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Background: It is difficult to differentiate between chronic obstructive pulmonary disease (COPD) and asthma in clinics; therefore, for diagnostic purposes, imaging-based measurements could be beneficial to differentiate between the two diseases. Objectives: We aim to analyze quantitative measurements of the lung and bronchial parameters that are provided by low-dose computed tomography (CT) to differentiate COPD and asthma from an imaging perspective. Materials and Methods: 69 COPD patients, 52 asthma patients, and 20 healthy subjects were recruited to participate in CT imaging and pulmonary function tests (PFTs). Comparative analysis was performed to identify differences between COPD and asthma in CT measurements. PFT measurements enabled validation of the differentiation between COPD and asthma patients. Results: There were significant differences among the COPD, asthma, and healthy control groups. The differences were more significant among the following: inspiratory emphysema index (EI)-950 (%), expiratory lung volume, expiratory mean lung density (MLD), and expiratory EI-950 (%) and EI-850 (%). The COPD group had a significantly higher EI-950 (%) than the asthma group (p = 0.008). There were significant differences among the three groups in lumen area (LA), wall area (WA), total area, and Pi10WA. The asthma group had significantly higher WA%/WV% than both the COPD (p = 0.002) and the control group (p = 0.012). There was high sensitivity in EI-950 (%), EI-850 (%) and expiratory MLD in the parenchyma and high sensitivity in LA and Pi10WA in small airways in the differential diagnosis of COPD and asthma. Conclusion: To aid the diagnosis, CT can provide quantitative measurements to differentiate between COPD and asthma patients.