Elevated Tissue Kallikrein Activity in Airway Secretions from Patients with Tracheobronchitis Associated with Prolonged Mechanical Ventilation

T. G. O'Riordan, M. D. Weinstein, W. M. Abraham, R. Forteza

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The clinical course of patients undergoing prolonged mechanical ventilation is often complicated by the development of purulent tracheobronchitis. The purpose of this study was to assess whether ventilator-associated hypersecretion is associated with elevated levels of tissue kallikrein (TK) activity. TK can induce marked bronchial inflammation in animal models and TK activity is increased in the airway secretions of symptomatic asthmatics. It has not been studied in conditions with predominantly neutrophilic bronchial secretions, although animal data indicate that neutrophil elastase may stimulate TK activity. We measured TK activity in airway secretions of patients undergoing mechanical ventilation for more than 4 weeks (PMV group) and in two comparator groups: patients with cystic fibrosis, who were colonized with Pseudomonas aeruginosa (CF group) and patients undergoing mechanical ventilation for less than one week who did not have clinical evidence of purulent airway secretions (acute mechanical ventilation, AMV group). We also compared the level of neutrophil elastase (NE) activity, an index of neutrophil activation, in the three patient groups. TK and NE activity in the sol phase were measured by the degradation of chromogenic substrates (DL Val-Leu-Arg pNA and N-Methoxy Succinyl Ala-Ala-Pro-Val pNA, respectively). Intergroup differences in cell counts were not significant. However, TK activity was significantly less in the AMV group than in the PMV and cystic fibrosis patients (Kruskal-Wallis ANOVA, p < 0.05). Elastase activity was significantly greater in the CF group (p < 0.05) than in the other two groups. Compared to patients undergoing short-term mechanical ventilation (AMV group), TK activity was elevated in patients with purulent tracheobronchitis associated with prolonged mechanical ventilation (PMV group). The elevation in TK activity in these patients is comparable to levels in sputum from patients with cystic fibrosis (CF group), although the latter had a significantly higher level of NE activity. The observation of increased TK activity in patients with neutrophilic airway inflammation suggests that TK may play a role in modulating inflammation in ventilator-associated tracheobronchitis and may be worthy of further study to determine its source and significance.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalLung
Volume181
Issue number5
DOIs
StatePublished - Nov 6 2003
Externally publishedYes

Fingerprint

Tissue Kallikreins
Artificial Respiration
Leukocyte Elastase
Cystic Fibrosis
Mechanical Ventilators
Inflammation
Chromogenic Compounds
Neutrophil Activation
Pancreatic Elastase
Polymethyl Methacrylate
Sputum
Pseudomonas aeruginosa
Analysis of Variance
Animal Models
Cell Count
Observation

Keywords

  • Airway inflammation
  • Bronchial secretions
  • Kinins
  • Neutrophil elastase
  • Proteases
  • Respiratory tract infection

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology

Cite this

Elevated Tissue Kallikrein Activity in Airway Secretions from Patients with Tracheobronchitis Associated with Prolonged Mechanical Ventilation. / O'Riordan, T. G.; Weinstein, M. D.; Abraham, W. M.; Forteza, R.

In: Lung, Vol. 181, No. 5, 06.11.2003, p. 237-244.

Research output: Contribution to journalArticle

O'Riordan, T. G. ; Weinstein, M. D. ; Abraham, W. M. ; Forteza, R. / Elevated Tissue Kallikrein Activity in Airway Secretions from Patients with Tracheobronchitis Associated with Prolonged Mechanical Ventilation. In: Lung. 2003 ; Vol. 181, No. 5. pp. 237-244.
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AB - The clinical course of patients undergoing prolonged mechanical ventilation is often complicated by the development of purulent tracheobronchitis. The purpose of this study was to assess whether ventilator-associated hypersecretion is associated with elevated levels of tissue kallikrein (TK) activity. TK can induce marked bronchial inflammation in animal models and TK activity is increased in the airway secretions of symptomatic asthmatics. It has not been studied in conditions with predominantly neutrophilic bronchial secretions, although animal data indicate that neutrophil elastase may stimulate TK activity. We measured TK activity in airway secretions of patients undergoing mechanical ventilation for more than 4 weeks (PMV group) and in two comparator groups: patients with cystic fibrosis, who were colonized with Pseudomonas aeruginosa (CF group) and patients undergoing mechanical ventilation for less than one week who did not have clinical evidence of purulent airway secretions (acute mechanical ventilation, AMV group). We also compared the level of neutrophil elastase (NE) activity, an index of neutrophil activation, in the three patient groups. TK and NE activity in the sol phase were measured by the degradation of chromogenic substrates (DL Val-Leu-Arg pNA and N-Methoxy Succinyl Ala-Ala-Pro-Val pNA, respectively). Intergroup differences in cell counts were not significant. However, TK activity was significantly less in the AMV group than in the PMV and cystic fibrosis patients (Kruskal-Wallis ANOVA, p < 0.05). Elastase activity was significantly greater in the CF group (p < 0.05) than in the other two groups. Compared to patients undergoing short-term mechanical ventilation (AMV group), TK activity was elevated in patients with purulent tracheobronchitis associated with prolonged mechanical ventilation (PMV group). The elevation in TK activity in these patients is comparable to levels in sputum from patients with cystic fibrosis (CF group), although the latter had a significantly higher level of NE activity. The observation of increased TK activity in patients with neutrophilic airway inflammation suggests that TK may play a role in modulating inflammation in ventilator-associated tracheobronchitis and may be worthy of further study to determine its source and significance.

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