| dc.description.abstract | Cystic fibrosis (CF) is the most common, genetically inherited, life-shortening condition in the Caucasian population, with ~11,000 people in the United Kingdom having the disease. The genetic defect responsible for CF results in accumulation of thick, sticky mucus that blocks the airways and digestive systems. As there is currently no cure for CF, it is a disease that is managed using antibiotics, nutrition, physiotherapy and exercise. Exercise capacity, as measured by peak oxygen uptake (V̇O2peak), and where possible, maximal oxygen uptake (V̇O2max), is reduced in patients with CF and a low V̇O2peak is associated with increased risk of hospitalisation, mortality and low quality of life. As a result, regular exercise testing is recommended, with cardiopulmonary exercise testing (CPET) considered the ‘gold standard’ procedure by leading international clinical organisations. The purpose of this thesis was to further our understanding surrounding the use of CPET in the assessment and treatment of children and adolescents with CF. The first component of this thesis sought to identify and evaluate submaximal parameters of aerobic function derived from CPET, namely the oxygen uptake efficiency slope (OUES) and plateau (OUEP). Findings revealed that allometric scaling for body surface area (BSA) was necessary when evaluating OUES, and a power function of 1.40 (i.e. OUES/BSA1.40) removed residual effects of body size (Chapter 4). Subsequently, results identified that the OUES was not a valid surrogate of aerobic fitness in CF, despite a significant correlation (r = 0.47, p = 0.004) with V̇O2max when expressed relative to body mass, as it was unable to discriminate aerobic fitness within a CF group, nor against a control group (Chapter 5). As OUES was not a valid surrogate of aerobic fitness, the utility of OUEP as an independent marker of aerobic fitness was explored. Whilst the OUEP was correlated with V̇O2peak in CF, when expressed as an absolute value (r = 0.43, p = 0.010) and when allometrically scaled for body mass (r = 0.52, p = 0.001), it was unable to discriminate aerobic fitness to the same extent as V̇O2peak. However, the OUEP was associated with disease status and severity, being significantly (p < 0.001) lower in the CF group, but also significantly and positively correlated with lung function (forced expiratory volume in one-second [FEV1]) in the CF group (r = 0.43, p = 0.010), a finding that warrants further, longitudinal investigation (Chapter 6). The second component of this thesis utilised CPET to investigate musculoskeletal limitations to the reduced V̇O2max that has previously been reported in CF. Parameters of muscle size (thigh cross-sectional area, muscle cross-sectional area and thigh muscle volume) were first quantified using magnetic resonance imaging, alongside the error associated with estimating muscle volume using alternative calculation techniques (Chapter 7). These parameters were then allometrically scaled for, which successfully removes residual effects of muscle size (i.e. muscle ‘quantity’) from V̇O2max. When this scaling is undertaken, V̇O2max is lower in children with CF relative to age- and sex-matched controls, indicating that exercise capacity is not size-dependent in CF and that intrinsic muscular factors (i.e. muscle ‘quality’) are likely responsible for the reduced V̇O2max observed in CF (Chapter 8). Finally, the third component identified applications of CPET for both patients with CF and staff responsible for care. CPET, using a case-study approach, was utilised to describe exercise-related changes in an 11 year old female with CF following surgical insertion of a percutaneous endoscopic gastrostomy and overnight nutritional supplementation. This evaluation identified a maintenance of V̇O2max over one year, in contrast to a fluctuation in FEV1, and increase in body mass index (BMI), therefore highlighting the independent prognostic information afforded by use of CPET (Chapter 9). Following this patient-centred application of CPET, two meetings were held with NHS staff, to provide a platform for exchange of ideas and best practice, but to also survey roles, responsibilities, prevalence of CPET and resources needed for effective implementation of exercise testing and training (Chapter 10). In conclusion, this thesis has further highlighted the utility of CPET in the management of CF. Moreover, it has explored the prognostic and diagnostic properties of CPET, as well as its implementation for patients and staff alike. | en_GB |
