Delivery and Safety of Inhaled Interferon-γ in Idiopathic Pulmonary Fibrosis

Abstract

Abstract

Background:

Inhaled interferon-γ aerosol (aINF-γ) may be effective treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and delivery of aIFN-γ (100 μg 3 times/week) in 10 IPF patients using the I-neb (Philips Respironics, Parsippany, NJ).

Methods:

IFN-γ activity in the aerosol was confirmed by viral inhibition. Ten patients with an average age of 68 diagnosed with IPF (American Thoracic Society/European Respiratory Society consensus guidelines) were enrolled. In vivo deposition was measured via a gamma camera. The nebulizer recorded patient adherence to therapy. Pulmonary function tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at baseline, and every 12–14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were analyzed for chemokines and cytokines, including INF-γ.

Results:

All 10 patients tolerated 80 weeks of inhaled IFN-γ well, with no systemic side effects. True adherence with aerosol treatment averaged 96.7±4.81% (±SEM). In vivo lung deposition averaged 65.4±4.8μg and oropharyngeal deposition 12.6±3.0 μg. BAL IFN-γ increased 60-fold and profibrotic cytokines (FGP-2, Flt-3 ligand, IL-5) were significantly decreased; IFN-γ plasma levels were unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min walk was unchanged.

Conclusions:

IFN-γ is safe in IPF and can be effectively delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal of pretherapy PFT decline may define an end-point for future clinical trials.