Faculty Collaboration Database

Markers of vascular perturbation correlate with airway structural change in asthma. Am J Respir Crit Care Med 2013 Jul 15;188(2):167-78

Date

07/17/2013

Pubmed ID

23855693

Pubmed Central ID

PMC3778758

DOI

10.1164/rccm.201301-0185OC

Scopus ID

2-s2.0-84881157401 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

RATIONALE: 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.

OBJECTIVES: 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]).

MEASUREMENTS AND MAIN 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.

Author List

Johansson MW, Kruger SJ, Schiebler ML, Evans MD, Sorkness RL, Denlinger LC, Busse WW, Jarjour NN, Montgomery RR, Mosher DF, Fain SB

Author

Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Asthma
Bronchi
Endothelium, Vascular
Enzyme-Linked Immunosorbent Assay
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
P-Selectin
Platelet Factor 4
Protein Precursors
Tomography, X-Ray Computed
von Willebrand Factor