INTRAVENOUS N-ACETYLCYSTEINE AND LUNG GLUTATHIONE OF PATIENTS WITH PULMONARY FIBROSIS AND NORMALS

Idiopathic pulmonary fibrosis (IPF) is characterized by a huge alveolar oxidant burden and a deficiency of glutathione, a major antioxidant, in the pulmonary epithelial lining fluid (ELF). Therefore, a rational therapeutic strategy is to increase lung glutathione to augment the pulmonary antioxidant protective screen. To evaluate this concept, different doses of N-acetylcysteine (NAG), a glutathione precursor, were administered intravenously to eight patients with pulmonary fibrosis and six control subjects. In patients, bronchoalveolar lavage fluid (BALF) total glutathione increased significantly from 0.99 +/- 0.25 mu M to 1.79 +/- 0.37 mu M within 3 h following 1.8 g NAG, whereas 4.8 g NAC had no additional effect (1.47 +/- 0.34 mu M). In the control subjects, NAC did not significantly alter BALF total glutathione (baseline: 0.79 +/- 0.17 mu M, 600 mg NAG: 0.92 +/- 0.33 mu M, 1.8 g NAG: 1.39 +/- 0.41 mu M, 4.8 g NAG: 1.33 +/- 0.46 mu M). The same was true in ELF, 1.8 g NAC significantly raised ELF total glutathione in patients from 186 +/- 47 mu M to near normal levels (373 +/- 103 mu M), with no further increase following 4.8 g NAC (293 +/- 62 mu M). In the control subjects, ELF total glutathione remained unchanged independent of the NAC dose (baseline: 342 +/- 91 mu M, 600 mg NAG: 385 +/- 135 mu M, 1.8 g NAG: 633 +/- 220 mu M, 4.8 g NAG: 646 +/- 263 mu M) The increases in total glutathione were almost entirely due to increased levels of reduced glutathione, the form functional as an antioxidant. No adverse effects were noted. In conclusion, intravenous NAC augments lung glutathione of patients with pulmonary fibrosis but had no significant effect on lung glutathione in the control subjects.