ObjectivesQuantitative computed tomography (CT) plays an increasingly important role in phenotyping airway diseases. Lung parenchyma and airway inflammation could be quantified by contrast enhancement at CT, but its investigation by multiphasic examinations is limited. We aimed to quantify lung parenchyma and airway wall attenuation in a single contrast-enhanced spectral detector CT acquisition.MethodsFor this cross-sectional retrospective study, 234 lung-healthy patients who underwent spectral CT in four different contrast phases (non-enhanced, pulmonary arterial, systemic arterial, and venous phase) were recruited. Virtual monoenergetic images were reconstructed from 40–160 keV, on which attenuations of segmented lung parenchyma and airway walls combined for 5th–10th subsegmental generations were assessed in Hounsfield Units (HU) by an in-house software. The spectral attenuation curve slope between 40 and 100 keV (λHU) was calculated.ResultsMean lung density was higher at 40 keV compared to that at 100 keV in all groups (p< 0.001).λHU of lung attenuation was significantly higher in the systemic (1.7 HU/keV) and pulmonary arterial phase (1.3 HU/keV) compared to that in the venous phase (0.5 HU/keV) and non-enhanced (0.2 HU/keV) spectral CT (p< 0.001). Wall thickness and wall attenuation were higher at 40 keV compared to those at 100 keV for the pulmonary and systemic arterial phase (p≤ 0.001).λHU for wall attenuation was significantly higher in the pulmonary arterial (1.8 HU/keV) and systemic arterial (2.0 HU/keV) compared to that in the venous (0.7 HU/keV) and non-enhanced (0.3 HU/keV) phase (p≤ 0.002).ConclusionsSpectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition, and may separate arterial and venous enhancement. Further studies are warranted to analyze spectral CT for inflammatory airway diseases.Key Points• Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition.• Spectral CT may separate arterial and venous enhancement of lung parenchyma and airway wall.• The contrast enhancement can be quantified by calculating the spectral attenuation curve slope from virtual monoenergetic images.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-023-09514-2.