title: Markers of vascular perturbation correlate with airway structural change in asthma.
abstract: BACKGROUND
  Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma.
  
  
  OBJECTIVE
  Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity.
  
  
  METHODS
  Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than -856 Hounsfield units [HU] at functional residual capacity and -950 HU at total lung capacity [TLC]).
  
  
  RESULTS
  VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than -950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements.
  
  
  CONCLUSIONS
  Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities.
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin, 4285A Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA. mwjohansson@wisc.edu
authors.forename: Mats W
authors.initials: MW
authors.lastname: Johansson
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Kruger
authors.forename: Mark L
authors.initials: ML
authors.lastname: Schiebler
authors.forename: Michael D
authors.initials: MD
authors.lastname: Evans
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: Loren C
authors.initials: LC
authors.lastname: Denlinger
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Robert R
authors.initials: RR
authors.lastname: Montgomery
authors.forename: Deane F
authors.initials: DF
authors.lastname: Mosher
authors.forename: Sean B
authors.initials: SB
authors.lastname: Fain
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010978:Platelet Factor 4 / Q000502:physiology; D011498:Protein Precursors / Q000097:blood; D014057:Tomography, X-Ray Computed; D014841:von Willebrand Factor
chemical_list: D019007:P-Selectin; D011498:Protein Precursors; D014841:von Willebrand Factor; C067003:von Willebrand factor propolypeptide; D010978:Platelet Factor 4