The role of quantitative morphological and functional imaging of the lung in COPD

Chronic obstructive pulmonary disease (COPD) is a lung disease characterised by chronic airflow limitation. It is a heterogeneous disorder and the identification of clinically relevant phenotypes may be important in predicting clinical outcome and guiding therapy. Imaging biomarkers may represent useful clinical tools in COPD studies and these include quantitative computed tomography (QCT), which can objectively assess emphysema and airways disease, and, quantitative positron emission tomography-computed tomography (PET-CT), which can generate data on pulmonary neutrophilic inflammation. The purpose of this study was to explore the utility of QCT and PET-CT in COPD phenotyping and therapeutic studies respectively. In addition, the aims were to assess interscanner variability of quantitative CT measures, explore methods of standardisation for multicentre studies and to determine the prevalence and clinical significance of lung nodules identified on CT scanning in patients with AATD. Methods of standardisation of QCT were explored by scanning an anthropomorphic dog lung in six CT scanners and adjusting lung densitometry by regression using measurements obtained from a novel standardisation phantom. The optimum standardisation methodology was applied to clinical data (n=140) from a multicentre study of subjects with COPD and the QCT data was utilised to delineate clinical phenotypes. A retrospective review of CT imaging in patients with alpha 1-antitrypsin deficiency (AATD, n=494) was conducted to identify the significance of pulmonary nodules with respect to systemic inflammation and disease progression. Finally, a comparative study of PET-CT imaging in AATD, usual COPD and healthy subjects (n=10 in each group) was undertaken; patients with AATD underwent a second scan following augmentation therapy. Standardisation significantly reduced the variability of densitometric measurements arising from differences in scanner models and scanning protocols and, standardised QCT measures were shown to be of critical importance in differentiating emphysema-dominate and airways disease-dominant clinical phenotypes in multicentre CT studies. The occurrence of resolving nodules in patients with AATD was shown to be associated with increased systemic inflammation and accelerated progression of emphysema. Upper zone lung inflammation assessed using PET-CT was greater in patients with usual COPD compared to patients with AATD and healthy controls. This data suggests that isotope uptake, assessed by quantitative PET-CT, may represent a novel outcome measure in usual COPD trials.