Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease

Richard B. Moss, Nicole Mayer-Hamblett, Jeffrey Wagener, Cori Daines, Kathryn Hale, Richard Ahrens, Ronald L. Gibson, Paula Anderson, George Retsch-Bogart, Samya Z. Nasr, Imre Noth, David Waltz, Pamela Zeitlin, Bonnie Ramsey, Karen Starko

Research output: Contribution to journalArticle

Abstract

Interferon gamma-1b (IFN-γ1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF Patients with CF (≥12 years old, FEV 1 ≥40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 μg IFN-γ1b, 1,000 μg IFN-γ1b, 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 FEV 1 of 74 ± 20 (SD) percent predicted) were studied. One patient had bronchospasm after the first dose of IFN-γ1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500 μg IFN-γ1b group, and 3 in the 1,000 μg IFN-γ1b group). The 500 μg IFN-γ1b dose was well-tolerated, but the 1,000 μg dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log10 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 μg IFN-γ1b 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-μg IFN-γ1b and placebo groups (95% CI, -0.16, 0.17, P = 0.96). No effects of IFN-γ1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks. Aerosolized IFN-γ1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease.

Original languageEnglish (US)
Pages (from-to)209-218
Number of pages10
JournalPediatric Pulmonology
Volume39
Issue number3
DOIs
StatePublished - Mar 2005

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Cystic Fibrosis
Lung Diseases
Placebos
Sputum
Confidence Intervals
Hospitalization
interferon gamma-1b
Bronchial Spasm
Leukocyte Elastase
Nebulizers and Vaporizers
Spirometry
Interleukin-8
Inhalation
Peroxidase
Biomarkers
Cytokines
Anti-Bacterial Agents
Inflammation
Safety
Lung

Keywords

  • Aerosol
  • Cystic fibrosis
  • Immunomodulation
  • Inflammation
  • Interferon
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease. / Moss, Richard B.; Mayer-Hamblett, Nicole; Wagener, Jeffrey; Daines, Cori; Hale, Kathryn; Ahrens, Richard; Gibson, Ronald L.; Anderson, Paula; Retsch-Bogart, George; Nasr, Samya Z.; Noth, Imre; Waltz, David; Zeitlin, Pamela; Ramsey, Bonnie; Starko, Karen.

In: Pediatric Pulmonology, Vol. 39, No. 3, 03.2005, p. 209-218.

Research output: Contribution to journalArticle

Moss, RB, Mayer-Hamblett, N, Wagener, J, Daines, C, Hale, K, Ahrens, R, Gibson, RL, Anderson, P, Retsch-Bogart, G, Nasr, SZ, Noth, I, Waltz, D, Zeitlin, P, Ramsey, B & Starko, K 2005, 'Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease', Pediatric Pulmonology, vol. 39, no. 3, pp. 209-218. https://doi.org/10.1002/ppul.20152
Moss, Richard B. ; Mayer-Hamblett, Nicole ; Wagener, Jeffrey ; Daines, Cori ; Hale, Kathryn ; Ahrens, Richard ; Gibson, Ronald L. ; Anderson, Paula ; Retsch-Bogart, George ; Nasr, Samya Z. ; Noth, Imre ; Waltz, David ; Zeitlin, Pamela ; Ramsey, Bonnie ; Starko, Karen. / Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease. In: Pediatric Pulmonology. 2005 ; Vol. 39, No. 3. pp. 209-218.
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N2 - Interferon gamma-1b (IFN-γ1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF Patients with CF (≥12 years old, FEV 1 ≥40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 μg IFN-γ1b, 1,000 μg IFN-γ1b, 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 FEV 1 of 74 ± 20 (SD) percent predicted) were studied. One patient had bronchospasm after the first dose of IFN-γ1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500 μg IFN-γ1b group, and 3 in the 1,000 μg IFN-γ1b group). The 500 μg IFN-γ1b dose was well-tolerated, but the 1,000 μg dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log10 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 μg IFN-γ1b 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-μg IFN-γ1b and placebo groups (95% CI, -0.16, 0.17, P = 0.96). No effects of IFN-γ1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks. Aerosolized IFN-γ1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease.

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