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


CONCLUSIONS
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.
Determann
Rogier M
RM
Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. r.m.determann@amc.uva.nl
Millo
Julian L
JL
Waddy
Sam
S
Lutter
Rene
R
Garrard
Chris S
CS
Schultz
Marcus J
MJ
D055371:Acute Lung Injury / Q000097:blood* / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D053717:Pneumonia, Ventilator-Associated / Q000097:blood* / Q000150:complications*; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D012372:ROC Curve; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000175:diagnosis*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014598:Uteroglobin / Q000097:blood*
D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1; D037663:Pulmonary Surfactant-Associated Protein D; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C556389:SCGB1A1 protein, human; D014598:Uteroglobin