Background: The mechanisms underlying airflow obstruction in COPD cannot be distinguished by standard spirometry. We ascertain whether mathematical modeling of airway biomechanical properties, as assessed from spirometry, could provide estimates of emphysema presence and severity, as quantified by computed tomography (CT) metrics and CT-based radiomics. Methods: We quantified presence and severity of emphysema by standard CT metrics (VIDA) and co-registration analysis (ImbioLDA) of inspiratory-expiratory CT in 194 COPD patients who underwent pulmonary function testing. According to percentages of low attenuation area below - 950 Hounsfield Units (%LAA-950insp) patients were classified as having no emphysema (NE) with %LAA-950insp < 6, moderate emphysema (ME) with %LAA-950insp ≥ 6 and < 14, and severe emphysema (SE) with %LAA-950insp ≥ 14. We also obtained stratified clusters of emphysema CT features by an automated unsupervised radiomics approach (CALIPER). An emphysema severity index (ESI), derived from mathematical modeling of the maximum expiratory flow-volume curve descending limb, was compared with pulmonary function data and the three CT classifications of emphysema presence and severity as derived from CT metrics and radiomics. Results: ESI mean values and pulmonary function data differed significantly in the subgroups with different emphysema degree classified by VIDA, ImbioLDA and CALIPER (p < 0.001 by ANOVA). ESI differentiated NE from ME/SE CT-classified patients (sensitivity 0.80, specificity 0.85, AUC 0.86) and SE from ME CT-classified patients (sensitivity 0.82, specificity 0.87, AUC 0.88). Conclusions: Presence and severity of emphysema in patients with COPD, as quantified by CT metrics and radiomics can be estimated by mathematical modeling of airway function as derived from standard spirometry.