A novel biomarker of serum Histidine-Rich Glycoprotein (HRG) for diagnosing and predicting prognosis of ventilator-associated pneumonia (VAP): a pilot study.

Abstract

Histidine-Rich Glycoprotein (HRG) has been reported to be associated with idiopathic pulmonary fibrosis, cancer, and sepsis as a novel biomarker. However, there is limited evidence regarding its value in diagnosing or prognosis evaluating of ventilator-associated pneumonia (VAP). A total of 186 patients intubated in ICU and 65 healthy volunteers were enrolled in this study. Patients were divided into VAP group (n = 116), non-VAP group (n = 70) and control group (n = 65). The HRG, C reactive protein (CRP) and procalcitonin (PCT) levels were measured 72 hours after intubation, while blood sample was acquired from healthy controls for the test. HRG of VAP group was significantly lower than non-VAP group and control group (p < 0.001), while CRP and PCT were significantly higher (p < 0.001). The ROC analysis showed that the AUC of HRG was 0.777 95% CI (0.708-0.847) with a cut-off value of 38.55 μg/mL, which was lower than CRP [AUC = 0.912, 95% CI (0.847-0.950)] and PCT [AUC = 0.818, 95% CI (0.759-0.876)]. No linear correlation was found between HRG and CRP, as well as PCT (p > 0.05). However, the survival analysis showed that patients with higher level of HRG had a significantly higher survival rate (p < 0.001). The multivariate Cox regression analysis also demonstrated that the higher level of HRG was associated with better survival [HR 0.290, 95% CI (0.131-0.641), p = 0.002]. Serum HRG decreases when the patient develops VAP, which might be used as a biomarker for the diagnosis of VAP, with relatively less accuracy than PCT and CRP. However, HRG is valuable in predicting the clinical outcomes of mechanical ventilation patients.