title: Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease.
abstract: BACKGROUND
  Endothelial dysfunction is of interest in relation to smoking-associated emphysema, a component of chronic obstructive pulmonary disease (COPD). We previously demonstrated that computed tomography (CT)-derived pulmonary blood flow (PBF) heterogeneity is greater in smokers with normal pulmonary function tests (PFTs) but who have visual evidence of centriacinar emphysema (CAE) on CT.
  
  
  OBJECTIVE
  We introduced dual-energy CT (DECT) perfused blood volume (PBV) as a PBF surrogate to evaluate whether the CAE-associated increased PBF heterogeneity is reversible with sildenafil.
  
  
  METHODS
  Seventeen PFT-normal current smokers were divided into CAE-susceptible (SS; n = 10) and nonsusceptible (NS; n = 7) smokers, based on the presence or absence of CT-detected CAE. DECT-PBV images were acquired before and 1 hour after administration of 20 mg oral sildenafil. Regional PBV and PBV coefficients of variation (CV), a measure of spatial blood flow heterogeneity, were determined, followed by quantitative assessment of the central arterial tree.
  
  
  RESULTS
  After sildenafil administration, regional PBV-CV decreased in SS subjects but did not decrease in NS subjects (P < 0.05), after adjusting for age and pack-years. Quantitative evaluation of the central pulmonary arteries revealed higher arterial volume and greater cross-sectional area (CSA) in the lower lobes of SS smokers, which suggested arterial enlargement in response to increased peripheral resistance. After sildenafil, arterial CSA decreased in SS smokers but did not decrease in NS smokers (P < 0.01).
  
  
  CONCLUSIONS
  These results demonstrate that sildenafil restores peripheral perfusion and reduces central arterial enlargement in normal SS subjects with little effect in NS subjects, highlighting DECT-PBV as a biomarker of reversible endothelial dysfunction in smokers with CAE.
authors.affiliation: 1 Department of Biomedical Engineering.
authors.forename: Krishna S
authors.initials: KS
authors.lastname: Iyer
authors.affiliation: 1 Department of Biomedical Engineering.|2 Department of Radiology.
authors.forename: John D
authors.initials: JD
authors.lastname: Newell
authors.affiliation: 3 Department of Electrical Engineering, and.
authors.forename: Dakai
authors.initials: D
authors.lastname: Jin
authors.affiliation: 4 Siemens Medical Solutions Inc., Malvern, Pennsylvania.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Fuld
authors.affiliation: 2 Department of Radiology.|3 Department of Electrical Engineering, and.
authors.forename: Punam K
authors.initials: PK
authors.lastname: Saha
authors.affiliation: 5 Division of Pulmonary Medicine, Department of Internal Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: Sif
authors.initials: S
authors.lastname: Hansdottir
authors.affiliation: 1 Department of Biomedical Engineering.|2 Department of Radiology.|5 Division of Pulmonary Medicine, Department of Internal Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000503:physiopathology; D015900:Radiography, Dual-Energy Scanned Projection; D012907:Smoking / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed
keywords: COPD; emphysema; endothelial dysfunction; pulmonary blood flow; sildenafil