Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis

Cystic fibrosis (CF) is characterized by the production of abnormally thick secretions in the airways, chronic bacterial endobronchial infections and a chronic, predominantly neutrophilic inflammatory response. Therefore, mye loperoxidase (MPO) and lactoferrin are frequently used as inflammatory mark ers. Recently, a new protein in the neutrophil granules, human neutrophil l ipocalin (HNL) has been discovered. The aim of the present study was to inv estigate HNL in sera of patients with CF and its relation to MPO and lactof errin as well as to acute pulmonary exacerbation. Serum concentrations of HNL, MPO and lactoferrin were determined in 42 pati ents with CF and in 25 healthy subjects. Patients with CF were divided into groups,vith and without acute pulmonary exacerbation (APE) and also with a nd without colonization with Pseudomonas aeruginosa (Pa). Median serum levels of HNL (200.5 mu g.L-1), MPO (595 mu g.L-1) and lactofe rrin (1,356.5 mu g.L-1) were significantly increased in patients with CF co mpared to control subjects (57.7, 178 and 478 mu g.L-1, respectively; p<0.0 001). CF patients with APE had significantly increased serum concentrations of HNL (321 versus 97.7 mu g.L-1 p<0.0001), MPO (1,125 versus 300 mu g.L-1 p<0.005) and lactoferrin (4,936 versus 980 mu g.L-1; p<0.001) compared wit h patients in stable clinical condition. Similarly, patients colonized with Pa had significantly higher concentrations of HNL, MPO and lactoferrin tha n Pa negative patients. These results indicate that in patients with cystic fibrosis, serum concent rations of human neutrophil lipocalin are markedly increased with a strong relationship to myeloperoxidase and lactoferrin, Thus, determination of ser um human neutrophil lipocalin concentrations may be another useful diagnost ic tool to monitor neutrophil inflammation in cystic fibrosis, The more mar ked difference in human neutrophil lipocalin compared with myeloperoxidase concentrations with no overlap between patients with acute pulmonary exacer bation and those in stable condition even suggests that human neutrophil li pocalin may be a more sensitive and specific discriminator.