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Comparative Study
. 2009 Jun;135(6):1440-1447.
doi: 10.1378/chest.08-2465. Epub 2009 Feb 2.

Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury

Jonathan A Kropski  1 , Richard D Fremont  1 , Carolyn S Calfee  2 , Lorraine B Ware  3
Affiliations
Comparative Study

Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury

Jonathan A Kropski et al. Chest. 2009 Jun.

Abstract

Background: Acute lung injury (ALI) and ARDS are common clinical syndromes that are underdiagnosed. Clara cell secretory protein (CC16) is an antiinflammatory protein secreted by the Clara cells of the distal respiratory epithelium that has been proposed as a biomarker of lung epithelial injury. We tested the diagnostic and prognostic utility of CC16 in patients with non-trauma-related ALI/ARDS compared to a control group of patients with acute cardiogenic pulmonary edema (CPE).

Methods: Plasma and pulmonary edema fluid samples were obtained from medical and surgical patients with ALI/ARDS or CPE requiring intubation for mechanical ventilation. The etiology of pulmonary edema was determined using consensus clinical criteria for ALI/ARDS and CPE and the edema fluid-to-plasma protein ratio. Plasma and edema fluid CC16 levels were measured by sandwich enzyme-linked immunosorbent assay. CC16 levels were log transformed for analysis, and comparisons were made by the Student t test or Chi(2) as appropriate.

Results: Compared to patients with CPE (n = 9), patients with ALI/ARDS (n = 23) had lower median CC16 levels in plasma (22 ng/mL [interquartile range (IQR), 9 to 44 ng/mL] vs 55 ng/mL [IQR, 18 to 123 ng/mL], respectively; p = 0.053) and pulmonary edema fluid (1,950 ng/mL [IQR, 1,780 to 4,024 ng/mL] vs 4,835 ng/mL [IQR, 2,006 to 6,350 ng/mL], respectively; p = 0.044). Relative to total pulmonary edema fluid protein concentration, the median CC16 level was significantly lower in patients with ALI/ARDS (45 ng CC16/mg total protein [IQR, 4 to 64 ng CC16/mg total protein] vs 120 ng CC16/mg total protein [IQR, 87 to 257 ng CC16/mg total protein], respectively; p = 0.005). Neither plasma nor edema fluid CC16 levels predicted mortality, the number of days of unassisted ventilation, or ICU length of stay.

Conclusion: CC16 is a promising diagnostic biomarker for helping to discriminate ALI from CPE. Larger scale validation is warranted to better characterize the utility of CC16 in the diagnosis of this underrecognized syndrome.

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Conflict of interest statement

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Figures

Figure 1
Figure 1
Box plot summary of CC16 levels in pulmonary edema fluid (left, A) and plasma (right, B) of patients with CPE or ALI/ARDS. Horizontal line represents median, box includes 25th to 75th percentile, error bars include tenth-ninetieth percentile.
Figure 2
Figure 2
Left, A: box plot summary of edema fluid CC16 levels compared to total pulmonary edema fluid protein (ng CC16/mg total protein) in patients with CPE or ALI/ARDS. Horizontal line represents median, box includes twenty-fifth to seventy-fifth percentile, error bars include tenth-ninetieth percentile. Right, B: box plot summary of the pulmonary edema fluid to plasma ratio of CC16 in patients with CPE or ALI/ARDS. Horizontal line represents median, box includes 25th to 75th percentile, error bars include the 10th to 90th percentile.
See this image and copyright information in PMC

Comment in

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