Abstract
BackgroundIdiopathic interstitial pneumonias such as idiopathic pulmonary fibrosis or fibrotic nonspecific interstitial pneumonia are irreversible progressive pulmonary diseases that often have fatal outcomes. Although the etiology of idiopathic interstitial pneumonias is not yet fully understood, anti-fibrotic and anti-inflammatory agents have shown limited therapeutic effectiveness. Reactive oxygen species and their cytotoxic effects on the lung epithelial cells have been reported to participate in the pathophysiology of the disease. Because superoxide dismutase catalyzes the detoxification of reactive oxygen species, we developed lecithinized superoxide dismutase for the treatment of patients with idiopathic interstitial pneumonias.MethodsA multicenter, randomized, placebo-controlled trial was conducted as a pilot study to investigate the safety and effectiveness of 40 or 80 mg lecithinized superoxide dismutase in patients with progressive idiopathic interstitial pneumonias who presented with either idiopathic pulmonary fibrosis or corticosteroid-resistant fibrotic nonspecific interstitial pneumonia and showed arterial oxygen tension compatible with stage III or IV on the Japanese severity grading scale for idiopathic interstitial pneumonias. Before and following infusion of lecithinized superoxide dismutase for 28 days, the primary endpoint of forced vital capacity and the secondary endpoints of lactate dehydrogenase, surfactant protein-A, surfactant protein-D and Krebs von den Lungen-6 levels were measured in the serum.ResultsThe primary endpoint of forced vital capacity did not improve significantly in the lecithinized superoxide dismutase groups in comparison with the placebo group. The secondary endpoints of lactate dehydrogenase and surfactant protein-A levels were significantly attenuated by 28 days in the higher-dose (80 mg) group. However, these changes returned to the baseline levels by 56 days after the cessation of lecithinized superoxide dismutase. Adverse events and mortality in the drug-treated groups did not differ from those in the placebo group.ConclusionsTreatment with lecithinized superoxide dismutase is safe and improves the levels of serum markers such as lactate dehydrogenase and surfactant protein-A in patients with advanced idiopathic interstitial pneumonias with severe respiratory dysfunction. Considering the results of the current study, further investigations into the effects and treatment potential of long-term administration of lecithinized superoxide dismutase may be warranted.Trial registrationUniversity hospital Medical Information Network (UMIN) clinical trials registry no. 000000752
Highlights
Idiopathic interstitial pneumonias such as idiopathic pulmonary fibrosis or fibrotic nonspecific interstitial pneumonia are irreversible progressive pulmonary diseases that often have fatal outcomes
Idiopathic interstitial pneumonia (IIP) is a broad term comprising a set of lung diseases, including idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and others [1]
Patients with IPF or srf-NSIP as diagnosed by clinical symptoms, chest radiography examination, and highresolution computed tomography (HRCT) scans were included in this study
Summary
Idiopathic interstitial pneumonias such as idiopathic pulmonary fibrosis or fibrotic nonspecific interstitial pneumonia are irreversible progressive pulmonary diseases that often have fatal outcomes. Reactive oxygen species and their cytotoxic effects on the lung epithelial cells have been reported to participate in the pathophysiology of the disease. Because superoxide dismutase catalyzes the detoxification of reactive oxygen species, we developed lecithinized superoxide dismutase for the treatment of patients with idiopathic interstitial pneumonias. Idiopathic interstitial pneumonia (IIP) is a broad term comprising a set of lung diseases, including idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and others [1]. Reactive oxygen species (ROS) and their effects on lung epithelial cells are reported to be involved in the pathophysiology of IIPs [4]. Antioxidant molecules are receiving considerable attention as therapeutic candidates for the treatment of IPF
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