longitudinal assessment of exercise capacity and vascular function in patients with cf

Conditions: Cystic Fibrosis

Summary: this project is an attempt to understand how orkambi treatment affects exercise capacity and the function of the arteries in cf patients who are homozygous f508del. our goal is to perform the exercise and vascular measurements every 3 months after a patient starts taking orkambi.

cystic fibrosis (cf) is the most common fatal genetic disease in north america. the most disturbing aspect of cf is the associated premature death, most often due to respiratory complications. clinical manifestations of cf include not only lung dysfunction, but many other systemic consequences as well. systemic oxidative stress and exercise intolerance are established phenotypes in patients with cf. additionally, for the first time the investigators have recently published the presence of systemic endothelial dysfunction in a cohort of young patients with cf who exhibited normal oxygen saturation and spirometric function. exercise intolerance, the limitation of the ability to perform exercise at the expected level, has been shown to predict mortality in patients with cf independent of lung function. exercise capacity (vo2 peak), an objective measurement of exercise tolerance, drops approximately 5-8% per year in patients with cf. this excessive decay in exercise capacity not only leads to more pulmonary infections and deterioration of lung function, it represents a 5-8 fold decline compared to healthy sedentary adults. preventing the excessive annual reduction in exercise capacity is essential to increasing the quality of life and longevity of patients with cf. however, a critical barrier to improving exercise capacity in cf is the investigators lack of knowledge regarding the different physiological mechanisms that contribute to exercise intolerance. it is important to emphasize that decreases in lung function (fev1) do not always contribute to reductions in vo2 peak. furthermore, less than 2% of patients who have an fev1 greater than 50% predicted will have a significant drop in hemoglobin oxygen saturation (spo2) during maximal exercise. these data suggest that mechanisms other than lung function induced hypoxemia may be contributing to exercise intolerance in patients with cf.

Eligibility criteria:
inclusion criteria: * patients diagnosed with cystic fibrosis (homozygous deltaf508del) * prescribed orkambi * men and women (\> 18 yrs. old) * boys and girls (7 -17 yrs. old) * fev1 percent predicted \> 40% * resting oxygen saturation (room air) \>85% * patients with or without cfrd * traditional cf-treatment medications * clinically stable for past 28 days (no exacerbations or change in medical status) * healthy controls exclusion criteria: * children 6 yrs. old and younger * fev1 percent predicted \< 40% * resting oxygen saturation (room air) \< 85% * clinical diagnosis of heart disease * pulmonary artery hypertension * febrile illness within two weeks of visit * current smokers * currently pregnant or nursing * individuals on vaso-active medications (i.e. nitrates, beta blockers, ace inhibitors, etc.) * use of vx-770 within 6 months prior to visit 1 * history of solid organ transplantation * presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient or the quality of the data.

Keywords: arterial stiffness flow-mediated dilation endothelial function orkambi exercise capacity