Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia

Abstract

Background: Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. Methods: The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor a (TNFa) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, >65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, >65 years of age) scales. A total of 453 hospitalised CAP patients were included. Results: The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. Conclusions: Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia

“…Previous studies have reported that an excess of proinflammatory cytokines is associated with poor prognosis of CAP [7][8][9][10][11][12][13][14]. Our results showed a similar relationship between high levels of cytokines and poor outcomes in the specific population with PP.…”

“…A recent study 11 found that the addition of biological markers such as C-reactive protein to severity scoring systems (PSI, CURB-65 and CRB-65) improves the 30-day mortality prediction. Further studies are currently needed to establish the potential role of IL-6 and IL-8 in supplementing prognosis scoring systems in order to achieve a more accurate identification of patients with a greater probability of death.…”

“…Excessive cytokine response in patients with severe CAP has been linked with deleterious effects and poor prognosis [7][8][9][10][11][12][13][14].…”

Validity of British Thoracic Society guidance (the CRB-65 rule) for predicting the severity of pneumonia in general practice: systematic review and meta-analysis

“…These tests have been shown to be an adjunct in the diagnosis of CAP, and preliminary results indicate they may also have predictive value for severity. 16,18,35,36 A role for these tests may be found as an additional predictor of severity alongside CRB-65, but it is more likely they could be used as a further discriminator for the appropriate site of care after application of CRB-65.…”

“…8,[11][12][13][14][15][16][17][18][19][20][21][22][23] Table 1 summarises the characteristics of the included studies. Additional data were provided from three studies, 13,15,23 and clarification of included overlapping subjects obtained from two other studies.…”