Urinary leukotriene excretion profile in children with exercise-induced asthma compared with controls: a preliminary study.

BACKGROUND: Leukotrienes are among the most important mediators associated with inflammatory responses in patients with exercise induced asthma (EIA). The aim of this study was to investigate the impact of exercise on the urinary leukotriene profile. Hence, we compared post exercise changes of urinary leukotriene E4 (LTE4) concentration between children with EIA and healthy controls. METHODS: Ten children with EIA and 15 controls were enrolled. Both groups underwent a standardised exercise challenge test (ECT). LTE4 concentration was measured in urine samples obtained pre and post ECT, using enzyme immunoassay and adjusted by urinary creatinine concentrations. RESULTS: Median (minimum-maximum) pre ECT concentration of LTE4 was 17.82 (7.58-90.23 pg/ml) in EIA and 17.24 (4.64-64.02 pg/ml) in controls, p=0.86. LTE4 concentration post ECT were 23.37 (4.02-93.00 pg/ml) in EIA and 11.74 (0.13-25.09 pg/ml) in controls, p=0.02. Changes of LTE4 concentration post ECT were 2.54 (-31.98 to 43.31 pg/ml) in cases and -13.53 (-46.00 to 11.02 pg/ml) in controls, p=0.03. There was no significant correlation between basal predicted FEV(1) [%] and changes in LTE4 concentration in cases (i.e., r(s)=0.14) nor controls (i.e., r(s)=0.12). There was a tendency towards more pronounced changes in LTE4 concentration post ECT in children with moderate/mild persistent asthma compared to those with mild but intermittent asthma. CONCLUSIONS: Children with EIA had significantly higher changes of urinary LTE4 concentrations post ECT compared to healthy controls. Urinary measurement of LTE4 may be an interesting and non-invasive option to assess control of EIA in children.

A humanized monoclonal antibody against respiratory syncytial virus (palivizumab) inhibits RSV-induced neurogenic-mediated inflammation in rat airways.

Respiratory syncytial virus (RSV) is the most important respiratory pathogen in infancy and early childhood and may predispose to subsequent lower respiratory tract illness. Recent data indicate that RSV up-regulates the substance P receptor, making the airways abnormally susceptible to the proinflammatory effects of this peptide released from sensory nerves. The present study was designed to determine whether the administration of RSV antibodies prevents the potentiation of neurogenic inflammation in rat airways. Five days after inoculation, sensory nerve-mediated extravasation of Evans blue-labeled albumin was significantly greater in the airways of RSV-infected rats than in pathogen-free controls. Polyclonal immune globulin enriched for RSV-neutralizing antibodies (RSVIG) reduced neurogenic extravasation when injected 24 h before intranasal inoculation of the virus but not when injected before endotracheal inoculation. A humanized MAb against RSV fusion protein (palivizumab) was twice as potent as RSVIG when given before intranasal inoculation and also caused significant inhibition after endotracheal inoculation. Furthermore, palivizumab inhibited neurogenic inflammation in RSV-infected rats when given 72 h after virus inoculation. These data suggest that palivizumab protects the respiratory tract from RSV-induced inflammation when given before or in the early phase of the viral infection. The administration of palivizumab to high-risk infants may limit the severity of the acute airway inflammation and may protect against subsequent lower respiratory tract illness.