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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Language: | English |
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Wiley
2021-06-01
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Series: | Immunity, Inflammation and Disease |
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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. |
first_indexed | 2024-04-09T13:52:18Z |
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id | doaj.art-57489f5d40f84acd8da5f945df91668c |
institution | Directory Open Access Journal |
issn | 2050-4527 |
language | English |
last_indexed | 2024-04-09T13:52:18Z |
publishDate | 2021-06-01 |
publisher | Wiley |
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series | Immunity, Inflammation and Disease |
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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