Serum biomarkers in Acute Respiratory Distress Syndrome an ailing prognosticator

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Abstract

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to acute respiratory distress syndrome (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in acute lung injury and acute respiratory distress syndrome and their potential value as prognostic tools and present some of the future perspectives and challenges.

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Most cited references 94

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Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.

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Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time.

G Köhler, E. Tolley, K Leeper … (1995)

Inflammatory cytokines have been related to the development of adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). We tested the hypothesis that unfavorable outcome in patients with ARDS is related to the presence of a persistent inflammatory response. For this purpose, we evaluated the behavior of inflammatory cytokines during progression of ARDS and the relationship of plasma inflammatory cytokines with clinical variables and outcome. We prospectively studied 27 consecutive patients with severe medical ARDS. Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukins (ILs) 1 beta, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation. Subgroups of patients were identified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared for levels of plasma inflammatory cytokines on day 1 of ARDS and over time. Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients with sepsis (86 vs 38%, p 200 pg/mL lost its usefulness after the first 48 h. A plasma IL-1 beta or IL-6 level > 400 pg/mL on any day in the first week of ARDS was associated with a low likelihood of survival. Our findings indicate that unfavorable outcome in acute lung injury is related to the degree of inflammatory response at the onset and during the course of ARDS. Patients with higher plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 on day 1 of ARDS had persistent elevation of these inflammatory cytokines over time and died. Survivors had lesser elevations of plasma inflammatory cytokines on day 1 of ARDS and a rapid reduction over time. Plasma IL-1 beta and IL-6 levels were consistent and efficient predictors of outcome.

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Author and article information

Journal

Journal ID (nlm-ta): Respir Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Print): 2005

Publication date (Electronic): 22 June 2005

Volume: 6

Issue: 1

Page: 62

Affiliations

[1 ]Interstitial Lung Disease Unit, Royal Brompton Hospital, Imperial College, Faculty of Medicine London, UK

[2 ]Department of Pneumonology, Medical School, Democritus University of Thrace, Greece

Article

Publisher ID: 1465-9921-6-62

DOI: 10.1186/1465-9921-6-62

PMC ID: 1168906

PubMed ID: 15972108

SO-VID: bcbd8e7a-bdb0-4cf0-859d-d9a8c4e4dffc

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Serum biomarkers in Acute Respiratory Distress Syndrome an ailing prognosticator

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Abstract

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Inflamed lung in vitro co-culture models

Most cited references 94

Shock and tissue injury induced by recombinant human cachectin.

Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time.

Pathogenetic mechanisms of septic shock.

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