Pulmonary Vascular Disease in CF

In this project, the investigators seek to understand the role of endothelial cells in Cystic Fibrosis (CF) lung disease. This objective will be achieved by conducting a cross sectional clinical study to define the morphology of the pulmonary circulation across a range of lung function coupled with a mechanistic study of the effect of dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) in endothelial cells on vasculogenesis, epithelial morphogenesis and epithelial CFTR function. Toward that end, the investigators propose the following hypotheses; (a). Loss of pulmonary small blood vessels begins early in the CF lung and worsens with disease progression, (b).VEGFR2-CFTR interactions happen at the plasma membrane of endothelial cells and is likely to be involved in transendothelial ion transport (c) impaired VEGFR2-CFTR interactions on the endothelial cells will have a profound effect on vasculogenesis, epithelial morphogenesis and ion transport. The first hypotheses will be tested through this clinical study. The following 2 hypotheses will be tested through laboratory studies that do not involve human subjects.

Cystic Fibrosis Patients: Inclusion Criteria: * 5-21 years of age * diagnosis of CF based on a positive sweat test and genetic testing * Baseline pulmonary condition defined as a) Absence of signs and symptoms of pulmonary exacerbation, b) Baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months, c) Patients should be off acute antibiotics for 2 weeks or longer. * Subjects should be able to perform an acceptable and reproducible spirometry * Study population will be equally divided between three groups based on FEV1%, (FEV1% ≥ 90); moderate (60 ≤ FEV1% \< 90) Exclusion Criteria: * Enrollment in clinical trials of CFTR correctors and or potentiator * Enrollment in gene therapy trial * Pregnancy. Historical Controls Inclusion Criteria: * solid tumor diagnosis * had chest CT scan to survey possible metastasis or any other lung disease * age and gender matched to Cystic Fibrosis patients