Abstract
In vivo presentation of airway hyper-responsiveness (AHR) at the different time points of the allergic reaction is not clearly understood. The purpose of this study was to investigate how AHR manifests in the airway and the lung parenchyma in vivo following exposure to different stimuli and in the early and late phases of asthma after allergen exposure. Ovalbumin (OVA)-induced allergic asthma model was established using 6-week female BALB/c mice. Enhanced pause was measured with a non-invasive method to assess AHR. The dynamic changes of the airway and lung parenchyma were evaluated with ultra-high-resolution computed tomography (128 multi-detector, 1024 × 1024 matrix) for 10 h. While the methacholine challenge showed no grossly visible changes in the proximal airway and lung parenchyma despite provoking AHR, the OVA challenge induced significant immediate changes manifesting as peribronchial ground glass opacities, consolidations, air-trapping, and paradoxical proximal airway dilatations. After resolution of immediate response, multiple episodes of AHRs occurred with paradoxical proximal airway dilatation and peripheral air-trapping in late phase over a prolonged time period in vivo. Understanding of airflow limitation based on the structural changes of asthmatic airway would be helpful to make an appropriate drug delivery strategy for the treatment of asthma.
Highlights
In vivo presentation of airway hyper-responsiveness (AHR) at the different time points of the allergic reaction is not clearly understood
Ultra-high-resolution computed tomography (UHRCT) was performed on BALB/c mice to compare the airway area before and after the methacholine or OVA challenge (Fig. 2)
There was no significant change in the Cardiac Lobe Right Main Bronchus 3 (CaRMB3) area after the methacholine challenge (0.684 ± 0.063 vs. 0.716 ± 0.092, p = 0.629, Fig. 2B) in spite of enhanced Penh (Supplement 2)
Summary
In vivo presentation of airway hyper-responsiveness (AHR) at the different time points of the allergic reaction is not clearly understood. The purpose of this study was to investigate how AHR manifests in the airway and the lung parenchyma in vivo following exposure to different stimuli and in the early and late phases of asthma after allergen exposure. The early asthmatic response (EAR) presents as a rapid bronchoconstriction reaction that usually occurs within 20 min of allergen exposure and improves within a couple of hours without treatment. In order to better understand the airflow dynamics behind AHR, in vivo monitoring of the allergic response to noxious stimuli is needed to evaluate both the immediate and progressive changes of different parts of airway and lungs. This study successfully evaluated such changes in airway dynamics in a non-invasive manner using enhanced pause (Penh) and created a real time, anatomical representation of AHR using Ultra-high-resolution computed tomography (UHRCT)
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