Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome.

Ware LB, Koyama T, Zhao Z, Janz DR, Wickersham N, Bernard GR, May AK, Calfee CS, Matthay MA.
Journal   Crit Care
Species  
Analytes Measured   IL-6 , IL-8 , MMP-1 , MMP-3 total , MMP-9
Matrix Tested   Plasma
Year   2013
Volume   17
Page Numbers   253
Application   Cytokines and Chemokines
Abstract
INTRODUCTION: Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.

METHODS: This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least 2 of their first 4 ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day 2. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.

RESULTS: Using the five best-performing biomarkers (surfactant protein-D [SP-D], receptor for advanced glycation end-products [RAGE], interleukin-8 [IL-8], club cell secretory protein [CC-16], and interleukin-6 [IL-6]) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.

CONCLUSIONS: Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury

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Multiplex
U-PLEX Biomarker Group 1 (mouse) 35-Plex
EPO, GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-1β, MIP-2, MIP-3α, TNF-α, VEGF-A | Mouse
Multiplex
U-PLEX TH17 Combo 2 (mouse)
IFN-γ, IL-1β, IL-6, IL-17A, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, TNF-α | Mouse
Multiplex
U-PLEX TH17 Combo 2 (human)
IFN-γ, IL-1β, IL-6, IL-10, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, TNF-α | Human
Multiplex
U-PLEX TH17 Combo 1 (NHP)
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, TNF-α | Non-human primate
Multiplex
U-PLEX TH1/TH2 Combo (NHP)
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, TNF-α | Non-human primate
Multiplex
U-PLEX Biomarker Group 1 (NHP) 59-Plex
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 | Non-human primate
Multiplex
U-PLEX Biomarker Group 1 (human) 71-Plex
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Custom Biomarker Group 1 (human) Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Biomarker Group 1 (NHP) Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 | Non-human primate
Multiplex
U-PLEX Human IL-6 Antibody Set
IL-6 | Human
U-PLEX Human IL-8 Antibody Set
IL-8 | Human
U-PLEX Mouse IL-6 Antibody Set
IL-6 | Mouse
U-PLEX Chemokine Combo 1 (NHP)
Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
U-PLEX Chemokine Combo 1 (human)
Eotaxin, Eotaxin-2, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
U-PLEX Proinflam Combo 4 (human)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
U-PLEX Proinflam Combo 3 (human)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
U-PLEX Proinflam Combo 2 (human)
GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 | Human
Multiplex
U-PLEX Proinflam Combo 1 (NHP)
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α | Non-human primate
Multiplex
U-PLEX Proinflam Combo 1 (human)
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
U-PLEX TH1/TH2 Combo (human)
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Proinflammatory Panel 2 Rat Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Multiplex
V-PLEX Plus Proinflammatory Panel 2 Rat Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Multiplex
V-PLEX Plus Human Biomarker 39-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Human Biomarker 39-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
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