Montuschi Paolo, Nightingale Julia A, Kharitonov Sergei A, Barnes Peter J
Department of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Free Radic Biol Med. 2002 Nov 15;33(10):1403-8. doi: 10.1016/s0891-5849(02)01084-5.
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.
本研究的目的是通过呼出气体冷凝物（EBC）中8-异前列腺素的浓度来量化短期臭氧暴露后的肺部氧化应激，并研究吸入布地奈德对这种反应的影响。8-异前列腺素是一种前列腺素-F（2α）异构体，它在体内由自由基催化的花生四烯酸过氧化反应形成。EBC是一种收集气道分泌物的非侵入性方法。我们进行了一项双盲、随机、安慰剂对照的交叉研究，9名健康非吸烟者在臭氧暴露（400 ppb）2小时前，每天两次吸入布地奈德（800微克）或安慰剂，共2周。通过酶免疫测定法测量呼出的8-异前列腺素。与暴露前的值相比，臭氧暴露后4小时，安慰剂组（36.9±3.9 pg/ml，平均值±标准误，vs. 16.9±0.7 pg/ml；p<.001）和布地奈德组（33.4±2.6 pg/ml vs. 15.8±0.3 pg/ml；p<.001）的8-异前列腺素均升高。布地奈德预处理对8-异前列腺素的升高没有影响（平均差异3.4 pg/ml，95%可信区间-8.9至15.7，p = 0.54）。短期臭氧暴露会导致肺部氧化应激急性增加，呼出的8-异前列腺素反映了这一点。这种增加对高剂量吸入布地奈德预处理具有抗性。
