Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis
Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis
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DOI：
10.1164/rccm.200308-1104oc
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发表时间：
2004-04-01
影响因子：
24.7
通讯作者：
Scheuch, G
中科院分区：
文献类型：
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作者：
Griese, M;Ramakers, I;Scheuch, G
慢性嗜酸性炎症导致氧化损伤，这可能在囊性纤维化肺病的发病机制中起重要作用。囊性纤维化患者支气管肺泡灌洗液中抗氧化剂谷胱甘肽水平降低。在这里，我们评估了谷胱甘肽气雾剂对下呼吸道谷胱甘肽水平、肺功能和氧化状态的影响。在6名患者中测定了使用Pari LC星星雾化器（Allergy Asthma Technology，Morton格罗夫，IL）与秋田吸入装置（Inamed，高廷，德国）连接产生的放射性标记单分散气雾剂的肺沉积。在另外17名患者中，在吸入300或450 mg谷胱甘肽的每日三次剂量14天之前和之后评估支气管肺泡灌洗液。胸内沉积为发射剂量的86.3 +/- 1.4%。吸入后1小时灌洗液中的谷氨酰胺浓度增加3 - 4倍，吸入后12小时仍几乎加倍。吸入后FEV 1短暂下降，但14天后与治疗前值相比增加（p < 0.001）。这种改善与灌洗液中氧化蛋白质和脂质的含量无关，这些物质不随治疗而改变。这些结果表明，使用一种新型高效吸入装置，谷胱甘肽治疗下呼吸道是可行的。氧化损伤标志物的逆转可能需要更长时间的治疗，更高的剂量或不同类型的抗氧化剂。
Chronic neutrophilic inflammation leads to oxidative damage, which may play an important role in the pathogenesis of cystic fibrosis lung disease. Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in patients with cystic fibrosis. Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels, lung function, and oxidative status. Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari LC Star nebulizer (Allergy Asthma Technology, Morton Grove, IL) connected to an AKITA inhalation device (Inamed, Gauting, Germany) was determined in six patients. In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg of glutathione. Intrathoracic deposition was 86.3 +/- 1.4% of the emitted dose. Glutathione concentration in lavage 1 hour postinhalation was increased three- to fourfold and was still almost doubled 12 hours postinhalation. FEV1 transiently dropped after inhalation but increased compared with pretreatment values after 14 days (p < 0.001). This improvement was not related to the lavage content of oxidized proteins and lipids, which did not change with treatment. These results show that, using a new inhalation device with high efficacy, glutathione treatment of the lower airways is feasible. Reversion of markers of oxidative injury may need longer treatment, higher doses, or different types of antioxidants.