Longitudinal Assessment of Exercise Capacity and Vascular Function in Patients With CF

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.