Airway morphology and inspiratory flow features in the early stages of Chronic Obstructive Pulmonary Disease

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.