Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis

  1. David W. REID1,*,
  2. Neil MISSO2,
  3. Shashi AGGARWAL2,
  4. Philip J. THOMPSON2,
  5. E. Haydn WALTERS1

Article first published online: 19 DEC 2006

DOI: 10.1111/j.1440-1843.2006.00962.x

Issue

Respirology

Respirology

Volume 12, Issue 1, pages 63–69, January 2007

Additional Information

How to Cite

REID, D. W., MISSO, N., AGGARWAL, S., THOMPSON, P. J. and WALTERS, E. H. (2007), Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis. Respirology, 12: 63–69. doi: 10.1111/j.1440-1843.2006.00962.x

Author Information

  1. 1

    Cardio-Respiratory Research Group, University of Tasmania Medical School, Hobart, Tasmania and

  2. 2

    Lung Institute of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

*David Reid, University of Tasmania Medical School, Collins Street, Hobart, Tas. 7001, Australia. Email: d.e.c.reid@utas.edu.au

Publication History

  1. Issue published online: 19 DEC 2006
  2. Article first published online: 19 DEC 2006
  3. Received 12 December 2005; invited to revise 22 December 2005 and 10 June 2006; revised 26 May and 17 July 2006; accepted 18 July 2006 (Associate Editor: YC Gary Lee).

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (116K)

Keywords:

  • cystic fibrosis;
  • exacerbation;
  • lipid mediator;
  • oxidative stress

Background and objective:  In cystic fibrosis (CF) very few studies have assessed sputum 8-iso-PGF2α levels during pulmonary exacerbations as a direct measure of airway oxidative stress. The role of other lipid-derived inflammatory mediators, such as the cysteinyl leukotrienes (cys-LTs) and prostaglandin (PG)-E2, during exacerbations is also poorly defined and the effect of conventional antibiotic therapy on these components of the inflammatory process is unclear.

Methods:  Sputum 8-iso-PGF2α, total cys-LT and PGE2 levels were measured in 17 CF patients experiencing a pulmonary exacerbation and repeated analysis were performed in 15 of these patients after antibiotic treatment. Eight stable CF and nine healthy subjects provided control data.

Results:  Sputum 8-iso-PGF2α was significantly elevated in acute, but not stable CF patients versus healthy controls (P < 0.001). Similarly, sputum cys-LT and PGE2 levels were increased in acute compared with stable CF patients and healthy controls (P ≤ 0.001). Although substantially lower than in acute patients, sputum cys-LT levels in stable patients were also significantly higher than in normal controls (P = 0.01). There were strong associations between cys-LT levels and sputum total cell counts, and blood neutrophils in acute patients (r2 = 0.53, P = 0.001 and r2 = 0.33, P < 0.05, respectively). Overall in the CF patients, FEV1%predicted was strongly and negatively correlated with sputum 8-iso-PGF2α (r2 = 0.34, P = 0.006), cys-LT (r2 = 0.40, P = 0.002) and PGE2 (r2 = 0.52, P < 0.001) levels. Antibiotic treatment reduced sputum total cell count (P = 0.03), but did not affect 8-iso-PGF2α, cys-LT or PGE2 levels.

Conclusions:  CF exacerbations are characterized by increased oxidative stress and sputum concentrations of bioactive lipid mediators. Treatment does not modulate these aspects of inflammation and more targeted therapy needs further study.

View Full Article (HTML) Get PDF (116K)