Temporal Changes of Protein Biomarkers in Sepsis-Induced Acute Respiratory Distress Syndrome Open Access
Yang, Philip (Spring 2022)
Abstract
Introduction: Protein biomarkers including soluble receptor for advanced glycation end-products (sRAGE), angiopoietin-2 (Ang-2), and surfactant protein-D (SP-D) have been studied for diagnosis and prognostication in the acute respiratory distress syndrome (ARDS). However, prior studies of ARDS biomarkers often included heterogeneous populations or did not assess longitudinal changes of the biomarkers. The aim of this study was to compare the differences in sRAGE, Ang-2, and SP-D levels and their changes over time between patients with sepsis who developed ARDS vs. those who did not develop ARDS.
Methods: This was a prospective observational cohort study that enrolled adult patients admitted to the medical intensive care unit within 72 hours of sepsis or septic shock diagnosis. Serial plasma samples were collected for three consecutive days after enrollment, and were analyzed for sRAGE, Ang-2, and SP-D levels. Patients were followed for ARDS development and other outcomes. The biomarker levels and their changes over the three-day period were compared between ARDS and non-ARDS patients, and between non-survivors and survivors. Logistic regression was performed to examine the association between the biomarker levels and important binary clinical outcomes.
Results: 111 patients were included, of whom 21 patients (18.9%) developed ARDS. ARDS patients had higher levels of sRAGE and SP-D compared to non-ARDS patients, though the mean differences were not statistically significant. Non-survivors had significantly higher levels of sRAGE, Ang-2, and SP-D compared to survivors across multiple days. The changes of the three biomarker levels over time were not different between ARDS vs. non-ARDS patients, and between non-survivors vs. survivors. In logistic regression analyses, absolute SP-D level on day 1 was significantly associated with ARDS development (odds ratio [OR] 1.83, 95% confidence interval [CI] 1.06-3.15, p=0.03) and mortality (OR 1.52, 95% CI 1.03-2.24, p=0.03).
Conclusions: Among critically ill patients with sepsis, sRAGE, Ang-2, and SP-D levels were not different between ARDS and non-ARDS patients, but were higher in non-survivors compared to survivors. The changes of the biomarker levels over time were not different between the outcome groups. Absolute SP-D level on day 1 was associated with ARDS development and mortality in multivariable logistic regression models.
Table of Contents
INTRODUCTION .................... 1
BACKGROUND .................... 2
METHODS .................... 4
RESULTS .................... 9
DISCUSSION AND CONCLUSIONS .................... 12
REFERENCES .................... 16
TABLES AND FIGURES .................... 19
Table 1. Baseline characteristics of the study participants at the time of study enrollment .................... 20
Table 2. Clinical course and outcomes of the study participants .................... 21
Table 3. Comparison of biomarker levels by ARDS diagnosis .................... 22
Table 4. Comparison of biomarker levels by mortality status .................... 23
Table 5. Results from multivariable logistic regression analyses .................... 24
Figure 1. Biomarker levels and their changes over time by ARDS diagnosis .................... 25
Figure 2. Biomarker levels and their changes over time by mortality status .................... 26
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