Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease - 06/09/18
Doi : 10.1016/j.jaci.2017.10.017
Patrick Mallia, PhD a, b, Jessica Webber c, Simren K. Gill, PhD d, Maria-Belen Trujillo-Torralbo, BSc a, Maria Adelaide Calderazzo, MD a, Lydia Finney, MD e, Eteri Bakhsoliani, MSc a, Hugo Farne, MD a, Aran Singanayagam, PhD a, b, Joseph Footitt, PhD a, †, Richard Hewitt, MD a, Tatiana Kebadze a, Julia Aniscenko a, Vijay Padmanaban, MPT b, Philip L. Molyneaux, PhD a, Ian M. Adcock, PhD e, Peter J. Barnes, PhD e, Kazihuro Ito, PhD e, Sarah L. Elkin, PhD a, b, Onn Min Kon, MD a, b, William O. Cookson, PhD f, Miriam F. Moffat, PhD f, Sebastian L. Johnston, PhD a, b, ‡, John S. Tregoning, PhD d, ⁎, ‡ 
a Airway Disease Infection Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
e Airways Disease Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
f Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
b Imperial College Healthcare, National Health Service Trust, London, United Kingdom
c Cardiff University School of Medicine, UHW Main Building Heath Park Cardiff, Cardiff, United Kingdom
d Mucosal Infection and Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, United Kingdom
∗Corresponding author: John S. Tregoning, PhD, Mucosal Infection and Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, United Kingdom.Mucosal Infection and Immunity GroupSection of Virology, Imperial College LondonSt Mary's CampusLondonUnited Kingdom
Abstract |
Background |
Patients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear.
Objectives |
The aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection.
Methods |
We measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function. Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations. Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined.
Results |
Sputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD. In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values. There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load. Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro.
Conclusions |
Airway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations. Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD. This has important implications for the development of nonantibiotic therapeutic strategies for the prevention or treatment of bacterial infection in patients with COPD.
Le texte complet de cet article est disponible en PDF.Key words : Chronic obstructive pulmonary disease, glucose, viral infection, airway inflammation, bacterial infection
Abbreviations used : ASL, BAL, COPD, DTT, GOLD, NL
Plan
| Supported by a Cystic Fibrosis Trust & British Lung Foundation (BLF) Summer Studentship (ss15-7), an Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), Academy of Medical Sciences and Wellcome Trust Starter Grant, Imperial College Antimicrobial Resistance consortium fellowship, Medical Research Council Program Grant G0600879, British Medical Association H.C. Roscoe Fellowships, BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, NIHR Senior Investigator Award, and the NIHR Clinical Lecturer funding scheme. |
|
| Disclosure of potential conflict of interest: P. Mallia's institution received grants from the Imperial College Healthcare Trust Biomedical Research Centre (P33132), an Academy of Medical Sciences and Wellcome Trust Starter Grant, British Medical Association H.C. Roscoe Fellowships, BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, the Imperial College and National Institute for Health Research (NIHR) BRC funding scheme, the NIHR Senior Investigator Award, and NIHR Clinical Lecturer funding scheme for this work. J. Webber received support for travel from Cystic Fibrosis Trust & British Lung Foundation (BLF) Summer Studentship (ss15-7) for this work. S. K. Gill's institution received an Academy of Medical Sciences and Wellcome Trust Starter Grant, an Imperial College Antimicrobial Resistance consortium fellowship, and Medical Research Council Program Grant G0600879 for this work. M.-B. Trujillo-Torralbo's institution received Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, and NIHR Senior Investigator Award for this work. M. A. Calderazzo's institution received Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, and NIHR Senior Investigator Award for this work. L. Finney's institution received Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, and NIHR Senior Investigator Award for this work and is employed by Chiesi Pharmaceuticals. E. Bakhsoliani's institution received an Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), British Medical Association H.C. Roscoe Fellowships, BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, and NIHR Senior Investigator Award for this work. A. Singanayagam's institution received ab Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), British Medical Association H.C. Roscoe Fellowships, BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, an NIHR Senior Investigator Award, and the NIHR Clinical Lecturer funding scheme for this work. R. Hewitt's institution received Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, and NIHR Senior Investigator Award for this work, and he personally received travel support NIHR Academic Clinical Fellowship TCC bursary and ATS International Travel Scholarship 2016. J. Aniscenko's institution received an Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), British Medical Association H.C. Roscoe Fellowships, BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, Imperial College and NIHR BRC funding scheme, and an NIHR Senior Investigator Award for this work. V. Padnamaban received payment from GlaxoSmithKline for lectures and travel expenses from Pfizer. I. M. Adcock's institution received MRC-ABPI COPD-MAP G1001367/1, Wellcome Trust 093080/Z/10/Z, and Dunhill Medical Trust R368/0714 grants for this work and 2 BBSRC and EPSRC grants for other works. P. J. Barnes' and O. M. Kon's institutions received an MRC Project Grant, a Boehringer Ingelheim Programme Grant, and a Wellcome Trust Programme Grant for this work and personally received consulting fees from AstraZeneca, Zambon, and Boehringer Ingelheim for this work; fees for reviews from GlaxoSmithKline and Menarini for this work; and consultancy fees from RespiVert for other works. K. Ito is employed by PULMOCIDE. S. L. Elkin's institution received payment for lectures from AstraZeneca and TEVA and travel expenses from ERS 2016. S. L. Johnston's institution received grants from a Cystic Fibrosis Trust & British Lung Foundation (BLF) Summer Studentship (ss15-7), an Imperial College Healthcare Trust Biomedical Research Centre Grant (P33132), and an Academy of Medical Sciences and Wellcome Trust Starter Grant; an Imperial College Antimicrobial Resistance Consortium Fellowship; Medical Research Council Program Grant G0600879, British Medical Association H.C. Roscoe Fellowships, BLF/Severin Wunderman Family Foundation Lung Research Program Grant P00/2, an Imperial College and NIHR BRC funding scheme, an NIHR Senior Investigator Award, and an NIHR Clinical Lecturer funding scheme for this work and personally received a board membership from Therapeutic frontiers; he personally received consultancy fees from Myelo Therapeutics GmbH, Concert Pharmaceuticals, Bayer, and Sanofi Pasteura, and Aviragen; he and his institution received consultancy fees from Synairgen, Novarits, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Centocor; and he personally received patents (Wark PA, Johnston SL, Holgate ST, Davies DE. Interferon-beta for anti-virus; therapy for respiratory diseases. International patent application no. PCT/GB05/50031 [March 12, 2004]; Wark PA, Johnston SL, Holgate ST, Davies DE. Anti-virus therapy for respiratory diseases. US Patent Application 11/517,763, patent no. 7569216, National Phase of PCT/GB2005/050031 [August 4, 2009]; Wark PA, Johnston SL, Holgate ST, Davies DE. Interferon-beta for anti-virus therapy for respiratory diseases. European patent no. 1734987 [May 5, 2010]; Wark PA, Johnston SL, Holgate ST, Davies DE. Anti-virus therapy for respiratory diseases (IFNb therapy). Hong Kong patent no. 1097181 [August 31, 2010]; Wark PA, Johnston SL, Holgate ST, Davies DE. Anti-virus therapy for respiratory diseases (IFNb therapy). Japanese patent no. 4807526 [August 26, 2011]; Wark PA, Johnston SL, Holgate ST, Davies DE. Interferon-beta for anti-virus therapy for respiratory diseases and New Hong Kong, Divisional Patent Application No. 11100187.0 [January 10, 2011]). J. S. Tregoning's institution received Imperial College Antimicrobial Resistance consortium fellowship and a Medical Research Council Program Grant G0600879 for this work. The rest of the authors declare that they have no relevant conflicts of interest. |
© 2017
The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
Vol 142 - N° 3
P. 815 - septembre 2018 Retour au numéro
Article précédent
- Influenza-derived peptides cross-react with allergens and provide asthma protection
- Chrysanthi Skevaki, Christoph Hudemann, Mikhail Matrosovich, Christian Möbs, Sinu Paul, Andreas Wachtendorf, Bilal Alashkar Alhamwe, Daniel P. Potaczek, Stefanie Hagner, Diethard Gemsa, Holger Garn, Alessandro Sette, Harald Renz
- Targeting of Rac1 prevents bronchoconstriction and airway hyperresponsiveness
- Gwennan André-Grégoire, Florian Dilasser, Julie Chesné, Faouzi Braza, Antoine Magnan, Gervaise Loirand, Vincent Sauzeau
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?