Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome.
BACKGROUND
Kerbs von Lungren 6 antigen (KL-6) is expressed on the surface of alveolar type II cells, and elevated plasma and epithelial lining fluid levels of KL-6 have previously been shown to correlate with the severity of disease and survival in acute respiratory distress syndrome (ARDS). The relationship between alveolar inflammation and KL-6 measurements has not been ascertained. We hypothesized that the elevation of KL-6 in ARDS is dependent upon the severity of neutrophilic inflammation. Furthermore we were interested in the relationship between significant alveolar infection and KL-6 levels.


METHODS
Plasma arterial samples were collected from ARDS patients on day 1 and when possible on day 4 along with bronchoalveolar lavage fluid (BALF) samples on the same day. Bacterial growth in the BALF was determined by quantitative cultures and was defined as significant at counts >1 x 10(4) colony-forming units.


RESULTS
Plasma KL-6 levels in ARDS patients were elevated compared with at-risk control individuals (P = 0.014) and with normal control individuals (P = 0.02). The plasma KL-6 level correlated with the Murray Lung Injury Score (r = 0.68, P = 0.001) and with BALF KL-6 (r = 0.3260, P = 0.04). The BALF KL-6 level was detectable in all ARDS cases and was lower on both day 0 and day 4 in those who survived. BALF KL-6 also correlated with the BALF myeloperoxidase activity (r = 0.363, P = 0.027), with the BALF cell count per millilitre (r = 0.318, P = 0.038), with BALF epithelial-cell-derived neutrophil attractant 78; (r = 0.37, P = 0.016) and with BALF vascular endothelial growth factor (r = 0.35, P = 0.024). The BALF KL-6 level of ARDS patients with significant pathogenic bacterial growth was similar compared with those without significant infection.


CONCLUSIONS
KL-6 may represent a useful marker of alveolar type II cell dysfunction in ARDS since the levels reflect the severity of lung injury and neutrophilic inflammation. KL-6 release across the alveolar epithelial barrier is associated with a poor prognosis. The pathophysiological roles of KL-6 in the development of ARDS warrant further study.
Nathani
Nazim
N
Lung Injury and Fibrosis Treatment Program, Department of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Perkins
Gavin D
GD
Tunnicliffe
William
W
Murphy
Nick
N
Manji
Mav
M
Thickett
David R
DR
D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood* / Q000502:physiology; D017063:Outcome Assessment, Health Care; D011014:Pneumonia / Q000097:blood*; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000145:classification / Q000401:mortality; D012720:Severity of Illness Index
D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1