Diagnostic value of neutrophil extracellular traps in community-acquired pneumonia and their potential in identifying mixed infection

Abstract Objective To explore the expression characteristics of neutrophil extracellular traps (NETs) in patients with community-acquired pneumonia (CAP), and analyze the diagnostic value of NETs as well as their correlation with different infection patterns in CAP. Methods A total of 222 CAP patients admitted to a tertiary hospital in Lanzhou from January 2021 to December 2022 were enrolled. Paired peripheral serum and bronchoalveolar lavage fluid (BALF) samples were collected. In addition, serum samples from 100 age- and gender-matched healthy subjects were included as controls. NETs levels in all specimens were detected via double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). SPSS 25.0 software was used for statistical analysis. Pearson correlation analysis was performed to analyze the association between NETs levels and clinical laboratory indicators. ROC curve analysis was conducted to evaluate the diagnostic efficiency of serum NETs for CAP. Results Serum NETs levels were significantly higher in CAP patients than in healthy controls, and serum NETs concentrations were markedly elevated compared with paired BALF NETs levels (both P < 0.001). Patients with detectable pathogens showed elevated NETs levels in both serum and BALF compared with pathogen-undetected patients ( P < 0.05). NETs levels did not differ significantly between single bacterial and single viral infection groups ( P > 0.05), whereas the mixed-infection group exhibited higher NETs levels in both specimens than the two single infection groups ( P < 0.05). NETs levels in serum and BALF were strongly correlated with neutrophil count and fibrin degradation products (FDP), moderately correlated with monocyte count, and weakly correlated with C-reactive protein (CRP) (all P < 0.05). ROC analysis revealed that serum NETs yielded an AUC of 0.8293 for CAP diagnosis, with an optimal cut-off value of 362.2, a sensitivity of 63.96% and a high specificity of 98.00%. Conclusion CAP induces significant NETs release, and pathogen invasion further upregulates NETs expression, which are prominently amplified in mixed‑infection conditions. Serum NETs possess high diagnostic specificity for CAP. As reliable biomarkers for the auxiliary diagnosis of CAP and identification of mixed‑infection, serum NETs have favorable prospects for clinical application.