Markers Of Vascular Perturbation Correlate With Airway Structural Change In Asthma

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 2856 Hounsfield units [HU] at functional residual capacity and 2950 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 2950 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.

Activation states of blood eosinophils in asthma

“…The N29 signal correlates with eosinophil‐bound or platelet surface P‐selectin in vivo . Thus, in vivo it is most likely the P‐selectin on the surface of activated platelets that is responsible for inducing the intermediate‐activity conformation of β 1 integrins on blood eosinophils , even though a proportion of soluble plasma P‐selectin in asthma appears to be derived from activated endothelial cells . The results on platelet P‐selectin are compatible with data showing that activated platelets promote eosinophil recruitment to the airway in mice in a P‐selectin‐dependent manner and an in vitro study that observed increased complex formation between activated P‐selectin‐bearing platelets and human blood eosinophils from subjects with allergic asthma and indicated that platelet association contributes to the enhanced tethering of such eosinophils to activated endothelium in a P‐selectin‐dependent manner .…”