[Truncated] Background and rationale
Progressive lung disease remains the leading cause of morbidity and mortality in cystic fibrosis. Despite widespread implementation of newborn screening programs, the rate of decline in pulmonary function in adolescents with cystic fibrosis has remained unchanged over successive cohorts, suggesting that current standards of management for cystic fibrosis are doing little to prevent progressive lung disease. Several exciting developments in the cystic fibrosis therapeutic pipeline have the potential to alter the disease trajectory in children with cystic fibrosis. The ability to confirm that these therapeutics can prevent progressive lung disease if commenced early in life is hindered, however, by a lack of suitable pulmonary endpoints for clinical trials in early childhood. Chest computed tomography (CT) is a promising endpoint that reflects altered lung structure in infants with cystic fibrosis, assessing key components of early structural lung disease, including bronchiectasis, mucous plugging, and air trapping. Before the widespread adoption of chest CT as a clinical marker of disease severity, and as an endpoint for clinical trials commencing in infancy, the ability of chest CT to reflect progressive lung disease must be demonstrated, and chest CT acquisition protocols must be standardised for use in multicentre studies.
Research objective and aims
The global objective of the research presented in this thesis was to contribute to the development of chest CT as a suitable endpoint for cystic fibrosis clinical trials commencing in infancy, by demonstrating the ability of chest CT to reflect progressive lung disease, and to contribute to standardisation of chest CT acquisition protocols for this population. The latter objective was addressed through a series of studies focussing on volumetric acquisition protocols, confirming the heterogeneous distribution of early lung disease, and determining whether assessment of early bronchiectasis is dependent on lung volume.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2013|