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Oxidative stress and lipid‐derived inflammatory mediators during acute exacerbations of cystic fibrosis
Author(s) -
REID David W.,
MISSO Neil,
AGGARWAL Shashi,
THOMPSON Philip J.,
WALTERS E. Haydn
Publication year - 2007
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2006.00962.x
Subject(s) - medicine , sputum , cystic fibrosis , exacerbation , oxidative stress , gastroenterology , immunology , pathology , tuberculosis
Background and objective: In cystic fibrosis (CF) very few studies have assessed sputum 8‐iso‐PGF 2α 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)‐E 2 , 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‐PGF 2α , total cys‐LT and PGE 2 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‐PGF 2α was significantly elevated in acute, but not stable CF patients versus healthy controls ( P < 0.001). Similarly, sputum cys‐LT and PGE 2 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 ( r 2 = 0.53, P = 0.001 and r 2 = 0.33, P < 0.05, respectively). Overall in the CF patients, FEV 1 %predicted was strongly and negatively correlated with sputum 8‐iso‐PGF 2α ( r 2 = 0.34, P = 0.006), cys‐LT ( r 2 = 0.40, P = 0.002) and PGE 2 ( r 2 = 0.52, P < 0.001) levels. Antibiotic treatment reduced sputum total cell count ( P = 0.03), but did not affect 8‐iso‐PGF 2α , cys‐LT or PGE 2 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.