A randomized controlled trial of inhaled L-arginine in patients with cystic fibrosis

Abstract

Background: Cystic fibrosis (CF) airways are nitric oxide (NO) deficient. We studied safety and efficacy of repeated inhalations of nebulized L-arginine, the substrate for NO synthase (NOS), in patients with CF.

Methods: Double-blind, randomized, placebo-controlled crossover treatment trial of twice daily inhalation of 500 mg L-arginine for two weeks compared to inhalation of saline in 19 CF patients (ClinicalTrials.gov Identifier: NCT00405665).

Results: L-arginine inhalation was well tolerated and resulted in a significant increase in exhaled NO. FEV1 increased by an average of 56 ml compared to -8 ml after saline solution; but this difference did not reach statistical significance. Sputum concentrations of L-ornithine, the product of arginase activity, increased significantly while the L-ornithine derived polyamines did not. There was no change in inflammatory markers in sputum.

Conclusion: Repeated inhalation of L-arginine in CF patients was safe and well tolerated. Inhaled L-arginine increased NO production without evidence for changes in airway inflammation.

Keywords: Airway inflammation; Clinical trial; Nitric oxide; Polyamines; l-Arginine.