Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome

Abstract

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 × 104 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. Conclusion: 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. © 2008 Nathani et al.; licensee BioMed Central Ltd.