title: Acute effects of aerosolized S-nitrosoglutathione in cystic fibrosis.
abstract: S-nitrosoglutathione (GSNO), a naturally occurring constituent of airway lining fluid, enhances ciliary motility, relaxes airway smooth muscle, inhibits airway epithelial amiloride-sensitive sodium transport, and prevents pathogen replication. Remarkably, airway levels of GSNO are low in patients with cystic fibrosis (CF). We hypothesized that replacement of airway GSNO would improve gas exchange in CF. In a double-blind, placebo controlled study, we administered 0.05 ml/kg of 10 mM GSNO or phosphate buffered saline by aerosol to patients with CF and followed oxygen saturation, spirometry, respiratory rate, blood pressure, heart rate, and expired nitric oxide (NO). Nine patients received GSNO and 11 placebo. GSNO inhalation was associated with a modest but sustained increase in oxygen saturation at all time points. Expired NO increased in the low ppb range with GSNO treatment, peaking at 5 minutes but remaining above baseline at 30 minutes. There were no adverse effects. We conclude that GSNO is well tolerated in patients with CF and improves oxygenation through a mechanism that may be independent of free NO. Further, GSNO breakdown increases expired NO. We suggest that therapy aimed at restoring endogenous GSNO levels in the CF airway may merit study.
authors.affiliation: Division of Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Ashley H
authors.initials: AH
authors.lastname: Snyder
authors.forename: Marianne E
authors.initials: ME
authors.lastname: McPherson
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
authors.forename: Michael
authors.initials: M
authors.lastname: Johnson
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Stamler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D001944:Breath Tests; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis; D010100:Oxygen / Q000097:blood; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D026422:S-Nitrosoglutathione / Q000008:administration & dosage*; D014797:Vital Capacity
chemical_list: D000336:Aerosols; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D010100:Oxygen