Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease

Inclusion Criteria: * Confirmed diagnosis of CF based on the following criteria: * Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or * Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype * Male or female patients ≥ 12 years of age * FEV1 ≥ 50% predicted (Knudson) 31 * Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit * Ability to reproducibly perform spirometry (according to ATS criteria) * Ability to produce at least 1mL of sputum spontaneously, or be willing to undergo sputum induction * Ability to understand and sign a written informed consent or assent and comply with the requirements of the study * Chronic bacterial colonization (3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization) Exclusion Criteria: * History of hypersensitivity to sildenafil * Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0) * Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study * Daily use of systemic corticosteroids and/or NSAIDs within 4 weeks of the study or as needed use within 72 hours prior to the screening visit * History of significant hepatic (SGOT or SGPT \> 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), cardiovascular (history of aortic stenosis, coronary artery disease, pulmonary hypertension with right ventricular systolic pressure \>55 mmHg or life-threatening arrhythmia), neurological (history of stroke), hematologic (history of bleeding diathesis), ophthalmologic (history of retinal impairment or non-arteritic ischemic optic neuritis) or renal impairment (creatinine \>1.8 mg/dL.) * Inability to swallow pills * Previous lung transplantation * Use of concomitant nitrates, α-blocker, or Ca channel blocker * Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin) * Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data * Weight less than 40 kg * History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening * Resting room air oxygen saturation \<93% * History of migraines