Abstract
BackgroundCommunity-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity. There are few studies focused on the expression of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 in patients with CAP.MethodsA prospective, multi-centre study was conducted between January 2014 and December 2016. A total of 103 patients with severe CAP (SCAP), 149 patients with non-SCAP, and 30 healthy individuals were enrolled. Clinical data were recorded for all enrolled patients. Serum suPAR and syndecan-4 levels were determined by quantitative enzyme-linked immunosorbent assay. The t test and Mann–Whitney U test were used to compare between two groups; one-way analysis of variance and the Kruskal–Wallis test were used to compare multiple groups. Correlations were assessed using Pearson and Spearman tests. Area under the curve (AUCs), optimal threshold values, sensitivity, and specificity were calculated. Survival curves were constructed and compared by log-rank test. Regression analyses assessed the effect of multiple variables on 30-day survival.ResultssuPAR levels increased in all patients with CAP, especially in severe cases. Syndecan-4 levels decreased in patients with CAP, especially in non-survivors. suPAR and syndecan-4 levels were positively and negatively correlated with severity scores, respectively. suPAR exhibited high accuracy in predicting SCAP among patients with CAP with an AUC of 0.835 (p < 0.001). In contrast, syndecan-4 exhibited poor diagnostic value for predicting SCAP (AUC 0.550, p = 0.187). The AUC for predicting mortality in patients with SCAP was 0.772 and 0.744 for suPAR and syndecan-4, respectively; the respective prediction threshold values were 10.22 ng/mL and 6.68 ng/mL. Addition of both suPAR and syndecan-4 to the Pneumonia Severity Index significantly improved their prognostic accuracy, with an AUC of 0.885. Regression analysis showed that suPAR ≥10.22 ng/mL and syndecan-4 ≤ 6.68 ng/mL were reliable independent markers for prediction of 30-day survival.ConclusionsuPAR exhibits high accuracy for both diagnosis and prognosis of SCAP. Syndecan-4 can reliably predict mortality in patients with SCAP. Addition of both suPAR and syndecan-4 to a clinical scoring method could improve prognostic accuracy.Trial registrationClinicalTrials.gov, NCT03093220. Registered on 28 March 2017 (retrospectively registered).
Highlights
Community-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity
Chest radiographs revealed that 84.47% and 29.13% of patients with severe CAP (SCAP) exhibited bilateral lung infection and pleural effusion, respectively; these proportions were significant higher than those observed in the non-SCAP group (29.53% and 4.70%, respectively; p < 0.001 for both comparisons)
Laboratory analyses showed that the SCAP group exhibited a higher whole blood leukocyte count (WBC) and higher neutrophil/lymphocyte ratio (NLR) than detected in the non-SCAP group (p < 0.001 for both comparisons)
Summary
Community-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity. Novel biomarkers, such as soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) [5], proadrenomedullin (proADM) [6], and copeptin [7] have been widely validated in clinical settings. Their sensitivity and specificity for prediction of pneumonia severity are variable and largely insufficient; there is a need for new biomarkers to provide effective risk stratification and assist in clinical judgement
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