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

Abstract

Background and objective: In cystic fibrosis (CF) very few studies have assessed sputum 8-iso-PGF₂ 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-PGF₂, 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-PGF₂ 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-PGF₂ (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-PGF₂, 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.

Keywords

peer-reviewed