Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection

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 pediatric asthma pa...

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Main Authors: 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, Shouichi Ohga, Shunji Hasegawa
Format: Article
Language:English
Published: Wiley 2021-06-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.406
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author 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
Shouichi Ohga
Shunji Hasegawa
author_facet 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
Shouichi Ohga
Shunji Hasegawa
author_sort Taira Ariyoshi
collection DOAJ
description 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 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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spelling doaj.art-57489f5d40f84acd8da5f945df91668c2023-05-08T13:20:47ZengWileyImmunity, Inflammation and Disease2050-45272021-06-019245746510.1002/iid3.406Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infectionTaira Ariyoshi0Junichiro Tezuka1Hiroki Yasudo2Yasufumi Sakata3Tamaki Nakamura4Takeshi Matsushige5Hideki Hasegawa6Noriko Nakajima7Akira Ainai8Atsunori Oga9Hiroshi Itoh10Komei Shirabe11Shoichi Toda12Ryo Atsuta13Shouichi Ohga14Shunji Hasegawa15Department of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Allergy and Pulmonology Fukuoka Children's Hospital Fukuoka JapanDepartment of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Pathology National Institute of Infectious Diseases Tokyo JapanDepartment of Pathology National Institute of Infectious Diseases Tokyo JapanDepartment of Pathology National Institute of Infectious Diseases Tokyo JapanDepartment of Molecular Pathology Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Molecular Pathology Yamaguchi University Graduate School of Medicine Yamaguchi JapanYamaguchi Prefectural Institute of Public Health and Environment Yamaguchi JapanYamaguchi Prefectural Institute of Public Health and Environment Yamaguchi JapanAkihabara Atsuta Clinic Tokyo JapanDepartment of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanDepartment of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi JapanAbstract 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.https://doi.org/10.1002/iid3.406airway resistanceinfluenzapandemicrespiratory function test
spellingShingle 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
Shouichi Ohga
Shunji Hasegawa
Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
Immunity, Inflammation and Disease
airway resistance
influenza
pandemic
respiratory function test
title Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
title_full Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
title_fullStr Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
title_full_unstemmed Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
title_short Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection
title_sort enhanced airway hyperresponsiveness in asthmatic children and mice with a h1n1 pdm09 infection
topic airway resistance
influenza
pandemic
respiratory function test
url https://doi.org/10.1002/iid3.406
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