Open Access Research article

Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study

Rogier M Determann12*, Julian L Millo3, Sam Waddy3, Rene Lutter45, Chris S Garrard3 and Marcus J Schultz126

Author Affiliations

1 Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands

2 Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A), Academic Medical Center, Amsterdam, The Netherlands

3 Department of Intensive Care Medicine, John Radcliffe Hospital, Oxford, UK

4 Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands

5 Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands

6 HERMES Critical Care Group, Amsterdam, The Netherlands

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BMC Pulmonary Medicine 2009, 9:49  doi:10.1186/1471-2466-9-49

Published: 3 December 2009

Abstract

Background

Despite consensus criteria, diagnosing acute lung injury, or its more severe form acute respiratory distress syndrome (ALI/ARDS) remains challenging. Adding objective measures, such as plasma levels of biological markers could facilitate recognition of ALI/ARDS. This study was designed to assess and compare the diagnostic accuracy of biological markers for ALI/ARDS with ventilator-associated pneumonia (VAP).

Methods

We performed serial measurements of Clara cell protein (CC16), soluble receptor for advanced glycation end products (sRAGE), surfactant protein D (SP-D) and Krebs von den Lungen (KL-6) in plasma of patients with VAP and mechanically ventilated control patients without VAP. ALI/ARDS was diagnosed using the criteria of the North-American European consensus conference.

Results

Thirty-seven patients were enrolled - 22 patients with VAP and 15 control patients. Ten patients with pneumonia met the ALI/ARDS consensus criteria. Control patients never met these criteria. Plasma CC16 had a good diagnostic capacity for ALI/ARDS as shown by the receiver operating characteristic curve with an area under the curve of 0.91 (95% confidence interval (CI) 0.79 - 1.00; p < 0.001). Identification of ALI/ARDS patients by sudden increases in plasma CC16 of 30% or more yielded a sensitivity of 90% and a specificity of 92%. Of note, levels of CC16 increased 2 days before ALI/ARDS diagnosis. A cut-off level of 50 ng/ml SP-D yielded a specificity of 100% while the sensitivity was 70%. The area under the curve for SP-D was 0.80 (95% CI 0.58 - 1.00; p = 0.02). The diagnostic accuracies of KL-6 and sRAGE were low.

Conclusion

Plasma CC16 seems a potential biological marker for ALI/ARDS in patients with VAP. Plasma levels of sRAGE, SP-D and KL-6 have limited discriminative power for diagnosing ALI/ARDS in VAP.