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dcyphr | Recent insight into potential acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) occurs when inflammation of the lungs leads to respiratory failure without cardiac failure. The mortality of patients with ARDS is still high despite efforts to develop treatments. Identifying biomarkers of ARDS will help decrease mortality. This study looks at soluble advanced glycation end-products, soluble tumor necrosis factor-receptor 1, interleukin-6, interleukin8, and plasminogen activator inhibitor-1 for ARDS treatment by a soluble inhibitor.


Introduction

Biomarkers are helpful in the diagnosis and treatment of a patient. Several biomarkers have been identified for ARDS, but the death rate of ARDS patients remains high. ARDS has 2 phases: exudative and fibroproliferative. Exudative phase is due to inflammation, which injures the alveoli and releases proteins into the blood and alveolar compartment. Fibroproliferative phase is due to an imbalance of profibrotic and antifibrotic mediators. This study attempts to identify a soluble inhibitor that will be effective against the biomarkers of ARDS. The biomarkers discussed are soluble advanced glycation end-products, soluble tumor necrosis factor-receptor 1, interleukin-6, interleukin8, and plasminogen activator inhibitor-1.


Soluble receptor for advanced glycation and end-products (RAGE)

The soluble receptor for advanced glycation and end-products (RAGE) is a cell surface immunoglobulin. RAGE can interact with multiple ligands. RAGE is highly expressed on alveolar type 1 cells. RAGE activates innate immune and inflammation, leading to activation of the transcription factor NF-kB. RAGE can be measured as soluble (sRAGE) or endogenous secretory (esRAGE). High levels of sRAGE indicate alveolar type 1 cells damage and low oxygen levels. sRAGE can also lead to the build up of inflammatory cells in the alveoli. Based on this study, sRAGE can be used to diagnose ARDS or an ARDS risk factor. There is conflicting data whether sRAGE levels can be used to determine the severity of a patient or if they are responding well to treatment.


Interleukin-6

Interleukin-6 (IL-6) is a complex cytokine that has pro and anti-inflammatory properties. IL-6 is usually present before the onset of ARDS because there is usually inflammation or an infection before ARDS begins. IL-6 becomes severely elevated during ARDS. Il-6 is known to recruit inflammatory cells, like neutrophils, to the alveoli. The neutrophil entering the alveoli will cause the lung tissue to express vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1). IL-6 is associated with worse patient outcomes. IL-6 in addition to other biomarkers may be helpful in diagnosing ARDS in patients with other conditions like sepsis. 


Interleukin-8 

Interleukin-8 (IL-8) is a pro-inflammatory cytokine that recruits neutrophils in response to inflammation.High levels of IL-8 are associated with severe cases and death. IL-8 alone may be able to identify high risk patients for severe ARDS, and may be able to determine a prognosis of ARDS. 


Soluble Tumor Necrosis Factor-Receptor 1

Tumor necrosis factor-receptor 1 (TNFR-1) is a receptor with transmembrane, extracellular, and intracellular domains.  TNFR-1 is associated with inflammation, tissue death, and neutrophil apoptosis. During inflammation, soluble TNFR-1 (sTNFR-1) is shed and binds to TNF-alpha. sTNFR-1 is associated with higher mortality rates. 


Coagulation and Fibrinolysis

Plasminogen activator inhibitor-1 (PAI-1) regulates coagulation and fibrinolysis. PAI-1 helps convert plasminogen to plasmin by binding to different plasminogen activators. PAI-1 promotes inflammation because fibrin accumulates, which activates pro-inflammatory mediators and vascular permeability. There is varying data whether PAI-1 can predict ARDS mortality.


Conclusion

More studies need to be done on the biomarkers of ARDS, but it is clear that sRAGE, IL-6, IL-8, sTNFR-1, and PAI-1 will be helpful in the diagnosis and prognosis of ARDS.