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

Abstract

BackgroundDespite 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).MethodsWe 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.ResultsThirty-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.ConclusionPlasma 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.

Diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with acute respiratory distress syndrome

“…ARDS patients in the present study had more than double the median values of CC16 when compared with non‐ARDS patients. While previous studies have demonstrated a relatively stable median CC16 value in normal controls (5‐7 ng/mL),12, 13 the median CC16 value of non‐ARDS patients in this study appeared to be higher (24.13±12.32 ng/mL). Some cases from the non‐ARDS patient group had developed pulmonary diseases such as pneumonia, which may have caused an elevated production of CC16 18.…”

“…The CC16 values of above 33.3 ng/mL statistically discriminated differentiates between ARDS and non‐ARDS patients, demonstrating a relatively high diagnostic accuracy. Although we did not compare the diagnostic value of CC16 with other biomarkers in this study, previous studies have demonstrated that CC16 had greater diagnostic capacity than surfactant protein‐D (SP‐D), Krebs von den Lungen‐6 (KL‐6), and soluble receptor for advanced glycation end‐products (sRAGE) for ARDS 13. A combination of CC16, SP‐D, and KL‐6 could provide enhanced efficacy in lung disease screening and diagnosis 14.…”

Biomarkers in acute respiratory distress syndrome

“…Data have been mixed with that of some authors showing strong correlations between plasma CC-16 levels and ARDS development [10,11], whereas others have shown poor or inverse correlations [12,14]. This may relate, in part, to the choice of control population, as CC-16 levels are also elevated in heart failure patients [14].…”

“…Unfortunately, serum KL-6 levels are elevated in other respiratory diseases including interstitial pneumonitis, so may not be specific for ARDS in patients with underlying lung disease. Indeed, a study of critically ill patients with ventilator-associated pneumonia showed no difference in serum KL-6 levels between those who developed ARDS and those who did not [11].…”

“…Its utility as a marker of ARDS in humans, however, is questionable and data have been very mixed. Some studies have shown an association between plasma sRAGE levels and ARDS development in mixed ICU patients [17, 36,86] and trauma patients [87], but several robust studies have not shown any association [7 & , 10,11] and it is likely that sRAGE is a marker of illness severity rather than ARDS.…”