Background:

Haemophilus has been identified as a key pathogen associated with adverse clinical outcomes in asthma. In vitro studies suggest bacteria-driven upregulation of MUC5AC as a potential mechanism (Wang, B et al. J Biol Chem. 2002 Jan 11;277(2):949-57)

Objective:

We analysed the airway microbiome in severe asthma subjects evaluated for evidence of airway remodelling. We hypothesised that relative abundance of Haemophilus in the airway microbiome would be associated with airway epithelial MUC5AC staining.

Methods:

We obtained protected bronchial brushings and biopsies from subjects with severe asthma participating in the RASP-UK bronchoscopy study (Khalfaoui et al. Allergy. 2022 Oct;77(10):2974-2986). 16S rRNA gene sequencing was performed on DNA extracted from brush samples. Biopsy samples were processed for immunohistochemistry (IHC) and stained for epithelial MUC5AC and other remodelling outcomes. 

Results:

37 subjects had paired microbiome and IHC data. Relative abundance of Haemophilus (%) was not significantly correlated with epithelial MUC5AC (% total epithelium stained positive), Spearman ? -0.043. No other associations were observed between Haemophilus and epithelial neutrophils, nor other measures of airway remodelling.

Conclusions:  

Airway mucus is not directly related to the proportion of Haemophilus in the airway microbiome suggesting a more complex relationship between mucus hypersecretion, airway microbial profile and airway inflammation.