A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis poses a significant therapeutic challenge because of its progressive course. Since oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis, an open, randomized trial of long-term inhalation therapy with the antioxidant, N-acetylcysteine was conducted. A total of 30 patients with idiopathic pulmonary fibrosis were randomly assigned to one of the following inhalation therapies: N-acetylcysteine (352 mg per day) or bromhexine hydrochloride (4 mg per day) as the control. Efficacy was assessed by analysing changes occurring from baseline to 12 months in pulmonary function, the 6-min walking test, high-resolution CT, health-related quality of life, and serum KL-6-values. Four patients (n = 2 in each group) died within 12 months due to progression of idiopathic pulmonary fibrosis. A total of 22 patients (control, n = 12; N-acetylcysteine, n = 10) completed the study. At 12 months there were significant differences between the N-acetylcysteine and control groups in terms of mean changes in lowest SaO(2) during the 6-min walking test (-0.3 +/- 2.1% vs -6.8 +/- 1.8%, P < 0.05), serum KL-6 (-482 +/- 220 U/mL vs 176 +/- 204 U/mL, P < 0.05), and the ground-glass score on high-resolution CT (-1.3 +/- 1.6 vs 6.7 +/- 1.5, P < 0.01). No significant differences were observed in pulmonary function, 6-min walking distance or quality of life. These data suggest that although long-term aerosolized N-acetylcysteine administration did not influence pulmonary function or quality of life, it may delay disease progression as evidenced by exercise desaturation, high-resolution CT, and serum KL-6.