Soluble RAGE as a Severity Marker in Pneumonia
Soluble RAGE as a Severity Marker in Pneumonia
Thirty-three patients with confirmed CAP were included in the study; three were excluded (one was pregnant and two because of problems with their blood sample). Of the remaining 30 patients, 14 (46.6%) had pandemic (H1N1) 2009 influenza virus confirmed by PCR and 2 patients (6.9%) had seasonal influenza A. No etiologic agent was found in the other 14 patients. Twenty-two patients (73.3%) had severe sepsis or septic shock detected at admission; of these, 17 developed acute respiratory distress syndrome (ARDS). The mortality rate of the study group was a total of 16 patients (53.3%) at the end of the 28 days. There were eight who never developed severe sepsis and survived to hospital discharge, six who developed severe sepsis and survived to discharge, and 16 who developed severe sepsis and died in the hospital.
There were no significant differences between survival and non-survival patients with respect to age, gender, ethnicity, microbiological etiology, initial CURB-65, initial PSI class, initial APACHE II score, or emergency room length of stay (P value range, .07-.99) nor between ARDS and non-ARDS patients with respect to gender, ethnicity, microbiological etiology, initial CURB-65, initial PSI class, initial APACHE II score, or emergency room length of stay (P value range, .36-.77) (Figure 1A). Group characteristics are provided in Table 1. Compared with those who did not survive, those who survived had lower SOFA scores (5.5, CI: 4.9–7.7 versus 3, CI: 2.3–4.2) (Figure 1B). Compared with patients that did not develop ARDS, those with ARDS had higher SOFA scores (3, CI: 2.1–4.9 versus 5, CI: 4.6–7.1) and were younger (Figure 2B and Table 1).
(Enlarge Image)
Figure 1.
Analysis of CURB-65 score, SOFA score, soluble RAGE, membrane RAGE and HMGB-1 levels in survival and non-survival patients. A) CURB-65 and B) SOFA scores were obtained using international protocols. C) Serological soluble RAGE and D) HMGB-1 levels were measured by ELISA. E) Membrane RAGE levels were analyzed by flow cytometry. Data represent the median and were analyzed using Mann Whitney U test.
(Enlarge Image)
Figure 2.
Analysis of soluble RAGE and SOFA score in ARDS and non-ARDS patients. Data represent the median and were analyzed using Mann Whitney U test.
There were no statistically different RAGE, sRAGE and HMGB-1 levels found during early CAP-associated sepsis in ARDS or non-surviving patients (Figure 1C, Figure 1E, Figure 2A and Table 2). No difference was found between influenza A H1N1 infected patients and the rest of the study group (2767 ± 1655 vs 2174 ± 1344, P = .327). We did not find a correlation between immunological molecules and severity assessment scores using Spearman's correlation coefficient (P value range = .16-.99). Finally, none of the studied severity assessment scores correlated with each other (P value range = .18-.79).
Using a logistic regression model involving age, gender, APACHE II, SOFA, HMGB-1, sRAGE and RAGE, we found that the only variables that modified the probability of the patient having a fatal outcome were SOFA (P = .013) with a relative risk of surviving of .347 (CI: .151-.797); and sRAGE (P = .05) with a relative risk of surviving of .998 (CI: .998–1) (Table 3).
According to multivariate Cox regression analysis we found that a high SOFA score was an independent predictor of non-survival (hazard ratio 1.53, CI: 1.2–1.97, P = .001) (Table 4).
Results
Study Population
Thirty-three patients with confirmed CAP were included in the study; three were excluded (one was pregnant and two because of problems with their blood sample). Of the remaining 30 patients, 14 (46.6%) had pandemic (H1N1) 2009 influenza virus confirmed by PCR and 2 patients (6.9%) had seasonal influenza A. No etiologic agent was found in the other 14 patients. Twenty-two patients (73.3%) had severe sepsis or septic shock detected at admission; of these, 17 developed acute respiratory distress syndrome (ARDS). The mortality rate of the study group was a total of 16 patients (53.3%) at the end of the 28 days. There were eight who never developed severe sepsis and survived to hospital discharge, six who developed severe sepsis and survived to discharge, and 16 who developed severe sepsis and died in the hospital.
There were no significant differences between survival and non-survival patients with respect to age, gender, ethnicity, microbiological etiology, initial CURB-65, initial PSI class, initial APACHE II score, or emergency room length of stay (P value range, .07-.99) nor between ARDS and non-ARDS patients with respect to gender, ethnicity, microbiological etiology, initial CURB-65, initial PSI class, initial APACHE II score, or emergency room length of stay (P value range, .36-.77) (Figure 1A). Group characteristics are provided in Table 1. Compared with those who did not survive, those who survived had lower SOFA scores (5.5, CI: 4.9–7.7 versus 3, CI: 2.3–4.2) (Figure 1B). Compared with patients that did not develop ARDS, those with ARDS had higher SOFA scores (3, CI: 2.1–4.9 versus 5, CI: 4.6–7.1) and were younger (Figure 2B and Table 1).
(Enlarge Image)
Figure 1.
Analysis of CURB-65 score, SOFA score, soluble RAGE, membrane RAGE and HMGB-1 levels in survival and non-survival patients. A) CURB-65 and B) SOFA scores were obtained using international protocols. C) Serological soluble RAGE and D) HMGB-1 levels were measured by ELISA. E) Membrane RAGE levels were analyzed by flow cytometry. Data represent the median and were analyzed using Mann Whitney U test.
(Enlarge Image)
Figure 2.
Analysis of soluble RAGE and SOFA score in ARDS and non-ARDS patients. Data represent the median and were analyzed using Mann Whitney U test.
There were no statistically different RAGE, sRAGE and HMGB-1 levels found during early CAP-associated sepsis in ARDS or non-surviving patients (Figure 1C, Figure 1E, Figure 2A and Table 2). No difference was found between influenza A H1N1 infected patients and the rest of the study group (2767 ± 1655 vs 2174 ± 1344, P = .327). We did not find a correlation between immunological molecules and severity assessment scores using Spearman's correlation coefficient (P value range = .16-.99). Finally, none of the studied severity assessment scores correlated with each other (P value range = .18-.79).
Logistic Regression Model
Using a logistic regression model involving age, gender, APACHE II, SOFA, HMGB-1, sRAGE and RAGE, we found that the only variables that modified the probability of the patient having a fatal outcome were SOFA (P = .013) with a relative risk of surviving of .347 (CI: .151-.797); and sRAGE (P = .05) with a relative risk of surviving of .998 (CI: .998–1) (Table 3).
Cox Regression Model
According to multivariate Cox regression analysis we found that a high SOFA score was an independent predictor of non-survival (hazard ratio 1.53, CI: 1.2–1.97, P = .001) (Table 4).