A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia
Ali Versi , Adnan Azim , Fransiskus Xaverius Ivan , Mahmoud I Abdel-Aziz , Stewart Bates , John Riley , Mohib Uddin , Nazanin Zounemat Kermani , Anke-H Maitland-Van Der Zee , Sven-Eric Dahlen , Ratko Djukanovic , Sanjay H Chotirmall , Peter Howarth , Ian M Adcock , Kian Fan Chung
Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (9) : e70007
A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia
Background: Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α-diversity microbiome.
Methods: Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α-diversity of mild-moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).
Findings: Fifty-one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF-κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6-transignalling signature and neutrophil activation.
Conclusion: We describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.
α-diversity / Haemophilus influenzae / metagenome / Moraxella catarrhalis / neutrophils / severe asthma / Tropheryma whipplei
2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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