Published ahead of print on April 20, 2006, doi:10.1164/rccm.200509-1439OC Am. J. Respir. Crit. Care Med., Volume 174, Number 2, July 2006, 208-212 A more recent version of this article appeared on July 15, 2006
Submitted on September 14, 2005 Inhaled L-arginine Improves Exhaled Nitric Oxide and Pulmonary Function in Cystic Fibrosis PatientsHartmut Grasemann1*,1 Children's Hospital, University of Duisburg-Essen, Essen, Germany * To whom correspondence should be addressed. E-mail: hartmut.grasemann{at}sickkids.ca.
Rationale: Nitric oxide formation is deficient in airways of patients with cystic fibrosis. Since nitric oxide has bronchodilatory effects, nitric oxide deficiency may contribute to airway obstruction in cystic fibrosis. 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 cystic fibrosis. 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 cystic fibrosis 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 cystic fibrosis patients. 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 CF patients. 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 cystic fibrosis 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 cystic fibrosis. Key words: respiratory therapy, administration, inhalation, respiratory tract disease
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