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.

Morphological and functional properties of the conducting human airways investigated by in vivo computed tomography and in vitro MRI.

The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyzed CT scans of a cohort of healthy subjects and obtained comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. Although some of the geometric parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluated several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we used phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the three-dimensional-printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e., transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models and persists within the first seven generations. NEW & NOTEWORTHY We performed a comprehensive computed tomography-based study of the conductive airway morphology in normal human subjects, including branch diameter, length, and mutual angles. We found significant departure from classic homothetic relationships. We also carried out MRI measurements of the three-dimensional inspiratory flow in an anatomy-based model and directly assessed structure-function relationships that have so far been assumed. We found that strong secondary flows (i.e., transverse velocity components) persist through the first seven generations of bronchial branching.