loading page

Enhanced airway hyperresponsiveness in a mouse model of asthma with A(H1N1)pdm09 infection
  • +13
  • Taira Ariyoshi,
  • Junichiro Tezuka,
  • HIROKI YASUDO,
  • Yasufumi Sakata,
  • Tamaki Nakamura,
  • Takeshi Matsushige,
  • Hideki Hasegawa,
  • Noriko Nakajima,
  • Akira Ainai,
  • Atsunori Oga,
  • Hiroshi Itoh,
  • Komei Shirabe,
  • Shoichi Toda,
  • Ryo Atsuta,
  • Shoichi Ohga,
  • Shunji Hasegawa
Taira Ariyoshi
Yamaguchi University Graduate School of Medicine
Author Profile
Junichiro Tezuka
Fukuoka Children’s Hospital
Author Profile
HIROKI YASUDO
Yamaguchi University Graduate School of Medicine
Author Profile
Yasufumi Sakata
Yamaguchi University Graduate School of Medicine
Author Profile
Tamaki Nakamura
Yamaguchi University Graduate School of Medicine
Author Profile
Takeshi Matsushige
Yamaguchi University Graduate School of Medicine
Author Profile
Hideki Hasegawa
National Institute of Infectious Diseases
Author Profile
Noriko Nakajima
National Institute of Infectious Diseases
Author Profile
Akira Ainai
National Institute of Infectious Diseases
Author Profile
Atsunori Oga
Yamaguchi University Graduate School of Medicine
Author Profile
Hiroshi Itoh
Yamaguchi University Graduate School of Medicine
Author Profile
Komei Shirabe
Yamaguchi Prefectural Institute of Public Health and Environment
Author Profile
Shoichi Toda
Yamaguchi Prefectural Institute of Public Health and Environment
Author Profile
Ryo Atsuta
Akihabara Atsuta Clinic
Author Profile
Shoichi Ohga
Kyushu University
Author Profile
Shunji Hasegawa
Yamaguchi University Graduate School of Medicine
Author Profile

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. Using a mouse model of asthma, we evaluated airway hyperresponsiveness (AHR) in mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison. We also measured AHR in paediatric participants infected with A(H1N1)pdm09. Methods: 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. AHRs in paediatric participants were defined as the provocative acetylcholine concentration causing a 20% reduction in FEV1.0 (PC20). Results: Airway resistance 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. AHRs in the paediatric participants were temporarily increased, and alleviated by 3 months after discharge. Conclusions: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.