Receptor for Advanced Glycation Endproducts in Sepsis-Induced Lung Injury
Objective: Acute lung injury (ALI) is a common, lethal disease that is associated with a high mortality. Sepsis is the most common cause of ALI and is common in the critically ill patient. However, not all patients with sepsis develop ALI; therefore, it is imperative to understand what may alter the development of ALI in patients with sepsis. The receptor for advanced glycation endproducts (RAGE) is known to be a marker of cell injury in ALI. Therefore, we sought to determine the association between RAGE and ALI development and to further determine if RAGE levels predicted mortality in sepsis patients.
Study design: Prospective cohort study of patients with severe sepsis or septic shock.
Methods: Patients in the intensive care unit were enrolled within 72 hours of the development of severe sepsis or septic shock. Bronchoscopy with bronchoalveolar lavage (BAL) and blood draws were performed at enrollment. Primary outcomes were development of ALI and death. BAL fluid (BALF) and blood were assayed for sRAGE using an Elisa based kit. TH1 and TH2 cytokines were measured in BALF using a multiplex kit.
Results: Forty-six patients with severe sepsis or septic shock were enrolled, 24 of who developed ALI. BALF sRAGE levels in ALI patients were significantly higher than in non-ALI patients (median, 4256 pg/ml vs. 1433 pg/ml, respectively, p=0.048. Plasma sRAGE levels in ALI patients (median, 1555 pg/ml) were not significantly higher than in non-ALI patients (median, 1103 pg/ml), p=0.15. There was poor correlation between BALF sRAGE levels and the ratio of TH1/TH2 cytokines (correlation coefficient of 0.21, p=0.34). Median BALF sRAGE level in survivors was 2428 pg/ml compared to 1354 pg/ml in non-survivors, p=0.38; median plasma sRAGE level in survivors was 945 pg/ml vs. 1518 in non-survivors, p=0.14.
Conclusion: BAL fluid sRAGE is elevated in patients with ALI compared to non-ALI patients with sepsis. There was no difference detected in plasma sRAGE between the two groups. BAL fluid and plasma sRAGE levels were not predictive of mortality. Further studies are needed to understand the role of RAGE in ALI pathogenesis.
Receptor for Advanced Glycation Endproducts in Sepsis-Induced
MD, University of Texas at Houston, 2002
Advisor: Gregory S. Martin, MD, MSc
A thesis submitted to the Faculty of the James T. Laney School of Graduate Studies of Emory University in partial fulfillment of the requirements for the degree of Master of Science in Clinical Research
Table of Contents
Table of Contents
Table 1. Baseline characteristics of sepsis patients...20
Figure 1. Box plots of sRAGE levels in BAL fluid and plasma of patients with and without ALI...21
Figure 2. Association between BALF and plasma sRAGE levels...21
Figure 3. Differences in sRAGE levels in BALF versus plasma in ALI vs. non-ALI...22
Table 2. Logistic regression model for ALI...22
Figure 4. Receiver-operating characteristic curve of BALF sRAGE levels...23
Table 3. Logistic regression model for ALI with sRAGE dichotomized as high or low...24
Table 4. Logistic regression model for ALI with sRAGE dichotomized as high or low...24
Figure 5. Correlation of BALF sRAGE with organ dysfunction and lung injury score...25
Figure 6. Association of BALF sRAGE levels and TH1/TH2 cytokine ratio...25
Table 5. Baseline characteristics of survivors vs. nonsurvivors...26
Figure 7. sRAGE levels in BALF and plasma of survivors vs. nonsurvivors...27
Table 7. Logistic regression model for mortality...27
Figure 8. Kaplan Meier Survival Curve in patients with high versus low sRAGE levels...28
About this Master's Thesis
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