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Decoy Receptor 3 Levels in Peripheral Blood Predict Outcomes of Acute Respiratory Distress Syndrome

¹ Institute of Clinical Medicine, ³ Department of Internal Medicine, School of Medicine, ⁵ Institute of Biochemistry and Molecular Biology, and ⁸ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei; ² Department of Internal Medicine, Taoyuan Veterans Hospital, Taoyuan, Taoyuan County; ⁴ Chest Department, and ⁹ Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital; ⁶ Institute of Statistical Science, Academia Sinica, Taipei; ⁷ Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Pan-Chiao, Taipei County; ¹⁰ Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan

Correspondence and requests for reprints should be addressed to Teh-Ying Chou, M.D., Ph.D., Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan. E-mail: tychou{at}vghtpe.gov.tw

Rationale: Acute respiratory distress syndrome (ARDS), a serious inflammatory reaction to acute lung injury, is associated with high mortality rates. Decoy receptor (DcR) 3 is a soluble protein with immunomodulatory effects. Biomarkers that reliably predict outcomes in ARDS are not currently available.

Objectives: Comparing DcR3 with the Acute Physiology and Chronic Health Evaluation (APACHE) II scores and three other plasma markers to explore the association of DcR3 and the clinical outcome in ARDS.

Methods: Eighty-eight patients with ARDS were studied. Baseline APACHE II scores and clinical data were recorded. Plasma levels of DcR3, soluble triggering receptor expressed on myeloid cells (sTREM)-1, tumor necrosis factor (TNF)-, and IL-6 were measured on Day 1 and later time points, and correlated with the survival status on Day 28 after the onset of ARDS. For validation, 59 patients with ARDS from another medical center were studied.

Measurements and Main Results: Among the biomarkers evaluated, only DcR3 discriminated the survivors and nonsurvivors at all time points in the first week of ARDS. DcR3 independently associated with and best predicted the 28-day mortality of patients with ARDS. Plasma DcR3 levels most correlated to multiple-organ dysfunction and ventilator dependence. Compared with survivors, the nonsurvivors had higher DcR3 levels regardless of the APACHE II scores. Kaplan-Meier survival analysis showed higher mortality in patients with ARDS with higher DcR3 levels. The outcome prediction of patients with ARDS by plasma DcR3 levels was recapitulated by the validation cohort.

Conclusions: High plasma DcR3 levels correlate with development of multiple-organ dysfunction and independently predict the 28-day mortality in patients with ARDS.

Key Words: acute lung injury • biomarker • prognosis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Decoy receptor (DcR) 3, belonging to the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play a role in immune modulation. The role of DcR3 as a biomarker for outcome prediction in acute respiratory distress syndrome (ARDS) has never been explored. What This Study Adds to the Field Elevated levels of DcR3 in peripheral blood may serve as an independent predictor for 28-day mortality in patients with ARDS. High plasma DcR3 levels may also predict the occurrence and progression of multiple-organ dysfunction in these patients. The prognostic information provided by circulating DcR3 levels appears superior to that provided by soluble triggering receptor expressed on myeloid cells-1, tumor necrosis factor-, or IL-6 levels.