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Haemophilus influenzae and moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation

Haemophilus influenzae and moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation
Haemophilus influenzae and moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation

Background: because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. 

Methods: whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). 

Results: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year. 

Conclusions: haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.

haemophilus influenzae, moraxella catarrhalis, severe asthma, tropheryma whipplei, α-diversity, alpha-diversity, Moraxella catarrhalis, Tropheryma whipplei, Haemophilus influenzae
0105-4538
2906-2920
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U-BIOPRED Consortium
Versi, Ali
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Versi, Ali, Ivan, Fransiskus Xaverius and Abdel-Aziz, Mahmoud I. , U-BIOPRED Consortium (2023) Haemophilus influenzae and moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation. Allergy: European Journal of Allergy and Clinical Immunology, 78 (11), 2906-2920. (doi:10.1111/all.15776).

Record type: Article

Abstract

Background: because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. 

Methods: whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). 

Results: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year. 

Conclusions: haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.

Text
Allergy - 2023 - Versi - Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and - Version of Record
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Accepted/In Press date: 24 April 2023
e-pub ahead of print date: 7 June 2023
Published date: November 2023
Additional Information: Funding Information: U‐BIOPRED has received funding from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115010, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007–2013), and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in‐kind contributions ( www.imi.europa.eu ). KFC and IMA are funded by UK Research and Innovation (UKRI). KFC is an Emeritus Senior Investigator of the UK National Institute for Health Research (NIHR). We acknowledge the contribution of the whole U‐BIOPRED team as listed below.
Keywords: haemophilus influenzae, moraxella catarrhalis, severe asthma, tropheryma whipplei, α-diversity, alpha-diversity, Moraxella catarrhalis, Tropheryma whipplei, Haemophilus influenzae

Identifiers

Local EPrints ID: 479948
URI: http://eprints.soton.ac.uk/id/eprint/479948
ISSN: 0105-4538
PURE UUID: a6fc8423-ea22-4778-b88b-b53bd3d592b6
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for A. Postle: ORCID iD orcid.org/0000-0001-7361-0756
ORCID for G. Roberts: ORCID iD orcid.org/0000-0003-2252-1248
ORCID for P.J. Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for S.J. Wilson: ORCID iD orcid.org/0000-0003-1305-8271

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Date deposited: 31 Jul 2023 16:40
Last modified: 18 Mar 2024 03:01

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Contributors

Author: Ali Versi
Author: Fransiskus Xaverius Ivan
Author: Mahmoud I. Abdel-Aziz
Author: Stewart Bates
Author: John Riley
Author: Frederic Baribaud
Author: Nazanin Zounemat Kermani
Author: Paolo Montuschi
Author: Sven Erik Dahlen
Author: Peter Sterk
Author: Anke H. Maitland-Van Der Zee
Author: Sanjay H. Chotirmall
Author: Peter Howarth
Author: Ian M. Adcock
Author: Kian Fan Chung
Author: L.I. Andersson
Author: C. Auffray
Author: Y.E. Badi
Author: P. Bakke
Author: A.T. Bansal
Author: E.H. Bel
Author: J. Bigler
Author: B. Billing
Author: H. Bisgaard
Author: M.J. Boedigheimer
Author: K. Bønnelykke
Author: J. Brandsma
Author: P. Brinkman
Author: E. Bucchioni
Author: D. Burg
Author: A. Bush
Author: V. Goss
Author: Y. Guo
Author: A.J. James
Author: R. G. Knowles
Author: C.X. Li
Author: J.G. Matthews
Author: C.S. Murray
Author: A. Postle ORCID iD
Author: A. Roberts
Author: G. Roberts ORCID iD
Author: A. Rowe
Author: J.P.R. Schofield
Author: D.E. Shaw
Author: P.J. Skipp ORCID iD
Author: K. Sun
Author: B. Thornton
Author: M. Uddin
Author: S.J. Wilson ORCID iD
Corporate Author: U-BIOPRED Consortium

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