The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients.

Despite the inflammatory nature of lung disease in CF, nitric oxide (NO) formation as well as the expression of NOS2 has been found to be decreased in CF airways. While the reasons for impaired airway NO formation remain incompletely understood, there is evidence that low NO formation contributes to lung pathophysiology in CF. Constitutive endogenous formation of Nitric oxide (NO) in airways is thought to play a role in neurotransmission, smooth muscle relaxation and bronchodilation. Previous animal experiments have shown that the addition of L-arginine, the precursor of enzymatic NO formation, resulted in a significantly greater relaxation of tracheas. There is also evidence that a single dose of inhaled L-arginine improves pulmonary function in CF. In this study we will assess the effect of L-arginine inhalation on lung function, nitric oxide formation, airway inflammation and bacterial infection in CF patients.

Inclusion Criteria:

• Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride concentration > 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
• 14 years of age and older at enrollment
• Clinically stable at enrollment
• Ability to comply with medication use, study visits and study procedures
• FEV1 % predicted > 40% < 80 % as calculated by reference equations

Exclusion Criteria:

• Respiratory culture positive for: B. cepacia complex within past year or at screening
• Use of systemic corticosteroids within 30 days of screening
• Use of intravenous antibiotics or oral quinolones within 14 days of screening
• History of biliary cirrhosis, portal hypertension, or splenomegaly
• Other major organ dysfunction
• History of lung transplantation or currently on lung transplant list
• Supplemental oxygen therapy
• Oxygen saturation < 95 % on room air
• Positive pregnancy test at screening
• Investigational drug use within 30 days of screening
• History of alcohol, illicit drug or medication abuse within 1 year of screening
• Acute respiratory symptoms
• Inability to take any form of bronchodilator
• Wheezing at the time of study