Acute Effects of Aerosolized S-Nitrosoglutathione in Cystic Fibrosis

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 wi...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2002-04, Vol.165 (7), p.922-926
Main Authors: Snyder, Ashley H, McPherson, Marianne E, Hunt, John F, Johnson, Michael, Stamler, Jonathan S, Gaston, Benjamin
Format: Article
Language:English
Subjects:
Administration, Inhalation
Adolescent
Adult
Aerosols
Biological and medical sciences
Breath Tests
Child
Cystic Fibrosis - drug therapy
Cystic Fibrosis - physiopathology
Double-Blind Method
Forced Expiratory Volume
Humans
Medical sciences
Nitric Oxide - analysis
Oxygen - blood
Pharmacology. Drug treatments
Pulmonary Gas Exchange - drug effects
Respiratory system
S-Nitrosoglutathione - administration & dosage
Vital Capacity
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Summary: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.
ISSN:1073-449X
1535-4970
DOI:10.1164/ajrccm.165.7.2105032