Increased serum concentration of urinary trypsin inhibitor with asthma exacerbation

Abstract

The aim of the study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by neutrophil elastase (NE), reflects the degree of bronchial inflammation in children with acute asthma exacerbation.The involvement of neutrophil-mediated inflammation plays as important a role as eosinophil-mediated inflammation in the pathogenesis of acute asthma exacerbation. However, no measurable marker is sensitive enough to assess neutrophil-mediated inflammation in the airways. The pre-a-/inter-a-trypsin inhibitors are assumed to be precursors of UTI. NE degrades pre-a-/inter-a-trypsin inhibitors to liberate UTI. UTI concentrations in 25 childhood patients admitted with asthma exacerbation and 15 control subjects were measured by means of one-step sandwich-type enzyme immunoassay.Serum UTI concentrations in the patients at admission were significantly higher than control values (10.597¡0.649 and 6.136¡0.303 U?mL -1 , respectively (mean¡SEM)). These levels returned to baseline values with improvement in the asthmatic symptoms. However, serum NE and a 1 antitrypsin concentrations were not significantly different between patients and controls, even during acute exacerbation in the former.The findings suggest that neutrophil-mediated inflammatory events are involved in exacerbation of childhood asthma. The monitoring of urinary trypsin inhibitor concentrations might be useful for evaluating the neutrophil-mediated inflammation in childhood asthma attack. Eur Respir J 2003; 22: 739-742.

Serine protease inhibitors nafamostat mesilate and gabexate mesilate attenuate allergen-induced airway inflammation and eosinophilia in a murine model of asthma

“…However, this protective effect seems not prominent in airway inflammation in patients with asthma, who had significantly higher serum UTI levels during an asthma attack. 31 Therefore, the administration of UTI in subjects with asthma as well as in our murine model of asthma may not have a beneficial effect for symptom controls. Serine protease inhibitors have been shown to have various beneficial anti-inflammatory effects by inhibiting the activation of leukocytes, and fibrogenolytic activity of human tryptase generated during the coagulation cascade and the inflammatory process, [19][20][21][22][23][24] but the mechanism is still not fully elucidated.…”

Differential Effects of Short-Acting β₂-Agonists on Human Granulocyte Functions

“…There is increasing evidence that neutrophilic inflammation is also involved in exacerbation of acute bronchial asthma [4, 31]. Prominent and dominant neutrophil infiltration was also demonstrated during asthmatic attacks triggered by viral infections [32, 33]. The control of neutrophil-mediated inflammation is feasible for the treatment of asthma attack.…”

Current and future biomarkers in allergic asthma

“…CXCR4 and CCR7 mediated fibrocyte transmigration in acute asthma exacerbation and in chronic obstructive asthma, respectively (183). Due to the systemic involvement, asthma exacerbation can also be monitored or even predicted by urinary metabolites including arachidonic derivatives such as leukotrienes (184,185) and urinary trypsin inhibitor (186). Exacerbated allergic asthma is accompanied with increased BAL levels of quinolinic acid, tryptophan, ECP, eosinophils (187), decreased CD29 (32) and CD44 (188) on eosinophils and elevated CD203c expression on basophils, which decreases significantly during remission (101 (189).…”