Background: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of death worldwide. Inhaled pollutants are the prime risk factor, but the pathogenesis and progression of the diseased is poorly understood. Most studies on the disease onset and trajectory have focused on genetic and molecular biomarkers. Here we investigate the role of the airway anatomy and the consequent respiratory fluid mechanics on the development of COPD. Methods: We segmented CT scans from a five-year longitudinal study in three groups of smokers (18 subjects each) having: (i) minimal/mild obstruction at baseline with declining lung function at year five; (ii) minimal/mild obstruction at baseline with stable function, and (iii) normal and stable lung function over the five year period. We reconstructed the bronchial trees up to the 7th generation, and for one subject in each group we performed MRI velocimetry in 3D printed models. Findings: The subjects with airflow obstruction at baseline have smaller airway diameters, smaller child-to-parent diameter ratios, larger length-to-diameter ratios, and smaller fractal dimensions. The differences are more significant for subjects that develop severe decline in pulmonary function. The secondary flows that characterize lateral dispersion along the airways are found to be less intense in the subjects with airflow obstruction. Interpretation: These results indicate that morphology of the conducting airways and inspiratory flow features are correlated with the status and progression of COPD already at an early stage of the disease. This suggests that imaging-based biomarkers may allow a pre-symptomatic diagnosis of disease progression.
Bibliographical noteFunding Information:
We gratefully acknowledge the access to the COPDGene database. We thank Sahar Jalal, Andras Nemes, and Omid Amili for help during the MRI measurements. Funding for this work was provided by the National Science Foundation ( CBET-1453538 ), the National Institutes of Health ( NHLBI-R21HL129906 ), and Boston Scientific Inc. ( CON000000057347 ) COPDGene was supported by Award Number R01 HL089897 and Award Number R01 HL089856 from the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens and Sunovion.
© 2017 Elsevier Ltd
- Airway morphology
- Chronic Obstructive Pulmonary Disease
- Computed tomography
- Magnetic resonance imaging
- Respiratory fluid dynamics