Elastase and granzymes during meningococcal disease in children: correlation to disease severity.

Abstract

To investigate the levels of human neutrophil elastase and lymphocyte-derived granzymes A and B in relation to disease severity in children with meningococcal disease. Clinical observational cohort study. Paediatric intensive care unit. All patients with meningococcal disease during the study period were included. Blood sampling was done on the day of admission and on days 3 and 7. Assays for elastase and granzymes were done with ELISA. Sixty-one patients were included: 19 having distinct meningitis; 17 meningitis and shock; and 25 fulminant septicaemia. On admission levels of elastase were increased in all patients, being highest in those with fulminant septicaemia and lowest in those with distinct meningitis. Granzyme A (although marginally) and granzyme B levels were only increased in patients with shock. In 20 of the 28 patients admitted for > or = 3 days elastase decreased from admission ("rapid-decrease" group). In the remaining 8 patients, elastase started to decrease after 2 days ("slow-decrease" group). Patients of the "slow-decrease" group had a higher temperature up to day 4, needed more respiratory support (mean airway pressure in cm H2O on days 3 and 4: p=0.02 and p<0.01, respectively), and more circulatory support (>2 inotropic agents on day 3; p=0.04) compared with the "rapid-decrease" group. Human neutrophil elastase and granzyme B are related with disease severity during the initial phase of meningococcal disease and prolonged neutrophil activation is associated with the extent of organ dysfunction during the period thereafter.