Griese Matthias, Ramakers Jan, Krasselt Angela, Starosta Vitaliy, Van Koningsbruggen Silke, Fischer Rainald, Ratjen Felix, Müllinger Bernhard, Huber Rudolf M, Maier Konrad, Rietschel Ernst, Scheuch Gerhard
Department of Pediatric Ludwig -Maximilians-University, Munich, Germany.
Am J Respir Crit Care Med. 2004 Apr 1;169(7):822-8. doi: 10.1164/rccm.200308-1104OC. Epub 2004 Jan 15.
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. FEV(1) 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.
慢性嗜中性粒细胞炎症会导致氧化损伤，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中的抗氧化剂谷胱甘肽水平降低。在此，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连接到秋田吸入装置（Inamed，德国高廷）的帕里LC Star雾化器（Allergy Asthma Technology，伊利诺伊州莫顿格罗夫）产生的放射性标记单分散气雾剂的肺部沉积情况。另外17名患者在每日三次吸入300或450毫克谷胱甘肽14天前后接受支气管肺泡灌洗评估。胸腔内沉积为发射剂量的86.3±1.4%。吸入后1小时灌洗中的谷胱甘肽浓度增加了三到四倍，吸入后12小时仍几乎增加了一倍。吸入后FEV(1)短暂下降，但14天后与治疗前值相比有所增加（p<0.001）。这种改善与氧化蛋白质和脂质的灌洗含量无关，后者在治疗后没有变化。这些结果表明，使用高效的新型吸入装置，对下呼吸道进行谷胱甘肽治疗是可行的。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。
