrome that was salvaged with extracorporeal life support and had excellent recovery. Discussion: The mechanistic reasons for the sudden outbreak of e-cigarette, or vaping, product use–associated lung injury are under active investigation. A predominantly diffuse, bilateral pattern of lung injury has been reported, with some cases meeting the criteria for severe acute respiratory distress syndrome. To date, 68 deaths from e-cigarette, or vaping, product use–associated lung injury have been confirmed by the centers of disease control. However, resolution of lung injury has been reported in most cases, thereby justifying candidacy for extracorporeal life support, if required. Conclusion: Extracorporeal life support can be successfully utilized as a bridge to recovery in vaping-induced severe acute respiratory distress syndrome.

Sign in / Sign up

Export Citation Format

Share Document