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Diffuse Lung Disease |

Efficacy of Inhaled N-Acetylcysteine Monotherapy on Lung Function and Redox Balance in Early Idiopathic Pulmonary Fibrosis

Sakae Homma, MD; Yoko Muramatsu, MD; Keishi Sugino, MD; Susumu Sakamoto, MD; Junko Tatebe, PhD; Toshisuke Morita, MD
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Toho University Omori Medical Center, Tokyo, Japan


Chest. 2014;145(3_MeetingAbstracts):247A. doi:10.1378/chest.1719798
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Abstract

SESSION TITLE: ILD Posters

SESSION TYPE: Poster Presentations

PRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PM

PURPOSE: This prospective study assessed the effect of inhaled N-acetylcysteine (NAC) monotherapy on lung function and redox balance in patients with idiopathic pulmonary fibrosis (IPF).

METHODS: We enrolled 22 patients with untreated early IPF (19 men, 3 women; mean age [SD], 71.8 ± 6.3 yrs, mean %VC:80%, %DLco:53%). At baseline and 6 and 12 months after initiating inhaled NAC monotherapy (352.4 mg b.i.d.), we assessed forced vital capacity (FVC) and measured levels of total glutathione (tGSH), oxidized glutathione (GSSG), and the ratio of reduced to oxidized glutathione (ratio) in whole blood. 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: Mean change in FVC was greater in patients with stable disease (n=16) than in those with progressive disease (n=6): 95±170 ml at 6 months and −70±120 ml at 12 months versus −210±80 ml at 6 months and −320±350 ml at 12 months (p=0.0002). In addition, serial mean change in GSSG from baseline decreased as the ratio of reduced to oxidized glutathione increased, in patients with stable disease, and increased as this ratio decreased, in patients with progressive disease. Furthermore, receiver operating characteristic curve analysis revealed that a baseline GSSG level of ≥1.579 μM was optimal for identifying treatment responders.

CONCLUSIONS: The present findings indicate that the clinical effect of inhaled NAC monotherapy on FVC is associated with improved redox imbalance in patients with early IPF.

CLINICAL IMPLICATIONS: This study showed that early therapeutic intervention with GSH precursor could delay the progression of IPF, especially in patients with high GSSG level in whole blood before the therapy. Inhaled NAC monotherapy should be considered as the one of therapies for IPF.

DISCLOSURE: The following authors have nothing to disclose: Sakae Homma, Yoko Muramatsu, Keishi Sugino, Susumu Sakamoto, Junko Tatebe, Toshisuke Morita

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