Jonathan A Kropski1, Richard D Fremont1, Carolyn S Calfee2, Lorraine B Ware3. 1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. 2. Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA. 3. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. Electronic address: Lorraine.Ware@vanderbilt.edu.
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.
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.
Authors: G R Bernard; A Artigas; K L Brigham; J Carlet; K Falke; L Hudson; M Lamy; J R Legall; A Morris; R Spragg Journal: Am J Respir Crit Care Med Date: 1994-03 Impact factor: 21.405
Authors: Roy G Brower; Michael A Matthay; Alan Morris; David Schoenfeld; B Taylor Thompson; Arthur Wheeler Journal: N Engl J Med Date: 2000-05-04 Impact factor: 91.245
Authors: P G Jorens; Y Sibille; N J Goulding; F J van Overveld; A G Herman; L Bossaert; W A De Backer; R Lauwerys; R J Flower; A Bernard Journal: Eur Respir J Date: 1995-10 Impact factor: 16.671
Authors: A K Sabharwal; S P Bajaj; A Ameri; S M Tricomi; T M Hyers; T E Dahms; F B Taylor; M S Bajaj Journal: Am J Respir Crit Care Med Date: 1995-03 Impact factor: 21.405
Authors: Carolyn S Calfee; Kevin Delucchi; Polly E Parsons; B Taylor Thompson; Lorraine B Ware; Michael A Matthay Journal: Lancet Respir Med Date: 2014-05-19 Impact factor: 30.700
Authors: R J Shah; N Wickersham; D J Lederer; S M Palmer; E Cantu; J M Diamond; S M Kawut; V N Lama; S Bhorade; M Crespo; E Demissie; J Sonett; K Wille; J Orens; A Weinacker; P Shah; S Arcasoy; D S Wilkes; J D Christie; L B Ware Journal: Am J Transplant Date: 2014-01-08 Impact factor: 8.086
Authors: J M Diamond; S M Kawut; D J Lederer; V N Ahya; B Kohl; J Sonett; S M Palmer; M Crespo; K Wille; V N Lama; P D Shah; J Orens; S Bhorade; A Weinacker; E Demissie; S Bellamy; J D Christie; L B Ware Journal: Am J Transplant Date: 2011-02-07 Impact factor: 8.086
Authors: Carolyn S Calfee; David R Janz; Gordon R Bernard; Addison K May; Kirsten N Kangelaris; Michael A Matthay; Lorraine B Ware Journal: Chest Date: 2015-06 Impact factor: 9.410
Authors: Carl J Johnston; Casey M Manning; Javier Rangel-Moreno; Troy D Randall; Eric Hernady; Jacob N Finkelstein; Jacqueline P Williams Journal: Radiat Res Date: 2012-03-15 Impact factor: 2.841