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H influenzae & M catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation
  • +13
  • Kian Fan Chung,
  • Ali Versi,
  • Fransiskus Xaverius Ivan,
  • Mahmoud Ibrahim,
  • Stewart Bates,
  • John Riley,
  • Frederic Baribaud,
  • Nazanin Zounemat Kermani,
  • Paolo Montuschi,
  • Sven-Erik Dahlén,
  • Ratko Djukanovic,
  • Peter Sterk,
  • Anke-Hilse Maitland-van der Zee,
  • Sanjay Haresh Chotirmall,
  • Peter Howarth,
  • Ian Adcock
Kian Fan Chung
Imperial College London National Heart and Lung Institute

Corresponding Author:[email protected]

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Ali Versi
Imperial College London National Heart and Lung Institute
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Fransiskus Xaverius Ivan
Lee Kong Chian School of Medicine
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Mahmoud Ibrahim
Amsterdam University Medical Centers
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Stewart Bates
GSK
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John Riley
GSK
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Frederic Baribaud
Janssen Research and Development High Wycombe
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Nazanin Zounemat Kermani
Imperial College London National Heart and Lung Institute
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Paolo Montuschi
Catholic University of the Sacred Heart
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Sven-Erik Dahlén
Karolinska Institutet
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Ratko Djukanovic
NIHR Southampton Biomedical Research Centre
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Peter Sterk
Amsterdam University Medical Centers
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Anke-Hilse Maitland-van der Zee
Amsterdam University Medical Centers
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Sanjay Haresh Chotirmall
Lee Kong Chian School of Medicine
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Peter Howarth
University of Southampton Faculty of Medicine
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Ian Adcock
Imperial College London National Heart and Lung Institute
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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 was 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.
29 Dec 2022Submitted to Allergy
29 Dec 2022Submission Checks Completed
29 Dec 2022Assigned to Editor
29 Dec 2022Review(s) Completed, Editorial Evaluation Pending
31 Dec 2022Reviewer(s) Assigned
27 Jan 2023Editorial Decision: Revise Minor
29 Mar 20231st Revision Received
29 Mar 2023Review(s) Completed, Editorial Evaluation Pending
29 Mar 2023Submission Checks Completed
29 Mar 2023Assigned to Editor
01 Apr 2023Reviewer(s) Assigned
19 Apr 2023Editorial Decision: Revise Minor
20 Apr 20232nd Revision Received
20 Apr 2023Submission Checks Completed
20 Apr 2023Assigned to Editor
20 Apr 2023Review(s) Completed, Editorial Evaluation Pending
24 Apr 2023Editorial Decision: Accept