Relationship of CT-quantified emphysema, small airways disease and bronchial wall dimensions with physiological, inflammatory and infective measures in COPD

Background: COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation. Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease. We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response. Methods: Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA(<-950)), small airways disease (E/I MLD) and bronchial wall thickening (Pi10). At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR. Results: 122 subjects were included in this analysis. Emphysema and small airways disease had independent associations with airflow obstruction (beta = -0.34, p < 0.001 and beta = -0.56, p < 0.001). % LAA<-950 had independent associations with gas transfer (beta = -0.37, p < 0.001) and E/I MLD with RV/TLC (beta = 0.30, p = 0.003). The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (beta = 0.73, p < 0.001). Pi10 did not show any independent associations with lung function or functional parameters. No CT parameters had any associations with sputum inflammatory cells. Greater emphysema was associated with lower levels of systemic inflammation (CRP beta = -0.34, p < 0.001 and fibrinogen beta = -0.28, p = 0.003). There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not. Conclusions: This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status. In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.