Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A cycle of chronic, persistent infections with CF-related pathogens and an excessive inflammatory response progressively damages the airways and lung parenchyma, resulting in widespread bronchiectasis and ultimately, respiratory failure. Despite tremendous advances in understanding the CF gene and the CFTR protein, it is not known exactly how mutations in the gene and defects in CFTR lead to persistent airway infection and inflammation.

Inhaled nitric oxide (NO) has potential to be an effective treatment in CF lung disease. Inhaled NO has been studied in other airways diseases characterized by infection and /or inflammation such as COPD and idiopathic pulmonary fibrosis.

NO has been shown to activate CFTR and alternative chloride channels, thereby increasing chloride current in epithelial cells. Therefore, NO treatment may be beneficial in individuals with CF.

Inclusion criteria

• Confirmed diagnosis of CF
• 12 years of age and older
• FEV1 greater than 40% of predicted
• Resting awake oxygen saturation of at least 88%
• Stable pulmonary disease as defined by both clinical impression and having had no recent hospitalizations or changes in antibiotic regimen within 1 month prior to enrollment
• Signed informed consent form

Exclusion criteria

• Pulmonary exacerbation resulting in antibiotic treatment (except prophylactic antibiotics) within 1 month of enrollment
• Isolation of B. cepacia from a respiratory tract culture within 6 months
• Severe nasal obstruction at the time of screening
• Receipt of any aerosolized experimental or investigational drugs within 1 month of enrollment
• Pregnancy (a negative pregnancy test must be documented prior to enrollment if applicable)
• Patients who have received treatment with nitric oxide for inhalation within 24 hours prior to study initiation or other investigational medications within 24 hours.