title: Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease.
abstract: Interferon gamma-1b (IFN-gamma1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF. Patients with CF (> or =12 years old, FEV1 > or =40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 microg IFN-gamma1b, 1,000 microg IFN-gamma1b, or placebo by Respirgard II nebulizer thrice weekly for 12 weeks. Sputum bacterial density and spirometry were measured. Safety, antibiotic use, hospitalization, and sputum neutrophils, elastase, DNA, IL-8, and myeloperoxidase were also evaluated. Sixty-six patients (mean age, 24 years, with mean baseline FEV1 of 74 +/- 20 (SD) percent predicted) were studied. One patient had bronchospasm after the first dose of IFN-gamma1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500-microg IFN-gamma1b group, and 3 in the 1,000 microg IFN-gamma1b group). The 500-microg IFN-gamma1b dose was well-tolerated, but the 1,000-mug dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log(10) CFU/g sputum, 95% confidence interval (CI), 0.1,2.8, P=0.04), had 24% more hospitalizations for exacerbation than placebo patients (95% CI, 2,45%, P=0.05). There was a 0.12-l difference between the 500-microg IFN-gamma1b and placebo groups with respect to the 12-week change in FEV1 (active group minus placebo group, 95% CI, -0.03,0.26, P=0.11), as compared to a 0.01-l difference between the 1,000-microg IFN-gamma1b and placebo groups (95% CI, -0.16,0.17, P=0.96). No effects of IFN-gamma1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks. Aerosolized IFN-gamma1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease.
authors.affiliation: Department of Pediatrics, Stanford University Medical Center, Palo Alto, California 94304-5786, USA. rmoss@stanford.edu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Moss
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wagener
authors.forename: Cori
authors.initials: C
authors.lastname: Daines
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hale
authors.forename: Richard
authors.initials: R
authors.lastname: Ahrens
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gibson
authors.forename: Paula
authors.initials: P
authors.lastname: Anderson
authors.forename: George
authors.initials: G
authors.lastname: Retsch-Bogart
authors.forename: Samya Z
authors.initials: SZ
authors.lastname: Nasr
authors.forename: Imre
authors.initials: I
authors.lastname: Noth
authors.forename: David
authors.initials: D
authors.lastname: Waltz
authors.forename: Pamela
authors.initials: P
authors.lastname: Zeitlin
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ramsey
authors.forename: Karen
authors.initials: K
authors.lastname: Starko
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000145:classification / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D006469:Hemoptysis / Q000139:chemically induced; D006760:Hospitalization; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D011994:Recombinant Proteins; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D013183:Sputum / Q000737:chemistry / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D016209:Interleukin-8; D011994:Recombinant Proteins; D007371:Interferon-gamma; D009195:Peroxidase; D010196:Pancreatic Elastase