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Sci Rep. 2021;11(1):17584.

Ultra-high-resolution computed tomography shows changes in the lungs related with airway hyperresponsiveness in a murine asthma model.

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제1저자 정재우, 오정석, 배보람 · 교신저자 강혜련, 이창현

소속 (10)
  1. Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
  2. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
  3. Department of Radiology, Catholic University, Seoul St. Mary's Hospital, Seoul, Korea.
  4. Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
  5. Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
  6. Department of Bioengineering, University of Kansas, Lawrence, KS, USA.
  7. Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
  8. Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea. helenmed@snu.ac.kr.
  9. Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea. helenmed@snu.ac.kr.
  10. Department of Radiology and Institute of Radiation, Seoul National University College of Medicine, Seoul National University Hospital, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea. changhyun.lee@snu.ac.kr.

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.

© 2021. The Author(s).

Figures

Figure 1
Figure 1 Mouse model of ovalbumin-induced asthma and study protocol. (A) Establishment of ovalbumin-induced asthma murine model, (B) noninvasive whole body plethysmography and UHRCT after methacholine challenge, (C) serial noninvasive whole body plethysmography and UHRCT after OVA challenge for 10 h in asthma model.
Figure 2
Figure 2 Airway changes during early phase reaction after methacholine and OVA challenge. (A) CaRMB3 change after methacholine challenge in control group, (B) CaRMB3 change after methacholine challenge in asthma group, (C) CaRMB3 change after OVA challenge in control group. (D) CaRMB3 change after OVA challenge in asthma group. In the control group, there was no change after methacholine or OVA challenge. The asthma group mice showed no significant change of airways to methacholine challenge. However, they showed slight but significant increase of airways to OVA challenge.
Figure 3
Figure 3 Parenchymal changes during early phase reaction in asthma model. (A) Baseline image before methacholine challenge. (B) Image of 5 min after methacholine challenge. (C) Baseline image before OVA challenge. (D) Image of 5 min after OVA challenge. Methacholine challenge did not induce any parenchymal changes nor bronchial changes. However, prominent peribronchial attenuation developed along with dilation of bronchus by OVA challenge.
Figure 4
Figure 4 Serial changes of Penh up to 10 h after OVA challenge. (A) Serial mean Penh after OVA challenge. (B–F) Penh change in each mouse 1–5. As all together, two peaks representing EAR and LAR were observed. However, interestingly some mice showed multiple peaks of LAR.
Figure 5
Figure 5 Corresponding changes of airway and Penh. (A) Serial changes of Penh after OVA challenge during 10 h. (B) Serial changes of CT imaging. When Penh increased, bronchial diameter significantly increased.
Figure 6
Figure 6 Correlation between imaging parameters. (A) In mouse 1, serial changes of Penh, bronchial diameter and bronchial area up to 10 h after OVA challenge. (B) Correlation between Penh and bronchial diameter. (C) In mouse 1, serial changes of bronchial area and lung histogram after OVA challenge. (D) Correlation between bronchial area and lung histogram. Penh was well correlated with diameter and area. Reduced airflow is correlated with wider bronchial diameter. Bronchial area was negatively correlated with lung histogram. These changes in proximal airway are also closely correlated with air trapping in periphery.

그림 출처: PubMed Central 공개 논문 (PMC8413288)

Conflict of interest statement

The authors declare no competing interests.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Scientific reports · eISSN 2045-2322
전자 출판
2021-09-02
MeSH
Animals · Asthma / chemically induced / diagnostic imaging / pathology · Bronchial Hyperreactivity / diagnostic imaging / etiology / pathology · Disease Models, Animal · Female · Lung / diagnostic imaging / pathology · Mice · Mice, Inbred BALB C · Respiratory Hypersensitivity / diagnostic imaging / etiology / pathology · Tomography, X-Ray Computed
참고문헌
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