BibTex format
@article{Versi:2024:10.1002/ctm2.70007,
author = {Versi, A and Azim, A and Ivan, FX and Abdel-Aziz, MI and Bates, S and Riley, J and Uddin, M and Zounemat, Kermani N and Maitland-Van, Der Zee A-H and Dahlen, S-E and Djukanovic, R and Chotirmall, SH and Howarth, P and Adcock, IM and Chung, KF and UBIOPRED, study group},
doi = {10.1002/ctm2.70007},
journal = {Clinical and Translational Medicine},
title = {A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia},
url = {http://dx.doi.org/10.1002/ctm2.70007},
volume = {14},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Versi,A
AU - Azim,A
AU - Ivan,FX
AU - Abdel-Aziz,MI
AU - Bates,S
AU - Riley,J
AU - Uddin,M
AU - Zounemat,Kermani N
AU - Maitland-Van,Der Zee A-H
AU - Dahlen,S-E
AU - Djukanovic,R
AU - Chotirmall,SH
AU - Howarth,P
AU - Adcock,IM
AU - Chung,KF
AU - UBIOPRED,study group
DO - 10.1002/ctm2.70007
PY - 2024///
SN - 2001-1326
TI - A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia
T2 - Clinical and Translational Medicine
UR - http://dx.doi.org/10.1002/ctm2.70007
UR - https://www.ncbi.nlm.nih.gov/pubmed/39187935
UR - https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70007
VL - 14
ER -