Antioxidant therapy in idiopathic pulmonary fibrosis: hope is kindled

Abstract

The new American Thoracic Society/European Respiratory Society classification of the idiopathic interstitial pneumonias 1 has redefined entities previously grouped as “idiopathic pulmonary fibrosis” (IPF), but carrying a much better prognosis than that disorder. As a result, the core entity of IPF is now diagnosed with greater precision than ever before. The outcome has worsened correspondingly, with an average survival of ∼3 yrs from the onset of dyspnoea. Until recently, therapeutic nihilism in IPF has prevailed. Treatment recommendations have come and gone, high-dose corticosteroid therapy has had its day 2, and “standard therapy” has essentially failed. Demedts et al. 3 recently reported outcome data that ought to encourage the optimists amongst us. For the first time, a widely available and inexpensive agent has effected a real difference in the rate of disease progression in a large cohort of patients. The methodology was straightforward. All patients remained on low-dose prednisolone and azathioprine throughout. The studied intervention consisted of the addition of N -acetylcysteine (NAC) at a dose of 600 mg t.i.d. , controlled against placebo. There were differences in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide ( D L,CO) at 12 months in favour of active treatment. With placebo, FVC and D L,CO fell 6 and 8% of predicted, respectively, but only 1.5 and 3% with active therapy. In other words, the rapidity of disease progression was curtailed by ∼70% when antioxidant therapy was added to “best current treatment”. It appears unlikely that flaws in the study design generated a spuriously positive result. The diagnosis of IPF was more robust than in previous studies, with biopsy and high-resolution computed tomography (CT) appearances reviewed by reference panels of leading histopathologists and CT radiologists. Unfortunately, this led to the removal of a significant number of patients after randomisation but as …