Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1897-1901

Antioxidative and Clinical Effects of High-dose N-Acetylcysteine in Fibrosing Alveolitis
Adjunctive Therapy to Maintenance Immunosuppression

JÜRGEN BEHR, KONRAD MAIER, BARBARA DEGENKOLB, FRITZ KROMBACH, and CLAUS VOGELMEIER

Abteilung für Pneumologie, Medizinische Klinik I, and Institut für Chirurgische Forschung, Klinikum Grosshadern der Ludwig-Maximilians-Universität München, München; and Institut für Inhalationsbiologie, GSF Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany

In fibrosing alveolitis (FA), activated phagocytes cause excessive oxidative stress in the lower respiratory tract. Additionally, levels of glutathione, a major antioxidant of the human lung, are markedly reduced. Since N-acetylcysteine (NAC) is a known precursor for glutathione synthesis, we investigated the effect of NAC on redox balance and lung function in FA. Eighteen patients with an established diagnosis of FA were treated with 600 mg NAC three times daily for 12 wk in addition to their latest immunosuppressive therapy. Before and after NAC therapy, pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) were performed. BAL fluid was analyzed with regard to cell differential, glutathione status, and methionine sulfoxide content of BAL proteins (Met(O)), as an indicator of oxidative stress at the alveolar surface. There was an increase of total glutathione (GSH_t = GSH + 2 × GSSG: 3.43 ± 0.30 µM versus 4.20 ± 0.66 µM, p < 0.05) and of reduced glutathione (GSH: 2.58 ± 0.24 µM versus 3.42 ± 0.54 µM, p < 0.005) in native BAL fluid and in the epithelial lining fluid (GSH_t: 267.3 ± 26.0 µM versus 367.1 ± 36.0 µM, p < 0.005; GSH: 204.5 ± 20.7 µM versus 302.9 ± 32.2 µM, p < 0.005). The increase of GSH was accompanied by a decrease of Met(O) (6.83 ± 0.71% versus 4.60 ± 0.40%, p < 0.005). PFTs significantly improved during NAC treatment. We conclude that high-dose NAC significantly improved the antioxidant screen of the lungs by elevating GSH levels. Moreover, the decrease of Met(O) levels indicated an antioxidant effect at the alveolar surface. These biochemical changes were accompanied by an improvement of PFTs in patients under maintenance immunosuppression. NAC supplementation should, therefore, be considered as an adjunct therapy for FA.

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