Glucocorticoid treatment reduces exhaled nitric oxide in cystic fibrosis patients

In cystic fibrosis (CF), low concentrations of exhaled nitric oxide (NO) an d reduced expression of inducible nitric oxide synthase (iNOS) in airway ep ithelium have been reported, Ilo,Fever, abundant iNOS expression has been f ound in the subepithelial tissues and elevated concentrations of NO metabol ites in breath condensate and sputum, These conflicting results may be expl ained by increased scavenging of NO by superoxide radicals, resulting in ra pid 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 i n the CF lung, exhaled NO would be further reduced by glucocorticoid treatm ent. CF patients (n = 13) were recruited to a double-blind, placebo-controlled s tudy with crossover. Treatment comprised prednisolone or placebo for 5 days with a 9 day washout. After each treatment, exhaled NO was measured, spiro metry performed and blood collected for measurement of serum nitrogen dioxi de/nitrous oxide (NO2/O-3). 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 conce ntration were unchanged. These findings support the hypothesis that glucocorticoids suppress nitric oxide production in cystic fibrosis airways by reducing inducible nitric ox ide synthase expression or by inhibiting recruitment of neutrophils, cells which express inducible nitric oxide synthase.