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Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
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  • Taira Ariyoshi,
  • Junichiro Tezuka,
  • Hiroki Yasudo,
  • Tamaki Nakamura,
  • Yasufumi Sakata,
  • Takeshi Matsushige,
  • Hideki Hasegawa,
  • Noriko Nakajima,
  • Akira Ainai,
  • Atsunori Oga,
  • Hiroshi Itoh,
  • Komei Shirabe,
  • Shoichi Toda,
  • Ryo Atsuta,
  • Shouichi Ohga,
  • Shunji Hasegawa
Taira Ariyoshi
Yamaguchi University Graduate School of Medicine
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Junichiro Tezuka
Fukuoka Children’s Hospital
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Hiroki Yasudo
Yamaguchi University Graduate School of Medicine
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Tamaki Nakamura
Yamaguchi University Graduate School of Medicine
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Yasufumi Sakata
Yamaguchi University Graduate School of Medicine
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Takeshi Matsushige
Yamaguchi University Graduate School of Medicine
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Hideki Hasegawa
National Institute of Infectious Diseases
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Noriko Nakajima
National Institute of Infectious Diseases
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Akira Ainai
National Institute of Infectious Diseases
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Atsunori Oga
Yamaguchi University Graduate School of Medicine
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Hiroshi Itoh
Yamaguchi University Graduate School of Medicine
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Komei Shirabe
Yamaguchi Prefectural Institute of Public Health and Environment
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Shoichi Toda
Yamaguchi Prefectural Institute of Public Health and Environment
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Ryo Atsuta
Akihabara Atsuta Clinic
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Shouichi Ohga
Yamaguchi University Graduate School of Medicine
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Shunji Hasegawa
Yamaguchi University Graduate School of Medicine
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Abstract

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 paediatric 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 FEV1.0 (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<0.001), peaking at 7 days post-infection and then becoming similar to control levels by 10 days post-infection. 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 post-infection than at 10 days post-infection. Conclusions: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.

Peer review status:UNDER REVIEW

14 Sep 2020Submitted to Pediatric Allergy and Immunology
18 Sep 2020Reviewer(s) Assigned