Small-Airway Dysfunction is Involved in the Pathogenesis of Asthma: Evidence from Two Mouse Models
| Autor: | Yan Zhou, Huijuan Hao, Wuping Bao, Min Zhang, Qiang Fu, Lei Han, Dongning Yin, Yingying Zhang, Yishu Xue, Xue Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Spirometry Vital capacity spirometry Inflammation airway inflammation FEV1/FVC ratio Journal of Asthma and Allergy medicine Immunology and Allergy small airway Original Research Asthma Lung medicine.diagnostic_test business.industry airway hyperresponsiveness asthma respiratory system medicine.disease Mucus respiratory tract diseases Bronchoalveolar lavage medicine.anatomical_structure Immunology medicine.symptom business |
| Zdroj: | Journal of Asthma and Allergy |
| ISSN: | 1178-6965 |
| Popis: | Yishu Xue,* Wuping Bao,* Yan Zhou,* Qiang Fu, Huijuan Hao, Lei Han, Dongning Yin, Yingying Zhang, Xue Zhang, Min Zhang Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Min ZhangDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, Peopleâs Republic of ChinaEmail maggie_zhangmin@163.comBackground: There has been growing evidence of small-airway dysfunction in patients with asthma. Few studies have evaluated the mechanism of small-airway dysfunction in mouse models of asthma.Purpose: We explored the correlation between small-airway spirometric variables and large-airway function or inflammation in different endotypes of asthma.Methods: Ovalbumin (OVA) sensitization/challenge was used to produce a type 2 (T2)-high asthma model, and OVA combined with ozone exposure (OVA + ozone) was used for the T2-low asthma model with increased neutrophils. Spirometry, airway responsiveness, cytokine levels in bronchoalveolar lavage fluid (BALF), and pathological analyses of lung slices stained with hematoxylin-eosin, periodic acidâSchiff, and Massonâs trichrome stain were all determined. Muc5ac expression in lung tissue was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR), and alpha-smooth muscle actin was measured by immunohistochemistry.Results: Inflammatory cells infiltrated the lung tissue and inflammatory cytokines were increased in the BALF of both the OVA and OVA + ozone groups, compared with the control group. Peribronchial hypersecretion and collagen deposition were evident in the models. The OVA + ozone group showed greater neutrophilic infiltration and peribronchial smooth muscle proliferation than the OVA group. Large-airway obstruction, small-airway dysfunction, and airway hyperresponsiveness were confirmed in both models. Small-airway functional variables, such as MMEF (mean midexpiratory flow, average flow from 25 to 75% forced vital capacity [FVC]) and FEF50 (forced expiratory flow at 50% of FVC), were positively correlated with large-airway function and had a stronger negative correlation with airway inflammation, mucus secretion, and responsiveness than large-airway function.Conclusion: Small-airway dysfunction was evident in the two endotypes of asthma and was correlated with severe airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The small airways may be an important target in asthma treatment, and further research in the role of small-airway variables in the pathogenesis of asthma is warranted.Keywords: small airway, spirometry, airway inflammation, asthma, airway hyperresponsiveness |
| Databáze: | OpenAIRE |
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