Am J Respir Crit Care Med. 2004 Apr 1;169(7):822-8. Epub 2004
Jan 15.
Improvement of alveolar glutathione and lung function
but not oxidative state in cystic fibrosis.
Griese M, Ramakers J, Krasselt A, Starosta V, Van Koningsbruggen
S, Fischer R, Ratjen F, Mullinger B, Huber RM, Maier K, Rietschel E, Scheuch
G.
Dr. von Haunersches Kinderspital, Ludwig-Maximilians-University, Lindwurmstrasse
4, D-80337 Munich, Germany. matthias.griese@med.uni-muenchen.de
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.