Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome

Meyer, Nuala J.; Calfee, Carolyn S.

doi:10.1016/s2213-2600(17)30187-x

Cited by 66 publications

(58 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NETs have been found in infection-related ALI models of influenza virus, bacteria or bacterial component LPS, and fungi. Substantial inflammation in the alveolar and plasma compartments has been a recognized characteristic of patients with ARDS since the 1980s (as reviewed by Meyer et al, 2017). High concentrations of inflammatory cytokines (cytokine storm) have been associated with both injurious ventilator strategies and poorer outcomes.…”

Section: Viral-induced Ards/cytokine Stormmentioning

confidence: 99%

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

Thierry¹,

Roch²

2020

Preprint

View full text Add to dashboard Cite

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 15 April 2020

show abstract

Section: Viral-induced Ards/cytokine Stormmentioning

confidence: 99%

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

Thierry¹,

Roch²

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Acute lung injury (ALI), which is induced by various acute stimuli such as excessive mechanical ventilation, sepsis, trauma, shock, and disseminated intravascular coagulation, manifests as acute respiratory distress syndrome (ARDS) in patients . With the clinical features of acute hypoxemic respiratory failure and bilateral pulmonary infiltrates, ALI and ARDS are characterized with high mortality as one in three patients diagnosed with ARDS were reported to die within 60 days . Up to now, supportive therapies, including lung‐protective mechanical ventilation, neuromuscular blockade, and prone positioning, were proved to be effective in reducing mortality of ALI and ARDS .…”

Section: Introductionmentioning

confidence: 99%

“…Up to now, supportive therapies, including lung‐protective mechanical ventilation, neuromuscular blockade, and prone positioning, were proved to be effective in reducing mortality of ALI and ARDS . However, pharmacological treatments for them remain scarce …”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of circulating fibrocytes on injury repair in acute lung injury/acute respiratory distress syndrome mice model

Tai

Zhou

Zheng

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

The study was aimed to explore the functions of circulating fibrocytes (CFs) on injury repair in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) mice model and its clinical value as a biomarker for ALI/ARDS. ALI/ARDS mice model was established by intratracheal instillation of lipopolysaccharide (LPS). Mononuclear cells were isolated from peripheral blood of ALI/ARDS model and flow cytometry was used to measure CFs defined as cells positive for CD45 and collagen-1. Histological changes of lung tissues were evaluated by H&E staining and Masson's trichrome staining. The correlations of CFs counts with damnification of lung tissue and the severity of pulmonary fibrosis were evaluated by Pearson correlation analyses. Western blot was used to detect the protein expression of collagen-1. ELISA was applied to determine cytokine CXCL12 concentration. Clinical relevance between CFs and ALI/ARDS was investigated. The greater number of CFs in the ALI/ARDS group implied higher degree of lung injury and more severe pulmonary fibrosis. The protein expression of collagen-1 and concentration of cytokine CXCL12 in ALI/ARDS group were higher than that in control group. Clinical and prognostic analysis revealed the higher injury degree and death rates in ALI/ARDS group than those in control group, and identified a greater severity and mortality for patients with ARDS than those with ALI. ROC curve analysis indicated the counts of CFs greater than 5.85% can predict death rates with AUC = 0.928. CFs had an inhibitory effect on injury repair in ALI/ARDS mice model. This might be unfavorable as a clinical marker for progression of ALI/ARDS.

show abstract

“…The results of this systematic review and meta-analysis will inform translational and clinical scientists, researchers, and clinicians internationally regarding the existing preclinical evidence for subphenotypes among preclinical, in vivo or ex vivo models of ARDS. Such data will be crucial to confirm the potential of personalized ARDS medicine [6,8,46], i.e. the promise to deliver the right -targeted-treatment to the right subject.…”

Section: Discussionmentioning

confidence: 94%

Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis

Carla

Pereira²,

Boukail

et al. 2020

Respir Res

View full text Add to dashboard Cite

Background: Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits. Methods: We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects.(Continued on next page) Discussion: This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation. Systematic review registration: PROSPERO (ID: CRD42019157236).

show abstract

Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome

Cited by 66 publications

References 105 publications

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

Inhibitory effect of circulating fibrocytes on injury repair in acute lung injury/acute respiratory distress syndrome mice model

Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis

Contact Info

Product

Resources

About