Impact of bacterial strain acquisition in the lung of patients with COPD: the AERIS study

on behalf of the AERIS Study Group

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Bacterial infections are associated with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but the mechanism is incompletely understood. Method: In a COPD observational study (NCT01360398), sputum samples were collected monthly at the stable state and exacerbation. Post-hoc analyses of 1307 non-typeable Haemophilus influenzae (NTHi) isolates from 20 patients and 756 Moraxella catarrhalis isolates from 38 patients in one year of follow-up were conducted by multilocus sequence typing (MLST). All isolates came from cultured sputum samples that were analyzed for bacterial species presence, apparition (infection not detected at the preceding visit), or acquisition (first-time infection), with the first study visit as a baseline. Strain apparition or new strain acquisition was analyzed by MLST. The odds ratio (OR) of experiencing an exacerbation vs. stable state was estimated by conditional logistic regression modelling, stratified by patient. Results: The culture results confirmed a significant association with exacerbation only for NTHi species presence (OR 2.28; 95% confidence interval [CI]: 1.12–4.64) and strain apparition (OR 2.38; 95% CI: 1.08–5.27). For M. catarrhalis, although confidence intervals overlapped, the association with exacerbation for first-time species acquisition (OR 5.99; 2.75–13.02) appeared stronger than species presence (OR 3.67; 2.10–6.40), new strain acquisition (OR 2.94; 1.43–6.04), species apparition (OR 4.18; 2.29–7.63), and strain apparition (OR 2.78; 1.42–5.42). This may suggest that previous M. catarrhalis colonization may modify the risk of exacerbation associated with M. catarrhalis infection. Conclusions: The results confirm that NTHi and M. catarrhalis infections are associated with AECOPD but suggest different dynamic mechanisms in triggering exacerbations.

Original languageEnglish
Pages (from-to)784-793
Number of pages10
JournalInfectious Diseases
Volume54
Issue number11
DOIs
Publication statusPublished - 2022
Externally publishedYes

Bibliographical note

Funding Information:
LM, MCM, BS, TGP, VW, LT, JMD, and ND are employed by GSK, and LT, TGP, VW, JMD, and ND hold shares in GSK. VW and JMD are designated inventors on patents owned by GSK. AY was a consultant of ICON for GSK during the conduct of the study and is now employed by GSK. KO received a grant from GSK during the conduct of her Ph.D. DWC reports a grant from GSK during the conduct of this study. SCC received a grant from Pfizer outside of the submitted work and a grant from GSK during the conduct of the study. TMAW has received grants and non-financial support from GSK during the conduct of the study as well as grants from AstraZeneca, Synairgen, and MyMHealth and fees, reimbursement for travel, and meeting attendance from Boehringer Ingelheim, Chiesi, AstraZeneca, Synairgen, and MyMHealth outside of the submitted work. In addition, TMAW has a patent 2018 US Patent 62/479562—Immunogenic Composition, Use and Methods of Treatment—A novel vaccine to prevent exacerbations of COPD pending to GSK and is Founder and Director of MyMHealth Ltd. All authors declare having no other financial and non-financial relationships and activities.

Funding Information:
GlaxoSmithKline Biologicals SA funded this study (NCT01360398) and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge of all costs associated with the development and publication of this manuscript. Members of the AERIS Study Group: J. Alnajar (University of Southampton, Southampton, UK), R. Anderson (University of Southampton, Southampton, UK), E. Aris (GSK, Wavre, Belgium), W.R. Ballou (GSK, Rockville, MD, USA), A. Barton (University Hospital Southampton NHS Foundation Trust, Southampton, UK), S. Bourne (University of Southampton, Southampton, and Portsmouth Hospitals NHS Trust, Portsmouth, UK), M. Caubet (GSK, Wavre, Belgium), S.C. Clarke (University of Southampton, Southampton, UK), D.W. Cleary (University of Southampton, Southampton, UK), C. Cohet (GSK, Wavre, Belgium), N.A. Coombs (University of Southampton, Southampton, UK), K. Osman (University of Southampton, Southampton, UK), J-M. Devaster (GSK, Rixensart, Belgium), V. Devine (University of Southampton, Southampton, UK), N. Devos (GSK, Rixensart, Belgium), E. Dineen (University Hospital Southampton NHS Foundation Trust, Southampton, UK), T. Elliott (University of Southampton, Southampton, UK), R. Gladstone (Wellcome Sanger Institute, Hinxton, UK), S. Harden (University Hospital Southampton NHS Foundation Trust, Southampton, UK), J. Jefferies (University of Southampton, Southampton, UK), V.L. Kim (University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK), P. Moris (GSK, Rixensart, Belgium), K.K. Ostridge (University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK), T.G. Pascal (GSK, Wavre, Belgium), M. Peeters (GSK, Rixensart, Belgium), S. Schoonbroodt (GSK, Rixensart, Belgium), B. Sente (GSK, Rixensart, Belgium), K.J. Staples (University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK), A.C. Tuck (University of Southampton, Southampton, UK), L. Welch (Solent NHS Trust, Southampton, UK), V. Weynants (GSK, Wavre, Belgium), T.M.A. Wilkinson (University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK), A.P. Williams (University of Southampton, Southampton, UK), N.P. Williams (University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK), C. Woelk (University of Southampton, Southampton, UK), M. Wojtas (University of Southampton, Southampton, UK), and S.A. Wootton (University Hospital Southampton NHS Foundation Trust, Southampton, UK). All members of the AERIS Study Group were involved in the planning, conduct, and/or reporting of the work described in the article. The authors thank Stephanie Van Horn and Stephano Censini for their contributions to Moraxella catarrhalis sequencing. The authors also thank Business & Decision Life Sciences and Modis platforms for editorial assistance, manuscript coordination, and writing support, on behalf of GSK. Salomé Murinello (Modis, on behalf of GSK) and Bruno Baudoux (Business & Decision Life Sciences, on behalf of GSK) coordinated manuscript development and editorial support. Joanne Knowles (independent medical writer for Modis and Business & Decision Life Sciences) provided medical writing support.

Publisher Copyright:
© 2022 GlaxoSmithKline Biologicals S.A. Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Exacerbation
  • Moraxella catarrhalis
  • acquisition
  • apparition
  • bacteria
  • non-typeable Haemophilus influenzae

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