Using Quantitative Computed Tomography to Provide Important and Novel Insights into Airway Remodelling in Asthma and COPD

Over the past 20 years, the technology behind Computed Tomography (CT) scan acquisition and image analysis has improved dramatically. The potential for CT to be a non-invasive method to probe the lungs has long been recognised, but there remain large gaps in our knowledge of how changes in airway structure influences airway physiology and clinical outcomes. In this thesis I examine quantitative CT (QCT) measures of airway remodelling between asthma, COPD and healthy controls, its relationship with immunohistology and its application in stratified medicine intervention studies. First I present one of the largest studies to date comparing QCT parameters in asthma, COPD and healthy controls. It confirms the heterogeneity within both diseases. However there are still distinct structural differences observed within each cohort, with striking differences seen within and between the cohorts when grouped by airflow limitation. I then present one of the largest studies to date looking at QCT measures and bronchial biopsies. This shows that changes seen on QCT correlate with typical remodelling parameters such as percentage airway smooth muscle, but not markers of inflammation. It also shows that the QCT marker of air trapping is associated with increased vascularity. Finally I present a study looking at the use of QCT in assessing the effects of a new drug, fevipiprant, aimed at reducing sputum eosinophilia, over a 12 week course. This study shows that fevipiprant, improves some clinical outcomes such as spirometry and reduces sputum eosinophilia, but no structural changes are seen on QCT.