Tuberculosis is an infectious disease caused by mycobacterium tuberculosis[1, 17].Significant increase in susceptibility to PTB and risk of death among people aged 65 and over[18].Elderly patients with PTB have a low sputum smear positivity rate, making diagnosis difficult and prone to delayed diagnosis. In addition, due to decreased immunity and more comorbidities, the elderly are more prone to treatment-related adverse drug reactions, poor therapeutic outcomes and high mortality rates[19].Co-infections with tuberculosis and bacterial pathogens have been reported, especially in populations with a high prevalence of tuberculosis.[20].Distinguishing tuberculosis from tuberculosis co-infection with bacterial infections is an important clinical challenge[21], and the inability to distinguish tuberculosis from tuberculosis co-infection with bacterial infections may lead to poorer health outcomes, including increased healthcare costs, antimicrobial drug resistance and mortality[22, 23].Bacterial culture is the gold standard for determining bacterial infection.However, the examination of bacterial cultures has a weakness; the cost of examination of bacterial cultures is quite expensive and the test takes a long time. The fastest culture results are known to exceed 24 hours [24].Therefore, combined lung infections in elderly patients with tuberculosis often lead to misdiagnosis and underdiagnosis due to the lack of effective diagnostic and therapeutic means, and the search for biomarkers for the early and rapid diagnosis of bacterial infections is a key issue that needs to be focused on by clinicians at present. The search for biomarkers for early and rapid diagnosis of bacterial infections is a key issue for clinicians to focus on.
NLR is a ratio that is more accurate than White blood cell count. Neutrophils and lymphocytes reflect not only the role of neutrophils in infection, but also the changes in lymphocytes in the body, in time to recognise the type of pathogen.The NLR is a low-cost, routinely used, reproducible assay that can be derived from a white blood cell count and has been shown to be a marker of the systemic inflammatory response[10, 25].In this study, the level of NLR in the infected group was significantly higher than that in the non-infected group (P < 0.05), and the level of NLR in the infected group was higher in the critically ill patients than in the non-critically ill patients, which is also in agreement with the findings of Nagai [26]et al.During infection, dendritic cells can present antigens to natural killer T cells, leading to local extravasation of neutrophils, which promotes the entry of natural killer T cells into tissues and affects peripheral blood lymphocytes. Therefore, NLR can better dynamically respond to the infection status of the organism[26, 27].
RDW is a parameter that reflects the heterogeneity of red blood cell volume. Previous studies have suggested that RDW may be a laboratory indicator of infection or inflammation[28].Hu et al. demonstrated high expression of RDW levels in elderly patients with lung infections undergoing general anesthesia for abdominal surgery with tracheal intubation, and that RDW was involved in the development of lung infections and aggravation of patients' conditions[29].In addition, one study reported that elevated RDW values were associated with the severity of neonatal sepsis[30].The levels of RDW were significantly higher in the infected group than in the non-infected group in this study (P < 0.05), which was also consistent with the severity of the disease. RDW levels were positively correlated with c-reactive protein、d-dimer、erythrocyte sedimentation rate and ferritin levels (all P < 0.05).
This is the first retrospective study of FAR in tuberculosis disease.Fibrinogen is an acute-phase protein synthesized by the liver that increases rapidly in acute-phase illnesses, such as bacterial infections and trauma[31].Albumin are negative counter-reactors that enhance catabolism to fight inflammation[32].FAR is a combination of fibrinogen and albumin levels that can be used as a potential prognostic biomarker for predicting risk of various diseases.Zhao et al. reported the relationship between FAR and diabetic cardiac autonomic neuropathy (DCAN) in patients with type 2 diabetes mellitus(T2DM). For the first time, FAR was found to be an independent predictor of the risk of developing DCAN in T2DM[33].Wang et al. demonstrated that high levels of fibrinogen to albumin ratios on admission may be closely related to hematoma expansion after cerebral hemorrhage[34].Other studies have reported tha higher FAR levels are associated with a higher increased risk of in-hospital mortality in critically ill patients with acute kidney injury[35].In this study, we found that FAR levels were significantly higher in the infected group compared to the non-infected group, and there was a positive correlation between FAR levels and the levels of leukocytes、platelets、c-reactive protein、d-dimer、erythrocyte sedimentation rate and ferritin (all P < 0.05) and that increased FAR levels correlated with the severity of tuberculosis and had a predictive value.ROC curve analysis showed that the AUC of NLR, FAR and RDW were 0.861, 0.818 and 0.799.Our attempt to combine NLR, RDW and FAR dramatically improved our ability to predict PTB combined with bacterial infection with an AUC value of 0.982, a sensitivity of 0.986% and a specificity of 89.6%. All of them were higher than individual indicators.The above results suggest that peripheral blood NLR, FAR and RDW levels may provide a better early diagnosis of PTB combined with bacterial infection.The present study is a retrospective study based on prospective data with many limitations such as small sample size from a single centre and inclusion of only patients with PTB and PTB with bacterial infections, which needs to be validated by further expansion of the specimen size.And the experimental subjects selected for this study were not stratified for pathogenesis, thus there may be differences in the results, future research is needed to study the changes in the levels of NLR, RDW and FAR in patients with tuberculosis due to infection by different pathogens, and to improve the sensitivity of NLR, RDW and FAR in the diagnosis of tuberculosis combined with bacterial infections.Further analysis shows that NLR, RDW, and FAR are calculated indicators in routine blood analysis, which are inexpensive, simple and practical, and it can be issued as a new combination of indicators in the blood analysis test report, which can be used in healthcare institutions, especially primary healthcare institutions, to assist in differential diagnosis of bacterial infections and, which is of certain significance for saving medical costs.
In summary, NLR, FAR and RDW indicators have certain clinical reference value for the differential diagnosis of PTB combined with bacterial infection. And the diagnostic value of the three combined tests is higher. Clinicians should closely monitor the changes of NLR, FAR and RDW indexes to reduce the misdiagnosis rate and omission rate, to facilitate the understanding of the patient's disease condition, and to provide reference for the clinical use of drugs.