Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma

Adnan Azim, Ben Green, Laurie Lau, Hitasha Rupani, Nivenka Jayasekera, Kenneth Bruce, Peter Howarth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2070-2078
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume76
Issue number7
Early online date26 Jan 2021
DOIs
Publication statusPublished - Jul 2021

Keywords

  • 16srRNA
  • IL-13
  • neutrophils
  • peripheral airways
  • severe asthma

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