title: Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis creator: Reid, DW creator: Misso, N creator: Aggarwal, S creator: Thompson, PJ creator: Walters, EH subject: 321027 Respiratory Diseases description: Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis REID DW, MISSO N, AGGARWAL S, THOMPSON PJ, WALTERS EH. Respirology 2007; 12: 63–69 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. publisher: Wiley-Blackwell Publishing Asia date: 2007 type: Article type: PeerReviewed format: application/pdf identifier: http://eprints.utas.edu.au/3971/1/3971.pdf relation: http://dx.doi.org/10.1111/j.1440-1843.2006.00962.x identifier: Reid, DW and Misso, N and Aggarwal, S and Thompson, PJ and Walters, EH (2007) Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis. Respirology, 12 (1). pp. 63-69. ISSN 1323-7799 relation: http://eprints.utas.edu.au/3971/