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Published ahead of print on January 15, 2004, doi:10.1164/rccm.200308-1104OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 7, April 2004, 822-828

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Submitted on August 12, 2003
Accepted on January 11, 2004

Improvement of Alveolar Glutathione, Lung Function, but Not Oxidative State in Cystic Fibrosis

Matthias Griese1*, Jan Ramakers1, Angela Krasselt2, Vitaliy Starosta1, Silke van Koningsbruggen3, Rainald Fischer4, Felix Ratjen5, Bernhard Mullinger6, Rudolf M Huber4, Konrad Maier7, Ernst Rietschel3, and Gerhard Scheuch6

1 Paediatrics, Ludwig-Maximilians-University, Munich, Germany, 2 Nutrition, University of Hohenheim, Hohenheim, Germany, 3 Paediatrics, University of Cologne, Cologne, Germany, 4 Internal Medicine, Ludwig-Maximilians-University, Munich, Germany, 5 Paediatrics, University of Essen, Essen, Germany, 6 Paediatrics, INAMED, Gauting, Germany, 7 Institute for Inhalation Biology, GSF-Research Centre for Environment and Health, Neuherberg, Germany

* To whom correspondence should be addressed. E-mail: griese{at}pk-i.med.uni-muenchen.de.

Chronic neutrophilic inflammation leads to oxidative damage, which may play an important role for the pathogenesis of cystic fibrosis lung disease. Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in cystic fibrosis patients. Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels, lung function and oxidative status. Pulmonary deposition of a radiolabelled monodisperse aerosol generated by a Pari LC star nebulizer connected to the AKITA inhalation device was determined in 6 patients. In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with 3x300 or 3x450 mg glutathione. Intrathoracic deposition was 86.3 ± 1.4 % of the emitted dose. Glutathione concentration in lavage 1 hour p.i. was increased 3-4 fold and was still almost doubled 12 hours p.i.. FEV1 transiently dropped after inhalation but increased compared to pre-treatment 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 to the lower airways is feasible. Reversion of markers of oxidative injury may need longer treatment, higher doses, or different types of antioxidants.
Key words: antioxidant, neutrophilis, deposition, aerosol, bronchoalveolar lavage fluid




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