Molecular and Immune Biomarkers in Acute Respiratory Distress Syndrome: A Perspective From Members of the Pulmonary Pathology Society

Abstract

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the greatest risk of developing ARDS, to evaluate response to therapy, to predict outcome, and to improve clinical trials. The ARDS pathogenesis is presented in this article, as well as concepts and information on biomarkers that are currently used clinically or are available for laboratory use by academic and practicing pathologists and the developing and validating of new assays, focusing on the assays' major biologic roles in lung injury and/or repair and to ultimately suggest innovative, therapeutic approaches.

Pulmonary fibrosis in the aftermath of the Covid-19 era (Review)

“…Previous studies in the literature have detected biomarkers of fibrogenesis in the bronchoalveolar fluid 24 h after the onset of ARDS that correlate with mortality. These include N-terminal pro-peptide of type III collagen, C-terminal pro-peptide of type I collagen, TGF-β, and alveolar fibroblasts and fibrocytes (24)(25)(26)(27). Fibrocytes have been shown to expand in the blood in the context of both physiologic wound repair and several diseases associated with fibrogenesis.…”

The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility

“…[10][11][12][13] Prior reviews of biomarkers in acute respiratory distress syndrome (ARDS), a serious critical care illness in dire need of validated and clinically useful biomarkers, have largely served as diligent but descriptive approaches outlining new technologies or summarizing the pathobiology of current biomarkers. [14][15][16][17][18][19][20] In contrast, this current review is highly divergent from prior reports and seeks to discuss the current state of ARDS biomarkers in the context of the drug development pipeline and to highlight the gaps between discovery and clinical implementation while proposing potential paths forward. Our intent is to shift the paradigm from a focus on biomarker discovery that is currently relegated to demonstrating a correlation between a specific biomarker and either the development of ARDS or ARDS severity, to a focus on the clinical utility and implementation of the biomarker within well-defined contexts of use including subject stratification in clinical trials.…”

New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome

“…Pathogens, such as viruses, bacteria, and other microorganisms, are believed to induce pulmonary cell injury, leading to ARDS. Although the detailed mechanisms of ARDS resulting from sepsis or pneumonia remain unknown, the innate immune system is known to play a profound role in the pathophysiology of ARDS [ 53 ]. Severe inflammatory responses are induced by pathogens via mediators such as toxins and pathogen-associated molecular patterns.…”

“…When alveolar macrophages are exposed to infectious agents, they activate the immune response upon recognition of Toll-like receptor ligands, pathogen-associated molecular patterns, and danger-associated molecular patterns [ 53 ]. The activated alveolar macrophages can be divided into two main phenotypes: M1 and M2 macrophages [ 54 ].…”