Biomarkers in acute lung injury--marking forward progress

Abstract

This article reviews the state of the art regarding biomarkers for prediction, diagnosis, and prognosis in acute lung injury. Biomarkers and the goals of biomarker research are defined. Progress along 4 general routes is examined. First, the results of wide-ranging existing protein biomarkers are reported. Second, newer biomarkers awaiting or with strong potential for validation are described. Third, progress in the fields of genomics and proteomics is reported. Finally, given the complexity and number of potential biomarkers, the results of combining clinical predictors with protein and other biomarkers to produce better prognostic and diagnostic indices are examined.

Figure 1

Receiver Operator Characteristic curve analysis for the seven best performing biomarkers from a 21 biomarker panel for the diagnosis of trauma-induced acute lung injury. The three most discriminatory biomarkers were RAGE, BNP and PCP III with an AUC of 0.83. Figure reproduced from Fremont RD, Koyama T, Calfee CS, et al., J Trauma. May 2010; 68(5):1124, with permission.

Figure 2

Schematic representation of an alveolus and the alveolar-capillary interface demonstrating causes, pathophysiology and important potential biomarkers for prediction, diagnosis and prognosis in acute lung injury. Abbreviations, RBC = red blood cell. T1 = type 1 epithelial cell. T2 = type 2 epithelial cell. ICAM-1=Intercellular adhesion molecule 1. vWF = von Willebrand factor. PAI-1 = Plasminogen activator inhibitor 1. SP = surfactant protein. RAGE = Receptor for Advanced Glycation Products. HMGB1= Human Mobility Group Box 1 protein. TNFR-1 = Tumor Necrosis Factor Receptor 1.

Figure 3

Multi-dimensional representation charting plasma protein C and PAI-1 levels by quartile against excessive relative risk of death calculated as the difference between the highest PAI-1 and lowest protein C quartiles in 779 patients with acute lung injury. Reproduced from Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med. Aug 2007;35(8):1826, with permission.

Figure 4

Receiver Operator Characteristic curve for multiple mortality prediction models in patients with acute lung injury. Full model includes six clinical predictors (age, cause of injury, APACHE III, plateau pressure, organ failures, alveolar-arterial difference and eight biomarkers (IL-8, IL-6, TNFR-1, SP-D, Protein C, PAI-1, ICAM-1) and has an AUC 0.850. The reduced model includes APACHE III score, age, surfactant protein D and interleukin 8 with an AUC 0.834. From Ware LB et al. Chest. Feb 2010;137(2):292, with permission.