The upper and lower airway microbiome in severe asthma

Conference item

Introduction: Severe asthma is complex and immunologically heterogenous; airways infection and innate immune dysregulation may confer inhaled corticosteroid resistance and remains clinically challenging. We hypothesise that marked airway microbiome compositional shifts in severe asthma represent a ‘treatable trait’, with dominance of pathogenic species, warranting targeted therapy. Additionally, these changes are thought to be distinct in the paucibacillary lower airway vs. heavily colonised nasopharynx.

Methods: We performed Oxford Nanopore metagenomic sequencing, and RT-qPCR of induced sputum (n=67), bronchoalveolar lavage (BAL;n=71) and nasal lavage (NL;n=28 paired with sputum) samples from the Wessex Severe Asthma Cohort encompassing mild/moderate/severe asthma and health. Findings were integrated with clinical and cytokine data.

Key Results: A dominant pathogenic organism (H.influenzae, S.pneumoniae, M.catarrhalis) was identified in sputua of 21% of patients with severe asthma and accompanied by sputum neutrophilia and elevated type-1 cytokines (including IL-1β, IL-6, IL-8, TNF;p<0.01, unpaired t-test, Benjamini-Hochberg correction). From BAL, airways infection was identified infrequently (Severe asthma, n=1/21 H.influenzae; Mild-Moderate asthma,n=2/25 T.whipplei). Metagenomic analysis of NL demonstrated a distinct microbiome; presence of pathogenic organisms in the upper airways did not predict concurrent presence in sputum of severe asthmatics.

Conclusion: Airways infection is reliably identified in sputum using metagenomic sequencing and is associated with neutrophilic inflammation. The microbiome in the upper and lower airway are distinct and ongoing work is exploring its impact on mucosal immune responses at these sites.

Authors: Jabeen, M; Sanderson, N; Barber, C; Lau, LCK; Pavord, ID

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: European Respiratory Society
• Journal: European Respiratory Journal
• Volume: 60
• Issue: S66
• Article number: 1761
• Publication date: 2022-12-01
• Event title: ERS International Congress 2022
• Event location: Barcelona
• Event website: https://www.ers-education.org/events/international-congress/barcelona-2022/
• Event start date: 2022-09-04
• Event end date: 2022-09-06
• DOI: 10.1183/13993003.congress-2022.1761
• EISSN: 1399-3003
• ISSN: 0903-1936
• Language: English
• Keywords: FFR; bacteria; severe asthma; mirobiome/microbiota