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Table 2 Summary of biological domains

From: Towards a biological definition of ARDS: are treatable traits the solution?

Domain Sample material Example biomarkers Advantage Disadvantage
Endothelial injury Plasma Ang2 Easy to obtain
Pathophysiological contributor to lung injury development
Reflective of all endothelial dysfunction, not only in lung
Epithelial injury Plasma sRAGE. SP-D Easy to obtain
Pathophysiological contributor to lung injury development
Not only related to epithelial injury but also to, i.e., clearance by the kidney
Epithelial injury BALF sRAGE Not influenced by clearance
Evaluation at site of injury
Difficult to obtain sample
Local injury may not be reflective of the rest of the lung
Protein rich pulmonary edema BALF Total protein Direct measurement of hallmark of ARDS Difficult to obtain sample
Local injury may not be reflective of the rest of the lung
May not be targetable and reflective of injury to endothelium and epithelium
Protein rich pulmonary edema EBC Total protein Non-invasive collection of EBC
Direct measurement of hallmark of ARDS
Requires specialized equipment that is not widely available
May not be targetable and reflective of injury to endothelium and epithelium
Protein rich pulmonary edema HME fluid Total protein Non-invasive collection using standard HME
Direct measurement of hallmark of ARDS
Novel technique that needs to be validated further
May not be targetable and reflective of injury to endothelium and epithelium
Systemic host response Plasma IL-6, IL-8, TNFRI Easy to collect
Used to classify subphenotypes
Not unique to ARDS and influenced by other organ dysfunction
Unclear contribution to lung injury
Not reflective of alveolar inflammation
Alveolar host response BALF Neutrophils, macrophages
IL-6, IL-8, TNFR1
Direct measurement of hallmark of ARDS
Pathophysiological contributor to lung injury development
Difficult to obtain sample
Local injury may not be reflective of the rest of the lung
  1. Ang angiopoietin, sRAGE soluble Receptor for Advanced Glycation End Product, SP-D Surfactant protein D, BALF broncho-alveolar lavage fluid, EBC exhaled breath condensate, HME heat moist exchanger, IL interleukin, TNFRI tumor necrosis factor receptor