title: Ozone-induced increase in exhaled 8-isoprostane in healthy subjects is resistant to inhaled budesonide.
abstract: The aim of this study was to quantify lung oxidant stress after short-term ozone exposure as reflected by 8-isoprostane concentrations in exhaled breath condensate (EBC) and to investigate the effects of inhaled budesonide on this response. 8-Isoprostane is a prostaglandin-F(2 alpha) isomer that is formed in vivo by free radical-catalyzed peroxidation of arachidonic acid. EBC is a noninvasive method to collect airway secretions. We undertook a double-blind, randomized, placebo-controlled, crossover study with inhaled budesonide (800 microg) or placebo twice daily for 2 weeks prior to ozone exposure (400 parts per billion) for 2 h in nine healthy nonsmokers. Exhaled 8-isoprostane was measured by an enzyme immunoassay. 8-Isoprostane was increased 4 h after ozone exposure compared to pre-exposure values in both placebo (36.9 +/- 3.9 pg/ml, mean +/- SEM, vs. 16.9 +/- 0.7 pg/ml; p <.001) and budesonide groups (33.4 +/- 2.6 pg/ml vs. 15.8 +/- 0.3 pg/ml; p <.001). Pretreatment with budesonide did not affect the increases in 8-isoprostane (mean differences 3.4 pg/ml, 95% CI -8.9 to 15.7, p =.54). Short-term ozone exposure causes acute increase in lung oxidative stress as reflected by exhaled 8-isoprostane. This increase is resistant to pretreatment with a high dose of inhaled budesonide.
authors.affiliation: Department of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy. p.montuschi@ic.ac.uk
authors.forename: Paolo
authors.initials: P
authors.lastname: Montuschi
authors.forename: Julia A
authors.initials: JA
authors.lastname: Nightingale
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kharitonov
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000328:Adult; D001944:Breath Tests; D019819:Budesonide / Q000494:pharmacology*; D018592:Cross-Over Studies; D015237:Dinoprost / Q000737:chemistry* / Q000031:analogs & derivatives; D004311:Double-Blind Method; D028441:F2-Isoprostanes / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000502:physiology; D008297:Male; D018384:Oxidative Stress; D010126:Ozone / Q000494:pharmacology; D010919:Placebos; D020033:Protein Isoforms; D011897:Random Allocation; D012907:Smoking; D013183:Sputum / Q000378:metabolism; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D028441:F2-Isoprostanes; D005609:Free Radicals; D010919:Placebos; D020033:Protein Isoforms; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D019819:Budesonide; D010126:Ozone; D015237:Dinoprost