Abstract
Background: We aimed to investigate whether dextromethorphan (DM), an antitussive agent, could improve the antifibrotic efficacy of pirfenidone in treating idiopathic pulmonary fibrosis, a fatal interstitial lung disease characterized by progressive and irreversible respiratory failure.Methods: A bleomycin-induced mouse pulmonary fibrosis model study and an open-label randomized clinical trial were performed to evaluate the effectiveness of pirfenidone combined with DM.Results: In the animal study, pirfenidone combined with DM protected the mice against bleomycin-induced pulmonary fibrosis with better capabilities than pirfenidone or DM alone, as indicated by lung histologic analysis and hydroxyproline levels. In the clinical study, pirfenidone plus DM markedly mitigated pulmonary function (FEV1 and FVC) decline and ameliorated chest HRCT imaging scores (ground glass opacities and reticulation) of patients with IPF compared with pirfenidone alone at one year after administration. There were no significant differences in adverse reactions between the pirfenidone-DM group and the pirfenidone group.Conclusions: Pirfenidone plus DM may be a better strategy to modify IPF than pirfenidone alone. The efficacy and safety of the combination of pirfenidone and DM for patients with IPF warrants further verification by a double-blind randomized controlled trial (RCT).
FDA-approved Antitussive Dextromethorphan Enhances Antifibrotic Effectiveness of Pirfenidone in Bleomycin-induced Mice and Patients with Idiopathic Pulmonary Fibrosis
