Abstract
IntroductionCommunity-acquired pneumonia (CAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory failure with high mortality. Kallistatin, an endogenous tissue kallikrein inhibitor, has been reported to be protective in various human diseases. The aim of this study was to assess the correlations of kallistatin with other biomarkers and to determine whether kallistatin levels have a prognostic value in severe CAP.MethodsPlasma samples and clinical data were prospectively collected from 54 patients with severe CAP requiring ICU admission. Seventeen healthy control subjects were included for comparison. Plasma kallistatin, kallikrein, and other biomarkers of inflammation (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, C-reactive protein (CRP)), and anti-coagulation (protein C, anti-thrombin III) were measured on days 1 and 4 of ICU admission. Comparison between survivors (n = 41) and nonsurvivors (n = 13) was performed.ResultsPlasma kallistatin was significantly consumed in severe CAP patients compared with healthy individuals. Lower day 1 kallistatin levels showed a strong trend toward increased mortality (P = 0.018) and higher day 1 CURB-65 scores (P = 0.004). Plasma kallistatin levels on day 1 of ICU admission were significantly decreased in patients who developed septic shock (P = 0.017) and who had acute respiratory distress syndrome (P = 0.044). In addition, kallistatin levels were positively correlated with anti-thrombin III and protein C and inversely correlated with IL-1β, IL-6, and CRP levels. In a multivariate logistic regression analysis, higher day 1 CURB-65 scores were independent predictors of mortality (odds ratio = 29.9; P = 0.009). Also, higher day 1 kallistatin levels were independently associated with a decreased risk of death (odds ratio, 0.1) with a nearly significant statistical difference (P = 0.056). Furthermore, we found that a cutoff level of 6.5 μg/ml of day 1 kallistatin determined by receiver operating characteristic curves could be used to distinguish between patients who survived in 60 days and those who did not.ConclusionsThese results suggest that kallistatin may serve as a novel marker for severe CAP prognosis and may be involved in the pathogenesis of CAP through antiinflammatory and anticoagulation effects.See related letter by Katz et al., http://ccforum.com/content/17/2/429
Highlights
Community-acquired pneumonia (CAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory failure with high mortality
135 patients admitted to ICUs with a diagnosis of pneumonia were screened during the enrollment period, and 13 patients were screened with a refusal of informed consent, 27 with prior hospitalization within 15 days before admission, 28 with an underlying terminal illness receiving palliative treatment, and 13 with delayed ICU admission more than 48 hours were excluded, leaving 54 patients with severe CAP included in this study
This study demonstrates that plasma kallistatin is consumed in patients with severe CAP requiring ICU admission as compared with healthy individuals, and its levels are associated with disease severity and outcome
Summary
Community-acquired pneumonia (CAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory failure with high mortality. Up to 36% of hospitalized CAP patients require admission to the intensive care unit (ICU). These patients present with more severe disease, more morbidities, and higher mortality rate [1]. In the carbon tetrachloride-induced liver-injury mouse model, transgenic expression of kallistatin was shown to attenuate liver damage through reduction of oxidative stress [19]. These findings indicate that kallistatin has protective effects against vascular and organ damage by preventing inflammation, apoptosis, and oxidative stress. Clinical studies investigating the association of plasma kallistatin levels with human infectious diseases, such as CAP, are still lacking
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