title: Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kropski
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Fremont
authors.affiliation: Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Calfee
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. Electronic address: Lorraine.Ware@vanderbilt.edu.
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
mesh_terms: D055371:Acute Lung Injury / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D003422:Critical Care / Q000379:methods; D016638:Critical Illness; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011654:Pulmonary Edema / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D012016:Reference Values; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D020545:Respiratory Mucosa / Q000378:metabolism; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014598:Uteroglobin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C556389:SCGB1A1 protein, human; D014598:Uteroglobin