TY - JOUR
T1 - Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
AU - Ariyoshi, Taira
AU - Tezuka, Junichiro
AU - Yasudo, Hiroki
AU - Sakata, Yasufumi
AU - Nakamura, Tamaki
AU - Matsushige, Takeshi
AU - Hasegawa, Hideki
AU - Nakajima, Noriko
AU - Ainai, Akira
AU - Oga, Atsunori
AU - Itoh, Hiroshi
AU - Shirabe, Komei
AU - Toda, Shoichi
AU - Atsuta, Ryo
AU - Ohga, Shouichi
AU - Hasegawa, Shunji
N1 - Funding Information:
This study was supported by Grant-in-Aid for Translational Research of Yamaguchi University Hospital 2013. We thank MT Kenzo Ikemoto (Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine) for providing technical support.
Publisher Copyright:
© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
PY - 2021/6
Y1 - 2021/6
N2 - Background: Severe asthma exacerbation is an important comorbidity of the 2009 HIN1 pandemic (A(H1N1)pdm09) in asthmatic patients. However, the mechanisms underlying severe asthma exacerbation remain unknown. In this study, airway hyperresponsiveness (AHR) was measured in pediatric asthma patients infected with A(H1N1)pdm09. We also evaluated AHR in asthmatic mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison. Methods: AHRs in asthmatic children were defined as the provocative acetylcholine concentration causing a 20% reduction in forced expiratory volume in 1 s (PC20). To investigate the pathophysiology using animal models, BALB/c mice aged 6-8 weeks were sensitized and challenged with ovalbumin. Either mouse-adapted A(H1N1)pdm09, seasonal H1N1 virus (1 × 105 pfu/20 μl), or mock treatment as a control was administered intranasally. At 3, 7, and 10 days after infection, each group of mice was evaluated for AHR by methacholine challenge using an animal ventilator, flexiVent. Lung samples were resected and observed using light microscopy to assess the degree of airway inflammation. Results: AHRs in the children with bronchial asthma were temporarily increased, and alleviated by 3 months after discharge. AHR was significantly enhanced in A(H1N1)pdm09-infected asthmatic mice compared to that in seasonal H1N1-infected mice (p <.001), peaking at 7 days postinfection and then becoming similar to control levels by 10 days postinfection. Histopathological examination of lung tissues showed more intense infiltration of inflammatory cells and severe tissue destruction in A(H1N1)pdm09-infected mice at 7 days postinfection than at 10 days postinfection. Conclusion: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.
AB - Background: Severe asthma exacerbation is an important comorbidity of the 2009 HIN1 pandemic (A(H1N1)pdm09) in asthmatic patients. However, the mechanisms underlying severe asthma exacerbation remain unknown. In this study, airway hyperresponsiveness (AHR) was measured in pediatric asthma patients infected with A(H1N1)pdm09. We also evaluated AHR in asthmatic mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison. Methods: AHRs in asthmatic children were defined as the provocative acetylcholine concentration causing a 20% reduction in forced expiratory volume in 1 s (PC20). To investigate the pathophysiology using animal models, BALB/c mice aged 6-8 weeks were sensitized and challenged with ovalbumin. Either mouse-adapted A(H1N1)pdm09, seasonal H1N1 virus (1 × 105 pfu/20 μl), or mock treatment as a control was administered intranasally. At 3, 7, and 10 days after infection, each group of mice was evaluated for AHR by methacholine challenge using an animal ventilator, flexiVent. Lung samples were resected and observed using light microscopy to assess the degree of airway inflammation. Results: AHRs in the children with bronchial asthma were temporarily increased, and alleviated by 3 months after discharge. AHR was significantly enhanced in A(H1N1)pdm09-infected asthmatic mice compared to that in seasonal H1N1-infected mice (p <.001), peaking at 7 days postinfection and then becoming similar to control levels by 10 days postinfection. Histopathological examination of lung tissues showed more intense infiltration of inflammatory cells and severe tissue destruction in A(H1N1)pdm09-infected mice at 7 days postinfection than at 10 days postinfection. Conclusion: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.
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U2 - 10.1002/iid3.406
DO - 10.1002/iid3.406
M3 - Article
C2 - 33470564
AN - SCOPUS:85100192364
SN - 2050-4527
VL - 9
SP - 457
EP - 465
JO - Immunity, inflammation and disease
JF - Immunity, inflammation and disease
IS - 2
ER -