SOME KEY BIOMARKERS IN ACUTE RESPIRATORY DISTRESS SYNDROME

Mazzon E. Some key biomarkers in acute respiratory distress syndrome. International Journal of Infection. 2022;6(3):86-87

E. Mazzon^*

IRCCS Neurolesi Center “Bonino-Pulejo”, Messina, Italy.

*Correspondence to:
Dr. Emanuela Mazzon,
IRCCS Centro Neurolesi “Bonino-Pulejo”,
Contrada Casazza,
98124 Messina, Italy.
e-mail: emanuela.mazzon@irccsme.it

KEYWORDS: Acute respiratory distress syndrome, infection, alveoli, lung, biomarker

INTRODUCTION

The inflammation that is caused by infection induced by foreign microorganisms increases the permeability of the alveolar-capillary barrier, allowing fluid to enter the alveoli. Infection results in the activation of immune cells, such as neutrophils, which increase in number and release proteases and reactive oxygen species (ROS) that damage tissue. The onset of edema in the lung alveoli causes reduced oxygen flow and reduced lung compliance and activated inflammatory cells release various cytokines that participate in inflammation and activation of endothelial cells.

Infection can cause acute respiratory distress syndrome (ARDS) that results in damage to type II pneumocytes with reduced surfactants, increased surface tension, and alveolar collapse. The discovery of biomarkers in ARDS has helped to improve the diagnosis and therapy for this disease. The primary biomarkers are soluble decoy receptors for advanced glycation end products (sRAGE), angiopoietin-2 (Ang-2), and pulmonary immune protein surfactant protein-D (SP-D). sRAGE is expressed by type I alveolar epithelial cells in the lungs and correlated with alveolar epithelial damage. In ARDS, Ang-2 is produced mainly by type II pneumocytes and secreted by endothelial cells and is an important marker mediating endothelial damage. SP-D is involved in the regulation of pulmonary surfactant homeostasis, binds pathogens, and promotes phagocytosis.

DISCUSSION

Infection by microorganisms causes inflammation with generation of extravascular fluid, which in the case of the lungs, can enter the alveoli, causing serious consequences. Microorganisms infect the lung and activate immune cells, including neutrophils that colonize the tissue and release inflammatory cytokines.  These reactions cause neutrophilia with the release of proteases and ROS that damage the alveolar epithelium and capillary endothelium, leading to hypoxia. Edema occurs in the alveoli with increased vascular permeability and leakage of protein-rich fluid. The inflammatory state alters gas exchange and causes the onset of ARDS in the pulmonary alveoli and consequent reduction in oxygen flow with reduced pulmonary compliance and pulmonary hypertension.

ARDS can cause rapid and difficult breathing, severe shortness of breath, and cyanosis. Symptoms that may appear after a few hours or a few days from the infection may also include mental confusion, pulmonary fibrosis, and fatigue. Inflammatory cells may cause a “cytokine storm”, in which they promote the recruitment of other cytokines and activate endothelial to release inflammatory compounds (1). Oxidative stress mediated by neutrophils and macrophages leads to the release of ROS and reactive nitrogen species (RNS).  This causes damage to DNA, lipids, and proteins of alveolar cells with loss of VE-cadherin in the endothelium and vascular leakage.  In addition, hyaline membranes consisting of fibrin-rich deposits and necrotic epithelial cells are formed.  In ARDS, there is damage to type II pneumocytes with reduced production of surfactant, a lipoprotein complex secreted by pneumocytes, and an increase in surface tension with alveolar collapse and decreased lung compliance (2).

Biomarkers have been found in ARDS that have helped to better understand the disease. sRAGE is a key biomarker in ARDS, particularly linked to alveolar epithelial injury. sRAGE is a soluble decoy receptor for RANGE expressed primarily on alveolar type I epithelial cells in the lungs (3). In inflammatory processes, sRANGE binds the proteins AGE, HMGB1, and S100 (4). In ARDS, where alveolar type I epithelial cells are damaged, plasma levels of sRANGE are highly and early expressed, and are an important marker for this disease (5).

Another important biomarker for ARDS is Ang-2, which mediates endothelial damage. Ang-2 is a glycoprotein that is secreted by endothelial cells and is involved in vascular permeability, edema, and inflammation. It regulates angiogenesis and stability of the vascular endothelium (6).  In diseases such as ARDS or sepsis, Ang-2 plays an important role in vascular damage and inflammatory processes (7).

A third biomarker in ARDS is the pulmonary immune protein SP-D, which is involved in the regulation of pulmonary surfactant homeostasis (8). It is produced mainly by type II pneumocytes, epithelial cells of the respiratory tract, which recognize and bind pathogens, promote macrophage phagocytosis, and modulate the inflammatory response.

CONCLUSIONS

ARDS is a condition characterized by reduced lung ventilation, edema, and alveolar collapse. Lung inflammation must be treated immediately to avoid serious consequences. The ARDS biomarkers sRAGE, Ang-2, and SP-D, which are elevated in individuals with ARDS, are important for improving diagnosis and therapy in this complicated disease.

Conflict of interest

The author declares that they have no conflict of interest.

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