KL-6 in acute lung injury: will it leave its mark?

In the previous issue of Critical Care Nathani and colleagues have assessed KL-6, a specific marker of type 2 alveolar epithelial cell injury, as a biomarker in acute lung injury (ALI) [1]. Biomarkers allow identification of patients at risk of developing disease or can be used as surrogate measures for clinical outcomes. Additionally, measuring biological markers may be a valuable tool in understanding disease pathogenesis. In ALI, the alveolar capillary barrier is disrupted and the alveolar epithelial cell function is critical to the recovery from ALI/acute respiratory distress syndrome (ARDS) [2]. This knowledge provides a rationale for measurement of alveolar epithelial cell injury using surrogate biochemical measures such as KL-6, as a biomarker of ALI.In the study of Nathani and colleagues, plasma and bronchoalveolar lavage samples were collected following inclusion and on day 4 from 30 ventilated ALI patients, from 12 patients at risk of developing ALI and from 10 nonsmoking volunteers free of respiratory disease The study therefore had the benefit of allowing the investigators to look at KL-6 both in physiological and pathological states. The important findings from the study are that plasma KL-6 levels are increased in patients with ALI, plasma KL-6 correlates with the severity of lung injury and plasma KL-6 is significantly elevated in nonsurvivors compared with survivors. Furthermore bronchoalveolar lavage KL-6 is elevated in patients with ALI and is higher in nonsurvivors. KL-6 did not identify patients at risk of developing ALI. These findings extend the previous data showing KL-6 is elevated in plasma and epithelial lining fluid in ALI [3,4].In relation to KL-6 in ALI, questions that still remain to be answered include the specificity of the type 2 epithelial cell as the source of KL-6 [5] as well as a need to confirm whether KL-6 elevation reflects epithelial cell injury, regeneration or secretion in response to inflammatory mediators. In addition, me