Abstract

Ex-smokers without spirometry or CT evidence of chronic obstructive pulmonary disease (COPD) but with mildly abnormal diffusing capacity of the lungs for carbon monoxide (DLCO) are at higher risk of developing COPD. It remains difficult to make clinical management decisions for such ex-smokers without other objective assessments consistent with COPD. Hence, our objective was to develop a machine-learning and CT texture-analysis pipeline to dichotomize ex-smokers with normal and abnormal DLCO (DLCO≥75%pred and DLCO<75%pred). In this retrospective study, 71 ex-smokers (50-85yrs) without COPD underwent spirometry, plethysmography, thoracic CT, and 3He MRI to generate ventilation defect percent (VDP) and apparent diffusion coefficients (ADC). PyRadiomics was utilized to extract 496 CT texture-features; Boruta and principal component analysis were used for feature selection and various models were investigated for classification. Machine-learning classifiers were evaluated using area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and F1-measure. Of 71 ex-smokers without COPD, 29 with mildly abnormal DLCO had significantly different MRI ADC (p<.001), residual-volume to total-lung-capacity ratio (p=.003), St. George's Respiratory Questionnaire (p=.029), and six-minute-walk distance (6MWD) (p<.001), but similar relative area of the lung <-950 Hounsfield-units (RA950) (p=.9) compared to 42 ex-smokers with normal DLCO. Logistic-regression machine-learning mixed-model trained on selected texture-features achieved the best classification accuracy of 87%. All clinical and imaging measurements were outperformed by high-high-pass filter high-gray-level-run-emphasis texture-feature (AUC=0.81), which correlated with DLCO (ρ=-0.29, p=.02), MRI ADC (ρ=0.23, p=.048), and 6MWD (ρ=-0.25, p=.02). In ex-smokers with no CT evidence of emphysema, machine-learning models exclusively trained on CT texture-features accurately classified ex-smokers with abnormal diffusing capacity, outperforming conventional quantitative CT measurements.

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