Large artery haemodynamics in cystic fibrosis

Cystic Fibrosis (CF) is the most common lethal autosomal recessive condition and affects approximately 1/2500 Caucasian newborns in the United Kingdom and 70,000 individuals worldwide. The gene defect classically leads to a phenotype comprising significant respiratory I and gastrointestinal manifestations, however is recognised to have multisystem consequences. Over the past 70 years there has been considerable progress in the understanding and treatment of CF such that it has moved from a poorly understood condition, almost universally fatal in infancy, to a complex multisystem disorder now affecting as many adults as children. This 'evolution' of the disease presents new challenges for clinicians and has increased focus on its extra-pulmonary components. In the general population cardiovascular disease is the leading cause of morbidity and mortality and it is now recognised that progressive changes in the structure and function of the large arterial system are a key determinant of this association. Furthermore these changes lead to alterations in large artery haemodynamics which have immediate physiological relevance for myocardial work and oxygen demand but also perfusion of the distal organs. Modern techniques permit large artery haemodynamics to be evaluated simply and effectively using the non-invasive technique of applanation tonometry with pulse wave analysis. The overall aim of this thesis was to use this technique to provide an evaluation of large artery haemodynamics in a cohort of adult patients with CF. The experimental work in this thesis includes a study assessing the validity of the haemodynamic techniques used in this thesis (study A) and three studies evaluating large artery haemodynamics in patients with CF; at rest (study I), in response to exercise (study II) and finally following a therapeutic intervention (study III)