Glucocorticoid treatment reduces exhaled nitric oxide in cystic fibrosis patients

Abstract

In cystic fibrosis (CF), low concentrations of exhaled nitric oxide (NO) and reduced expression of inducible nitric oxide synthase (iNOS) in airway epithelium have been reported. However, abundant iNOS expression has been found in the subepithelial tissues and elevated concentrations of NO metabolites in breath condensate and sputum. These conflicting results may be explained by increased scavenging of NO by superoxide radicals, resulting in rapid conversion to peroxynitrite, so that only a small proportion of the NO produced in the lung tissue reaches the airway lumen. If iNOS were active in the CF lung, exhaled NO would be further reduced by glucocorticoid treatment. CF patients (n = 13) were recruited to a double-blind, placebo-controlled study with crossover. Treatment comprised prednisolone or placebo for 5 days with a 9 day washout. After each treatment, exhaled NO was measured, spirometry performed and blood collected for measurement of serum nitrogen dioxide/nitrous oxide (NO2/NO3). Ten patients (8 male) completed the study. Following prednisolone treatment (mean ± SD) exhaled NO concentration (3.1 ± 1.6 parts per billion (ppb)) was significantly reduced versus placebo treatment (4.9 ± 4.2 ppb; p < 0.05, Wilcoxon signed-rank test). Spirometric indices and serum NO2/NO3 concentration were unchanged. These findings support the hypothesis that glucocorticoids suppress nitric oxide production in cystic fibrosis airways by reducing inducible nitric oxide synthase expression or by inhibiting recruitment of neutrophils, cells which express inducible nitric oxide synthase.