Inhaled L-arginine improves exhaled nitric oxide and pulmonary function in patients with cystic fibrosis

Rationale: Nitric oxide formation is deficient in airways of patients with cystic fibrosis (CF). Since nitric oxide has bronchodilatory effects, nitric oxide deficiency may contribute to airway obstruction in CF. Objectives: We reasoned that inhalation of L-arginine, the precursor of enzymatic nitric oxide formation, could improve airway nitric oxide formation and pulmonary function in patients with CF. Measurements: Exhaled nitric oxide, pulmonary function, and peripheral oxygen saturation were measured before and after a single inhalation of nebulized L-arginine solution in patients with CF and in healthy subjects. A saline solution of similar osmolarity (1.7%) was used as control. Results: Nebulized L-arginine not only significantly increased exhaled nitric oxide concentrations but also resulted in a sustained improvement of FEV1 in patients with CF. Oxygen saturation also increased significantly after the inhalation Of L-arginine. Nebulized saline resulted in a small but significant increase in exhaled nitric oxide but a decrease in FEV1 in patients with CF. In control subjects inhalation of L-arginine increased exhaled nitric oxide concentrations, but FEV1 decreased. No effect of saline on exhaled nitric oxide, pulmonary function, or oxygen saturation was observed in healthy subjects. Conclusions: These data suggest that a single inhalation Of L-arginine acutely and transiently improves pulmonary function in CF through the formation of nitric oxide. Augmentation of airway nitric oxide formation by inhalation Of L-arginine is a promising therapeutic approach in patients with CF.