Effect of inhaled N-acetylcysteine monotherapy on lung function and redox balance in idiopathic pulmonary fibrosis.
BACKGROUND
An oxidant-antioxidant imbalance is considered to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, administration of antioxidants, such as N-acetylcysteine (NAC), may represent a potential treatment option for IPF patients.


METHODS
The aim of this study was to evaluate the effect of inhaled NAC monotherapy on lung function and redox balance in patients with IPF. A retrospective observational study was done, involving 22 patients with untreated early IPF (19 men; mean [±S.D.] age, 71.8 [±6.3]y). At baseline and at 6 and 12 months after initiating inhaled NAC monotherapy, we assessed forced vital capacity (FVC) and measured the levels of total glutathione, oxidized glutathione (GSSG), and the ratio of reduced to oxidized glutathione in whole blood (hereafter referred to as the ratio), and of 8-hydroxy-2'-deoxyguanosine in urine. To evaluate response to treatment, we defined disease progression as a decrease in FVC of ≥5% from baseline and stable disease as a decrease in FVC of <5%, over a period of 6 months.


RESULTS
Change in FVC in the stable group at 6 and 12 months were 95±170mL and -70±120mL, while those in the progressive group at 6 and 12 months were -210±80mL, -320±350mL, respectively. The serial mean change in GSSG from baseline decreased as the ratio of reduced to oxidized glutathione increased in patients with stable disease, while it increased as this ratio decreased in patients with progressive disease. Receiver operating characteristic curve analysis revealed that a baseline GSSG level of ≥1.579μM was optimal for identifying treatment responders.


CONCLUSIONS
Inhaled NAC monotherapy was associated with improved redox imbalance in patients with early IPF.
Department of Respiratory Medicine, Toho University School of Medicine (Omori), Omori-nishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: youko.muramatsu@med.toho-u.ac.jp.
Yoko
Y
Muramatsu
Department of Respiratory Medicine, Toho University School of Medicine (Omori), Omori-nishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: keishi.sugino@med.toho-u.ac.jp.
Keishi
K
Sugino
Department of Respiratory Medicine, Toho University School of Medicine (Omori), Omori-nishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: f-ishida@mug.biglobe.ne.jp.
Fumiaki
F
Ishida
Department of Clinical Laboratory Medicine, Toho University School of Medicine (Omori), Omori-nishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: cvlabo@med.toho-u.ac.jp.
Junko
J
Tatebe
Department of Clinical Laboratory Medicine, Toho University School of Medicine (Omori), Omori-nishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: toshimrt@med.toho-u.ac.jp.
Toshisuke
T
Morita
Department of Respiratory Medicine, Toho University School of Medicine (Omori), Omori-nishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: sahomma@med.toho-u.ac.jp.
Sakae
S
Homma
D000111:Acetylcysteine / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000368:Aged; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D012372:ROC Curve; D012189:Retrospective Studies; D014797:Vital Capacity
D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine
Glutathione; Idiopathic pulmonary fibrosis; N-acetylcysteine; Redox balance