title: Inhaled Interferon and Diffusion Capacity in Idiopathic Pulmonary Fibrosis (IPF).
abstract: BACKGROUND
  Using data from a previously reported phase 2 safety trial, testing inhaled interferon gamma (IFN-γ) for IPF, we analyzed effects on full pulmonary function tests (PFTs) for efficacy before and after therapy and designed a randomized controlled trial of inhaled IFN-γ to treat IPF.
  
  
  METHODS
  Ten patients with IPF had received inhaled IFN-γ (Actimmune, InterMune) for 80 weeks. Full PFTs were available 20-50 weeks before Rx and monthly during Rx. Eighty-nine observations were used in the analysis. Linear mixed models for modeling longitudinal data were used to test if the PFT change over time was significantly different before and after IFN-γ. Autoregressive dependence structure with order one was consistently selected as the best one to model the intra-patient correlation over time. Normality assumption was confirmed. Significance level was set at 0.05. Using published literature and our data we performed a sample size calculation based on simulated data.
  
  
  RESULTS
  The change over time in DLCO was significantly different before and after IFN-γ treatment. DLCO decreased over time before treatment but increased after treatment (p-value=0.03). Changes in TLC, FRC, RV and FVC were not statistically significant. With a sample size of 60, a placebo controlled, randomized trial has about 90% power to detect a significant difference in the change rate of DLCO in the groups of patients treated with IFN-γ vs placebo.
  
  
  CONCLUSIONS
  DLCO was significantly improved following inhaled (IFN-γ) as treatment for IPF. Our data suggest that previous studies utilizing parenteral IFN-γ may have failed because of the mode of delivery. Future randomized, controlled, phase 3 trials, comparing the difference in PFT behavior (specifically DLCO) longitudinally may be more sensitive to drug effect and serve as a valuable clinical endpoint.
authors.affiliation: Stony Brook University Medical Center, Pulmonary, Critical Care & Sleep Medicine. gerald.smaldone@stonybrook.edu.
authors.forename: S D
authors.initials: SD
authors.lastname: Skaria
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Rany
authors.initials: R
authors.lastname: Condos
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Smaldone
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D007371:Interferon-gamma / Q000008:administration & dosage*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011237:Predictive Value of Tests; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects*; D011728:Pyridones / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012016:Reference Values; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D011728:Pyridones; D011994:Recombinant Proteins; C554125:interferon gamma-1b; D007371:Interferon-gamma; C093844:pirfenidone