Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

Xiangdong Wang,Lin Shi,Yuping Li,Chengshui Chen,Shuanying Yang

doi:10.1007/s10565-016-9322-4

Abstract

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers.Electronic supplementary materialThe online version of this article (doi:10.1007/s10565-016-9322-4) contains supplementary material, which is available to authorized users.

Highlights

Adult respiratory distress syndrome (ARDS) is a lifethreatening condition manifested as non-cardiogenic pulmonary edema, respiratory distress, and hypoxemia with a high mortality and morbidity in critically ill patients and resulted from various processes that directly or indirectly compromise the lung (Schneider and Sweberg 2013)
The present study aims at investigating dynamic differences of proteomic profiles between patients with severe pneumonia (SP) or SP accompanied with ARDS (SP-ARDS) on days 1, 3, and 7 after hospital admission, as compared with healthy controls
We have developed the protocol of disease-specific biomarker selection and evaluation by integrating proteomic profiles of inflammatory mediators in pulmonary diseases, e.g., chronic obstructive pulmonary disease, at different stages and durations, with clinical informatics and phenotypes (Chen et al 2012b)

Summary

Introduction

Adult respiratory distress syndrome (ARDS) is a lifethreatening condition manifested as non-cardiogenic pulmonary edema, respiratory distress, and hypoxemia with a high mortality and morbidity in critically ill patients and resulted from various processes that directly or indirectly compromise the lung (Schneider and Sweberg 2013). ARDS was defined as an acute inflammation with neutrophil infiltration and lung epithelial and/or endothelial cell dysfunction, associated with infection (Grommes and Soehnlein 2011). Infectionassociated ARDS is characterized by an uncontrolled inflammatory response to a local or systemic insult, compromising lung alveolar epithelial and endothelial barriers, acute inflammation, edema, or injury. The concomitant clinical course and outcome of ARDS are associated with the degree of systemic inflammation (Lundberg et al 2000), by which altered production of cytokines and chemokines may occur among different stages and severities of the disease. Local infections (e.g., pneumonia and tuberculosis) and inflammation often occur in patients with lung cancer (Engels 2008)

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Conclusion