THE EFFECT OF ORAL N-ACETYLCYSTEINE ON LUNG GLUTATHIONE LEVELS IN IDIOPATHIC PULMONARY FIBROSIS

Idiopathic pulmonary fibrosis (IPF) is characterized by an increased o xidant burden and by a deficiency of glutathione, a major antioxidant, in the lung epithelial lining fluid (ELF). Therefore, a rational ther apeutic approach is to reverse the imbalance between oxidants and anti oxidants in the lung by enhancing the antioxidant screen. With this ba ckground, the aim of our study was to evaluate oral N-acetylcysteine ( NAC) as a strategy to augment lung glutathione levels in patients with IPF. Concentrations of total glutathione in bronchoalveolar lavage fl uid (BALF) wert quantified spectrophotometrically, before and followin g oral therapy with 3 x 600 mg NAC per day for 5 days, in 17 nonsmokin g patients with biopsy-proven IPF The volume of ELF recovered by BAL w as determined using the urea method. Pretherapy, total glutathione lev els in ELF in IPF patients were significantly less than normal (187+/- 36 vs 368+/-60 muM), in contrast to levels in BALF (0.99+/-0.12 vs 1.1 8+/-0.19 muM). Following therapy with oral NAC, glutathione levels in BALF were 1.54+/-0.24 muM (a significant increase compared to prethera py), whereas the increase in ELF levels (319+/-92 muM) did not reach s ignificance. The therapy was well tolerated, and all routine clinical and bronchoscopic parameters remained unchanged It is thus feasible an d safe to augment deficient lung glutathione levels in patients with I PF; thereby, potentially augmenting pulmonary antioxidant protection.