Measurement of lipocalin-2 and syndecan-4 levels to differentiate bacterial from viral infection in children with community-acquired pneumonia

Abstract

BackgroundIn this study, we evaluated the lipocalin-2 (LIP2) and syndecan-4 (SYN4) levels in children who were hospitalized for radiologically confirmed CAP in order to differentiate bacterial from viral infection. The results regarding the LIP2 and SYN4 diagnostic outcomes were compared with the white blood cell (WBC) count and C reactive protein (CRP) levels.MethodsA total of 110 children <14 years old who were hospitalized for radiologically confirmed CAP were enrolled. Serum samples were obtained upon admission and on day 5 to measure the levels of LIP2, SYN4, and CRP as well as the WBC. Polymerase chain reaction of the respiratory secretions and tests on blood samples were performed to detect respiratory viruses, Streptococcus pneumoniae, and Mycoplasma pneumoniae.ResultsCAP was considered to be due to a probable bacterial infection in 74 children (67.3 %) and due to a probable viral infection in 16 children (14.5 %). Overall, 84 children (76.4 %) were diagnosed with severe CAP. The mean values of the WBC count and the LIP2 and SYN4 levels did not differ among the probable bacterial, probable viral, and undetermined cases. However, the CRP serum concentrations were significantly higher in children with probable bacterial CAP than in those with probable viral disease (32.2 ± 55.5 mg/L vs 9.4 ± 17.0 mg/L, p < 0.05). The WBC count was the best predictor of severe CAP, but the differences among the studied variables were marginal. The WBC count was significantly lower on day 5 in children with probable bacterial CAP (p < 0.01) and in those with an undetermined etiology (p < 0.01). The CRP and LIP2 levels were significantly lower 5 days after enrollment in all of the studied groups, independent of the supposed etiology of CAP (p < 0.01 for all comparisons). No statistically significant variation was observed for SYN4.ConclusionsMeasuring the LIP2 and SYN4 levels does not appear to solve the problem of the poor reliability of routine laboratory tests in defining the etiology and severity of pediatric CAP. Currently, the CRP levels and WBC, when combined with evaluation of clinical data, can be used to limit the overuse of antibiotics as much as possible and to provide the best treatment to the patient.

Host-response biomarkers for the diagnosis of bacterial respiratory tract infections

“…The conflicting difference between higher syndecan-4 levels in mild vs. severe pneumonia is unexpected and raises questions about the validity of the study findings. In another study in pediatric patients with bacterial or viral CAP, syndecan-4 showed poor discriminatory power (AUROC ≈ 0.5) [14]. However, the viral pneumonia subgroup in this study was underrepresented (16 patients) compared to the bacterial subgroup (74 patients).…”

“…Lipocalin-2 levels increase during infection and inflammation; lipocalin-2 plays a key role in innate immunity through interference with bacterial iron uptake [30]. In pediatric patients with bacterial and viral pneumonia, lipocalin-2 failed to discriminate between these groups (AUROC ≈ 0.5) [14]. Here, lipocalin-2 was studied in the same study as syndecan-4, which under-represented the viral pneumonia group.…”

Blood biomarkers differentiating viral versus bacterial pneumonia aetiology: a literature review

“…After duplicate removal, the title and abstracts were manually sorted and matched according to the inclusion and exclusion criteria. A total of 16 articles were fully reviewed [7,[10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Afterward, details were extracted for each article as described in methods.…”

“…A total of eleven studies involved CRP [14,16,17,19,20,22,23,[25][26][27][28][29]. In all the studies analysing CRP as a diagnostic marker, the average CRP level was higher in the bacterial group than viral group [14,20,22,23,[25][26][27][28][29]. In an investigation by Esposito et al [20] the mean level of CRP was 32.2 mg/L in 74 bacterial CAP cases as compared to 9.4 mg/L from 16 viral CAP cases.…”

Diagnostic Value of Different Biomarkers to Identify Bacterial Coinfection in Vietnamese Children with Severe Rhinovirus Pneumonia

“…31 In this study, the CRP values were significantly higher among the coinfection group than others, which was similar to the results of previous reports. 20,21,[32][33][34] The optimal cutoff point for hs-CRP was 1.53 mg/dl (sensitivity 90%, specificity 56%), and the AUC for hs-CRP was 0.772, indicating this diagnostic value was valid. Although some authors were arguing that CRP is not useful in distinguishing coin-fected bacterial infections in patients with Rhinovirus community pneumonia, 26,35 other studies were confirming the ability to distinguish between viral and bacterial agents that cause pneumonia with CRP limit point > 0.8mg/dl.…”