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. 2009 Dec 3:9:49.
doi: 10.1186/1471-2466-9-49.

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

Rogier M Determann  1 , Julian L Millo, Sam Waddy, Rene Lutter, Chris S Garrard, Marcus J Schultz
Affiliations

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

Rogier M Determann et al. BMC Pulm Med. .

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.

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Figures

Figure 1
Figure 1
Respiratory data in VAP patients and control patients. Tidal volume (VT) per kilogram ideal body weight (IBW), positive end-expiratory pressure and peak airway pressure in patients developing ventilator-associated pneumonia (upper graphs) and control patients (lower graphs).
Figure 2
Figure 2
CC16 and sRAGE levels in VAP patients and control patients. Plasma levels of Clara cell protein (CC16) and soluble receptor for advanced glycation end products (sRAGE) in patients who developed ventilator-associated pneumonia (left graphs) and mechanically ventilated control patients (right graphs). In the left graphs day 0 represents the day of ventilator-associated pneumonia diagnosis. In the right graphs day 0 represents the day of start of mechanical ventilation.
Figure 3
Figure 3
SP-D and KL-6 levels in VAP patients and control patients. Plasma levels of surfactant protein D (SP-D) and Krebs von den Lungen (KL-6) in patients who developed ventilator-associated pneumonia (left graphs) and mechanically ventilated control patients (right graphs).
Figure 4
Figure 4
Biomarker levels in VAP patients with and without ALI/ARDS. Plasma levels of CC16, sRAGE, SP-D and KL-6 in patients developing ventilator-associated pneumonia. Open circles: patients without ALI/ARDS after onset of ventilator-associated pneumonia, closed circles: patients who progressed to ALI/ARDS at or after onset of ventilator-associated pneumonia.
Figure 5
Figure 5
ROC curves. Receiver operating characteristic curves of CC16, sRAGE, SP-D and KL-6 for the diagnosis of ALI/ARDS on the day patients developed ventilator-associated pneumonia. AUC area under the curve.
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