title: Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis.
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.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, State University of New York, Stony Brook, New York 11794-8172, USA.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Diaz
authors.forename: Shibu
authors.initials: S
authors.lastname: Skaria
authors.forename: Keith
authors.initials: K
authors.lastname: Harris
authors.forename: Mario
authors.initials: M
authors.lastname: Solomita
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lau
authors.forename: Kristy
authors.initials: K
authors.lastname: Bauer
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Smaldone
authors.forename: Rany
authors.initials: R
authors.lastname: Condos
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D012189:Retrospective Studies; D014109:Total Lung Capacity; D014797:Vital Capacity
chemical_list: D000336:Aerosols; D000998:Antiviral Agents; D016207:Cytokines; D007371:Interferon-gamma