Serum cortisol predicts death and critical disease independently of CRB-65 score in community-acquired pneumonia: a prospective observational cohort study

Martin Kolditz, Gert Höffken, Peter Martus, Gernot Rohde, Hartwig Schütte, Robert Bals, Norbert Suttorp, Mathias W Pletz, CAPNETZ study group, T Bauer, F Kunitz, B Hauptmeier, S Ewig, C Schumann, T Schaberg, I Hering, K Dalhoff, P Heyer, M Prediger, K Kaube, T Welte, J Rademacher, B Drewelow, J Majcher-Peszynska, N Suttorp, A Tessmer, O Burghuber, G Rainer, W Petermann, H Buschmann, R Kröning, Y Aydin, S Krüger, W Pankow, R Marre, G Barten, L Gosman, H von Baum, T Illmann, M Wallner, Martin Kolditz, Gert Höffken, Peter Martus, Gernot Rohde, Hartwig Schütte, Robert Bals, Norbert Suttorp, Mathias W Pletz, CAPNETZ study group, T Bauer, F Kunitz, B Hauptmeier, S Ewig, C Schumann, T Schaberg, I Hering, K Dalhoff, P Heyer, M Prediger, K Kaube, T Welte, J Rademacher, B Drewelow, J Majcher-Peszynska, N Suttorp, A Tessmer, O Burghuber, G Rainer, W Petermann, H Buschmann, R Kröning, Y Aydin, S Krüger, W Pankow, R Marre, G Barten, L Gosman, H von Baum, T Illmann, M Wallner

Abstract

Background: Several biomarkers and prognostic scores have been evaluated to predict prognosis in community-acquired pneumonia (CAP). Optimal risk stratification remains to be evaluated. The aim of this study was to evaluate serum cortisol as biomarker for the prediction of adverse outcomes independently of the CRB-65 score und inflammatory biomarkers in a large cohort of hospitalised patients with CAP.

Methods: 984 hospitalised CAP-patients were included. Serum cortisol was measured and its prognostic accuracy compared to the CRB-65 score, leucocyte count and C-reactive protein. Predefined endpoints were 30-day mortality and the combined endpoint critical pneumonia, defined as presence of death occurring during antibiotic treatment, mechanical ventilation, catecholamine treatment or ICU admission.

Results: 64 patients died (6.5%) and 85 developed critical pneumonia (8.6%). Cortisol levels were significantly elevated in both adverse outcomes (p < 0.001) and predicted mortality (AUC 0.70, cut-off 795 nmol/L) and critical pneumonia (AUC 0.71) independently of all other measured variables after logistic regression analysis (p = 0.005 and 0.001, respectively). Prognostic accuracy of CRB-65 was significantly improved by adding cortisol levels (combined AUC 0.81 for both endpoints). In Kaplan-Meier analysis, cortisol predicted survival within different CRB-65 strata (p = 0.003). In subgroup analyses, cortisol independently predicted critical pneumonia when compared to procalcitonin, the CURB65 score and minor criteria for severe pneumonia according to the 2007 ATS/IDSA-guideline.

Conclusion: Cortisol predicts mortality and critical disease in hospitalised CAP-patients independently of clinical scores and inflammatory biomarkers. It should be incorporated into trials assessing optimal combinations of clinical criteria and biomarkers to improve initial high risk prediction in CAP.

Figures

Figure 1
Figure 1
Boxplots of cortisol levels by severity of CAP according to CRB-65 score. * 1 case (cortisol 4509 nmol/l) not shown; # 3 cases (cortisol 3894-7817 nmol/l) not shown; § 2 cases (cortisol 4116, 9558 nmol/l) not shown; & 2 cases (cortisol 3858, 3924 nmol/l) not shown.
Figure 2
Figure 2
ROC-Plot for 30-day mortality, comparing CRB-65 score, cortisol and CRB65-score plus cortisol (p = 0.001 versus CRB65 score alone).
Figure 3
Figure 3
ROC-Plots for 30-day critical pneumonia, comparing CRB-65 score, cortisol and CRB65-score plus cortisol (p = 0.002 versus CRB65 score alone).
Figure 4
Figure 4
Kaplan-Meyer analysis for 30-day mortality according to cortisol quartiles (2/984 cases censored before day 30).
Figure 5
Figure 5
Kaplan-Meyer analysis for 30-day mortality within CRB-65 score class 0 (2/984 cases censored before day 30).
Figure 6
Figure 6
Kaplan-Meyer analysis for 30-day mortality within CRB-65 score class 1 (2/984 cases censored before day 30).
Figure 7
Figure 7
Kaplan-Meyer analysis for 30-day mortality within CRB-65 score class 2-4 (2/984 cases censored before day 30).

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