Airway fractal dimension predicts respiratory morbidity and mortality in COPD

Abstract

BACKGROUND. Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling. Characterization of airway changes on computed tomography has been challenging due to the complexity of the recurring branching patterns, and this can be better measured using fractal dimensions. METHODS. We analyzed segmented airway trees of 8,135 participants enrolled in the COPDGene cohort. The fractal complexity of the segmented airway tree was measured by the Airway Fractal Dimension (AFD) using the Minkowski-Bougliand boxcounting dimension. We examined associations between AFD and lung function and respiratory morbidity using multivariable regression analyses. We further estimated the extent of peribronchial emphysema (%) within 5 mm of the airway tree, as this is likely to affect AFD. We classified participants into 4 groups based on median AFD, percentage of peribronchial emphysema, and estimated survival. RESULTS. AFD was significantly associated with forced expiratory volume in one second (FEV 1 ; P < 0.001) and FEV 1 /forced vital capacity (FEV 1 /FVC; P < 0.001) after adjusting for age, race, sex, smoking status, pack-years of smoking, BMI, CT emphysema, air trapping, airway thickness, and CT scanner type. On multivariable analysis, AFD was also associated with respiratory quality of life and 6-minute walk distance, as well as exacerbations, lung function decline, and mortality on longitudinal follow-up. We identified a subset of participants with AFD below the median and peribronchial emphysema above the median who had worse survival compared with participants with high AFD and low peribronchial emphysema (adjusted hazards ratio [HR]: 2.72; 95% CI: 2.20-3.35; P < 0.001), a substantial number of whom were not identified by traditional spirometry severity grades. CONCLUSION. Airway fractal dimension as a measure of airway branching complexity and remodeling in smokers is associated with respiratory morbidity and lung function change, offers prognostic information additional to traditional CT measures of airway wall thickness, and can be used to estimate mortality risk. TRIAL REGISTRATION. ClinicalTrials.gov identifier: NCT00608764.

Fractal Analysis of Lung Structure in Chronic Obstructive Pulmonary Disease

“…Target of the powerlaw and fractal analysis Outcomes Parenchyma Mishima et al, 1999 LAA size distribution Detection of early COPD (exponent D: healthy 1.68, COPD with mild emphysema 1.38) Coxson et al, 2003 LAA size distribution LVRS response (exponent D: 0.56) Gietema et al, 2011 LAA size distribution Association with visual emphysema assessment (exponent D: panacinar emphysema 1.63, CLE 1.99, PSE 2.12) Yuan et al, 2010 LAA size distribution Estimate pathological emphysema (exponent D range: 0.1-2.5) Camp et al, 2009 LAA size distribution Sex difference in emphysema (exponent D: male 1.65, female 1.67) Tanabe et al, 2011 LAA size distribution Exacerbation and emphysema progression (exponent D: exacerbator 1.29, non-exacerbator 1.45) Tanabe et al, 2012 LAA size distribution Spatial pattern of smoking-induced emphysema progression (exponent D: former 1.83, current smokers 1.80) Hwang et al, 2019 LAA size distribution Long-term mortality (exponent D: 0.43) Tanabe et al, 2018a Relatively lower attenuation area size distribution Sensitive detection of emphysema progression in current smoker (exponent D: former 1.25 current smokers 1.30) Tobino et al, 2017 LAA size distribution Differential diagnosis of COPD from other cystic lung diseases (exponent D not shown) Mondoñedo et al, 2019 LAA size distribution Super emphysema cluster emergence in disease progression (exponent D: control 1.63, COPD 1.30) Shimizu et al, 2020 LAA size distribution Future exacerbation (exponent D: 1.50) Airway Bodduluri et al, 2018 Airway tree (boxcounting)…”

Fractal analysis of concurrently prepared latex rubber casts of the bronchial and vascular systems of the human lung

“…By any criterion, the human lung is a structurally complex organ [ 2 , 42 , 43 , 63 , 64 , 95 , 107 ]. The fractal properties of its parts have been investigated to understand its structure and function in health and disease states [ 2 , 5 , 89 , 95 , 101 , 127 ]. Various D F values have been determined for the bronchial and the vascular systems of the human lung [ 5 , 30 , 88 , 89 , 91 , 92 , 106 ] ( table 4 ).…”

Artificial Intelligence in COPD: New Venues to Study a Complex Disease

“…An airway fractality index computed from airway tree CT reconstructions was positively associated with FEV 1 , FEV 1 /FVC as well as exercise capacity, quality of life and 5-year decline in FEV 1 in subjects from COPDGene. Subjects with the unique phenotype of low fractality (tree simplification) and peribronchial emphysema had a higher mortality risk that those that did not present tree simplification but still have emphysema 32 . These findings suggest the implications of advanced phenotyping beyond traditional wall thickness measurements and how AI is critical to its translation.…”