Oxidative stress during acute respiratory exacerbations in cystic fibrosis
Oxidative stress during acute respiratory exacerbations in cystic fibrosis
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DOI：
10.1136/thx.54.6.518
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发表时间：
1999-06-01
期刊：
影响因子：
10
通讯作者：
Elborn, S
中科院分区：
文献类型：
--
作者：
McGrath, LT;Mallon, P;Elborn, S
囊性纤维化患者经历慢性全身氧化应激。这与涉及支气管多形核白细胞积聚和活化的慢性肺部炎症相结合。我们假设，在急性呼吸恶化期间，自由基活性和随之而来的损害将是最显着的，并且感染的强化治疗将导致向稳定期发现的值的改善。方法从12名健康正常志愿者和12名患有囊性纤维化的急性呼吸恶化患者中收集血浆和红细胞（呼吸道症状增加，一秒用力呼气量（FEV）减少超过10%，并决定用静脉注射抗生素治疗）。在治疗两周后从患者中收集进一步的样品。分析样本的炎症标志物、自由基损伤标志物以及水相和脂质相清除剂。结果呼吸恶化期间FEV 1和用力肺活量（FVC）低于对照组（平均差异-2.82（95% CI -2.12至-3.52）和-3.79（分别为-3.03至-4.55）1），但治疗后改善（平均变化分别为0.29（95% CI 0.18至0.40）和0.33（0.23至0.43）1）。急性发作期间患者的炎症标志物显著高于对照组，平均（95% CI）差异如下：C反应蛋白（CRP），46（17 - 75）gn;中性粒细胞弹性蛋白酶α（1），抗蛋白酶复合物（NEAPC），4.4（1.77 - 7.07）mg/l;白色细胞计数（WCC），5.3（4.7 - 5.9）x 10（9）/l。治疗后这些标志物显著降低，平均（95% CI）变化如下：CRP -26（-10至42）g/l; NEAPC -3.1（-1.3至4.9）mg/l; WCC -1.5（-1.3至1.7）x 10（9）/l。急性发作期间患者的丙二醛（MDA）作为自由基活性的标志物显著高于对照组，平均（95% CI）差异为193（107至279），治疗后改善（平均变化-56（95% CI -28至-84）nmol/mmol胆固醇）。患者的红细胞多不饱和脂肪酸显著低于对照组，平均差异为-4.4（95%CI-2.6至-6.2）摩尔百分比，但治疗后没有显著改善。急性发作期间的蛋白质羰基与对照组无差异，但与急性发作期间的水平相比，治疗组的蛋白质羰基确实增加（平均变化0.39（95% CI 0.11 - 0.67）μ mol/g蛋白质）。急性加重期患者的水相和脂质相清除剂显著低于对照组，平均差异（95% CI）如下：抗坏血酸，-19.0（-2.7至-35.3）μ mol/l;巯基，-122（-77至-167）μ mol/l;视黄醇，-237（-47至-427）nmol/mmol胆固醇; B-胡萝卜素，-52.8（-11.8至-93.8）nmol/mmol胆固醇;叶黄素，-50.4（-10.4至-90.4）nmol/mmol胆固醇;番茄红素，-90.1（-30.1至-150.1）nmol/mmol胆固醇。治疗导致改善，平均（95% CI）变化如下：（32至68）μ mol/l;视黄醇，152（47至257）nmol/mmol胆固醇; α-和β-胡萝卜素，0.6（0.0至1.2）和7.6（0.0 - 15.2）nmol/mmol胆固醇; α-生育酚，839（283至1405）nmol/mmol胆固醇;番茄红素，8.2（0.0至16.2）nmol/mmol胆固醇。结论“炎症标志物，自由基活性，和自由基清除剂在急性呼吸恶化期间显著更极端，并显示出治疗的改善。因此，提供保护免受炎症和自由基损伤的需要应该是动态的，并且与炎症和氧化过程相关。
Background-Patients with cystic fibrosis experience chronic systemic oxidative stress. This is coupled with chronic inflammation of the lung involving bronchial polymorphonuclear neutrophil accumulation and activation. We hypothesised that, during periods of acute respiratory exacerbation, free radical activity and consequent damage would be most marked and that intensive treatment of the infection would result in improvement towards values found during stable periods.Methods-Plasma and red blood cells were collected from 12 healthy normal volunteers and from 12 patients with cystic fibrosis with an acute respiratory exacerbation (increased respiratory symptoms, reduction in forced expiratory volume in one second (FEV,) of more than 10%, and a decision to treat with intravenous antibiotics). Further samples were collected from patients following two weeks of treatment. Samples were analysed for inflammatory markers, markers of free radical damage, and aqueous and Lipid phase scavengers.Results-During respiratory exacerbations FEV1, and forced vital capacity (FVC) were lower than in controls (mean differences -2.82 (95% CI -2.12 to -3.52) and -3.79 (-3.03 to -4.55) 1, respectively) but improved following treatment (mean change 0.29 (95% CI 0.18 to 0.40) and 0.33 (0.23 to 0.43) 1, respectively). Inflammatory markers during exacerbations were significantly higher in patients than in controls with the following mean (95% CI) differences: C reactive protein (CRP), 46 (17 to 75)gn; neutrophil elastase alpha(1), antiprotease complexes (NEAPC), 4.4 (1.77 to 7.07)mg/l; white cell count (WCC), 5.3 (4.7 to 5.9) x 10(9)/l. These markers decreased significantly following treatment with the following mean (95% CI) changes: CRP -26 (-10 to -42) g/l; NEAPC -3.1 (-1.3 to -4.9) mg/l; WCC -1.5 (-1.3 to -1.7) x 10(9)/l. Malondialdehyde (MDA) as a marker of free radical activity was significantly higher in patients during exacerbations than in controls with a mean (95% CI) difference of 193 (107 to 279) which improved with treatment (mean change -56 (95% CI -28 to -84) nmol/mmol cholesterol). Red blood cell polyunsaturated fatty acids were significantly lower in patients than in controls with a mean difference of -4.4(95% CI -2.6 to -6.2) moles percent, but did not improve significantly after treatment. Protein carbonyls during exacerbations were not different from controls but did increase with treatment compared with levels during the exacerbation (mean change 0.39 (95% CI 0.11 to 0.67) mu mol/g protein). Aqueous and lipid phase scavengers in patients during exacerbations were significantly lower than in controls with the following mean (95% CI) differences: ascorbate, -19.0 (-2.7 to -35.3)mu mol/l; sulphydryls, -122 (-77 to -167)mu mol/l; retinol, -237 (-47 to -427)nmol/mmol cholesterol; B-carotene, -52.8 (-11.8 to -93.8)nmol/mmol cholesterol; luteine, -50.4 (-10.4 to -90.4) nmol/mmol cholesterol; lycopene, -90.1 (-30.1 to -150.1) nmol/mmol cholesterol. Treatment resulted in improvement with the following mean (95% CI) changes: sulphydryls, 50 (32 to 68) mu mol/l; retinol, 152 (47 to 257) nmol/mmol cholesterol; alpha- and beta-carotene, 0.6 (0.0 to 1.2) and 7.6 (0.0 to 15.2) nmol/mmol cholesterol, respectively; alpha-tocopherol, 839 (283 to 1405) nmol/mmol cholesterol; and lycopene, 8.2 (0.0 to 16.2) nmol/mmol cholesterol.Conclusions "Abnormalities of markers of inflammation, free radical activity, and radical scavengers were significantly more extreme during acute respiratory exacerbations and showed improvement with treatment. The need to provide protection from inflammation and free radical damage should therefore be dynamic and related to the inflammatory and oxidative processes.