title: Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis.
abstract: 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.
authors.affiliation: Department of Pediatric Ludwig -Maximilians-University, Munich, Germany. matthias.griese@med.uni-muenchen.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Jan
authors.initials: J
authors.lastname: Ramakers
authors.forename: Angela
authors.initials: A
authors.lastname: Krasselt
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Starosta
authors.forename: Silke
authors.initials: S
authors.lastname: Van Koningsbruggen
authors.forename: Rainald
authors.initials: R
authors.lastname: Fischer
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Müllinger
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Huber
authors.forename: Konrad
authors.initials: K
authors.lastname: Maier
authors.forename: Ernst
authors.initials: E
authors.lastname: Rietschel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Scheuch
mesh_terms: D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003257:Consumer Product Safety; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009330:Nebulizers and Vaporizers; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012044:Regression Analysis
chemical_list: D000336:Aerosols; D000975:Antioxidants; D005978:Glutathione