Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma.
Allergy
; 76(7): 2070-2078, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33411348
ABSTRACT
BACKGROUND:
IL-13 is considered an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL-13 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high-dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways. We have sought to further understand IL-13 in the peripheral airways in severe asthma through bronchoalveolar analysis.METHODS:
Bronchoalveolar lavage samples were collected from 203 asthmatic and healthy volunteers, including 78 with severe asthma. Inflammatory mediators were measured using a multiple cytokine immunoassay platform. This analysis was replicated in a further 59 volunteers, in whom 16S rRNA analysis of BAL samples was undertaken by terminal restriction fragment length polymorphism.RESULTS:
Severe asthma patients with high BAL IL-13, despite treatment with high-dose inhaled corticosteroids, had more severe lung function and significantly higher BAL neutrophil percentages, but not BAL eosinophils than those with normal BAL-13 concentrations. This finding was replicated in the second cohort, which further associated BAL IL-13 and neutrophilia with a greater abundance of potentially pathogenic bacteria in the peripheral airways.CONCLUSION:
Our findings demonstrate a steroid unresponsive source of IL-13 that is associated with BAL neutrophilia and bacterial dysbiosis in severe asthma. Our findings highlight the biological complexity of severe asthma and the importance of a greater understanding of the innate and adaptive immune responses in the peripheral airways in this disease.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Disbiose
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article