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Cytokeratin 19 fragments in patients with acute lung injury: a preliminary observation
Jean-Baptiste Stern1, Catherine Paugam, Pierre Validire
1Institut Mutualiste Montsouris, Département Thoracique, 42 bd Jourdan, 75014 Paris, France. jean-baptiste.stern@imm.fr
Objective:
Cytokeratin 19 (CK19) is a specific cytoskeletal structure for alveolar epithelium. We hypothesized that the levels of CK19 fragments in bronchoalveolar lavage (BAL) fluid could serve as an index of epithelial injury and as a prognosis marker in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aims of our study were, in patients with ALI/ARDS: (1) to measure CK19 fragments concentrations in BAL fluid, (2) to assess its prognostic value, and (3) to identify the cellular source of CK19 in the alveolar space.
Design:
Prospective preliminary study.
Setting:
University hospital surgical ICU.
Patients:
Twenty-two mechanically ventilated patients with ALI/ARDS and 10 non-ventilated control patients. Plasma samples were obtained for 11 ALI/ARDS patients.
Measurements And Results:
The concentration of BAL CK19 fragments was higher in patients (median 4916 pg/ml, 25th-75th percentile 2717-10533) than in controls (2208 pg/ml. 767-3923; p =0.05), and higher in 10 non-survivors (7051 pg/ml, 4372-13371) than in 12 survivors (2888 pg/ml, 1315-5639; p =0.03 among ALI/ARDS patients). BAL CK19 fragment concentration did not correlate with simplified acute physiologic score, lung injury score or PaO(2)/FIO(2) ratio, but correlated positively with BAL albumin concentration (p =0.002) and with number of BAL macrophages (p=0.0001). Plasma CK19 fragment concentrations were 10 times lower than those in BAL. Immunohistochemical staining for CK19 showed a strong labelling of injured detached epithelial cells and hyperplastic epithelium in ALI/ARDS lung samples.
Conclusion:
CK19 fragment concentrations were found to be elevated in BAL fluid in ALI/ARDS patients compared with control subjects. High BAL CK19 fragment levels were associated with a poor prognosis.