Abstract
Acute lung injury (ALI) affects over 10% of patients hospitalised in critical care, with acute respiratory distress syndrome (ARDS) being the most severe form of ALI and having a mortality rate in the region of 40%. There has been slow but incremental progress in identification of biomarkers that contribute to the pathophysiology of ARDS, have utility in diagnosis and monitoring, and that are potential therapeutic targets (Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Thompson T, Ware LB, Matthay MA, Lancet Respir Med 2014, 2:611–-620). However, a major issue is that ARDS is such a heterogeneous, multi-factorial, end-stage condition that the strategies for “lumping and splitting” are critical (Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX, Am J Respir Crit Care Med 2016, 194:147–-155). Nevertheless, sequencing of the human genome, the availability of improved methods for analysis of transcription to mRNA (gene expression), and development of sensitive immunoassays has allowed the application of network biology to ARDS, with these biomarkers offering potential for personalised or precision medicine (Sweeney TE, Khatri P, Toward precision medicine Crit Care Med; 2017 45:934-939).Biomarker panels have potential applications in molecular phenotyping for identifying patients at risk of developing ARDS, diagnosis of ARDS, risk stratification and monitoring. Two subphenotypes of ARDS have been identified on the basis of blood biomarkers: hypo-inflammatory and hyper-inflammatory. The hyper-inflammatory subphenotype is associated with shock, metabolic acidosis and worst clinical outcomes. Biomarkers of particular interest have included interleukins (IL-6 and IL-8), interferon gamma (IFN-γ), surfactant proteins (SPD and SPB), von Willebrand factor antigen, angiopoietin 1/2 and plasminogen activator inhibitor-1 (PAI-1). In terms of gene expression (mRNA) in blood there have been found to be increases in neutrophil-related genes in sepsis-induced and influenza-induced ARDS, but whole blood expression does not give a robust diagnostic test for ARDS.Despite improvements in management of ARDS on the critical care unit, this complex disease continues to be a major life-threatening event. Clinical trials of β2-agonists, statins, surfactants and keratinocyte growth factor (KGF) have been disappointing. In addition, monoclonal antibodies (anti-TNF) and TNFR fusion protein have also been unconvincing. However, there have been major advances in methods of mechanical ventilation, a neuromuscular blocker (cisatracurium besilate) has shown some benefit, and stem cell therapy is being developed. In the future, by understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care (Seymour CW, Gomez H, Chang CH, Clermont G, Kellum JA, Kennedy J, Yende S, Angus DC, Crit Care 2017, 21:257).
Highlights
Definition of acute respiratory distress syndrome (ARDS) The definition and the criteria for the diagnosis of ARDS have changed many times during the years
The 1994 American–European Consensus Conference (AECC) defined ARDS according to the presence of all the following clinical criteria: a) recent onset of symptoms after a known risk factor, b) severe hypoxemia defined by a PaO2/FiO2 ratio less than 200 mmHg, c) bilateral infiltrates on chest radiograph, d) absence of cardiogenic pulmonary edema [2]
In the revised Berlin definition, the term ARDS was redefined as a broader concept including a milder condition of lung injury; it became equivalent to acute lung injury (ALI), which was the previous AECC definition
Summary
Definition of ARDS The definition and the criteria for the diagnosis of ARDS have changed many times during the years. The 1994 American–European Consensus Conference (AECC) defined ARDS according to the presence of all the following clinical criteria: a) recent onset of symptoms after a known risk factor, b) severe hypoxemia defined by a PaO2/FiO2 ratio less than 200 mmHg, c) bilateral infiltrates on chest radiograph, d) absence of cardiogenic pulmonary edema [2]. Risk factors are divided into direct and indirect causes of lung injury (Table 2). And late phases of lung injury Pathologically and clinically, ARDS can be divided into early and late phases of lung injury, corresponding to exudative and fibroproliferative phases [10] (Fig. 1) This involves endothelial and epithelial damage, the inflammatory cascade, and increased vascular permeability. There are associated alterations in lung matrix, activation of coagulation and fibrosis pathways, with cell proliferation and apoptosis
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